2-Quinoxalinol Based Schiff Base Ligands in Copper(II)-Mediated C-H Activation by Yuancheng Li A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama Aug 4 th , 2012 Keywords: 2-Quinoxalinol, Schiff Base, Copper(II), Allylic Oxidation Copyright 2012 by Yuancheng Li Approved by Anne E. V. Gorden, Chair, Associate Professor of Department of Chemistry and Biochemistry Stewart Schneller, Professor of Department of Chemistry and Biochemistry Michael Squillacote, Associate Professor of Department of Chemistry and Biochemistry Christian Goldsmith, Associate Professor of Department of Chemistry and Biochemistry Jack DeRuiter, Professor of Department of Pharmacal Sciences ii Abstract As environment and energy issues become of increasing concern, so too does our awareness of the impacts of chemical industry. Numerous successful attempts toward ?green? or ?greener? chemistry have been made. Among these, transition metal mediated homogeneous catalysis is of great interest to us because of its broad capability and fundamental importance. In this dissertation, Cu(II) catalyzed allylic oxidation reactions are investigated. 2- quinoxalinol is introduced as the backbone to a series of new salen ligands to adjust the electronic properties of their Cu(II) complexes. The allylic oxidation of steroids is investigated using tert-butyl hydroperoxide (TBHP) as the oxidant. A variety of ? 5 -steroidal substrates are selectively oxidized to the corresponding enones. Excellent yields are achieved (up to 99% under optimized conditions) while significantly reduced reaction time is required as compared to other current oxidation methods. In addition, simple olefin substrates are also oxidized using the same catalyst. Excellent yields are achieved (up to 99%) within a very short reaction time and with great tolerance for additional functional groups. Using the oxidation of simple alkenes as a probe, mechanistic studies are performed using Raman spectroscopy, cyclic voltammetry, and theoretical calculations. It is believed that the Cu(II) complex binds to TBHP to form the tert- butyl peroxo- Cu(II) complex that undergoes a homolytic cleavage of the O-O bond of the peroxo-. The resulting species will carry out the oxidations of substrates. Besides salen-type ligands, a tridentate Schiff base ligand with 2-quinoxalinol as backbone is also employed to the oxidation reaction. UV-Vis spectroscopy and cyclic voltammetry are employed to study the iii electronic properties of such tridentate ligand bound Cu(II) complex. It has been found that the tridentate ligand bound Cu(II) complex exhibited different electronic properties from the tetradentate salen-type ligand bound Cu(II) complex. Theoretical calculation provides two different possible reaction pathways leading to the same product exist during the reaction when the tridentate ligand bound Cu(II) complex is used as catalyst. One of the pathways involves the homolytic cleavage of the O-O bond of the peroxo Cu(II) complex, while, the other pathway undergoes a direct H atom abstraction. The experimental results suggest the concurrence of two different reaction pathways. iv Acknowledgments First, I would love to express my sincere gratitude to my advisor, Dr. Anne E. V. Gorden, who has been mentoring me since I started my graduate study at Auburn University. She is not only an excellent supervisor in science, but also a very good friend in life. This dissertation would not be accomplished without her guidance and persistent help. I would also like to thank my committee members, Dr. Stewart Schneller, Dr. Michael Squillacote, Dr. Christian Goldsmith, and Dr. Jack DeRuiter, for their help with my research, publications, and dissertation. Especially during the writing of this dissertation, they have been continuously supportive when I was overwhelmed by all kinds of things. In addition, my deepest appreciation also belongs to my beloved wife and collaborator. Thank you! Last but not least, I want to thank the department of chemistry and biochemistry, and all the faculties, lab-mates, and colleagues that helped me. I have learnt a lot during my study at Auburn, and I believe I will benefit from this experience through my life. v Adapted with permission from Li, Yuancheng; Wu, Xianghong; Lee, Tae Bum; Isbell, Eleanor, K.; Parish, Edward J.; Gorden, Anne E. V. J. Org. Chem., 2010, 75 (5), 1807-1810. Copyright (2010) American Chemical Society. Li, Yuancheng; Lee, Tae Bum; Wang, Tanyu; Gamble, Audrey V.; Gorden, Anne E. V. J. Org. Chem., 2012, 77 (10), 4628-4633. Copyright (2012) American Chemical Society. vi Table of Contents Abstract.........................................................................................................................................ii Acknowledgments........................................................................................................................iv List of Tables ..............................................................................................................................vii List of Figures............................................................................................................................viii List of Schemes............................................................................................................................. x Chapter 1 Introduction ................................................................................................................. 1 Chapter 2 Salqu Cu(II) Catalyzed Allylic Oxidation of ? 5 -Steroids ......................................... 15 Chapter 3 Oxidation of Simple Olefins Using a Salqu Cu(II) Complex ................................... 30 Chapter 4 2-Quinoxalinol Based Tridentate Schiff Base Ligand in Cu(II) Mediated Allylic Oxidation................................................................................................................... 49 Chapter 5 Conclusion and Future Work .................................................................................... 70 Chapter 6 Experimental Section ................................................................................................ 76 References ............................................................................................................................... 137 vii List of Tables Table 2.1 Oxidation of steroids using optimized condition........................................................ 20 Table 2.2 Oxidation of steroids using further optimized conditions .......................................... 25 Table 2.3 Calculations of free energies of model radicals.......................................................... 29 Table 3.1 Cu(II) Salqu Catalyzed Allylic Oxidation of Olefins ................................................. 38 Table 4.1 Tridentate Cu(II) Complex 3 Catalyzed Allylic Oxidation of Olefins ....................... 54 viii List of Figures Figure 1.1 Jacobsen?s catalyst....................................................................................................... 5 Figure 1.2 CuSalen and tetrahydrosalen CuSalen red ................................................................... 11 Figure 1.3 Structures of 2-quinoxalinol, diamino-2-quinoxalinol,salqu-imine, asymmetric salqu ligand, complex 2, complex 1, complex 3. ............................................................... 13 Figure 2.1 Complex 1 and complex 2......................................................................................... 17 Figure 2.2 Isolated yields with reaction time and isolated yields with oxidant ratio.................. 18 Figure 2.3 Resonance structures of 7-radical species (upper) and 4-radical species (lower)..... 27 Figure 3.1 Cu(II) salqu complex 1 and complex 2 ..................................................................... 32 Figure 3.2 Cu(II) Effects of oxidant ratio and solvents on reaction yields................................. 34 Figure 3.3 Cu(II) Resonance Raman spectroscopy of Cu(II) salqu with TBHP ........................ 41 Figure 3.4 Cyclic voltamagram of Cu(II) salqu with supporting electrolyte 0.1 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 and 1 mM ferrocene internal standard, reference Ag/AgCl, counter electrode Pt gauze (A = 0.77 cm 2 ), and the working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ) ............................. 43 Figure 3.5 Cu(II) Spin density of [LCu(III)] + with 0.0004 a.u. isosurface density (L = salen and salqu)......................................................................................................................... 45 Figure 4.1 Structures of complex 1 (catalyst for allylic oxidation), complex 2 (catalyst for benzylic oxidation), complex 3, and diamino-2-quinoxalinol.................................. 51 Figure 4.2 UV-vis spectra of salqu ligand, salqu Cu(II) complex 1, and tridentate Cu(II) complex 3................................................................................................................................. 56 Figure 4.3 Cyclic voltamagram of salqu ligand with supporting electrolyte 0.04 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 , reference Ag/AgCl, counter electrode Pt gauze (A = 0.77 cm 2 ), and the working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ). Scan rate = 100 mV/s .............................................................. 58 ix Figure 4.4 MS spectrum of reaction solution using regular TBHP as the oxidant under 18 O 2 atmosphere ................................................................................................................ 69 Figure 5.1 Structures of complex 1 (catalyst for allylic oxidation), complex 2 (catalyst for benzylic oxidation), complex 3, and diamino-2-quinoxalinol.................................. 71 x List of Schemes Scheme 1.1 Consensus Mechanism for the Oxidation Reaction Catalyzed by GOase .............. 10 Scheme 2.1 Further optimization of reaction conditions............................................................ 23 Scheme 3.1 Decomposition of tert-Butyl Peroxy Ether under Basic Condition ........................ 36 Scheme 3.2 Possible Reaction Pathways of LCu(II)OOtBu....................................................... 42 Scheme 3.3 Postulated Catalytic Cycle for Allylic Oxidation Catalyzed by Cu(II) Salqu......... 46 Scheme 4.1 Synthesis of 2-Quinoxalinol Based Tridenate Schiff Base Ligand......................... 53 Scheme 4.2 Calculated Reaction Pathway 1 for Allylic Oxidation using Complex 3 as the Catalyst .................................................................................................................. 60 Scheme 4.3 Calculated Reaction Pathway 2 for Allylic Oxidation using Complex 3 as the Catalyst .................................................................................................................. 64 1 Chapter 1 Introduction As we as a society are becoming increasingly conscious of the environmental impacts of chemical industry, how to make the best use of limited natural resources is of tremendous concern. One of the contributions from chemists is the proposal of the concept of ?green chemistry?. Green chemistry, also known as environmentally benign chemistry or sustainable chemistry, is the philosophy of chemical research and engineering that encourages the design of products and processes that minimize the use and generation of hazardous substances. 1 The term ?green chemistry? was first coined in 1991 by the chemist Paul Anastas. In 1998, Paul Anastas and John Warner developed the ?12 principles of green chemistry?. 1 These principles have served as guidelines for chemists to achieve the goal of lowering the ecological footprint of industry and covered concepts including: designing processes to be atom economical (i.e, maximizing the amount of raw material that ends up in the product) using more environmentally friendly or less toxic chemicals whenever possible, including solvents; designing more energy efficient processes (e.g. eliminating purification steps), using catalytic rather than stoichiometric reagents, and reducing wastes produced instead of remediating them afterwards. 1 Great strides have been made towards the goal of ?green? or ?greener? chemistry since people realized its importance. Numerous successful outcomes related to the media 2 in which chemical reaction are performed are well documented. 2-17 For example, the applications of ionic liquids as chemical reaction environment have been extensively investigated and characterized. 3-5 Unlike conventional industrial solvents, most of which are volatile organic compounds (VOCs), ionic liquids are salts in the liquid state, and thus provide little/no vapor pressure. Hence, the replacement of traditional solvents by ionic liquids can prevent the emission of VOCs, a major source of environmental pollution. 3 In addition, ionic liquids can dissolve enzymes, 18 and form versatile biphasic systems for separations. 19 Ionic liquids can also be highly conducting. 20 These extraordinary physical and chemical properties enable ionic liquids to be excellent media for a variety of organic and inorganic reactions. 21-23 Another driving force behind the research towards the application of ionic liquid relies on its diversity. There are at least one million binary ionic liquids, and 1018 ternary ionic liquids that are potentially applicable to chemical processes, 2 however, only about 600 molecular solvents are currently in use. 2 Such a large combination allows for the design and adjustment of ionic liquids for the optimization of the reaction yields, region/chemo-selectivity, substrate solubility, product separation, and even enantioselectivity. 2,24 Ionic liquids are not always ?green?, as the starting materials used to produce them can be extremely toxic. 24 Consequently, while we can benefit from ionic liquids, extra care must be taken to avoid risk. Another approach to ?green? media is to use water as reaction solvent. As a solvent, water has many unique properties, such as high heat capacity, a high dielectric constant, extensive hydrogen bonding, and a wide range of reaction temperature. 17,25,26 Many accomplishments have been made for using water as a solvent or as a cosovlent in chemical reactions. Water has been proven to enhance the rates and to affect the 3 selectivity of a wide range of organic reactions, such as Diels-Alder reactions, 27-33 1,3- dipolar cycloadditions, 34-43 azodicarboxylates cycloadditions, 27 Claisen rearrangement, 27,44 Passerini and Ugi reactions, 45-48 nucleophilic substitution reactions, 49- 52 carbon-carbon bond formation, 39,53-55 bromination reactions, 56-58 and certain oxidations and reductions. 59-64 In spite of these advantages and accomplishments, water is still not commonly used in organic synthesis. One major issue that prevents water from being used widely is that most organic compounds do not dissolve in water to a significant extent requiring the use of cosolvents; however, the involvement of organic solvents can diminish or even cancel out the initial benefits brought by using water as solvent. Investigations are being undertaken to overcome this problem. 17 Besides using alternative reaction media, one other strategy is to use little or no solvent. The benefits arising from solvent-free/high concentration processes include cost saving and a large reduction in reactor size. Many reactions have been successfully carried out under solvent-free condition, such as polymerizations, 65-68 radical additions, 65,69,70 ionic reactions, 71-77 solid-state reactions, 78-81 and photochemical reactions. 78,82-84 The catalyst efficiency and enantioselectivity of enantioselective transformations are usually very sensitive to solvent. 85,86 As a result, the optimizations that can be brought about by tuning solvent properties and concentrations are disabled under solvent-free conditions. Moreover, in solvent-free reactions, the medium will change as the reagents convert to products during the reaction processes. The impacts of the changes are currently unpredictable and this complicates their development and practical use. 13 Reactions under solvent-free conditions can also be highly exothermic. The generated heat can also subsequently affect the reaction ? in particular, the selectivity 4 for a specific product. Thus, it is crucial to attend to this type of reactions closely to keep them under control. 13 In addition to altering the reaction media, another strategy toward ?green? or ?greener? chemistry is to improve the efficiency of reactions, and improve the overall yield of a desired product using fewer synthetic steps. This has numerous benefits, including the elimination of protection/deprotection steps during synthesis and the reduction of the amount of solvents needed for purification. One key strategy to improve overall reaction yields is through the addition of a catalyst. A catalyst is a compound that takes part in a reaction, leading to an increased reaction rate, but it is not consumed during the overall reaction. 87 Catalysts can be categorized into non-metallic based (organo-) and metallic based (organometallic or coordination compounds) catalyst systems. Among numerous types of catalytic strategies, transition metal mediated homogeneous catalysis is of great interest to us because of its broad capability and fundamental importance. In particular, my research focuses on the application of 2- quinoxalinol based Schiff base ligands in the copper-mediated catalysis. A Schiff base is a compound containing the functional group of carbon-nitrogen double bond with the nitrogen connected to a non-hydrogen group. Due to their ease of preparation and the ability to form stable complexes with a wide array of metal ions, 88-91 Schiff base compounds have been extensively used as ligands in a wide range of fields, such as pharmaceutics and biology. 92-94 They also have played several key roles in catalysis. One of the most successful applications is in the enantioselective epoxidation as catalyzed by Jacobsen?s catalyst, (Figure 1.1) whose ligand bears two Schiff bases and 5 N N O O Mn Cl Figure 1.1. Jacobsen?s catalyst 6 two phenolate units, forming a tetradentate chelating environment of the type [O, N, N, O]. This type of ligand is named salen, coming from its two precursors: salicylic aldehyde and ethylene diamine. 95 In catalysis, salen and related structures have proved effective metal catalyst ligand supports. Salen type ligands can form stable complexes with main group metals to help aid in catalytic transformations, providing solubility and modulating accessibility to the metal center. For example, salen-Al complexes can be used to facilitate Michael additions with excellent enantioselectivity. 96,97 Other notable work has included the enantioselective formal hydration of ?,?-unsaturated imides catalyzed by a salen-Al complex. 98 This conversion used to be quite challenging to accomplish in good yields in part due to the relative weakness of O-nucleophiles and the reversibility of the reaction. 98- 100 In addition to main group metals, numerous catalytic systems involving salen supported transition metals have been documented. Ti salen complexes have proved to be effective for asymmetric ring opening of epoxides. 101 It has also been reported that Ti salen complexes can catalyze the asymmetric addition of KCN and Ac 2 O to aldehydes to prepare cyanohydrin esters with excellent enantioselectivity. 102,103 The products of this reaction are very useful intermediates, and are widely used in organic synthesis. 104-114 Ti salen complexes are also used as the catalysts in the enantioselective oxidation of cyclic dithioacetals 115 and the enantioselective coupling of aryl aldehydes to form diol analogs. 116 Cr salen complexes catalyze a wide range of enantioselective transformations, such as asymmetric ring opening, 117,118 the allylation of aldehyde, 119-121 and the aminolytic kinetic resolution (AKR) of epoxdies. 122 The coupling of CO 2 into aziridines 7 can be catalyzed by Cr salen complex as well, 123 leading to the 5-substituted oxazolidinone products that exhibits antibacterial activity and are widely used in the pharmaceutical industry. 124-128 As noted above, Jacobsen?s catalyst, i.e. Mn salen complex, is excellent for the asymmetric epoxidation of olefins. 129 This transformation is one of the most important reactions in organic chemistry and has been investigated extensively by many chemists. 130,131 The resultant chiral epoxide products are versatile intermediates that can be further converted to many chiral synthetic building blocks. 132-136 Ru salen complexes can be used to catalyze the oxidation of primary alcohols to aldehydes 137 and the asymmetric sulfimidations. 138-140 The latter can be further used in the olefination of aldehydes to address the problems encountered in Witting reaction. 141-143 Co salen complexes are capable of catalyzing a wide range of reactions, including asymmetric ring opening of epoxides, 144-147 asymmetric intramolecular cyclopropanation, 148 enanitoselective Baeyer-Villiger oxidation, 149 oxidation of alcohols to carboxylic acids and ketones, 150,151 arylation of azole heteroarenes, 152,153 hydrolytic kinetic resolution (HKR) of terminal epoxides, 154 and enantioselective cyclopropanation. 155 Among all the transition metals, copper is of particular interest to us. Copper is widely used in metalloenzymes for oxygen binding, activation, and reduction. 156 For instance, hemocyanin, an oxygen transport protein, uses two copper atoms to bind dioxygen reversibly. 157 Dopamine ?-monooxygenase (D?M) is a copper-containing metalloenzyme that catalyze the oxidation of dopamine to norepinephrine. This enzyme is crucial to organism because of its role in controlling the levels of the neurotransmitters/hormones dopamine and norepinephrine. 158 Copper Amine Oxidases 8 (CAOs) are widely distributed in nature. They can be found in bacteria, yeast, plants, and mammals. 159,160 The function of CAOs is to convert primary amines to aldehydes. In prokaryotes, CAOs allows the microorganisms to grow on primary amines as a nitrogen source via an oxidative release of ammonium ion; whereas in eukaryotes, they regulate biogenic amine levels through oxidative metabolism. 158 Galactose Oxidase is a fungal protein consisting of a single polypeptide chain with one copper atom per active center. 161,162 It catalyzes the two-electron reduction of O 2 to hydrogen peroxide and the oxidation of primary alcohols to aldehydes. 156,158 Tyrosinase, one of the most well- studied multicopper oxygenases, is ubiquitous among eukarya. 163 It contains a coupled binuclear copper active site that catalyzes the ortho-hydroxylation of monophenols and the subsequent two-electron oxidation of ortho-diphenols to ortho-quinones. Its numerous mutations play a wide range of physiological roles in different living systems. 164 Dopamine ?-hydroxylase (D?H) and peptidylglycine ?-hydroxylating monooxygenase (PHM) also have binuclear copper sites, although the two coppers are not coupled. 156,158 One copper center is thought to be responsible for the hydrogen atom abstraction from the substrate, as the other copper provides one electron to form hydroperoxide. 156,158 Another class of copper-containing metalloenzyme is monooxygenase, such as methane monooxygenase (pMMO) and ammonia monooxygenase (AMO). pMMO is a copper-containing membrane-bound metalloenzyme 165 that catalyzes the monooxygenation of methane to methanol in methanotrophic eubacteria. 163 AMO is a membrane-bound protein that catalyzes the monooxygenation of ammonia to hydroxylamine. This transformation is the first step of the oxidation of ammonia to nitrite, and is used by ammonia-oxidizing eubacteria to 9 produce energy. 163 In addition to ammonia, AMO can also catalyze the oxidation of a variety of hydrocarbons, 166 halogenated organic, 163 carbon monoxide, 163 and thioethers. 167 To better understand these functions of the enzymes, copper salen complexes have been studied as functional mimics. 168-170 It has been demonstrated that salen Cu(II) complexes are models for galactose oxidase (GOase). 169,170 GOase is responsible for the aerobic oxidation of primary alcohols to aldehydes in living system. 171 The oxidation reaction involves a copper atom and a cysteine-modified tyrosine residue. It is commonly believed that the oxidized form of enzyme (GOase ox ) contains a Cu(II)-tyrosine radical. This reactive intermediate binds primary alcohols in an exchangeable fashion, followed by hydrogen abstraction and electron transfer from the alcoholic substrate to Cu center leading to the formation of aldehyde product and the reduced form of enzyme (GOase red ). (Scheme 1.1) In the investigation of using salen Cu(II) complex (Figure 1.2) as model for GOase, the oxidizing half-reaction (oxidation of primary alcohols into aldehydes) is successfully duplicated. 169 This study also showed that salen is a non-innocent ligand in its Cu(II) complex. The oxidation of the Cu-salen complex resulted in a metal-base product [Cu(III)Salen] + in the solid state; however, a temperature-dependent equilibrium existed in solution between high-valent metal form [Cu(III)Salen] + and ligand-radical form [Cu(II)Salen?] + , in which the [Cu(III)Salen] + form is stabilized at low temperature. 170 In addition, investigations with the reduced tetrahydrosalen Cu(II) species [CuSalen red ] + suggested that this oxidized complex existed as a temperature-independent species [Cu(II)Salen red ] + in solution. In the oxidation of benzyl alcohol to benzaldehyde, [CuSalen red ] + exhibited faster reactivity compared to [CuSalen] + , even though [CuSalen] + is a much stronger oxidant. 168 The conflicting results might stem from the more 10 Scheme 1.1. Consensus Mechanism for the Oxidation Reaction Catalyzed by GOase. Cu(II) N His N His O O S GOase ox RCH 2 OH (II) Cu N His N His OH O O S H H R (II) Cu N His N His OH O O S R H H (a) (b) (C) Cu(I) N His N His OH HO S O R H GOase red (a) Binding of primary alcohol to the Cu(II) center and subsequent deprotonation by the axial tyrosine ligand. (b) Hydrogen abstraction by the organic radical cofactor, resulting in a ketyl radical intermediate. (c) Electron transfer from the bound radical substrate to the Cu(II) center, leading to the formation of Cu(I) and aldehyde product. 11 CuSalen CuSalen red Figure 1.2. CuSalen and tetrahydrosalen CuSalen red 12 unfavorable axial substrate binding to Cu(III) of [Cu(III)Salen] + species than to Cu(II) of [Cu(II)Salen red ] + species. 170 2-Quinoxalinol is a highly conjugated heterocyclic compound. (Figure 1.3) The advantages of substituting the ethylenediamine compound of salen with 2-quinoxalinol include: (1) the conjugation of 2-quinoxalinol will extend to the phenolic moieties through Schiff bases resulting in a more conjugated system. Since subtle changes in ligand structure can have big influence on the metal center, 168 this new system should possess different electronic properties from salen structure and may provide unique features when used as a catalyst. (2) The diamino-2-quinoxalinol intermediate (Figure 1.3) has two chemically different amino groups at the 6- and 7-positions. The 6-amino group is more reactive. 172 This feature allows the preparation of the tridentate Schiff base ligand Salqu-imine (Figure 1.3) and the asymmetric salqu ligand (Figure 1.3), whose phenolic moieties are different. 172 Neither the tridentate Schiff base ligands nor the asymmetric salen-type ligand has been investigated previously as a catalyst support. Previously, the benzylic oxidation of a methylene (CH 2 ) group into a carbonyl using Salqu Cu(II) complex 2 (Figure 1.3) as catalyst has been reported. 173 The salqu Cu(II) complex exhibited an improved catalytic effect as compared to the salen Cu(II) complex and has a low sensitivity with respect to moisture and air. The rationale for the superiority of salqu ligand was not immediately clear. In this dissertation, the salqu Cu(II) complex 1 (Figure 1.3) has been used to promote the allylic oxidations of ? 5 -steroids and simple olefin substrates using tert-butyl hydroperoxide (TBHP) as the terminal oxidant. Mechanistic studies were also performed to characterize the catalytic cycle of salqu Cu(II) complex 1, and determine why it is a better catalyst than the salen analog. 13 N N OH N NN H 2 N OH R 1 OH R 2 2-quinoxalinol diamino-2-quinoxalinol Salqu-imine N NN N OH R 1 OH R 2 OH R 3 N NN N OH O O (II)Cu asymmetric salqu complex 2 N NN N OH O O (II)Cu complex 1 complex 3 Figure 1.3. Structures of 2-quinoxalinol, diamino-2-quinoxalinol,salqu-imine, asymmetric salqu ligand, complex 2, complex 1, complex 3. 14 Furthermore, a 2-quinoxalinol based tridentate Schiff base ligand is also used to prepare a Cu(II) complex 3 (Figure 1.3), which also promotes allylic oxidations. In spite of the similar oxidation results, complex 1 and complex 3 exhibit different electronic characteristics. Theoretical calculations also indicate a possible alternative reaction mechanism. 15 Chapter 2 Salqu Cu(II) Catalyzed Allylic Oxidation of ? 5 -Steroids Easy access to the 7-keto-? 5 -steroids can be achieved via allylc oxidation of ? 5 - steroids, and the oxidations of ? 5 -steroids have attracted significant attention because of the biological and physiological properties of the resultant 7-keto-? 5 -steroid prodcucts. 174-183 Although a variety of chromium(VI) compounds have been used in the synthetic modifications of ? 5 -steroids, 177,184-188 complications in applying these methods remain because of the harsh reaction conditions required and the frequently very difficult work-up and/or purification procedures. In addition, the accumulations of chromic acid or chromium salt wastes that are the side products of these reactions are of great environmental concern. 189 To complete such modifications in a more environmentally friendly yet still efficacious manner, other metal complexes/salts have been employed, such as sodium chlorite, 190 copper iodide, 178 dirhodium caprolactamate, 191 ruthenium trichloride, 192 bismuth salt, 193 cobalt acetate, 194 palladium(II) salts, 195 and manganese(III) acetate; 196 however, numerous limitations remain. All of these methods must strike a balance between good yields and functional group compatibility and they continue to suffer from long reaction time requirements. Oxidations using manganese(III) acetate and dirhodium caprolactamate as catalysts are two more recent representative examples of the current methods. 191,196 The use of manganese(III) acetate allowed for excellent yields in ? 5 -steroidal oxidation under ambient temperature when tert-butyl hydroperoxide (TBHP) 16 was used as the oxidant. The reaction times were reduced remarkably when the reaction mixture was heated, but with a significant loss in yield. This method is also not compatible with some sensitive functionalities near allylic sites (e.g. hydroxyl group). 196 The use of dirhodium caprolactamates as the catalyst in such an allylic oxidation showed a wide tolerance for a variety of functional groups, yet it also had only moderate yields. 191 Previously, a catalytic system that consists of salqu Cu(II) complex 2 (Figure 2.1) as the catalyst and TBHP as the oxidant has been reported. 173 This system was demonstrated to oxidize benzylic methylenes into carbonyl groups in near quantitative yields with the use of catalyst loading of 1 mol % and 3 equiv of TBHP when different functional groups remained intact. On the basis of this previous success, we sought to modify this system to develop mild conditions that would retain satisfying yields and also be efficacious for allylic oxidations. The investigation began by using salqu Cu(II) complex 2 (Figure 2.1) as the catalyst and pregnenolone acetate 4 as the substrate (eq. 1). Two factors were varied to determine the optimal reaction conditions: reaction time and oxidant ratio. The oxidation was performed on a millimole scale using 1 mol % of catalyst complex 2. CH 3 CN/CHCl 3 (50/50) was chosen as the solvent to dissolve the steroids. The solution was heated to 70 ?C, and then the TBHP was added. The reaction progress was followed by thin layer 17 N NN N OHO O (II)Cu Complex 1 Complex 2 Figure 2.1. Complex 1 and complex 2. 18 53 64 68 68 0 20 40 60 80 100 3 6 12 16 Reaction Time (hour) Yie l d ( % ) 38 54 64 60 0 20 40 60 80 100 3 6 10 20 Oxidant Ratio, TBHP (equiv.) Yie l d ( % ) Figure 2.2. Isolated yields with various reaction times and oxidant ratios (equiv. to steroidal substrate). 19 chromatography (TLC). When the reaction was judged to be complete, the solution was concentrated under reduced pressure, and the residue was purified by flash column chromatography using hexane/ethyl acetate as eluent. Initially, 10 equiv of TBHP was used to determine the optimal reaction time (Figure 2.2). The isolated yields slightly increased when the reaction time was extended from 3 h to 12 h, and did not change when the time was elongated from 12 h to 16 h. Because there is little difference in isolated yields between 6 h and 16 h, the reaction time was set to 6 h to optimize the oxidant ratio (Figure 2.2) A general trend of increasing isolated yield was observed as the oxidant ratio was increased from 3 equiv to 20 equiv. The highest yield was achieved when 10 equiv of TBHP was used, and the additional amount of oxidant did not result in a higher yield. It is remarkable that the remaining starting material, pregnenolone acetate 3, was recovered after reaction time of 6 h. When carried out at ambient temperature, the reaction rate was found to be much slower (51% isolated yield for 24 h and 65% isolated yield for 48 h). In the absence of the catalyst complex 2, only 39% isolated yield was obtained after being heated for 6 h at 70 ?C. A variety of ? 5 -steroidal substrates were oxidized using these optimized conditions with 1 mol % of catalyst loading and 10 equiv of oxidant TBHP heated to 70 ?C for 12 h (Table 2.1). The even more challenging oxidation of 3-hydroxy-? 5 -steroids can also be successfully realized with a small decrease in yields (Table 2.1, entry 5 and 6); however, in all cases, the mass balance was found to be the unreacted steroidal starting materials, and these were readily recovered. Given the fact that the structurally similar salen Cu(II) complexes have been shown to slowly decompose in most organic solvents 169 and the 20 Table 2.1. Oxidation of steroids using optimized conditions. R 1 R 2 R 3 CH 3 CN/CHCl 3 70 ?C 12 h 1 mol % complex 1 10 equiv TBHP R 1 R 2 R 3 O Entry Substrate Yield (%) 1 64 2 O H O 62 3 O H O O 55 4 O H O 61 21 5 44 6 53 7 49 22 observation that the color of the reaction solution changes from its initial red to yellowish during the course of the reaction, it would appear that the ligand-metal complex 2 was consumed to some extent as the reaction proceeded. To verify this hypothesis, the oxidation of cholesteryl chloride was carried out in CH 3 CN and CHCl 3 independently. Interestingly, the reaction in CH 3 CN had an isolated yield of 57%; whereas, the one in CHCl 3 had only 28% isolated yield, despite the fact that complex 2 has much better solubility in CHCl 3 than in CH 3 CN. According to the consensus radical mechanism of current allylic oxidation methods using TBHP, 191,196,197 the reason for this lower yield is likely the stabilizers added to the commercially purchased CHCl 3 that can function as radical scanvengers. The reaction was then repeated, this time using CDCl 3 as solvent. Since the NMR solvent CDCl 3 does not contain stabilizers as commercially available CHCl 3 does, the reaction in CDCl 3 should have a higher yield than that in CHCl 3 . Indeed, 48% isolated yield was achieved. Thus, it is clearly shown that the oxidation reaction proceeds better in CH 3 CN than in CHCl 3 , and the results of reactions in CHCl 3 and CDCl 3 are in accordance with the hypothesis about stabilizers. Although a negative factor was found, the mystery of complex 2 appearing to be consumed over the course of the reaction remained. It was then decided to change the reaction procedure conditions to increase the catalyst loading and amount of oxidant slightly by adding additional portions of them. Cholesteryl chloride was used for this additional further optimization (Scheme 2.1). Here, the reaction was performed in CH 3 CN at 70 ?C, and 0.5 mol % of complex 2 and 5 equiv of TBHP were added simultaneously with multiple portions used. For cholesteryl 23 Scheme 2.1. Further optimization of reaction conditions. 1mmol cholesteryl chloride, 0.5 mol% complex1, 5 equiv. TBHP, 10ml CH 3 CN time period 1 Add 5 equiv. TBHP and 0.5 mol% complex 1 time period 2 Add 5 equiv. TBHP and 0.5 mol% complex 1 Add 5 equiv. TBHP and 0.5 mol% complex 1 Column chromatography separation time period 3 time period 4 time period 3 + time period 4 Column chromatography separation 73% 97% 24 chloride, 3 portions of catalyst and oxidant gave an isolated yield of 73% while the addition of 4 portions resulted in 97% isolated yield. For the reaction using 3 portions, after the addition of the third portion, the reaction was let react for the same length of time as if the fourth portion had been added. The same reaction time consumed in total confirms the necessity of the fourth addition of catalyst and oxidant. Different ? 5 -steroidal substrates were tested using these additional optimized reaction conditions (Table 2.2). For each substrate, different numbers of portions were tested to find optimal conditions. Cholesteryl acetate required 3 portions (each addition contains 0.5 mol % of complex 2 and 5 equiv of TBHP) to achieve 99% yield (Table 2.2, entry 1); benzoyl protected pregnenolone required 5 portions to get 77% yield (Table 2.2, entry 2). Simple cholesterol only required 2 portions (Table 2.2, entry 3) while pregnenolone and cholesteryl chloride each required 4 portions (Table 2.2, entry 4 and 5). Generally excellent yields were obtained albeit the unprotected substrates had generally lower yields than the protected ones. The addition of subsequent additional portions of catalyst and oxidant did not increase yields. The benzoyl protected cholesterol is oxidized in significantly lower yield than other protected steroids even though 5 portions were added. This could be due to the insolubility of substrate in CH 3 CN. In ? 5 -steroids, there are two potentially reactive allylic sites. These two sites do not have much difference in reactivity at first glance; however, from our series of reactions, only the 7-keto products were obtained. From the resonance structures, this difference in reactivity becomes clear (Figure 2.3). The species bearing a radical at the 7-position will have two possible resonance structures, one of which is a tertiary radical, and this can significantly lower the energy. Meanwhile, the species bearing a radical at the 4-position 25 Table 2.2. Oxidation of steroids using further optimized conditions. Entry Substrate Yield (%) 1 O H O 97 a 2 O H O O 77 b 3 69 c 4 88 d 26 5 99 d a 3 Portions of TBHP and complex 1 were used. b 5 Portions of TBHP and complex 1 were used. 1 ml CHCl 3 was added to help dissolve the substrate. c 2 Portions of TBHP and complex 1 were used. d 4 Portions of TBHP and complex 1 were used. 27 Figure 2.3. Resonance structures of 7-radical species (upper) and 4-radical species (lower). 28 also has two possible resonance structures, but neither contributes to the lower energy state. Of course, the preference of reactivity is also affected by the configuration of the steroids. This speculation about the origins of regioselectivity was later supported by theoretical study and computational modeling. Compound 5 was selected as a model to examine the energy differences between the species bearing radicals at two different sites through ab initio computational studies at the B3LYP/6-31G(2d,p) level using the Gaussian03 package (Table 2.3). The free energy at 298 K of the 7-position radical is less than that of the 4-position radical by 3.43 kcal/mol. The relative stability becomes more significant (6.21 kcal/mol) when calculations with the more complicated steroid molecule (pregnenolone acetate 4) were performed with the same level of theory. A series of calculations were carried out for the model compound 5 bearing different functional groups. In each case, compounds with the radical at the 7-position were more stable (lower in energy) than those at the 4-position. It is interesting that the trend of energy difference bearing different functional groups is in agreement with the trend of numbers of portions needed for the corresponding subtrates (See Table 2.2, entry 1, 3, and 5). In summary, a novel system for allylic oxidation of ? 5 -steroids using TBHP as the oxidant with salqu Cu(II) complex as the catalyst has been demonstrated. A variety of ? 5 - steroids can be selectively converted to the corresponding enones with excellent yields (up to 99% under optimized conditions) with a significantly reduced reaction compared to other current methods. This system also exhibits the tolerance for a variety of functional groups and low sensitivity to air and water. In addition, the regioselectivity is studied from the substrate point of view via theoretical calculation. 29 Table 2.3. Calculations of free energies of model radicals. Model molecule Relative stability of C7 vs V4 radical a (kcal/mol) -3.43 O O O 4 -6.21 -4.65 Cl -2.85 O O -3.38 OO -3.30 a Value reported as ?G at 298 K. 30 Chapter 3 Oxidation of Simple Olefins Using a Salqu Cu(II) Complex The regioselective activation and subsequent oxidation of the allylic C-H bonds is of great interest. Enone or enedione products from such reactions are commonly used as building blocks in multistep organic synthesis. 198,199 Direct transformation of alkenes to the corresponding ?,?-unsaturated enones or 1,4-enediones are particular important, because of their wide potential for applications in the synthesis of pharmaceuticals and related natural products. 200-207 Although non-metal based allylic oxidations have been reported, 208-210 there has been wide interest on the study of highly efficient metal catalyzed allylic oxidations. 190,191,193,196,197,211-221 Extensive research has been carried out where tert-butyl hydroperoxide (TBHP) was used as the oxidant with various metal catalysts, such as chromium compounds, 211,212 sodium chlorite, 190 copper iodide, 222 dirhodium caprolactamate, 191,197,216-218 ruthenium trichloride, 192 bismuth salt, 193 cobalt acetate, 219,220 palladium(II) salts, 213-215 manganese(III) acetate, 196 and ferric chloride. 221 While promising results are reported, numerous limitations remain, e.g., harsh reaction conditions, difficult workup and/or purification procedures, production of harmful waste, low functional group tolerance, and high cost. In addition, there are two major drawbacks of the current methods using TBHP as oxidant: long reaction times and low regioselectivity of the tert-butyl peroxy radical, resulting in numerous isomers formed as byproducts (eq. 3.1). 197 The first disadvantage has been addressed to some extent by 31 researchers in Doyle group using a dirhodium caprolactamate system, with which the reaction could be completed in 1 hour. 216 In this system, since tBuOO? still formed and acted as an oxidant, the lack of regioselectivity remains a concern. 197 Although the most effective metal catalysts for allylic oxidations are those that are capable of carrying out 1- electron redox processes, such as Cu(I)/Cu(II), 216,223 little research has been using Cu for catalyzing allylic oxidation, even though Cu is widely used in naturally occurring metalloenzymes to facilitate synthesis. 156 For example, galactose oxidase (GOase), a copper-containing metalloenzyme secreted by the fungus Fusarium spp., is critical in the oxidation of primary alcohols to aldehydes. 224,225 Previously, our group reported a catalytic system that consists of Salqu Cu(II) complex 2 (Figure 3.1) as the catalyst and used TBHP as the oxidant for the oxidation of benzylic methylenes into carbonyl groups in quantitative yields. 173 When our interest shifted from benzylic oxidation to allylic oxidation, several questions arose: (1) will the salqu Cu(II) complex be able to catalyze the allylic oxidation as well, and (2) if so, what is the regioselectivity of the salqu Cu(II)/TBHP system? In benzylic oxidation, there was only one reactive site where reaction could happen, while in allylic oxidation reaction could occur at multiple sites. The first question is answered by the results of the allylic oxidation of various ? 5 -steroidal substrates (Chapter 2), while the second one remains unclear. In the oxidation of ? 5 -steroids, the regioselectivity was studied from the substrate?s perspective. The more stable 7-radical and the geometry of steroids made a great contribution to the regioselectivity of the 32 N NN N OHO O (II)Cu Complex 1 Complex 2 Figure 3.1. Cu(II) salqu complex 1 and complex 2. 33 reaction; however, these determining factors from thermodynamics and geometry disappear when we turn to the oxidation of simple olefin substrates. Based on our previous success, 226 salqu Cu(II) complex 1 is employed in the allylic oxidation of simple olefins to address the commonly encountered problems as found in other similar catalytic systems, specifically, long reaction time, low selectivity, harsh conditions, low functional group tolerance, and high cost. 190,191,193,196,197,212-221 In addition, these reactions are probed to better characterize the reactivity of the copper complex and the nature of catalytic mechanism, and thus subsequently gain insight as to how to further exploit this complex as catalyst. Investigations began by examining the allylic oxidation of 1-acetyl-1-cyclohexene 6 using salqu Cu(II) complex 1 as the catalyst (eq. 3.2). For ease of comparison with other catalytic systems, the oxidation reaction was carried out on a millimole scale using catalyst loading of 0.5 mol %. Acetonitrile (CH 3 CN) was first used as solvent for the optimization of TBHP ratio needed. The reaction was monitored by gas chromatography (GC). Within 1 h of reaction, the yield of the corresponding 1,4-enedione product (7) increased from 65% to 99% when the TBHP ratio changed from 1 equiv to 3 equiv. Further additions of TBHP did not result in further improvement in yield (Figure 3.2). It is worth noting that the salqu Cu(II) system only requires 3 equiv of TBHP, which is much less than other catalytic methods (5 equiv to 10 equiv). Theoretically, only 1 equiv of TBHP is consumed in the allylic oxidation of olefins to enones; however, excess 34 65 77 99 99 99 0 20 40 60 80 100 12345 oxidant ratio, TBHP (equiv) Yi e l d ( % ) 36 41 99 12 68 0 20 40 60 80 100 DCM Chloroform Acetonitrile DMSO DMF Yie l d ( %) Figure 3.2. Effects of oxidant ratio and solvents on reaction yields. 35 TBHP is required because of decomposition of TBHP during the reaction process. The lower requirement for TBHP in the salqu Cu(II) system is indicative of the better activation of TBHP, and hence a different yet more efficient manner of using it. Using 3 equiv of TBHP and 0.5 mol % of complex 1, different solvents were also tested for 1-acetyl-1cyclohexene 6 for 1 h (Figure 3.2). Reaction yields in 1 h are used as the indicators for reaction rates. Reactions proceeded much more slowly in dichloromethane and chloroform than in acetonitrile. This is consistent with our previous observation in the oxidation of ? 5 -steroids (Chapter 2). The reaction in DMF had a moderate yield, while the yield of the reaction in DMSO was extremely low. In chapter 2, the effects of chloroform and acetonitrile as solvents were discussed. It is believed that the stabilizers often found in commercially available chloroform can function as radical scavengers and consequently lead to the lower yields; however, the results here of reactions in different solvents suggest the possibility of another negative factor. One noticeable feature that distinguishes acetonitrile from other solvents is oxygen solubility. Oxygen has a greater solubility in acetonitrile (8.1 mM) than in most other commonly used organic solvents, such as DMF (4.5 mM) and DMSO (2.1 mM). 227 To determine whether the oxygen concentration has an influence on the reaction rate, a control experiment was performed in CH 3 CN degassed with argon. In this case, only 18% yield was observed after 1 h of reaction as compared to 99% yield in regular acetonitrile. This result indicated the crucial role of dioxygen in this conversion. The surprisingly low yields in DMSO could be ascribed to the ligation of the solvent molecule by the catalyst complex, which prevents the catalyst from functioning normally. 228 In most metal-catalyzed allylic oxidations using TBHP as the oxidant, the addition of 36 Scheme 3.1. Decomposition of tert-Butyl Peroxy Ether under Basic Conditions. 37 base would accelerate the reaction because of the facile decomposition of the tert-butyl peroxy ether intermediates under basic conditions (Scheme 3.1); 214,216,229 however, the addition of 50 mol % of K 2 CO 3 did not bring any change to the reaction rate in our system. This result suggested two possibilities: (1) the decomposition of tert-butyl peroxy ether intermediate is not the rate-determining step, or (2) the tert-butyl peroxy ether intermediate was not formed. Since the decomposition of tert-butyl peroxy ether is known to be slow and can be greatly accelerated by the addition of base, 214,216,229 the reaction time should decrease with the addition of a base if tert-butyl peroxy ether is formed in our system. Thus, it is reasonable to rule out the first scenario. A reaction mechanism bypassing the formation of tert-butyl peroxy ether represents a new and an alternative pathway to those reported previously. 196,213-216 Such a mechanism might consequently lead to improved selectivity because additional isomers can be obtained as side products along with the formation of desired peroxy ether (eq. 3.1). 197,214,215 Allylic oxidations of a variety of representative olefins are examined using 0.5 mol % of complex 1 and 3 equiv of TBHP in CH 3 CN at 70 ?C (Table 3.1). Most of the substrates were converted to the corresponding products with excellent yields within a very short reaction time. The low yield for 1-nitro-1-cyclohexene (Table 3.1, entry 11) could be due to strong binding between the nitro group and the Cu(II) of complex 1 that would poison the catalyst. It could also arise from the strong electron withdrawing capability of the nitro group that could destabilize the radical intermediate. Also worth noting is that 3-methyl-1-cyclohexene and 1-methyl-1-cyclohexene yielded the same oxidation product (Table 3.1, entry 4 and 5). This is further evidence indicative of a radical mechanism. 38 Table 3.1. Cu(II) Salqu Catalyzed Allylic Oxidation of Olefins. O 0.5 mol% complex 1 3 equiv TBHP CH 3 CN 70 ?C Entry Substrate Product Time (h) Yield a (%) 1 1 74 2 O O 1 99 3 Ph O 1 91 88 b 4 O 1 86 5 O 1 78 6 O OAc 2 88 7 O O O 2 89 8 1 94 39 9 CN O 1 94 10 NO 2 NO 2 O 24 11 a GC yields with 1,2-dichlorobenzene added as internal standard. b Isolated yield obtained from flash column chromatography using hexane/ethyl acetate (4:1) as eluent. 40 To further explore the nature of this catalytic cycle, additional experiments were performed. It has been documented that TBHP can easily bind to tridentate mononuclear Cu(II) species to form a Cu(II) tert-butyl peroxo complex whose crystal structure showed a distorted tetrahedral binding geometry of Cu(II) center. 230 By comparing the resonance Raman spectra of LCu(II)OOtBu and LCu(II) 18 O 18 OtBu obtained at 77 K with an excitation at 568.2 nm, 5 peaks at 471, 640, 754, 834, and 884 cm -1 assigned to the O-O moiety, while the one at 754 cm -1 was very small. 231 Little has been done to demonstrate the binding of TBHP to a tetradentate mononuclear Cu(II) complex. Resonance Raman was also employed to provide evidence about the binding between TBHP and salqu Cu(II) (Figure 3.3). The peaks at 596, 749, 915, and 955 cm -1 are in a similar pattern with reported resonance Raman data associated with the O-O moiety from TBHP upon binding. 231 All these bands shifted from 70 to 120 cm -1 to greater wavenumbers as compared to reported data, indicating a higher vibration frequency of the O-O moiety, i.e., a higher energy for the O-O bond. For the Cu(II) tert-butyl peroxo intermediate, the two possible energetically favorable reaction pathways are (1) reductive cleavage of the Cu-O bond forming Cu(I) and tert- butyl peroxyl radical, or (2) the homolytic cleavage of the O-O bond caused by direct H atom abstraction from the substrate resulting in a Cu(III)-oxo and tert-butyl alcohol (Scheme 3.2). 231 Given the fact that the addition of 50 mol % of K 2 CO 3 to the reaction of 1-acetyl-1-cyclohexene did not bring in change to the reaction rate, indicating that the intermediacy of tert-butyl peroxy ether did not form, the reductive cleavage of the Cu-O bond was not likely to occur in the salqu Cu(II) catalytic system. Although it is challenging to prove the formation of Cu(III)-oxo, it is notable that Cu(III) can be 41 Figure 3.3. Resonance Raman spectroscopy of Cu(II) salqu with TBHP. 400 460 520 580 640 700 760 820 880 940 wavenumber(cm -1 ) Cu salqu+tbhp 749 915 524 553 596 674 955 42 Scheme 3.2. Possible Reaction Pathways of LCu(II)OOtBu. 43 0.00 0.30 0.60 0.90 1.20 1.50 1.80 E vs. Ag/AgCl (V) 10 ?A Fc+/Fc Figure 3.4. Cyclic voltamagram of Cu(II) salqu with supporting electrolyte 0.1 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 and 1 mM ferrocene internal standard, reference Ag/AgCl, counter electrode Pt gauze (A = 0.77 cm 2 ), and the working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ). 44 stabilized by a non-innocent ligand, such as salen. 169,170 Cyclic voltammetry with salqu Cu(II) demonstrated two quasi-reversible oxidations (E?? = +547, +802 mV vs Fc + /Fc) (Figure 3.4) that could be ascribed to the sequential single electron oxidations of the phenolic moieties. 169 The pattern of quasi-reversible CV peaks of salqu Cu(II) complex suggested the capability of stabilizing Cu(III) by enabling the equilibrium between [Cu(III)L] + and [Cu(II)L?] + as seen in previous reports with salen complexes. 169,170 Calculation at the B3LYP/6-311+G(d,p) level also showed that a salqu ligand could stabilize Cu(III) better than salen by enhancing the spin density dispersion on the heterocyclic quinoxalinol backbone, i.e. the spin density of triplet [Cu(III)L] + is more delocalized with salqu ligand than salen ligand (Figure 3.5). In addition, an EPR signal loss during the reaction was observed. From the oxidation reaction of 1-acetyl-1-cyclohexene, 1 mL of solution was taken after 30 min and EPR spectrum was collected from it. Only typical organic radial signal was observed. Such signal loss suggested the transformation of an EPR-active species (LCu(II), d 9 ) to an EPR-silent species. This could be rationalized in terms of the formation of a LCu(I) d 10 species, or a low-spin, diamagnetic Cu(III) d 8 species that equilibrates with a ferromagnetically coupled Cu(II)-ligand-radical species as reported previously with salen Cu(II) complex. 170 Based on the study, it is reasonable to believe that TBHP will bind to salqu Cu(II) complex (LCu(II)) at the beginning of the reaction (Scheme 3.3). As mentioned before, the resulting Cu(II) tert-butyl peroxo complex 8 is likely to undergo a homolytic cleavage of the O-O bond upon reacting with substrate, yielding tert-butyl alcohol, allylic radical 45 Figure 3.5. Spin density of [LCu(III)] + with 0.0004 a.u. isosurface density (L = salen and salqu). 46 Scheme 3.3. Postulated Catalytic Cycle for Allylic Oxidation Catalyzed by Cu(II) Salqu. tBuOH O O O 2 tBuOOH LCu(II) O O tBu LCu(II) O LCu(III) O + OO O 2 LCu(I) LCu(II) 8 910 11 12 13 47 9, and LCu(II)-O?/LCu(III)=O 10. As proved earlier, dioxygen played a crucial role in this system. One possible way for dioxygen to participate is to react with the allylic radical to form allylic peroxyl radical 11 that can be converted to enone product. The active copper complex 10 can also react with the allylic radical 9 resulting in LCu(I) 12 and allylic oxyl radical 13, the latter can be converted to enone as well. Both LCu(I) and LCu(II)-O?/LCu(III)=O are EPR-silent species. The postulated formation of LCu(I) and LCu(II)- O?/LCu(III)=O is in agreement with the observation in EPR experiment. Copper at oxidation state of +1 favors a tetrahedral geometry, while the rigid salqu ligand only provides a square planar environment. Hence, the oxidation of LCu(I) 12 to LCu(II) will easily occur. This could be another place where a reaction with dioxygen is involved. In addition, the mismatch of Cu(I) and the binding geometry gives an explanation of the earlier observation of salqu Cu(II) catalyst becoming consumed in the steroid oxidation. Further kinetic studies will be performed to better exploit the reaction mechanism. 226 By using this proposed catalytic cycle, the regioselectivity and other experimental results can be well explained. The allylic radical 9 is formed by H atom abstraction when olefin reacted with LCu(II)OOtBu 8, instead of H atom abstraction by tBuOO?. Because of the bulkiness of the reactive Cu(II) peroxo core induced by the two tert-butyl groups from the ligand, the H atom abstraction would prefer to take place at the less sterically hindered position. The regioselectivity is thus enhanced. For 3-methyl1-1-cyclohexene (Table 3.1, entry 5), the radical formed at the 3-position is thermodynamically more favored, while the radical at the 6-position is sterically more favored. Since the methyl group provids little steric bulkiness, the formation of the energetically favored intermediate overrides the other. Once the radical formed at the 3-position, the enone 48 product was energetically more favored than the allylic alcohol than can be formed by the oxidation at 3-position. In addition, the reaction at the 1-position of the radical intermediate was sterically favored. Affected by these factors, the oxidation of 3-methyl- 1-cyclohexene did not have yield as good as other substrate. In the cyclic voltammetry experiment, although the oxidation potentials of the Cu(II) salqu complex were 100 and 150 mV higher than those of the Cu(II) salen complex (+450, +650 mV vs Fc + /Fc in CH 2 Cl 2 at the same scan rate), 169 indicating the more difficult formation of the [Cu(II)L?] + , no direct electron transfer from the salqu ligand was required in this system based on the proposed catalytic cycle. In summary, a highly regioselective allylic oxidation of olefins to enones or 1,4- enediones using salqu Cu(II) complex as the catalyst is demonstrated. Excellent yields (up to 99%) can be achieved in a very short reaction time. Tolerance with a variety of functional groups is exhibited. The behavior of Cu(II) salqu complex as catalyst is studied to explain the regioselectivity, and a different mechanism of using TBHP from current methods is provided. 49 Chapter 4 2-Quinoxalinol Based Tridentate Schiff Base Ligand in Cu(II) Mediated Allylic Oxidation Copper containing enzymes play important roles in oxygen binding, activation, and reduction in biological systems. 156,158,163,232,233 Numerous modeling studies have been performed to interpret the mechanism of corresponding copper containing proteins, and to extend the understanding of reactive copper species. 168-171,234-241 Inspired by the modeling studies, many promising results with copper catalysts have been reported. 168,169,242 Among these modeling studies, investigations into the utility of copper-peroxide chemistry have been performed mostly with copper/peroxide ratios of 1:1 and 2:1. 156,243- 253 2:1 Copper/peroxide species have been studied more extensively, since the thermodynamically favored Cu 2 O 2 species can be stabilized at low temperatures. 156,243-245 To date, only a few examples of mononuclear Cu(II)-peroxide species have been reported. 231,238,254-260 In these examples, the Cu(II) cation is coordinated mainly with N- ligands, while the bound peroxide is stabilized through hydrogen bonding between the pendant ligand and oxygen of peroxide that is bound to copper. Given the extra stability provided by the hydrogen bonding between pendant ligand and peroxide, the mononuclear Cu(II)-peroxide species is stable enough to be examined; however, this increase in stability leads to a loss of reactivity. Very few Cu(II)-peroxide compounds 50 have been reported to exhibit catalytic ability in oxidation reactions. 230,231 Previously, we have developed a modified ligand system, abbreviated ?salqu?. 173,226 Salqu is a tetradentate ligand with two Schiff bases and two oxo- units forming a rigid square planar coordinating environment of the type [O, N, N, O]. Salqu Cu(II) complexes (Figure 4.1) have been used as catalysts in benzylic and allylic oxidations of C-H bonds with tert-butyl hydroperoxide (TBHP) as terminal oxidant. 173,226 It is believed that the salqu Cu(II) complex will form a mononuclear Cu(II)-tert-butylperoxo complex with the addition of TBHP in solution (chapter 3). Although the peroxide tends to coordinate with two copper cations to form the thermodynamically more favored Cu 2 O 2 binuclear species, 156,243-245 the steric hinderance provided by the two tert-butyl groups near Cu site is sufficient to prevent the formation of a multimetallic species. This strategy is particularly useful for stabilizing mononuclear Cu-peroxides from obtaining binuclear or aggregated species. 261 In allylic oxidation, this reaction is believed to have a different mechanism from current oxidation methods using TBHP as oxidant. In this mechanism, an unusual LCu(II)-oxyl (LCu(II)-O?) is believed to form. We propose an equilibrium between LCu(II)-oxyl and LCu(III)-oxo (LCu(III)=O). By using the salqu Cu(II) complex/TBHP system, various olefin substrates can be converted to corresponding enone products with excellent yields and regioselectivity. It is possible that the regioselectivity is also in part the result of steric hinderance from the two tert-butyl groups near the copper center; however, there is one complication with this system, namely, the salqu Cu(II) complex catalyst decomposes as the reaction proceeds. The decomposition can be ascribed to the mismatch of the rigid square planar binding environment provided by the salqu ligand 51 N NN N OH O O (II)Cu N NN N OH O O (II)Cu complex 1 complex 2 complex 3 diamino-2-quinoxalinol Figure 4.1. Structures of complex 1 (catalyst for allylic oxidation), complex 2 (catalyst for benzylic oxidation), complex 3, and diamino-2-quinoxalinol. 52 and the Cu(I) cation formed by the reduction of LCu(II)-oxyl intermediate as Cu(I) greatly favors tetrahedral binding geometry. To address this problem, a tridentate Cu(II) complex 3 (Figure 4.1) is prepared. The different reactivity of the two amino groups of the diamino-2-quinoxalinol synthetic intermediate makes the synthesis possible. The amino group at the 6-position is slightly more reactive than the other amino group at the 7-position because of the hydoxy group on heterocycle, and the formation of the Schiff base at the 6-position also deactivates the 7-position (Figure 4.1). 172 Therefore, the tridentate ligand can be obtained by reacting the diamino-2-quinoxalinol intermediate with 1.1 equiv of 3,5-di-tert-butyl-2- hydroxybenzaldehyde (Scheme 4.1). By removing one phenolic moiety from the salqu ligand, the coordination environment of tridentate ligand remains enough flexibility to accommodate the Cu(I) intermediate while still providing enough steric hinderance for good regioselectivity. It is hoped that the Cu(I) complex with the tridentate ligand can persist under the reaction conditions. Meanwhile, given that a subtle change in ligand structure can have a big influence on the properties of the complex, 168,170 whether the Cu(II) complex will function as a catalyst with the replacement of the tetradentate ligand with a tridentate one becomes a question. The substrate 1-acetyl-1-cyclohexene 6 was used to test the catalytic capability of the new complex 3 (eq. 4.1). The reaction was performed on a millimole scale for ease of comparison with previous results. As shown before (chapter 3), acetonitrile is the best 53 Scheme 4.1. Synthesis of 2-Quinoxalinol Based Tridenate Schiff Base Ligand. (a) L-Leucine methyl ester hydrochloride, DIPEA, THF/EtOH; (b) NH 3 ?H 2 O, THF/EtOH; (c) Pd/C, HCOONH 4 , EtOH, 60?C; (d) 3,5-di-tert-butyl-2- hydroxybenzaldehyde, EtOH, reflux. 54 Table 4.1. Tridentate Cu(II) Complex 3 Catalyzed Allylic Oxidation of Olefins. O 0.5 mol% complex 3 3 equiv TBHP CH 3 CN 70 ?C Entry Substrate Product Time (h) Yield a (%) 1 O O 1 98 b 96 2 1 85 3 O OAc 2 72 4 O O O 3 96 5 1 91 6 CN 3 89 a Isolated yields unless stated otherwise. b GC yields with 1,2-dichlorobenzene added as internal standard. 55 solvent for this type of reaction under our conditions. All reactions were monitored by gas chromatography (GC). When 0.5 mol % of complex 3 was used as the catalyst and 3 equiv of TBHP was used as the oxidant, 3-acetyl-2-cyclohexenone 7 can be obtained with a yield of 98% in 1 h (Table 4.1, entry 1). The yield was determined by GC with 1 equiv of 1,2-dichlorobenzene added as the internal standard (yield = area of peak for product/area of peak for internal standard). The product yield is similar to that using the salqu Cu(II) complex as the catalyst (99%). A variety of olefin substrates were also tested using 3 equiv of TBHP and 0.5 mol % of complex 3 as the catalyst (Table 4.1). All the substrates were effectively converted to the corresponding enone products in excellent yields. When comparing to the results with tetradentate Cu(II) complex, there was not much difference in yields between using salqu Cu(II) complex 1 and complex 3 as the catalyst. The tridentate Cu(II) complex 3 seemed to have the same catalytic effect with the tetradentate one. Surprisingly, no phenolic based redox features were observed in the cyclic voltagram of complex 3. For complex 1, two quasi-reversible CV peaks were observed (chapter 3) and can be ascribed to the sequential one-electron oxidations of the two phenolic moieties. 169 Therefore, one CV peak was expected for complex 3 for its phenolic moiety. The lack of this feature suggests that the single electron oxidation of the phenolic moiety of Cu(II) complex 3 is no longer feasible. In another words, the energy gap between the HOMO and the LUMO for the tridentate complex 3 is much greater than that for tetradentate complex 1. Electronic spectroscopy data also supports these conclusions. The salqu ligand had an UV-Vis absorption band at 371 nm (? = 24 100 M -1 cm -1 ), while the salqu Cu(II) complex 56 0 1 2 3 4 240 440 640 840 salqu?ligand salqu?Cu(II)?complex?1 tridentate?Cu(II) complex?3 Figure 4.2. UV-vis spectra of salqu ligand, salqu Cu(II) complex 1, and tridentate Cu(II) complex 3. 57 1 had two UV-Vis absorptions at 327 nm (? = 20 000 M -1 cm -1 ) and 450 nm (? = 13 000 M -1 cm -1 ) in CHCl 3 .(Figure 4.2) The absorption of the salqu ligand can be ascribed to the electron excitation from the HOMO to the LUMO. Upon binding of Cu(II), the salqu complex 3 exhibited two absorptions. The one at 450 nm can be ascribed to the electron excitation from the HOMO of complex to the LUMO, while the other intense absorption band at 327 nm is typical of a ligand-to-metal charge transfer (LMCT) transition. 170 The absorptions at 371 nm for the salqu ligand and at 450 nm for salqu Cu(II) complex 1 correspond to the CV peaks for the salqu ligand and complex 1 respectively. As seen in the CV experiment, the salqu ligand exhibited one redox pair within the scan window (Figure 4.3), and its Cu(II) complex 1 exhibited two quasi-reversible peaks (chapter 3). For the tridentate Cu(II) complex 3, only one UV-vis absorption was observed at 334 nm (? = 9 000 M -1 cm -1 ). This band is the result of the LMCT transition. It is around the same wavenumbers as the LMCT band of the tetradentate complex 1. In addition, this peak is about half of the intensity as compared to the LMCT peak of complex 1. Since tetradentate complex 1 has two phenolic ligands that can contribute to the LMCT, while tridentate complex 3 only has one phenolic ligand, the ratio of the intensities of complex 1 and complex 3 make sense. Since the Cu(II) complex 3 has been shown to have different electronic properties compared to the Cu(II) complex 1, they are not likely to have the same catalytic effect. This conclusion seems contradictory to our experimentally derived results in the allylic oxidations of olefin substrates. To probe these differences, the reaction was repeated using a perdeuterated substrate, cyclohexene-d 10 . The oxidation of cyclohexene-d 10 was carried out in acetonitrile using 0.5 mol % of catalyst loading and 3 equiv of TBHP. 58 0.50 0.70 0.90 1.10 1.30 1.50 1.70 E vs. Ag/AgCl (V) 20 ?A Figure 4.3. Cyclic voltamagram of salqu ligand with supporting electrolyte 0.04 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 , reference Ag/AgCl, counter electrode Pt gauze (A = 0.77 cm 2 ), and the working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ). Scan rate = 100 mV/s. 59 Under exactly the same reaction conditions, reaction yields at 30 min (GC yields, as 1,2- dichlorobenzene added as the internal standard) were used as the indicator of reaction rates. When using the tetradentate complex 1 as catalyst, the k H /k D = 1.5; meanwhile, when the complex 3 was used as the catalyst, the reaction had the k H /k D value of 3.7. This big change in kinetic isotope effect or KIE value, when the catalyst was change from tetradentate Cu(II) complex 1 to tridentate Cu(II) complex 3 for the same reaction, confirms the difference in their catalytic mechanism. To further explore these differences, density functional theory (DFT) calculations in acetonitrile media were used to characterize their possible catalytic mechanism, and two possible reaction pathways were provided. All calculations were simplified by replacing the tert-butyl groups with methyl groups. In the first pathway (Scheme 4.2), the reaction is initiated by the formation of a Cu(II) peroxo complex 14 that can be obtained from the binding of peroxide to the tridentate Cu(II) complex 3. The homolytic cleavage of the O- O bond results in the formations of the methoxyl radical 15 and the Cu(II)-oxyl radical 16. The species 16 is in the triplet state after the cleavage of the O-O bond. A singlet intermediate 16 was formed afterwards through intersystem crossing (ISC). The energy of singlet state is about 2.9 kcal lower in energy than the triplet state intermediate. The triplet state is corresponding to the LCu(II)-oxyl radical species, while the singlet state is corresponding to the LCu(III)=O species. The facile ISC is in agreement with the previously reported research on equilibrium between LCu(II)-O? and LCu(III)=O in solution. 170 The free energy barrier for this step (14 ? 14TS15,16 ? 15, 16) is calculated to be 37.2 kcal. The methoxyl radical 15 can react with the substrate cyclohexene 17 by abstracting the H atom at allylic position, yielding the methanol 18 60 Scheme 4.2. Calculated Reaction Pathway 1 for Allylic Oxidation using Complex 3 as the Catalyst. 1.36? 14 37.2 14TS15,16 18.9 16 15 + 15 17 0.0 + 15,17TS18,19 11.4 1 18 + 0.0 - 21.1 0.0 - 28.2 16 17 + 16,17TS19,20 1.38? 12.8 20 19 + 21.3 61 19 0.0 + 21 -4.9 21TS22 32.6 1.33? 22 -45.0 1.86? -50.1 23 + 1.50? 62 and cyclohexenyl radical 19. This step is thermodynamically favored, as the products are 21.1 kcal lower in free energy. The energy barrier for this step (15, 17 ? 15,17TS18,19? 18, 19) is 11.4 kcal. The substrate 17 can also react with Cu(II)-oxyl radical 16. The H atom at the allylic position will be pulled away by the Cu(II)-oxyl species, cyclohexenyl radical 19 will be obtained along with the Cu(II)-OH complex 20. Such Cu(II)-OH complexes have been reported to carry out the ligand exchange with peroxides to form Cu(II)-peroxo species. 252,261 Under our reaction conditions, Cu(II)-OH 20 can be converted to Cu(II)-peroxo 14 to maintain the catalytic activity. The reaction between dioxygen and the cyclohexenyl radical 19 is spontaneous. The resulting cyclohexenyl peroxyl radical will go through a transition state, in which the O-O bond is breaking and O-H bond is forming. The free energy barrier of this step is 37.5 (32.6 + 4.9) kcal. Eventually, the enone product 23 forms along with a hydroxyl radical. The other possible reaction pathway (Scheme 4.3) involves H atom abstraction from the allylic site by the oxygen connected to the Cu center. The cyclohexenyl radical 19 will be formed as in the first pathway, while a different intermediate 24 was formed in this pathway. The transition state (14,17TS19,24) had an energy of 43.7 kcal as compared to the initial reactants. In the transition state, along with the H atom abstraction, the peroxo O-O bond is breaking and the bond between Cu center and the other oxygen of the peroxo is forming. In intermediate 24, the Cu center was bound to the oxygen and one nitrogen from the ligand, as well as the methoxyl and a hydroxide. The cyclohexenyl radical 19 can further react with the hydroxide of the intermediate 24, leading to complex 25 with the Cu center bound to an allylic alcohol. The conformational rearrangement of complex 25 resulted in the formation of complex 26 with a slight 63 difference in free energy. The unbound nitrogen ligand would come to bind to Cu center again in the transition state (26TS27) to allow for the dissociation of the allylic alchohol. In intermediate 27, the Cu center is bound to the ligand as well as to the methoxyl group, while the allylic alcohol is still in association with the complex through H-bonding. After a series of configurational and conformational changes, the free allylic alcohol 29 and methoxyl group bound to Cu complex 30 are obtained. In a fashion much the same as the Cu(II)-OH species, Cu(II)-OMe can also be converted to Cu(II)-peroxo complex with the presence of TBHP. 257,261 The catalytic activity of the Cu complex is therefore maintained. These computational results also provided a possible reaction pathway for allylic alcohol 29 to be converted to the enone product 23 (Scheme 4.3). In this calculation, dioxygen is employed to abstract the H atom at the allylic site, resulting in an allylic alcohol 33 bearing a radical at its allylic position. Species 33 will further react with another dioxygen molecule, and is subsequently oxidized to the enone product 23. The formation of the enone product 23 from the allylic alcohol through calculated pathway has not been supported by experimental evidence. In the first pathway, the homolytic cleavage of O-O bond in Cu(II) peroxo complex 14 (14 ? 14TS15,16 ? 15, 16) and the intramolecular H atom abstraction (21 ? 21TS22 ? 22) are the two steps that have the greatest energy barriers (37.2 and 37.5 kcal respectively). Therefore, these two steps may be considered as the rate-determining steps. In the second pathway, the rate-determining step is the H atom abstraction by complex 14 (14, 17 ? 14,17TS19,24 ? 19, 24), and has a free energy barrier of 43.7 kcal. A calculated KIE value of 4.0 was obtained based on the second calculated pathway. This value is very close to the experimental result (k H /k D = 3.7). thus, the second 64 Scheme 4.3. Calculated Reaction Pathway 2 for Allylic Oxidation using Complex 3 as the Catalyst. 0.0 43.7 -6.7 4.3 -31.6 -30.7 14 17 + 14,17TS19,24 24 19 + 19,24TS25 25 26 65 -21.6 -35.8 -37.4 -45.1 -48.8 26 -30.7 26TS27 27 27TS28 28 29 30 + 66 0.0 0.0 7.5 37.9 30.3 19.2 33 34 -2.8 -0.2 1.94? + 34TS35 1.14? 1.72? 35 -14.3 23 -18.1 + 33 + 2.02? 32 31TS32 2.01? 1.19?29 + 31 67 computationally derived pathway seems agree most closely with the experimentally obtained results. Another difference between these two possible pathways is how TBHP is utilized. In the first pathway, TBHP is used to coordinate with the Cu center to produce the Cu(II)- oxyl radical/Cu(III)-oxo species, and a methoxyl radical. Both this Cu-oxygen species and the methoxyl radical are responsible for the H atom abstraction from the substrate; however, it is the dioxygen molecule that oxidizes the substrate to yield the final enone product. Hence, the oxygen of the enone product is from dioxygen molecule. On the other hand, in the second pathway, the allylic H atom of substrate is still abstracted by Cu(II)-peroxo complex 14; however, the resulting allylic radical species is oxidized by the hydroxide bound to the Cu center leading to the allylic alcohol compound. Although dioxygen might participate in the oxidation of the allylic alcohol to the enone product, the oxygen atom of the enone product is still from TBHP. Since these two pathways will lead to the same product with the oxygen atom having different sources, an experiment was designed to elucidate the oxygen source of the product. 1-Phenyl-1-cyclohexene was used as the substrate with 0.5 mol % of complex 3 as the catalyst. The oxidation reaction was performed in acetonitrile degassed with argon under 18 O 2 atmosphere. Regular TBHP was used as the oxidant. If the oxygen incorporated into the product comes from TBHP, only the 16 O product will be obtained; otherwise, 18 O containing enone will be in the product. After 1 h of reaction time, the reaction solution was analyzed by GC-MS (Figure 4.4). As a result, both 16 O and 18 O containing products were observed. The ratio of 16 O product to 18 O one is about 3:1. This result indicates that both pathways can be happening during the course of the oxidation 68 reaction. The ratio of 16 O product to 18 O product shows that the second pathway is more favored than the first, since the first pathway leads to the 18 O product while the second one leads to the 16 O product. The ratio of 16 O/ 18 O products are also in accordance with the calculated and experimental KIE value. Based on the second pathway, a k H /k D value of 4 was obtained from the calculations. Experimentally, a k H /k D value of 3.7 was measured for the reaction using tridentate complex 3 as the catalyst, and a k H /k D value of 1.5 was measure for the reaction using tetradentate complex 1 as the catalyst. The oxidation using complex 1 is believed to have the reaction pathway similar to the first one calculated for complex 3 (chapter 3). Therefore, when the reaction using complex 3 goes through the first pathway, a k H /k D value close to 1.5 will be expected. Considering the second pathway is more favored concluded from the 16 O/ 18 O products ratio, it is reasonable to expect a k H /k D value between 4 and 1.5 for complex 3 with the value closer to 4. The experimental k H /k D value of 3.7 for complex 3 perfectly falls into this range. In conclusion, a tridentate Cu(II) complex has exhibited the same catalytic effect as its structurally related tetradentate Cu(II) complex; however, the tridentate complex possesses very different properties from the tetradentate one. Electronic spectroscopy and cyclic voltammetry have been used to reveal such differences. DFT calculations provide two possible reaction pathways for the tridentate Cu(II) complex in allylic oxidation. Experimental results suggest the existence of two concurrent pathways in these oxidation reactions. 69 purified m/z 166 168 170 172 174 176 178 180 182 % 0 100 YC_013012_tetra_1 392 (16.626) Cm (385:392-342:354) TOF MS EI+ 7.56e4172.0884 171.0806 170.0767 169.0690 166.9739 173.0933 174.0994 175.0901 176.1030 181.1040177.1561 179.0771 183.1299 Figure 4.4. MS spectrum of reaction solution using regular TBHP as the oxidant under 18 O 2 atmosphere. 70 Chapter 5 Conclusion and Future Work In this dissertation, the salqu Cu(II) complex 1 (Figure 5.1) is used as catalyst in the allylic oxidation of ? 5 -steroids into 7-keto- ? 5 -steroids with tert-butyl hydroperoxide (TBHP) as oxidant. After the reaction time and oxidant ratio are optimized using pregnenolone acetate as substrate, a variety of ? 5 -steroidal substrates are oxidized with moderate yields; meanwhile, unreacted ? 5 -steroidal starting materials can be recovered after column chromatography. Given the observation that the color of the reaction solution changes from its initial red to yellowish, as well as the reported slow decomposition of salen Cu(II) complex in organic solvent, 169 the Cu(II) complex catalyst is thought to be consumed as the reaction proceeds. The effects of acetonitrile and chloroform as solvents are also examined, and acetonitrile is found to be the better solvent for this oxidation reaction. Therefore, the oxidation reactions are carried out in acetonitrile with 0.5 mol % of complex 1 and 5 equiv of TBHP added simultaneously with multiple portions used. With these further optimized reaction conditions, ? 5 -steroids can be converted to the 7-keto-? 5 -steroidal products in excellent yields (up to 99%). This salqu Cu(II)/TBHP catalytic system for ? 5 -steroids exhibits great tolerance with a various functional groups, and has low sensitivity to air or water, while significantly reduced reaction time is required as compared to other current oxidation methods. In addition, the regioselectivity of the oxidation is also rationalized from the 71 N NN N OH O O (II)Cu complex 1 complex 3 complex 36 complex 37 N N OHN HNO (I)Cu R R complex 38 Figure 5.1. Structures of complex 1 (catalyst for allylic oxidation), complex 2 (catalyst for benzylic oxidation), complex 3, and diamino-2-quinoxalinol. 72 substrate?s perspective. As predicted by resonance structure theory, the species bearing radical at the 7-position is more stable than the one having unpaired electron at the 4- position, and therefore 7-keto products are obtained. This results is supported by theoretical calculations at the B3LYP/6-31G(2d,p) level. In addition to ? 5 -steroids, simple olefin substrates are also oxidized using salqu Cu(II)/TBHP catalytic system. In the oxidations of simple olefins, only 0.5 mol % of complex 1 and 3 equiv of TBHP are needed to complete the oxidation reactions in 1 ? 2 hours. Using 1-acetyl-1-cyclohexene as substrate, dichloromethane (DCM), chloroform, acetonitrile, dimethyl sulfoxide (DMSO), and dimethyl formamide (DMF) are tested as solvents. Among these solvents, acetonitrile is found to be the best for the oxidation reaction. The investigation on solvent effects implies the crucial role of dioxygen molecules in the oxidation. The importance of dioxygen is further confirmed by the result of the oxidation reaction in acetonitrile degassed with argon under N 2 atmosphere. Analytical techniques and theoretical calculations are also employed to investigation this salqu Cu(II)/TBHP catalytic system. Resonance Raman experiment provides evidence for the binding of TBHP to the Cu(II) center of salqu Cu(II) complex. Cyclic voltammetry (CV) experiment of the salqu Cu(II) complex suggests the capability of the salqu ligand in stabilizing Cu(III) cation by achieving the equilibrium between a Cu(II)- ligand-radical species [Cu(II)L?] + and a Cu(III)-ligand species [Cu(III)L] + . The theoretical calculations at B3LYP/6-311+G(d,p) level show that salqu ligand could stabilize Cu(III) cation better than salen by enhancing the spin density dispersion on the heterocyclic quinoxalinol backbone. 73 Combining all the results and the conclusion from experimental facts that the tert- butylperoxy ether intermediate is not formed in our catalytic system, a reaction mechanism is proposed. In this mechanism, TBHP is utilized in a different fashion from current oxidation method. Upon binding to the salqu Cu(II) complex, the O-O bond of TBHP becomes more reactive. The homolytic cleavage of the O-O bond results in a Cu(II) oxyl radical (Cu(II)-O?) that will participate in the reaction as an oxidant. From this mechanism, the earlier observation of complex 1 consumption in the oxidation of ? 5 - steroids can be explained, as well as the regioselectivity and some experimental observations in the oxidation of simple olefins. When tetradentate salqu Cu(II) complex 1 is used as catalyst in the allylic oxidations, the catalyst decomposes to some extent as the reaction proceeds. The decomposition is ascribed to the mismatch of the rigid square planar binding geometry provided by the salqu ligand and the Cu(I) formed from the reduction of Cu(II)-O? species, as Cu(I) greatly favors a tetrahedral binding geometry. Hence, the tridentate Cu(II) complex 3 (Figure 5.1) is prepared to provide more flexible binding environment for the copper cation, yet enough steric hinderance to maintain the regioselectivity for substrate. Although the results of the allylic oxidations of simple olefin substrates using complex 3 is similar to those using complex 1 as catalyst, CV experiment of complex 3 and the UV- Vis spectroscopy suggest different properties of tridentate complex 3 from tetradentate complex 1. The density functional theory (DFT) calculations provide two possible reaction pathways. In the kinetic isotope effect (KIE) experiment, a k H /k D value of 3.7 is obtained experimentally, while a k H /k D value of 4.0 is calculated based on one of the two possible 74 pathways. Meanwhile, the result of the oxidation reaction under 18 O 2 atmosphere using regular TBHP indicates the existence of two concurrent pathways in these oxidation reactions. Based on the experimental results and the theoretical calculations, the allylic oxidation using tridentate Cu(II) complex 3 as catalyst and TBHP as oxidant is believed to undergo two different reaction pathways yielding the same product. The problem of catalyst consumption is solved in this system. Although some understanding on the properties of 2-quinoxalinol based Schiff base ligand bound Cu(II) complex has been obtained, questions remain. For example, in the second computationally derived reaction pathway (chapter 4), allylic alcohol is obtained and further oxidized by molecular oxygen into enone product. In this step, the complex 3 catalyst is not involved. Such oxidation of allylic alcohol has not been studied experimentally. Hence, investigations of oxidizing allylic alcohol using complex 3 as catalyst with/without molecular oxygen will be of great interest. If the oxidation of allylic alcohols using complex 3 as catalyst led to the enone product, how is the Cu(II) complex 3 functioning will be another question of interest. In addition, if the allylic alcohol was obtained as intermediate as predicted by calculations, will it be possible to stop the reaction at this step experimentally to have the allylic alcohol as the final product, and will this reaction be enantioselective? Besides continuous investigation on tridentate Cu(II) complex 3, another tridentate Cu(II) complex 36 (Figure 5.1) is also interesting. In complex 3, one of the three binding sites provided by the salqu ligand is a NH 2 group. According to the calculation results, the H atom of this NH 2 group can provide extra stability through H-bonding; however, 75 free H atoms from ligand will introduce uncertainty in catalytic reaction. Thus the replacements of the two H atoms with R groups will provide a simpler model for investigations, and will also provide a comparison to study the effect of H-bonding in the reaction process. One other work can be performed is to study the tridentate Cu(I) complex 37 and 38 (Figure 5.1). Cu(I) complexes are know to bind and activate molecular oxygen in different fashions;(ref) however, very few Schiff base ligand or salen-type ligand have been utilized in such study. The binding and activation of molecular oxygen with tridentate Cu(I) complexes might be a good point to start with, and might be applied to catalytic oxidations as well. To sum up, tetradentate Cu(II) complex 1 and tridentate Cu(II) complex 3 have been used as catalysts in allylic oxidation. Excellent results are achieved. A possible reaction mechanism is proposed for oxidation using tetradentate Cu(II) complex 1 based on the experimental results and theoretical calculations. When tridentate Cu(II) complex 3 is used as catalyst, the oxidation reaction is believed to undergo two concurrent reaction pathways yielding the same product. In the follow-up investigations, the studies on allylic alcohol oxidation using complex 3, catalytic effect of complex 36, and molecular oxygen binding and activation by complex 37 and 38 will be of great interest. 76 Chapter 6 Experimental Section General. All reagents were obtained commercially without further purification. Yields reported are for isolated mass yield after chromatography, unless indicated otherwise. The leucine methyl ester hydrochloride, 1,5-di-fluoro-2,4-di-nitrobenzene (DFDNB), ammonium formate, 3,5-di-tert-butyl-2-hydroxybenzaldehyde, ammonium hydroxide (5.0 N), palladium on carbon (wet, 5%), tert-butyl hydroperoxide (TBHP, 5.0 - 6.0 M solution in decane) are purchased from Aldrich. 18 O 2 is purchased from Icon in a 100 mL breakseal (gas at atmos pressure, 98 atom %). 1 H NMR and 13 C NMR spectra were recorded on 250 or 400 MHz instruments as solutions in CDCl 3 or DMSO-d 6 ; chemical shift (?) are reported in ppm relative to Me 4 Si. Reaction process was monitored by thin-layer chromatography (TLC) using 0.25mm silica gel precoated plates; spots were detected with UV light and revealed with I 2 . Chromatographic purifications were performed using Fisher (60?, 70-230 mesh) silica gel. HRMS data were collected with electronspray ionization. IR spectroscopic data was collected using a SHIMADZU Inc. IR, Prestige-21 Fourier Transfer Infrared Spectrophotometer and KBr solid samples. All UV-Vis data was collected using a Cary 50 UV-Vis spectrophotometer with a xenon lamp and an equipment range from 200 to 1000 nm. Atomic absorption spectrum (Varian AA240), its software (AA240FS) and hollow cathode lamp (HLC; Ni 232.0 nm, optimum working range: 0.1 ? 20 mg/L; Mn 279.5 nm, optimum working range: 0.02 ? 5 mg/L; Cu 77 324.8 nm, optimum working range: 0.03 ? 10 mg/L) are from Varian Inc. Raman spectroscopy was performed using the 785 nm line (6 mW) from an air-cooled argon ion laser (model 163-C42, Spectra-Physics Lasers, Inc.) as the excitation source. Raman spectrum was collected and analyzed using a Renishaw via Raman microscope system. In cyclic voltammetry experiment, the electrochemical circuit was controlled using an Epsilon electrochemistry workstation (Bioanalytical Systems, Inc.). CW EPR spectrum was measured at X-band (9 GHz) frequency on a Bruker EMX spectrometer, fitted with the ER-4119-HS high sensitivity perpendicular-mode cavity. General EPR conditions were: microwave frequency, 9.385 GHz; field modulation frequency, 100 kHz; field modulation amplitude, 0.6 mT. The Oxford Instrument ESR 900 flow cryostat in combination with the ITC4 temperature controller was used for measurements in the 4 K to 300 K range using a helium flow. Measurements at 77 K were performed by fitting the cavity with a liquid nitrogen finger Dewar. All products have been previously described, and 1 H, 13 C NMR and IR data are in accordance with literature data. Synthesis of Diamino-2-quinoxalinol intermediate. To a 150 mL round-bottomed flask charged with a stirring bar, were sequentially added 1,5-difluoro-2,4-dinitrobenzene (DFDNB, 4.0 mmol, 0.8168 g), leucine methyl ester hydrochloride (4.0 mmol, 0.7268 g), tetrahydrofuran (THF, 30 mL), ethanol (30 mL), and di-isopropyl-ethylamine (DIPEA, 8.8 mmol, 1.6 mL). The reaction solution was stirred for 12 h at room temperature. After it was confirmed by thin-layer chromatography (TLC) that the starting material (DFDNB) had been converted, ammonium hydroxide was added as 5.0 N in aqueous solution (12 mmol, 9.6 mL) to the reaction mixture. The reaction solution was stirred at 78 room temperature for additional 5 h until the reaction was determined to be complete by TLC monitoring. The solvent was then removed under reduced pressure to yield a yellow oily solid. The yellow solid was then dissolved with ethanol (80 mL). To the solution, HCOONH 4 (80mmol, 4.8 g) and Palladium on carbon (Pd/C, wet, 5%, 1.2 g) were added. The reaction mixture was stirred at 60 ?C for 12 h, followed by the filtration of the solution mixture. The filtered solution was concentrated using a rotary evaporator. Precipitation was formed in the concentrated solution, and filtered from the solution. Brown solid (854 mg, 92%) was obtained as the product. Diamino-2-quinoxalinol. IR (solid): 3352 (br), 3277, 2949, 2868, 2818, 1653, 1512, 1420, 1402, 1271 cm -1 . 1 H NMR (250 MHz, DMSO-d 6 ): ? 12.01 (bs, 1H), 6.81 (s, 1H), 6.36 (s, 1H), 5.39 (bs, 2H), 4.61 (bs, 2H), 2.51 (d, 2H), 2.15 (m, 1H), 0.91 (d, J = 6.7 Hz, 6H), 13 C NMR (62.5 MHz, DMSO-d 6 ): ? 156.0, 153.7, 140.6, 133.3, 126.5, 126.4, 111.5, 97.2, 41.9, 26.9, 23.1. Formula (M + H): C 12 H 17 N 4 O. HRMS: found 233.1410 (M + H), calcd. 233.1402 (M + H). Synthesis of Tetradentate Salqu Ligand. To a 250 mL round-bottomed flask charged with a stirring bar, were sequentially added diamino-2-quinoxalinol (0.6960 g, 3.00 mmol), 3,5-di-tert-butyl-2-hydroxybenzaldehyde (1.5454 g, 6.60 mmol), ethanol (120 mL), trifluoroacetic anhydride (0.15 mmol, 20 ?L). After the reaction was stirred at refluxing temperature for 6 h, precipitation formed. The reaction mixture was filtered, 79 and the filtrate was washed with water and ethanol 3 times each to obtain yellow solid as the product (1.2948 g, 65%). Tetradentate Salqu Ligand. IR (solid): 3426, 2960, 2922, 2879, 1657, 1616, 1584, 1475, 1431, 1389, 1368, 1256, 1206 cm -1 . UV-Vis (CHCl 3 ): 371 nm (? = 24 100 M -1 cm - 1 ). 1 H NMR (400 MHz, CDCl 3 ): ? 13.23 (s, 1H), 13.14 (s, 1H), 12.04 (bs, 1H), 8.58 (s, 1H), 8.48 (s, 1H), 7.47 (s, 1H), 7.22 (d, 2H), 7.22 (d, 2H), 7.06 (m, 2H), 6.89 (s, 1H), 2.57 (d, J = 7.1 Hz, 2H), 2.12 (m, 1H), 1.22 (s, 9H), 1.19 (s, 9H), 1.12 (s, 9H), 1.11 (s, 9H), 0.83 (d, J = 6.6 Hz, 6H). 13 C NMR (100 MHz, CDCl 3 ): ? 166.6, 164.1, 161.4, 158.4, 158.1, 155.6, 144.4, 140.4, 138.7, 136.9, 136.8, 131.3, 128.5, 128.0, 127.0, 126.8, 118.2, 118.0, 117.8, 105.4, 42.0, 34.9, 34.0, 31.3, 29.3, 26.5, 22.6. Formula (M + H): C 42 H 57 N 4 O 3 . HRMS: found 665.4434 (M + H), calcd. 665.4430 (M + H). Synthesis of Tridentate 2-Quinoxalinol Based Ligand. To a 100 mL round- bottomed flask charged with a stirring bar, were sequentially added diamino-2- quinoxalinol (0.6960 g, 3.00 mmol), 3,5-di-tert-butyl-2-hydroxybenzaldehyde (0.7727 g, 3.30 mmol), ethanol (60 mL), trifluoroacetic anhydride (0.075 mmol 10 ?L). After the reaction was stirred at refluxing temperature for 6 h, it was confirmed by TLC that the diamino-2-quinoxalinol starting material had been converted. The reaction solution was then concentrated using a rotary evaporator, and the resulting residue was purified by flash column chromatography with hexanes/ethyl acetate (4:1) as the eluent. Yellow solid was obtained as the product (0.7526 g, 56%). 80 Tridentate 2-Quinoxalinol Based Ligand. 1 H NMR (400 MHz, CDCl 3 ): ? 13.08 (s, 1H), 11.64 (bs, 1H), 8.74 (s, 1H), 7.52 (s, 1H), 7.49 (d, 1H), 7.25 (d, 1H), 6.56 (s, 1H), 4.52 (bs, 2H), 2.82 (d, J = 7.2 Hz, 2H), 2.36 (m, 1H), 1.48 (s, 9H), 1.34 (s, 9H), 1.04 (d, J = 6.6 Hz, 6H). 13 C NMR (100 MHz, CDCl 3 ): ? 164.2, 157.8, 156.9, 156.1, 143.3, 141.2, 137.0, 133.8, 131.6, 128.5, 127.1, 118.6, 117.4, 98.2, 92.3 41.8, 36.7, 35.1, 34.2, 31.6, 31.5, 29.4, 28.4, 27.1, 24.7, 23.4, 22.8. Formula (M + H): C 27 H 37 N 4 O 2 . HRMS: found 449.2932 (M + H), calcd. 449.2917 (M + H). Synthesis of Salqu Copper(II) Complex 1. In a 100 mL round-bottomed flask charged with a stirring bar, 0.20 mmol of salqu ligand (133 mg) and 0.24 mmol of Cu(OAc) 2 ?H 2 O (48 mg) were dissolved with 20 mL of dichloromethane and 20 mL of methanol. After 1.2 mmol of tirethylamine (0.2 mL) was added, the reaction was stirred for 2 h at refluxing temperature. After solvent was removed, the resulting dark red solid was washed with water and cold ether 3 times each. A product of 127 mg of solid was obtained (87%). Salqu Copper(II) Complex 1. IR (solid): 3429 (br), 2955, 2909, 2868, 1661, 1556, 1524, 1495, 1462, 1423, 1385, 1202 cm -1 . UV-Vis (CHCl 3 ): 327 (? = 20 000 M -1 cm -1 ), 450 nm (? = 13 000 M -1 cm -1 ). Formula (M + H): C 42 H 55 N 4 O 3 Cu. HRMS: found 726.3575 (M + H), calcd. 726.3570 (M + H). Synthesis of Copper(II) Complex 3. In a 100 mL round-bottomed flask charged with a stirring bar, 0.20 mmol of tridentate ligand (89.6 mg) and 0.24 mmol of 81 Cu(OAc) 2 ?H 2 O (48 mg) were dissolved with 20 mL of dichloromethane and 20 mL of methanol. After 1.2 mmol of tirethylamine (0.2 mL) was added, the reaction was stirred for 2 h at refluxing temperature. After solvent was removed, the resulting dark red solid was washed with water and cold ether 3 times each. A product of 93.2 mg of solid was obtained (82%). Salqu Copper(II) Complex 3. UV-Vis (CHCl 3 ): 334 nm (? = 9 000 M -1 cm -1 ). Formula (M + H): C 29 H 39 N 4 O 4 Cu. HRMS: found 571.2351 (M + H), calcd. 571.2346 (M + H). Representative Procedure for Allylic Oxidation of ? 5 -Steroids Using Optimized Condition (Table 2.1). To a 50 mL round-bottomed flask charged with a stirring bar, were sequentially added pregnenolone acetate (358 mg, 1 mmol), complex 1 (7.3 mg, 0.01 mmol), CH 3 CN (10 mL), CHCl 3 (10 mL), and t-BuOOH (2 mL, 10 mmol). After the reaction was stirred at 70 ?C for 12 h, solvent was removed under reduced pressure. The residue was purified by flash column chromatography with hexanes/ethyl acetate (5:1) as eluent to yield product as a white solid (239 mg). 3?-Acetoxypregn-5-ene-7,20-dione (Entry 1, Table 2.1). IR (solid) 1730, 1707, 1672 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.72 (d, J=1.6 Hz, 1H), 4.75-4.69 (m, 1H), 2.59-1.26 (comp,18H), 2.12 (s, 3H), 2.05 (s, 3H), 1.22 (s, 3H), 0.64 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 209.7, 201.2, 170.3, 164.3, 126.4, 72.0, 62.2, 49.9, 49.6, 45.2, 44.4, 38.3, 37.7, 37.6, 35.9, 31.6, 27.2, 26.4, 23.5, 21.2, 21.0, 17.2, 13.2. 82 3?-Acetoxycholest-5-ene-7-one (Entry 2, Table 2.1). IR (solid) 1728, 1671 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.70 (d, J=1.6 Hz, 1H), 4.76-4.67 (m, 1H), 2.58-1.00 (comp. 26H), 2.05 (s, 3H), 1.21 (s, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 201.9, 170.2, 164.0, 126.6, 72.2, 54.7, 49.9, 49.8, 45.4, 43.1, 39.4, 38.6, 38.3, 37.6, 36.2, 36.0, 35.7, 28.5, 28.0, 27.3, 26.3, 23.8, 22.8, 22.6, 21.2, 21.1, 18.8, 17.2, 11.9. 3?-Benzoyloxypregn-5-ene-7,20-dione (Entry 3, Table 2.1). IR (solid) 1707, 1672 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 8.04 (d, J=7.2 Hz, 2H), 7.57 (t, 1H), 7.45 (t, 2H), 5.77 (d, J=1.6 Hz, 1H), 5.02-4.94 (m, 1H), 2.78-0.68 (comp. 24H), 2.14 (s, 3H), 1.27 (s, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 209.9, 201.4, 166.0, 164.4, 133.2, 130.4, 130.3, 129.7, 128.5, 126.8, 72.8, 62.4, 50.1, 49.8, 45.4, 44.6, 38.6, 38.0, 37.8, 36.2, 31.8, 27.6, 26.6, 23.8, 21.3, 17.5, 13.4. 3?-[(Tetrahydropyran-2R,S-yl)oxy]-7-oxo-cholest-5-ene (Entry 4, Table 2.1). IR (solid) 1676, 1630 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.68 (d, J=1.0 Hz, 1H), 4.72 (s, 1H), 3.55-3.64 (m, 1H), 3.45-3.49 (m, 2H), 0.93 (s, 3H), 0.90 (d, J=6.6 Hz, 3H), 0.85 (d, J=6.6 Hz, 6H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 202.2, 165.6, 126.0, 97.4, 75.0, 62.9, 54.8, 50.0, 45.4, 43.1, 40.1, 39.5, 38.8, 38.5, 36.5, 36.2, 31.2, 29.4, 28.5, 28.0, 27.7, 26.3, 25.4, 23.8, 22.6, 21.2, 19.9, 19.0, 17.4, 12.0. 83 3?-Hydroxycholest-5-ene-7-one (Entry 5, Table 2.1). IR (solid) 1670 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.69 (d, J=1.6 Hz, 1H), 3.71-3.64 (m, 1H), 2.54-1.00 (comp. 26H), 1.21 (s, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 202.6, 165.6, 126.0, 70.5, 54.8, 50.0, 49.9, 45.4, 43.1, 41.8, 39.5, 38.7, 38.3, 36.4, 36.2, 35.7, 31.1, 28.6, 28.0, 26.3, 23.8, 22.8, 22.6, 21.2, 18.9, 17.3, 12.0. 3?-Hydroxypregn-5-ene-7,20-dione (Entry 6, Table1 2.1). IR (solid) 1681, 1666 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.68 (d, J=1.6 Hz, 1H), 3.67-3.63 (m, 1H), 2.52- 1.18 (comp. 19H), 2.10 (s, 3H), 1.18 (s, 3H), 0.63 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 210.0, 201.8, 166.0, 125.8, 70.3, 62.3, 50.0, 49.8, 45.1, 44.4, 41.8, 38.4, 37.7, 36.4, 31.6, 31.0, 26.5, 23.6, 21.1, 17.3, 13.3. 3?-Chlorocholest-5-ene-7one (Entry 7, Table 2.1). IR (solid) 1669 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.68 (s, 1H), 3.86-3.82 (m,1H), 2.71 (d, J=8.3 Hz, 2H), 2.43-2.36 (m, 1H), 2.26-2.15 (comp, 2H), 2.04-1.88 (comp, 4H), 1.57-1.05 (comp, 20H), 1.22 (s, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 201.9, 163.9, 126.2, 57.8, 54.8, 49.9, 49.8, 45.4, 43.1, 42.6, 39.5, 38.6, 38.1, 36.2, 35.7, 32.8, 28.5, 28.0, 26.3, 23.8, 22.8, 22.6, 21.1, 18.9, 17.2, 12.0. Representative Procedure for Allylic Oxidation of ? 5 -Steroids Using Further Optimized Condition (Table 2.2). To a 50 mL round-bottomed flask charged with a stirring bar, were sequentially added cholesteryl chloride (203 mg, 0.5 mmol), complex 1 84 (1.8 mg, 0.0025 mmol), CH 3 CN (10 mL), and t-BuOOH (0.5 mL, 2.5 mmol). Additional complex 1 (1.8 mg, 0.0025 mmol) and t-BuOOH (0.5 mL, 2.5 mmol) were added three times every 2 h. Solvent was then removed under reduced pressure. The residue was purified by flash column chromatography with hexanes/ethyl acetate (15:1) as eluent to yield product as a white solid (201 mg). 3?-Acetoxycholest-5-ene-7-one (Entry 1, Table 2.2). IR (solid) 1728, 1671 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.70 (d, J=1.6 Hz, 1H), 4.76-4.67 (m, 1H), 2.58-1.00 (comp. 26H), 2.05 (s, 3H), 1.21 (s, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 201.9, 170.2, 164.0, 126.6, 72.2, 54.7, 49.9, 49.8, 45.4, 43.1, 39.4, 38.6, 38.3, 37.6, 36.2, 36.0, 35.7, 28.5, 28.0, 27.3, 26.3, 23.8, 22.8, 22.6, 21.2, 21.1, 18.8, 17.2, 11.9. 3?-Benzoyloxypregn-5-ene-7,20-dione (Entry 2, Table 2.2). IR (solid) 1707, 1672 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 8.04 (d, J=7.2 Hz, 2H), 7.57 (t, 1H), 7.45 (t, 2H), 5.77 (d, J=1.6 Hz, 1H), 5.02-4.94 (m, 1H), 2.78-0.68 (comp. 24H), 2.14 (s, 3H), 1.27 (s, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 209.9, 201.4, 166.0, 164.4, 133.2, 130.4, 130.3, 129.7, 128.5, 126.8, 72.8, 62.4, 50.1, 49.8, 45.4, 44.6, 38.6, 38.0, 37.8, 36.2, 31.8, 27.6, 26.6, 23.8, 21.3, 17.5, 13.4. 3?-Hydroxycholest-5-ene-7-one (Entry 3, Table 2.2). IR (solid) 1670 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.69 (d, J=1.6 Hz, 1H), 3.71-3.64 (m, 1H), 2.54-1.00 (comp. 26H), 1.21 (s, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.6 Hz, 85 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 202.6, 165.6, 126.0, 70.5, 54.8, 50.0, 49.9, 45.4, 43.1, 41.8, 39.5, 38.7, 38.3, 36.4, 36.2, 35.7, 31.1, 28.6, 28.0, 26.3, 23.8, 22.8, 22.6, 21.2, 18.9, 17.3, 12.0. 3?-Hydroxypregn-5-ene-7,20-dione (Entry 4, Table1 2.2). IR (solid) 1681, 1666 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.68 (d, J=1.6 Hz, 1H), 3.67-3.63 (m, 1H), 2.52- 1.18 (comp. 19H), 2.10 (s, 3H), 1.18 (s, 3H), 0.63 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 210.0, 201.8, 166.0, 125.8, 70.3, 62.3, 50.0, 49.8, 45.1, 44.4, 41.8, 38.4, 37.7, 36.4, 31.6, 31.0, 26.5, 23.6, 21.1, 17.3, 13.3. 3?-Chlorocholest-5-ene-7one (Entry 5, Table 2.2). IR (solid) 1669 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): ? 5.68 (s, 1H), 3.86-3.82 (m,1H), 2.71 (d, J=8.3 Hz, 2H), 2.43-2.36 (m, 1H), 2.26-2.15 (comp, 2H), 2.04-1.88 (comp, 4H), 1.57-1.05 (comp, 20H), 1.22 (s, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz, 3H), 0.68 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): ? 201.9, 163.9, 126.2, 57.8, 54.8, 49.9, 49.8, 45.4, 43.1, 42.6, 39.5, 38.6, 38.1, 36.2, 35.7, 32.8, 28.5, 28.0, 26.3, 23.8, 22.8, 22.6, 21.1, 18.9, 17.2, 12.0. Representative Procedure for Allylic Oxidation of Simple Olefins using Complex 1. To a 50 mL round-bottomed flask charged with a stirring bar, were sequentially added complex 1 (2.5 ?mol), CH 3 CN (10 mL), 1-acetyl-1-cyclohexene (0.5 mmol), and t- BuOOH (1.5 mmol). After the reaction was stirred at 70 ?C for 1 h, solvent was removed under reduced pressure. The residue was purified by flash column chromatography with hexane/ethyl acetate as eluent to yield product as yellowish oil. 86 Procedure for Yield Determination by GC. To the reaction flask, 1,2- dichlorobenzene (0.5 mmol) was added after 1 h. 150 ?L of reaction solution was then taken to collect GC data. The yield was determined by the equation Yield = (area of the peak for product)/(area of the peak for internal standard). 2-Cyclohexenone (Entry 1, Table 3.1). 1 H NMR: ? 7.03 (m, 1 H), 6.01 (m, 1 H), 2.43, (m, 2 H), 2.37 (m, 2 H), 2.03 (m, 2 H). 13 C NMR: ? 199.6, 150.9, 129.8, 38.1, 25.7, 22.8. Formula: C 6 H 8 O. HRMS: found 96.0582, calcd. 96.0575. 3-Acetyl-2-cyclohexenone (Entry 2, Table 3.1). 1 H NMR: ? 6.58 (bs, 1 H), 2.50 (m, 2 H), 2.48 (m, 2 H), 2.41 (s, 3 H), 2.00 (m, 2 H). 13 C NMR: ? 201.5, 200.1, 154.6, 132.5, 37.9, 26.2, 23.4, 21.9. Formula: C 8 H 10 O 2 . HRMS: found 138.0687, calcd. 138.0681. 3-Phenyl-2-cyclohenenone (Entry 3, Table 3.1). 1 H NMR: ? 7.55-7.53 (m, 2 H), 7.42-7.41 (m, 3H), 6.43 (t, J = 1.2 Hz, 1 H), 2.78 (m, 2 H), 2.49 (t, J = 6.0 Hz, 2 H), 2.18- 2.13 (m, 2 H). 13 C NMR: ? 200.0, 159.9, 139.0, 130.0, 128.8, 126.1, 125.5, 37.3, 28.1, 22.8. Formula: C 12 H 12 O. HRMS: found 172.0881, calcd. 172.0888. 3-Methyl-2-cyclohexenone (Entry 4 and 5, Table 3.1). 1 H NMR: ? 5.88 (d, J = 1.5 Hz, 1 H), 2.32 (t, J = 6.3 Hz, 2 H), 2.31-2.26 (m, 2 H), 2.02-1.98 (m, 2 H), 1.96 (s, 3 H). 13 C NMR: ? 199.9, 162.9, 127.0, 37.4, 31.4, 24.9, 23.1. Formula: C 7 H 10 O. HRMS: found 110.0728, calcd. 110.0732. 87 3-Acetoxy-2-cyclohexenone (Entry 6, Table 3.1). 1 H NMR: ? 5.92 (s, 1 H), 2.54 (t, J = 6.8 Hz, 2 H), 2.42 (t, J = 6.4 Hz, 2 H), 2.23 (s, 3 H), 2.09 (m, 2 H). 13 C NMR: ? 200.0, 170.0, 167.4, 117.5, 36.6, 28.3, 21.2, 21.2. Formula: C 8 H 10 O 3 . HRMS: found 154.0626, calcd. 154.0630. 3-Acetyl-2-cyclopentenone (Entry 7, Table 3.1). 1 H NMR: ? 6.67 (t, J = 2.0 Hz, 1 H), 2.83-2.80 (m, 2 H), 2.56-2.51 (m, 2 H), 2.50 (s, 3 H). 13 C NMR: ? 210.6, 197.3, 169.3, 137.0, 35.4, 27.8, 26.3. Formula: C 7 H 8 O 2 . HRMS: found 124.0520, calcd. 124.0524. 4-Cyclopentene-1,3-dione Monoethylene Ketal (Entry 8, Table 3.1). 1 H NMR: ? 7.20 (d, J = 6.0 Hz, 1 H), 6.19 (d, J = 6.0 Hz, 1 H), 4.03 (m, 4 H), 2.60 (s, 2 H). 13 C NMR: ? 204.0, 156.3, 135.4, 111.6, 65.2, 45.2. Formula: C 7 H 8 O 3 . HRMS: found 140.0465, calcd. 140.0473. 3-Cyano-2-cyclohexenone (Entry 9, Table 3.1). 1 H NMR: ? 6.52 (s, 1 H), 2.57 (dt, J = 6.0 Hz, 2.0 Hz, 2 H), 2.54 (t, J = 6.2 Hz, 2 H). 2.13 (m, 2 H). 13 C NMR: ? 196.6, 138.6, 131.1, 117.0, 37.2, 27.6, 22.0. Formula: C 7 H 7 NO. HRMS: found 121.0525, calcd. 121.0528. 3-Nitro-2-cyclohexenone (Entry 10, Table 3.1). 1 H NMR: ? 6.91 (m, 1 H), 2.10 (m, 2 H), 2.51 (t, J = 6.4 Hz, 2 H), 2.19-2.15 (m, 2 H). 13 C NMR: ? 198.0, 164.0, 125.8, 37.1, 24.4, 21.0. Formula: C 6 H 7 NO 3 . HRMS: found 141.0431, calcd. 141.0426. 88 Procedure for Cyclic Voltammetry Experiment (Chapter 3). Electrochemical measurement was carried out at room temperature using a three electrode set-up in a home built glass cell (20 mL total volume). The supporting electrolyte was 0.1 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 with 1 mM ferrocene as internal standard, the reference electrode was home made Ag/AgCl wire, and the counter electrode was Pt gauze (A = 0.77 cm 2 ). The working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ). Before electrochemical measurement, the solution was purged with N 2 for 15 min. Cyclic voltammogram of 1 mM Cu(II) salqu was recorded in 5 mL CH 2 Cl 2 described above between 0.0 V and 1.7 V using a scan rate of 100 mV/s. Procedure for Raman Spectroscopy. In a 20 mL vial equipped with a stirring bar, Cu(II) salqucomplex (5 ?mol) was dissolved in CH2Cl2 (10 mL) followed by the addition of TBHP (20 ?mol). After 15 min strring, several drops of the Cu(II) salqu solution was taken and let evaporate on a gold foil. The residue was excited by 785 nm line (6 mW) and Raman spectrum was collected. Representative Procedure for Allylic Oxidation of Simple Olefins using Complex 3. To a 50 mL round-bottomed flask charged with a stirring bar, were sequentially added complex 3 (2.5 ?mol), CH 3 CN (10 mL), 1-acetyl-1-cyclohexene (0.5 mmol), and t- BuOOH (1.5 mmol). After the reaction was stirred at 70 ?C for 1 h, solvent was removed under reduced pressure. The residue was purified by flash column chromatography with hexane/ethyl acetate as eluent to yield product as yellowish oil. 89 3-Acetyl-2-cyclohexenone (Entry 1, Table 4.1). 1 H NMR: ? 6.58 (bs, 1 H), 2.50 (m, 2 H), 2.48 (m, 2 H), 2.41 (s, 3 H), 2.00 (m, 2 H). 13 C NMR: ? 201.5, 200.1, 154.6, 132.5, 37.9, 26.2, 23.4, 21.9. Formula: C 8 H 10 O 2 . HRMS: found 138.0687, calcd. 138.0681. 3-Phenyl-2-cyclohenenone (Entry 2, Table 4.1). 1 H NMR: ? 7.55-7.53 (m, 2 H), 7.42-7.41 (m, 3H), 6.43 (t, J = 1.2 Hz, 1 H), 2.78 (m, 2 H), 2.49 (t, J = 6.0 Hz, 2 H), 2.18- 2.13 (m, 2 H). 13 C NMR: ? 200.0, 159.9, 139.0, 130.0, 128.8, 126.1, 125.5, 37.3, 28.1, 22.8. Formula: C 12 H 12 O. HRMS: found 172.0881, calcd. 172.0888. 3-Acetoxy-2-cyclohexenone (Entry 3, Table 4.1). 1 H NMR: ? 5.92 (s, 1 H), 2.54 (t, J = 6.8 Hz, 2 H), 2.42 (t, J = 6.4 Hz, 2 H), 2.23 (s, 3 H), 2.09 (m, 2 H). 13 C NMR: ? 200.0, 170.0, 167.4, 117.5, 36.6, 28.3, 21.2, 21.2. Formula: C 8 H 10 O 3 . HRMS: found 154.0626, calcd. 154.0630. 3-Acetyl-2-cyclopentenone (Entry 4, Table 4.1). 1 H NMR: ? 6.67 (t, J = 2.0 Hz, 1 H), 2.83-2.80 (m, 2 H), 2.56-2.51 (m, 2 H), 2.50 (s, 3 H). 13 C NMR: ? 210.6, 197.3, 169.3, 137.0, 35.4, 27.8, 26.3. Formula: C 7 H 8 O 2 . HRMS: found 124.0520, calcd. 124.0524. 4-Cyclopentene-1,3-dione Monoethylene Ketal (Entry 5, Table 4.1). 1 H NMR: ? 7.20 (d, J = 6.0 Hz, 1 H), 6.19 (d, J = 6.0 Hz, 1 H), 4.03 (m, 4 H), 2.60 (s, 2 H). 13 C NMR: ? 204.0, 156.3, 135.4, 111.6, 65.2, 45.2. Formula: C 7 H 8 O 3 . HRMS: found 140.0465, calcd. 140.0473. 90 3-Cyano-2-cyclohexenone (Entry 6, Table 4.1). 1 H NMR: ? 6.52 (s, 1 H), 2.57 (dt, J = 6.0 Hz, 2.0 Hz, 2 H), 2.54 (t, J = 6.2 Hz, 2 H). 2.13 (m, 2 H). 13 C NMR: ? 196.6, 138.6, 131.1, 117.0, 37.2, 27.6, 22.0. Formula: C 7 H 7 NO. HRMS: found 121.0525, calcd. 121.0528. Procedure for Cyclic Voltammetry Experiment (Chapter 3). Electrochemical measurement was carried out at room temperature using a three electrode set-up in a home built glass cell (20 mL total volume). The supporting electrolyte was 0.04 M tetrabutyl ammonium tetrafluroborate in 5 mL CH 2 Cl 2 , the reference electrode was home made Ag/AgCl wire, and the counter electrode was Pt gauze (A = 0.77 cm 2 ). The working electrode was a glassy carbon disk (d = 0.3 cm, A = 0.071 cm 2 ). Before electrochemical measurement, the solution was purged with N 2 for 15 min. Cyclic voltammogram of 1 mM Cu(II) salqu was recorded in 5 mL CH 2 Cl 2 described above between 0.0 V and 1.7 V using a scan rate of 100 mV/s. Theoretical Calculation (Chapter 3) Procedure of optimization by varying reaction time Total Energies (hartrees), Zero-point Energies (kcal/mol), Thermal Corrections (kcal/mol), and Entropies (cal/mol?K) PG B3LYP/ ZPE c TC d S e R=AcO, position 4 C 1 -398.86712 185.95(0) 9.81 121.37 R=AcO, position 7 C 1 -399.43226 185.79(0) 9.80 121.19 R=OH, position 4 C 1 -399.43226 219.61(0) 11.57 136.79 R=OH, position 7 C 1 -398.86713 219.41(0) 11.57 136.80 R=OBz, position 4 C 1 -398.86712 153.68(0) 7.68 104.21 R=OBz, position 7 C 1 -399.43226 153.57(0) 7.78 106.12 91 R=Cl, position 4 C 1 -399.43226 162.06(0) 7.71 102.90 R=Cl, position 7 C 1 -398.66959 161.87(0) 7.78 103.88 R=OTHP, position 4 C 1 -398.86712 241.58(0) 11.12 132.32 R=OTHP, position 7 C 1 -399.23309 241.37(0) 11.15 132.74 a Point group. b Based on structures optimized at the B3LYP/6-31G(2d,p) level. c Zero- point energies and number of imaginary frequencies. d Thermal corrections to 298K. e Entropies. 92 Cartesian Coordinates of Geometries Optimized at the B3LYP/6-31G(2d,p) Level ___________________________________________________________ R=AcO, position 4 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -1.211150 0.094849 -0.864531 2 6 0 -0.414243 1.014946 0.070389 3 6 0 1.063892 0.739444 -0.013923 4 6 0 1.529515 -0.708347 0.060621 5 6 0 0.626168 -1.593903 -0.840064 6 6 0 -0.878068 -1.376990 -0.630023 7 6 0 1.987046 1.780364 -0.045307 8 6 0 2.983375 -0.822285 -0.459417 9 6 0 3.941292 0.221586 0.132405 10 6 0 3.356876 1.597862 0.027515 11 1 0 1.601359 2.797179 -0.100272 12 1 0 -0.957292 0.348193 -1.899396 13 1 0 -0.620560 2.061911 -0.176892 14 1 0 0.875294 -2.649033 -0.674726 15 1 0 -1.446775 -1.995353 -1.333657 16 1 0 2.968991 -0.687261 -1.547864 17 1 0 3.358196 -1.835614 -0.271438 18 1 0 4.165250 -0.014583 1.185275 19 1 0 4.907542 0.172230 -0.384697 20 1 0 4.018388 2.458184 0.038888 21 1 0 0.868820 -1.379434 -1.889453 22 1 0 -1.183164 -1.666802 0.377266 23 1 0 -0.776854 0.848488 1.092538 24 6 0 1.453463 -1.201985 1.527814 25 1 0 1.772769 -2.248801 1.594807 26 1 0 2.101063 -0.606519 2.177561 27 1 0 0.439036 -1.134955 1.929829 28 6 0 -3.351373 0.167778 0.290262 29 8 0 -2.638207 0.373032 -0.833797 30 8 0 -2.904703 -0.243377 1.335307 31 6 0 -4.801111 0.527030 0.059438 32 1 0 -4.884081 1.574412 -0.244302 33 1 0 -5.212995 -0.079608 -0.752072 34 1 0 -5.365799 0.358028 0.975458 --------------------------------------------------------------------- R=AcO, position 7 Standard orientation: 93 --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 1.334616 0.316497 -1.139208 2 6 0 0.384823 -0.803862 -0.867207 3 6 0 -0.915172 -0.642420 -0.392623 4 6 0 -1.351847 0.717867 0.164660 5 6 0 -0.585591 1.838392 -0.574577 6 6 0 0.935824 1.656685 -0.515078 7 6 0 -1.817922 -1.695425 -0.443410 8 6 0 -2.869400 0.906392 -0.057388 9 6 0 -3.700496 -0.260438 0.486437 10 6 0 -3.284827 -1.594003 -0.154755 11 1 0 -1.461046 -2.651002 -0.823760 12 1 0 1.394978 0.444755 -2.229573 13 1 0 -0.856776 2.810408 -0.144827 14 1 0 1.441325 2.468184 -1.048745 15 1 0 -3.059077 1.013046 -1.134382 16 1 0 -3.188314 1.846210 0.410526 17 1 0 -3.583005 -0.321503 1.573226 18 1 0 -4.765629 -0.078567 0.307090 19 1 0 -3.827513 -1.730439 -1.105729 20 1 0 -3.608822 -2.437268 0.471132 21 1 0 -0.912600 1.860140 -1.623216 22 1 0 1.276819 1.688732 0.520217 23 1 0 0.693657 -1.783210 -1.226623 24 6 0 -1.021537 0.767414 1.676292 25 1 0 -1.256171 1.757278 2.086407 26 1 0 -1.599257 0.026421 2.234130 27 1 0 0.031430 0.547789 1.860718 28 6 0 3.067617 -0.379708 0.408860 29 8 0 2.726313 -0.038448 -0.847973 30 8 0 2.316179 -0.396173 1.354434 31 6 0 4.533803 -0.742641 0.472649 32 1 0 4.737456 -1.591724 -0.186135 33 1 0 5.143783 0.094361 0.121487 34 1 0 4.799474 -0.995145 1.498449 --------------------------------------------------------------------- R=OH, position 4 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 94 1 6 0 -2.221548 0.391379 -0.395634 2 6 0 -1.186226 1.177341 0.413008 3 6 0 0.228026 0.760602 0.116915 4 6 0 0.550966 -0.727347 0.086948 5 6 0 -0.570358 -1.494152 -0.664902 6 6 0 -1.989634 -1.111363 -0.230405 7 6 0 1.242054 1.703810 -0.022632 8 6 0 1.882980 -0.961856 -0.666516 9 6 0 3.027343 -0.046864 -0.207467 10 6 0 2.580414 1.383445 -0.168276 11 1 0 0.961351 2.755272 0.011954 12 1 0 -2.106475 0.652348 -1.461654 13 1 0 -1.316876 2.250136 0.238576 14 1 0 -0.414496 -2.573109 -0.543569 15 1 0 -2.721888 -1.670351 -0.828457 16 1 0 1.708806 -0.775242 -1.733238 17 1 0 2.174015 -2.015173 -0.573040 18 1 0 3.394156 -0.356653 0.784515 19 1 0 3.886492 -0.163870 -0.879718 20 1 0 3.322880 2.172649 -0.230645 21 1 0 -0.469479 -1.287118 -1.738506 22 1 0 -2.173162 -1.377314 0.817709 23 1 0 -1.427888 1.007066 1.475208 24 6 0 0.668493 -1.260013 1.537662 25 1 0 0.896243 -2.332600 1.534138 26 1 0 1.462940 -0.744513 2.084411 27 1 0 -0.257869 -1.117144 2.100701 28 8 0 -3.503384 0.797914 0.071370 29 1 0 -4.166736 0.302419 -0.421546 --------------------------------------------------------------------- R=OH, position 7 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -2.322406 0.429185 -0.388107 2 6 0 -1.119694 1.255059 -0.060017 3 6 0 0.185689 0.777834 0.016997 4 6 0 0.448727 -0.733804 0.038620 5 6 0 -0.680095 -1.467732 -0.719424 6 6 0 -2.075502 -1.074810 -0.223345 7 6 0 1.258723 1.660843 0.056485 8 6 0 1.804160 -1.027181 -0.643304 9 6 0 2.961515 -0.233204 -0.027894 95 10 6 0 2.702009 1.281885 -0.084966 11 1 0 1.035820 2.726227 0.071214 12 1 0 -2.569995 0.624638 -1.450662 13 1 0 -0.537330 -2.551434 -0.625726 14 1 0 -2.844952 -1.638364 -0.765522 15 1 0 1.721292 -0.780186 -1.710424 16 1 0 2.013621 -2.102862 -0.586454 17 1 0 3.108845 -0.544841 1.011372 18 1 0 3.896235 -0.468740 -0.548010 19 1 0 3.060573 1.679611 -1.049566 20 1 0 3.309848 1.801907 0.668990 21 1 0 -0.597356 -1.235603 -1.789984 22 1 0 -2.195786 -1.320618 0.836264 23 1 0 -1.289759 2.328417 -0.017554 24 6 0 0.486174 -1.216614 1.508923 25 1 0 0.687720 -2.293615 1.554393 26 1 0 1.260557 -0.701442 2.081734 27 1 0 -0.460410 -1.024493 2.018919 28 8 0 -3.410347 0.890603 0.420691 29 1 0 -4.211953 0.467826 0.091672 --------------------------------------------------------------------- R=OBz, position 4 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.245195 0.268001 0.817124 2 6 0 -0.959873 0.794083 -0.435158 3 6 0 -2.456197 0.696566 -0.295916 4 6 0 -3.046663 -0.615227 0.203089 5 6 0 -2.222812 -1.130796 1.414297 6 6 0 -0.705758 -1.140705 1.185416 7 6 0 -3.284718 1.732370 -0.717099 8 6 0 -4.503989 -0.391713 0.675595 9 6 0 -5.368009 0.397611 -0.318333 10 6 0 -4.665408 1.647075 -0.756436 11 1 0 -2.811523 2.649968 -1.063132 12 1 0 -0.472145 0.937958 1.653205 13 1 0 -0.661699 1.831150 -0.622826 14 1 0 -2.563714 -2.138667 1.680057 15 1 0 -0.191711 -1.464704 2.097244 16 1 0 -4.475983 0.169875 1.617392 17 1 0 -4.966274 -1.360753 0.898967 18 1 0 -5.613335 -0.224765 -1.194057 96 19 1 0 -6.334072 0.639261 0.141857 20 1 0 -5.249222 2.479813 -1.135347 21 1 0 -2.443636 -0.491385 2.279463 22 1 0 -0.429106 -1.837083 0.391759 23 1 0 -0.615284 0.200672 -1.291177 24 6 0 -3.016067 -1.664111 -0.937465 25 1 0 -3.425455 -2.619373 -0.587983 26 1 0 -3.610202 -1.332152 -1.793555 27 1 0 -2.000170 -1.846722 -1.297689 28 6 0 1.891002 -0.303917 -0.196777 29 8 0 1.200342 0.392920 0.724048 30 8 0 1.398901 -1.065068 -1.002751 31 6 0 3.355751 -0.030395 -0.114491 32 6 0 3.906528 0.849346 0.823800 33 6 0 4.192370 -0.690675 -1.020717 34 6 0 5.281295 1.063849 0.852074 35 1 0 3.254923 1.357880 1.523059 36 6 0 5.565246 -0.474382 -0.990100 37 1 0 3.742724 -1.367153 -1.738079 38 6 0 6.111339 0.403454 -0.053311 39 1 0 5.705614 1.746764 1.580809 40 1 0 6.210062 -0.988832 -1.695014 41 1 0 7.183197 0.572837 -0.028888 --------------------------------------------------------------------- R=OBz, position 7 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.210410 1.207385 -0.728236 2 6 0 -0.990283 0.010133 -1.162895 3 6 0 -2.264064 -0.314131 -0.700960 4 6 0 -2.828541 0.407291 0.528905 5 6 0 -2.260190 1.843709 0.580575 6 6 0 -0.727512 1.878256 0.547263 7 6 0 -3.029058 -1.266081 -1.360533 8 6 0 -4.369237 0.472463 0.429326 9 6 0 -5.009409 -0.899499 0.192905 10 6 0 -4.473788 -1.556748 -1.089182 11 1 0 -2.582103 -1.772578 -2.214225 12 1 0 -0.241908 1.941631 -1.545996 13 1 0 -2.619023 2.345551 1.487429 14 1 0 -0.364642 2.910524 0.584932 15 1 0 -4.642470 1.144851 -0.395594 97 16 1 0 -4.771179 0.922745 1.345615 17 1 0 -4.812970 -1.550653 1.050890 18 1 0 -6.098504 -0.800146 0.131710 19 1 0 -5.058648 -1.204270 -1.955878 20 1 0 -4.645385 -2.641968 -1.063737 21 1 0 -2.659490 2.414523 -0.269017 22 1 0 -0.321195 1.360869 1.416885 23 1 0 -0.586225 -0.534195 -2.013686 24 6 0 -2.406744 -0.368547 1.800328 25 1 0 -2.740947 0.162230 2.700124 26 1 0 -2.843823 -1.369823 1.818096 27 1 0 -1.324145 -0.498087 1.846770 28 6 0 1.698990 0.003993 0.158518 29 8 0 1.231399 0.953133 -0.672009 30 8 0 1.012572 -0.657911 0.906907 31 6 0 3.180655 -0.144975 0.056228 32 6 0 3.796937 -1.099203 0.872723 33 6 0 3.956356 0.627720 -0.814869 34 6 0 5.174263 -1.280078 0.819331 35 1 0 3.175118 -1.685697 1.538940 36 6 0 5.335072 0.444827 -0.865667 37 1 0 3.474389 1.364803 -1.444701 38 6 0 5.945091 -0.507790 -0.050075 39 1 0 5.647765 -2.021795 1.454213 40 1 0 5.934251 1.045644 -1.542095 41 1 0 7.020600 -0.648294 -0.091979 --------------------------------------------------------------------- R=Cl, position 4 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 1.864613 -0.156466 -0.432057 2 6 0 0.929711 -1.026209 0.410448 3 6 0 -0.516419 -0.722706 0.113531 4 6 0 -0.957440 0.734278 0.089981 5 6 0 0.090795 1.585783 -0.675835 6 6 0 1.547450 1.323114 -0.263869 7 6 0 -1.446131 -1.748309 -0.031623 8 6 0 -2.312309 0.861122 -0.648864 9 6 0 -3.371051 -0.150034 -0.186308 10 6 0 -2.807123 -1.538515 -0.166321 11 1 0 -1.078374 -2.772706 -0.006685 12 1 0 1.805200 -0.443263 -1.484618 98 13 1 0 1.141292 -2.086090 0.242851 14 1 0 -0.141083 2.649986 -0.547532 15 1 0 2.225165 1.925233 -0.876143 16 1 0 -2.134654 0.697279 -1.718657 17 1 0 -2.689584 1.885374 -0.544119 18 1 0 -3.750136 0.117529 0.813133 19 1 0 -4.244881 -0.098972 -0.847371 20 1 0 -3.481620 -2.386207 -0.231577 21 1 0 -0.008155 1.375266 -1.748638 22 1 0 1.721579 1.610853 0.778915 23 1 0 1.157610 -0.825865 1.468945 24 6 0 -1.099868 1.257223 1.541991 25 1 0 -1.415488 2.307067 1.540274 26 1 0 -1.842269 0.678970 2.098933 27 1 0 -0.158302 1.193474 2.094448 28 17 0 3.609431 -0.490801 0.027141 --------------------------------------------------------------------- R=Cl, position 7 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 1.968718 -0.154914 -0.655901 2 6 0 0.857391 -1.098287 -0.412515 3 6 0 -0.460810 -0.729739 -0.144229 4 6 0 -0.811453 0.748456 0.052492 5 6 0 0.154837 1.602795 -0.798591 6 6 0 1.627557 1.326034 -0.470271 7 6 0 -1.458367 -1.694654 -0.109734 8 6 0 -2.263916 1.001589 -0.411776 9 6 0 -3.272854 0.050801 0.240825 10 6 0 -2.929031 -1.417784 -0.053360 11 1 0 -1.161732 -2.734125 -0.237109 12 1 0 2.410551 -0.342006 -1.638068 13 1 0 -0.057793 2.667242 -0.640532 14 1 0 2.286723 1.933480 -1.097159 15 1 0 -2.310594 0.883469 -1.502862 16 1 0 -2.533860 2.043260 -0.198614 17 1 0 -3.290765 0.216099 1.323090 18 1 0 -4.283914 0.273862 -0.115776 19 1 0 -3.364226 -1.712242 -1.023395 20 1 0 -3.411930 -2.080603 0.677946 21 1 0 -0.035153 1.399330 -1.860448 22 1 0 1.835345 1.614059 0.562174 99 23 1 0 1.085560 -2.152392 -0.544738 24 6 0 -0.665354 1.113460 1.549214 25 1 0 -0.871773 2.178753 1.705960 26 1 0 -1.357520 0.539502 2.169602 27 1 0 0.338979 0.901026 1.922544 28 17 0 3.425988 -0.595015 0.457674 --------------------------------------------------------------------- R=PTHP, position 4 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 0.143112 0.705952 -0.989711 2 6 0 -0.422436 -0.642913 -0.515578 3 6 0 -1.916189 -0.590081 -0.336796 4 6 0 -2.509798 0.575074 0.443831 5 6 0 -1.826309 1.899669 0.009003 6 6 0 -0.294712 1.832406 -0.049868 7 6 0 -2.729670 -1.629295 -0.779548 8 6 0 -4.024142 0.695476 0.144260 9 6 0 -4.787438 -0.632672 0.248131 10 6 0 -4.088060 -1.708142 -0.527335 11 1 0 -2.256619 -2.439138 -1.332513 12 1 0 -0.272409 0.916755 -1.982284 13 1 0 -0.141813 -1.430606 -1.220339 14 1 0 -2.142843 2.706985 0.680895 15 1 0 0.111209 2.783479 -0.411256 16 1 0 -4.140177 1.071601 -0.879443 17 1 0 -4.468756 1.445926 0.809214 18 1 0 -4.894262 -0.934193 1.302861 19 1 0 -5.813362 -0.498719 -0.116832 20 1 0 -4.653803 -2.569126 -0.868817 21 1 0 -2.196434 2.166352 -0.989625 22 1 0 0.117450 1.672078 0.953709 23 1 0 0.064604 -0.904405 0.435317 24 6 0 -2.292865 0.345935 1.961145 25 1 0 -2.705854 1.182246 2.537675 26 1 0 -2.781978 -0.573213 2.295599 27 1 0 -1.232369 0.258232 2.213207 28 8 0 1.555012 0.702702 -1.239941 29 6 0 2.425245 0.330479 -0.224326 30 6 0 3.783429 0.971492 -0.498699 31 1 0 2.052984 0.645615 0.768242 32 6 0 3.419265 -1.575881 0.774410 100 33 6 0 4.834531 0.474037 0.503374 34 1 0 4.066276 0.702460 -1.522772 35 1 0 3.679802 2.060599 -0.459461 36 6 0 4.840905 -1.059135 0.555997 37 1 0 3.372553 -2.666895 0.716928 38 1 0 3.060751 -1.277307 1.775716 39 1 0 5.824594 0.860909 0.240443 40 1 0 4.601572 0.868592 1.502417 41 1 0 5.496429 -1.423072 1.355728 42 1 0 5.220342 -1.464030 -0.390007 43 8 0 2.532850 -1.092143 -0.225602 --------------------------------------------------------------------- R=OTHP, position 7 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 0.198489 1.215602 -1.153039 2 6 0 -0.442156 -0.137810 -1.129490 3 6 0 -1.656526 -0.433169 -0.513191 4 6 0 -2.309256 0.583870 0.432768 5 6 0 -1.892066 2.013463 0.020524 6 6 0 -0.373923 2.177293 -0.104680 7 6 0 -2.300949 -1.637035 -0.775325 8 6 0 -3.846642 0.450778 0.344043 9 6 0 -4.334879 -0.977275 0.609389 10 6 0 -3.702658 -1.980256 -0.370124 11 1 0 -1.797410 -2.345990 -1.429986 12 1 0 0.012522 1.649324 -2.148159 13 1 0 -2.289819 2.733401 0.746688 14 1 0 -0.114879 3.204399 -0.380806 15 1 0 -4.168598 0.763592 -0.658410 16 1 0 -4.312301 1.146540 1.053462 17 1 0 -4.094860 -1.262905 1.638899 18 1 0 -5.426543 -1.021103 0.531779 19 1 0 -4.314061 -2.032577 -1.286994 20 1 0 -3.743163 -2.997332 0.044958 21 1 0 -2.361542 2.254148 -0.942982 22 1 0 0.107870 1.987582 0.860019 23 1 0 0.020605 -0.888198 -1.762751 24 6 0 -1.845745 0.303073 1.882654 25 1 0 -2.321880 1.002399 2.580411 26 1 0 -2.096004 -0.713081 2.195812 27 1 0 -0.763054 0.405292 1.987341 101 28 8 0 1.641583 1.196272 -1.108898 29 6 0 2.248451 0.369659 -0.172610 30 6 0 3.594001 0.975048 0.218018 31 1 0 1.612498 0.241962 0.723556 32 6 0 3.045448 -1.841319 0.114013 33 6 0 4.371025 0.023277 1.139108 34 1 0 4.150053 1.157218 -0.708747 35 1 0 3.425869 1.944435 0.698457 36 6 0 4.444490 -1.379627 0.522349 37 1 0 3.075830 -2.794017 -0.422116 38 1 0 2.417344 -1.981482 1.011483 39 1 0 5.373564 0.417113 1.336512 40 1 0 3.863050 -0.036595 2.111944 41 1 0 4.883344 -2.096367 1.226319 42 1 0 5.082612 -1.362378 -0.369521 43 8 0 2.432958 -0.912372 -0.769055 --------------------------------------------------------------------- Theoretical Calculation (Chapter 4) Point group, Electronic state, total energies (hartrees) with aug-cc-pvtz basis set, zero- point Energies (kcal/mol), thermal corrections (kcal/mol), entropies (cal/mol?K), and solvation free energies (kcal/mol) PG a ES b SCF Energy ZPE c (NIF) TC d S e Solvation Free Energy f 1 C 1 2 A -2896.86773 233.53(0) 17.54 182.47 -26.54 2 C 2 1 A -234.72318 92.26(0) 4.03 72.37 -4.22 1,2TS3,4 C 1 2 A -3131.54240 321.89(1) 22.13 220.21 -24.50 3 C 1 1 A -2897.51628 239.88(0) 18.21 186.70 -24.04 4 C S 2 A " -234.08297 83.47(0) 4.04 74.98 -4.40 3,4TS5 C 1 2 A -3131.59951 323.35(1) 22.68 227.84 -27.76 5 C 1 2 A -3131.66672 326.69(0) 22.37 221.44 -26.43 6 C 1 2 A -3131.67303 327.02(0) 22.15 220.45 -21.99 6TS7 C 1 2 A -3131.65941 326.09(1) 21.96 218.80 -20.86 7 C 1 2 A -3131.67667 326.78(0) 22.35 222.84 -24.07 7TS8 C 1 2 A -3131.67855 326.60(1) 21.96 221.07 -24.48 8 C 1 2 A -3131.68971 327.31(0) 21.99 223.11 -25.31 9 C 1 1 A -309.96884 95.00(0) 4.71 79.31 -7.11 10 C 1 2 A -2821.69973 230.93(0) 17.07 178.55 -23.16 1TS11,12 C 1 2 A -2896.79585 230.05(1) 18.22 189.72 -29.47 11 C 1 3 A -2781.70645 206.23(0) 15.70 168.16 -28.49 102 11 f C 1 1 A -2781.70155 206.20(0) 15.71 166.19 -29.18 12 C 1 2 A -115.09697 23.10(0) 2.48 56.57 -3.30 2,12TS14,15 C 1 2 A -349.81611 113.96(1) 6.35 96.94 -6.69 15 C S 1 A ' -115.76963 32.30(0) 2.66 56.74 -3.62 14 C S 2 A " -234.08297 83.47(0) 4.04 74.98 -4.40 2,11TS13,14 C 1 3 A -3016.42769 295.57(1) 19.99 206.76 -28.56 2,11TS13,14 f C 1 1 A -3016.42390 295.99(1) 19.99 205.40 -29.25 13 C 1 2 A -2782.39162 213.34(0) 15.96 168.97 -25.88 O2 D ?h 3 S g -150.37835 2.37(0) 2.08 49.01 -2.40 16 C 1 2 A -384.48870 89.67(0) 5.23 86.27 -8.69 16TS17 C 1 2 A -384.42030 85.62(0) 5.18 86.06 -10.08 17 C 1 2 A -384.53981 87.62(0) 5.93 92.50 -13.55 18 C 1 1 A -308.76956 80.29(0) 4.41 77.73 -8.86 OH C ?V 2 ? -75.76403 5.21(0) 2.07 42.61 -3.79 19 C 1 3 A -460.34693 97.71(0) 7.40 111.90 -8.01 19TS20 C 1 3 A -460.29642 94.37(1) 6.43 97.49 -9.30 20 C 1 3 A -460.31335 96.93(0) 6.97 101.44 -8.24 21 C 1 2 A -309.33823 86.38(0) 4.73 80.64 -7.08 OOH C S 2 A " -150.96573 8.81(0) 2.38 54.71 -6.44 22 C 1 2 A -459.74373 91.94(0) 5.84 90.66 -9.05 22TS23 C 1 2 A -459.73324 88.69(1) 5.82 91.7 -9.52 23 C 1 2 A -459.75382 91.02(0) 6.64 99.65 -11.44 a Point group. b Electronic state. c Zero-point energies and number of imaginary frequencies. d Thermal corrections to 298K. e Entropies (cal/mol?K). f Result from the open shell singlet state (broken symmetry). 103 Geometry at B3LYP/6-31G(d) level of calculation 1 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.308570 1.519379 -0.242579 2 6 0 -5.354226 -1.797293 0.355398 3 6 0 -3.217317 -0.987638 0.070552 4 6 0 -3.732774 0.272663 -0.351161 5 6 0 -5.848396 -0.512639 -0.080572 6 1 0 -1.482529 -2.157127 0.503960 7 6 0 -1.823618 -1.193322 0.142790 8 6 0 -2.828965 1.303695 -0.694985 9 6 0 -1.473283 1.082683 -0.620228 10 6 0 -0.941937 -0.181259 -0.209336 11 1 0 -3.226776 2.262624 -1.013697 12 6 0 1.115021 -1.379676 -0.088039 13 6 0 2.522897 -1.527647 -0.030844 14 6 0 3.433515 -0.409958 -0.103528 15 6 0 3.038778 -2.854108 0.077596 16 6 0 4.843475 -0.695013 -0.054887 17 6 0 4.386351 -3.114052 0.127839 18 1 0 2.326785 -3.676924 0.126124 19 6 0 5.270336 -2.000245 0.059219 20 1 0 6.342514 -2.190898 0.097404 21 1 0 0.540423 -2.310369 -0.088978 22 7 0 0.463622 -0.240446 -0.155666 23 8 0 3.070108 0.824307 -0.228019 24 6 0 5.801227 0.463707 -0.131291 25 1 0 5.615954 1.181372 0.676150 26 1 0 6.839131 0.121664 -0.067803 27 1 0 5.672216 1.021051 -1.066590 28 6 0 4.935411 -4.514742 0.252202 29 1 0 5.527533 -4.637149 1.168657 30 1 0 4.130560 -5.256618 0.276457 31 1 0 5.594718 -4.766557 -0.588734 32 7 0 -4.061886 -2.009060 0.423541 33 7 0 -5.080448 0.487082 -0.420164 34 8 0 -7.189932 -0.360269 -0.130516 35 1 0 -7.351524 0.551428 -0.436795 36 6 0 -6.311376 -2.891157 0.731621 37 1 0 -5.749579 -3.777001 1.033936 38 1 0 -6.964466 -2.574980 1.553730 39 1 0 -6.967481 -3.144538 -0.109649 40 7 0 -0.491826 2.093060 -0.949991 104 41 1 0 -0.617578 2.995005 -0.470924 42 1 0 -0.458821 2.279546 -1.953086 43 8 0 1.853022 3.237646 0.203639 44 8 0 0.710606 4.136844 0.367987 45 6 0 0.677157 4.478569 1.737636 46 1 0 0.494635 3.597621 2.371423 47 1 0 1.620877 4.946357 2.042216 48 1 0 -0.145457 5.195407 1.852327 --------------------------------------------------------------------- 2 C 2 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.005187 1.503056 0.047817 2 6 0 -0.371449 0.671579 -1.192338 3 6 0 0.371449 -0.671579 -1.192338 4 6 0 0.005187 -1.503056 0.047817 5 6 0 -0.005187 -0.668485 1.306185 6 6 0 0.005187 0.668485 1.306185 7 1 0 0.983277 1.970244 -0.089870 8 1 0 -1.454055 0.482516 -1.192849 9 1 0 0.149634 -1.236805 -2.105944 10 1 0 0.708859 -2.339186 0.163919 11 1 0 -0.019119 -1.204621 2.254763 12 1 0 0.019119 1.204621 2.254763 13 1 0 1.454055 -0.482516 -1.192849 14 1 0 -0.149634 1.236805 -2.105944 15 1 0 -0.708859 2.339186 0.163919 16 1 0 -0.983277 -1.970244 -0.089870 --------------------------------------------------------------------- 1,2TS3,4 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 0.911597 -0.383565 0.188246 2 6 0 -6.610100 0.080816 -0.367472 3 6 0 -4.318461 0.112883 -0.146239 4 6 0 -4.286133 -1.310518 -0.080067 5 6 0 -6.549116 -1.358596 -0.290505 6 1 0 -3.197158 1.924495 -0.177954 105 7 6 0 -3.117264 0.848167 -0.076450 8 6 0 -3.041289 -1.960359 0.067383 9 6 0 -1.878284 -1.226374 0.150075 10 6 0 -1.897247 0.203872 0.075732 11 1 0 -3.022969 -3.044886 0.122975 12 6 0 -0.499076 2.126003 0.174992 13 6 0 0.711566 2.858323 0.053156 14 6 0 1.974715 2.237925 -0.254636 15 6 0 0.632804 4.275056 0.187944 16 6 0 3.107378 3.101344 -0.448321 17 6 0 1.727075 5.090945 0.022152 18 1 0 -0.335615 4.712957 0.425976 19 6 0 2.960910 4.465398 -0.303203 20 1 0 3.838167 5.096587 -0.443320 21 1 0 -1.395085 2.731704 0.332433 22 7 0 -0.630138 0.822820 0.098082 23 8 0 2.146093 0.959770 -0.380527 24 6 0 4.431690 2.471263 -0.787915 25 1 0 5.211543 3.230293 -0.906408 26 1 0 4.743681 1.769104 -0.005195 27 1 0 4.367142 1.891731 -1.717172 28 6 0 1.646822 6.591320 0.170584 29 1 0 0.627226 6.913020 0.406660 30 1 0 2.302635 6.954361 0.972885 31 1 0 1.953197 7.106796 -0.749104 32 7 0 -5.504763 0.783610 -0.296311 33 7 0 -5.441522 -2.036790 -0.156132 34 8 0 -7.723321 -2.025153 -0.366923 35 1 0 -7.502841 -2.972667 -0.298862 36 6 0 -7.930288 0.778286 -0.529954 37 1 0 -7.767980 1.857206 -0.569588 38 1 0 -8.436609 0.451956 -1.446248 39 1 0 -8.604519 0.541602 0.301829 40 7 0 -0.583655 -1.828566 0.274005 41 1 0 -0.495401 -2.686674 -0.265086 42 1 0 -0.293915 -2.029537 1.250091 43 8 0 2.199750 -1.687562 0.618585 44 8 0 1.032867 -1.295697 2.229161 45 6 0 1.933297 -1.382482 3.280013 46 1 0 2.357646 -2.395067 3.389902 47 1 0 2.769991 -0.673002 3.180582 48 1 0 1.406624 -1.141162 4.222707 49 6 0 5.722487 -4.010833 -0.364336 50 6 0 4.212430 -4.302391 -0.364364 51 6 0 3.481951 -3.456051 -1.416465 52 6 0 3.733341 -1.982758 -1.177726 106 53 6 0 5.105478 -1.619264 -0.833425 54 6 0 6.022564 -2.539627 -0.463685 55 1 0 6.191025 -4.422597 0.540263 56 1 0 4.034417 -5.370401 -0.536042 57 1 0 3.848860 -3.713521 -2.424299 58 1 0 3.225246 -1.291498 -1.850091 59 1 0 5.373062 -0.566072 -0.865871 60 1 0 7.040331 -2.220087 -0.244576 61 1 0 3.125696 -1.635757 -0.017496 62 1 0 2.408055 -3.663765 -1.403710 63 1 0 3.792103 -4.054676 0.617503 64 1 0 6.213074 -4.529514 -1.205386 --------------------------------------------------------------------- 3 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.372345 -1.621649 -0.381425 2 6 0 -5.271570 1.446290 -0.742210 3 6 0 -3.149919 0.751758 -0.190531 4 6 0 -3.659655 -0.076295 0.853994 5 6 0 -5.764490 0.606332 0.318451 6 1 0 -1.377463 1.377501 -1.242777 7 6 0 -1.756040 0.780700 -0.419229 8 6 0 -2.772868 -0.831761 1.646026 9 6 0 -1.405220 -0.795160 1.416619 10 6 0 -0.900903 0.034709 0.361095 11 1 0 -3.186274 -1.443320 2.442937 12 6 0 1.158114 1.161640 0.177340 13 6 0 2.574355 1.311234 0.068040 14 6 0 3.432161 0.177947 0.177066 15 6 0 3.122202 2.615578 -0.022944 16 6 0 4.840653 0.396345 0.212172 17 6 0 4.485953 2.828528 -0.024022 18 1 0 2.439760 3.460240 -0.098217 19 6 0 5.320333 1.691678 0.099995 20 1 0 6.399300 1.840642 0.109840 21 1 0 0.577418 2.071941 0.344968 22 7 0 0.505571 0.032886 0.145032 23 8 0 2.987128 -1.051670 0.320227 24 6 0 5.759240 -0.788180 0.357552 25 1 0 5.613314 -1.505151 -0.459301 26 1 0 6.807529 -0.474640 0.357108 107 27 1 0 5.561566 -1.332867 1.288440 28 6 0 5.083969 4.209598 -0.148302 29 1 0 5.675728 4.311545 -1.067091 30 1 0 4.305709 4.979059 -0.169885 31 1 0 5.753634 4.435948 0.690861 32 7 0 -3.979387 1.502522 -0.973372 33 7 0 -5.006439 -0.125433 1.091380 34 8 0 -7.103348 0.588063 0.513526 35 1 0 -7.257786 -0.026345 1.254994 36 6 0 -6.218979 2.255411 -1.581869 37 1 0 -5.651281 2.822687 -2.322433 38 1 0 -6.940727 1.609547 -2.096350 39 1 0 -6.803022 2.948028 -0.963781 40 7 0 -0.513362 -1.555539 2.157297 41 1 0 -0.880920 -1.966939 3.004914 42 1 0 0.419712 -1.181270 2.269591 43 8 0 2.151341 -3.152432 -0.837448 44 8 0 -0.166717 -2.110415 -1.128071 45 6 0 -0.367613 -3.406616 -1.619243 46 1 0 0.347558 -3.684821 -2.403093 47 1 0 -0.336790 -4.170879 -0.830352 48 1 0 -1.379111 -3.401017 -2.056160 49 1 0 3.063876 -3.029892 -0.521134 --------------------------------------------------------------------- 4 C s Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.108186 -0.694320 1.274119 2 6 0 0.502718 -1.305691 0.000000 3 6 0 -0.108186 -0.694320 -1.274119 4 6 0 -0.108186 0.809006 -1.218098 5 6 0 -0.098409 1.478107 0.000000 6 6 0 -0.108186 0.809006 1.218098 7 1 0 -1.141713 -1.062139 1.400211 8 1 0 1.582547 -1.108573 0.000000 9 1 0 0.437306 -1.045154 -2.160460 10 1 0 -0.098916 2.567160 0.000000 11 1 0 -0.139485 1.370009 2.148664 12 1 0 -1.141713 -1.062139 -1.400211 13 1 0 0.374759 -2.394745 0.000000 14 1 0 0.437306 -1.045154 2.160460 15 1 0 -0.139485 1.370009 -2.148664 108 --------------------------------------------------------------------- 3,4TS5 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.225231 -0.060533 -0.151628 2 6 0 -6.054488 -0.239692 -1.001256 3 6 0 -3.891905 0.089474 -0.290856 4 6 0 -4.088894 -0.792708 0.813585 5 6 0 -6.232310 -1.122942 0.119777 6 1 0 -2.473578 1.341724 -1.319087 7 6 0 -2.627873 0.699649 -0.457803 8 6 0 -3.033720 -1.030179 1.715169 9 6 0 -1.794788 -0.429043 1.540583 10 6 0 -1.600733 0.457507 0.427829 11 1 0 -3.212231 -1.697256 2.553871 12 6 0 -0.280856 2.375471 0.232346 13 6 0 0.874590 3.195140 0.070889 14 6 0 2.186961 2.642047 -0.030114 15 6 0 0.695519 4.604805 0.070483 16 6 0 3.294589 3.544692 -0.111189 17 6 0 1.759931 5.474802 -0.025850 18 1 0 -0.318063 4.994568 0.148941 19 6 0 3.056058 4.906824 -0.113759 20 1 0 3.911051 5.578166 -0.187421 21 1 0 -1.227148 2.906750 0.366950 22 7 0 -0.323428 1.068814 0.270032 23 8 0 2.435095 1.360855 -0.044475 24 6 0 4.684765 2.973829 -0.206167 25 1 0 4.791501 2.336169 -1.092086 26 1 0 5.434243 3.769517 -0.260520 27 1 0 4.913718 2.341541 0.660418 28 6 0 1.577611 6.973866 -0.036453 29 1 0 1.951966 7.420100 -0.966912 30 1 0 0.521481 7.245999 0.058700 31 1 0 2.119934 7.453454 0.788627 32 7 0 -4.892122 0.347643 -1.182464 33 7 0 -5.303304 -1.396225 0.997704 34 8 0 -7.449888 -1.699778 0.261591 35 1 0 -7.387425 -2.258324 1.058486 36 6 0 -7.180763 0.017822 -1.962322 37 1 0 -6.844079 0.712930 -2.734453 38 1 0 -7.517751 -0.912379 -2.435748 109 39 1 0 -8.052136 0.441632 -1.448346 40 7 0 -0.743303 -0.670270 2.406101 41 1 0 -0.981343 -1.065669 3.305079 42 1 0 -0.015882 0.029528 2.445855 43 8 0 2.652597 -1.191599 -0.025968 44 8 0 0.108261 -1.324399 -0.765621 45 6 0 0.485461 -2.654897 -0.932094 46 1 0 1.197459 -2.802917 -1.760448 47 1 0 0.926418 -3.095196 -0.024626 48 1 0 -0.431093 -3.222583 -1.164924 49 1 0 3.392039 -0.558927 0.004652 50 6 0 3.362635 -5.446702 -0.681419 51 6 0 4.659905 -4.819434 -1.220204 52 6 0 4.710143 -3.306386 -0.943253 53 6 0 4.384876 -2.991716 0.487589 54 6 0 3.628614 -3.876299 1.265384 55 6 0 3.100430 -5.034753 0.739147 56 1 0 2.510846 -5.135190 -1.309073 57 1 0 5.514902 -5.302782 -0.729255 58 1 0 5.693974 -2.899902 -1.211557 59 1 0 3.422043 -3.617244 2.301162 60 1 0 2.471564 -5.671538 1.357065 61 1 0 3.976995 -2.782500 -1.573763 62 1 0 4.757309 -5.010324 -2.295097 63 1 0 3.403801 -6.541161 -0.758616 64 1 0 4.829809 -2.120164 0.955265 --------------------------------------------------------------------- 5 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.196157 0.303290 0.695463 2 6 0 -5.972414 -1.024257 0.544217 3 6 0 -3.732954 -0.814990 0.062076 4 6 0 -3.991009 0.306849 -0.780551 5 6 0 -6.209717 0.106452 -0.312791 6 1 0 -2.206717 -2.072384 0.914965 7 6 0 -2.399412 -1.252260 0.231042 8 6 0 -2.922030 0.941025 -1.445994 9 6 0 -1.619968 0.501632 -1.274075 10 6 0 -1.361166 -0.613812 -0.411728 11 1 0 -3.146576 1.777741 -2.101765 12 6 0 0.344811 -2.221764 -0.426019 110 13 6 0 1.654664 -2.784548 -0.283208 14 6 0 2.803541 -2.003655 0.061288 15 6 0 1.799657 -4.171521 -0.548931 16 6 0 4.071940 -2.659765 0.110492 17 6 0 3.022408 -4.807922 -0.487243 18 1 0 0.908204 -4.740410 -0.808637 19 6 0 4.147692 -4.016408 -0.153963 20 1 0 5.123725 -4.498028 -0.102709 21 1 0 -0.432623 -2.911540 -0.771323 22 7 0 -0.004303 -0.981661 -0.216961 23 8 0 2.747751 -0.720368 0.311432 24 6 0 5.290291 -1.846576 0.461570 25 1 0 5.176639 -1.362998 1.439332 26 1 0 6.187947 -2.472169 0.487698 27 1 0 5.455957 -1.041624 -0.266064 28 6 0 3.175296 -6.285426 -0.760877 29 1 0 3.565820 -6.820903 0.114246 30 1 0 2.215712 -6.741444 -1.025223 31 1 0 3.871754 -6.474503 -1.588002 32 7 0 -4.744370 -1.461289 0.712956 33 7 0 -5.272589 0.752122 -0.955457 34 8 0 -7.494070 0.513561 -0.452895 35 1 0 -7.465693 1.280819 -1.054034 36 6 0 -7.112181 -1.708107 1.245323 37 1 0 -6.725073 -2.542932 1.833399 38 1 0 -7.641534 -1.013621 1.908990 39 1 0 -7.852391 -2.081921 0.527555 40 7 0 -0.538040 1.120578 -1.904592 41 1 0 -0.799691 1.755906 -2.648893 42 1 0 0.195969 0.485232 -2.193620 43 8 0 2.605009 1.825004 0.595148 44 8 0 -0.122073 1.134400 1.641680 45 6 0 0.256041 1.743621 2.842854 46 1 0 0.759561 1.054551 3.548770 47 1 0 0.927259 2.610586 2.701371 48 1 0 -0.642548 2.117662 3.361477 49 1 0 3.352688 1.261581 0.317786 50 6 0 2.287459 5.917242 -0.422316 51 6 0 3.438105 5.126697 -1.068308 52 6 0 3.702711 3.819789 -0.307154 53 6 0 2.457585 2.934769 -0.336489 54 6 0 1.216003 3.689953 0.050069 55 6 0 1.147994 5.023910 0.003869 56 1 0 2.657079 6.467951 0.457139 57 1 0 3.178668 4.891507 -2.110038 58 1 0 4.561640 3.285765 -0.735474 111 59 1 0 0.374581 3.078447 0.369861 60 1 0 0.222283 5.515503 0.300170 61 1 0 3.940329 4.035841 0.742148 62 1 0 4.348785 5.735677 -1.103322 63 1 0 1.921644 6.687232 -1.115521 64 1 0 2.328152 2.502481 -1.342152 --------------------------------------------------------------------- 6 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -1.459952 -0.216569 0.410934 2 6 0 6.188136 0.173955 0.553340 3 6 0 3.918545 0.053840 0.208401 4 6 0 4.066090 -1.145118 -0.547343 5 6 0 6.315134 -1.034231 -0.219658 6 1 0 2.530648 1.500951 0.963668 7 6 0 2.623949 0.587915 0.384447 8 6 0 2.919113 -1.792490 -1.040715 9 6 0 1.639567 -1.285208 -0.837208 10 6 0 1.502984 -0.018790 -0.158521 11 1 0 3.050532 -2.732004 -1.570708 12 6 0 0.241712 1.918255 -0.348137 13 6 0 -0.819142 2.873363 -0.247355 14 6 0 -2.148181 2.548166 0.163441 15 6 0 -0.499628 4.218760 -0.578244 16 6 0 -3.110341 3.600409 0.250115 17 6 0 -1.427592 5.235826 -0.500387 18 1 0 0.517836 4.441876 -0.894703 19 6 0 -2.734040 4.891256 -0.076092 20 1 0 -3.481528 5.680658 -0.004159 21 1 0 1.188016 2.333818 -0.702682 22 7 0 0.233904 0.634887 -0.074362 23 8 0 -2.521386 1.328825 0.452887 24 6 0 -4.509962 3.263003 0.692435 25 1 0 -4.508461 2.763952 1.668640 26 1 0 -5.128714 4.162926 0.763254 27 1 0 -4.995317 2.571621 -0.008925 28 6 0 -1.084716 6.665383 -0.846824 29 1 0 -1.240446 7.337308 0.007070 30 1 0 -0.038436 6.758984 -1.154965 31 1 0 -1.707310 7.042759 -1.668348 32 7 0 4.996620 0.692084 0.752133 112 33 7 0 5.310281 -1.678128 -0.751841 34 8 0 7.566462 -1.520054 -0.396720 35 1 0 7.465103 -2.327247 -0.934528 36 6 0 7.401991 0.844781 1.131620 37 1 0 7.094086 1.737046 1.680876 38 1 0 7.941784 0.171349 1.808365 39 1 0 8.109623 1.130649 0.343862 40 7 0 0.513755 -1.943360 -1.319001 41 1 0 0.747980 -2.834206 -1.745402 42 1 0 -0.199358 -2.076716 -0.585431 43 8 0 -3.175197 -0.903722 -0.643289 44 8 0 -1.045757 -1.887085 1.039254 45 6 0 -0.177822 -2.062734 2.128506 46 1 0 0.771528 -1.511822 2.017651 47 1 0 -0.631460 -1.742449 3.082560 48 1 0 0.081395 -3.128395 2.234707 49 1 0 -3.737897 -0.131864 -0.454787 50 6 0 -3.861335 -5.015603 0.072653 51 6 0 -4.886848 -4.036024 0.666869 52 6 0 -4.313772 -2.613079 0.727535 53 6 0 -3.967931 -2.120487 -0.679260 54 6 0 -3.196955 -3.146259 -1.464433 55 6 0 -3.156851 -4.439391 -1.130379 56 1 0 -3.107692 -5.276268 0.831833 57 1 0 -5.795189 -4.042441 0.047473 58 1 0 -5.025283 -1.924838 1.202626 59 1 0 -2.674835 -2.775889 -2.344384 60 1 0 -2.581775 -5.130325 -1.745847 61 1 0 -3.386871 -2.600577 1.311522 62 1 0 -5.189410 -4.364606 1.667981 63 1 0 -4.349434 -5.961781 -0.198443 64 1 0 -4.888025 -1.867046 -1.230230 --------------------------------------------------------------------- 6TS7 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -1.259523 -0.289071 0.505518 2 6 0 6.257391 0.641997 0.103382 3 6 0 3.964213 0.453155 0.101669 4 6 0 4.054528 -0.922591 -0.257659 5 6 0 6.321866 -0.750004 -0.268527 6 1 0 2.669652 2.091665 0.550791 113 7 6 0 2.694955 1.044357 0.270342 8 6 0 2.869535 -1.679065 -0.375602 9 6 0 1.629234 -1.100694 -0.180288 10 6 0 1.534254 0.309340 0.079249 11 1 0 2.953061 -2.740026 -0.592807 12 6 0 0.073630 2.142561 -0.188067 13 6 0 -1.144561 2.885696 -0.192770 14 6 0 -2.427582 2.300146 0.063306 15 6 0 -1.053145 4.273465 -0.493247 16 6 0 -3.577040 3.152438 0.020357 17 6 0 -2.159963 5.092815 -0.530204 18 1 0 -0.067134 4.691001 -0.690895 19 6 0 -3.418054 4.495616 -0.264758 20 1 0 -4.306266 5.126252 -0.288412 21 1 0 0.959046 2.710089 -0.484218 22 7 0 0.234889 0.878525 0.111413 23 8 0 -2.603519 1.033640 0.316616 24 6 0 -4.929379 2.547142 0.290149 25 1 0 -4.950689 2.042094 1.262930 26 1 0 -5.712829 3.311225 0.276323 27 1 0 -5.183157 1.785990 -0.459168 28 6 0 -2.060859 6.568118 -0.837047 29 1 0 -2.655308 6.838752 -1.719298 30 1 0 -2.429170 7.180560 -0.003724 31 1 0 -1.025126 6.864374 -1.032268 32 7 0 5.089332 1.213304 0.280891 33 7 0 5.275040 -1.510947 -0.442901 34 8 0 7.554153 -1.279916 -0.442031 35 1 0 7.414991 -2.214099 -0.685002 36 6 0 7.516173 1.440350 0.288419 37 1 0 7.258162 2.463556 0.568816 38 1 0 8.151065 0.999217 1.066140 39 1 0 8.112300 1.454604 -0.631929 40 7 0 0.417430 -1.835202 -0.258118 41 1 0 0.473312 -2.627370 -0.892697 42 1 0 0.079911 -2.161848 0.663411 43 8 0 -2.727628 -1.232716 -0.995067 44 8 0 -1.254009 -1.624654 1.833540 45 6 0 -1.279698 -1.405345 3.213563 46 1 0 -2.204873 -0.897337 3.540012 47 1 0 -1.226030 -2.358957 3.766697 48 1 0 -0.435707 -0.783275 3.566734 49 1 0 -3.399798 -0.566557 -0.765870 50 6 0 -2.905051 -5.385425 -0.301572 51 6 0 -4.152513 -4.580196 0.098078 52 6 0 -3.827242 -3.084463 0.213853 114 53 6 0 -3.338972 -2.533600 -1.130577 54 6 0 -2.320187 -3.438423 -1.773082 55 6 0 -2.126917 -4.708965 -1.403750 56 1 0 -2.248003 -5.519465 0.571846 57 1 0 -4.935682 -4.731674 -0.658690 58 1 0 -4.709594 -2.521548 0.546903 59 1 0 -1.747502 -2.997910 -2.587372 60 1 0 -1.375910 -5.306761 -1.920182 61 1 0 -3.033424 -2.914473 0.951540 62 1 0 -4.556734 -4.954511 1.045864 63 1 0 -3.188098 -6.399099 -0.617083 64 1 0 -4.190816 -2.422544 -1.823162 --------------------------------------------------------------------- 7 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -0.952784 -0.275556 1.000622 2 6 0 6.314003 0.869727 -0.181655 3 6 0 4.023452 0.673185 -0.056668 4 6 0 4.133554 -0.739824 0.096157 5 6 0 6.396577 -0.562877 -0.032433 6 1 0 2.717651 2.366798 -0.115900 7 6 0 2.751066 1.284731 -0.049268 8 6 0 2.958266 -1.513030 0.236135 9 6 0 1.726060 -0.900561 0.231261 10 6 0 1.604764 0.519122 0.087019 11 1 0 3.051899 -2.589626 0.342597 12 6 0 -0.056575 2.182951 -0.279037 13 6 0 -1.368028 2.741517 -0.254571 14 6 0 -2.531995 1.999012 0.148068 15 6 0 -1.508119 4.086708 -0.698512 16 6 0 -3.799808 2.665561 0.092280 17 6 0 -2.727693 4.724248 -0.739449 18 1 0 -0.610069 4.620621 -1.005887 19 6 0 -3.864120 3.978557 -0.333204 20 1 0 -4.838747 4.465002 -0.360214 21 1 0 0.714349 2.808997 -0.737928 22 7 0 0.283753 1.006211 0.179024 23 8 0 -2.509528 0.751203 0.529183 24 6 0 -5.027358 1.897670 0.506149 25 1 0 -5.185848 1.024081 -0.138485 26 1 0 -4.924726 1.509180 1.525722 115 27 1 0 -5.921231 2.527535 0.457677 28 6 0 -2.874432 6.156364 -1.194905 29 1 0 -3.289698 6.792205 -0.402161 30 1 0 -1.908878 6.581301 -1.487852 31 1 0 -3.549152 6.239569 -2.056807 32 7 0 5.140311 1.455911 -0.189888 33 7 0 5.358888 -1.344137 0.103194 34 8 0 7.633559 -1.107180 -0.034730 35 1 0 7.509441 -2.068018 0.077170 36 6 0 7.561655 1.692785 -0.325985 37 1 0 7.291941 2.746068 -0.424638 38 1 0 8.218748 1.564685 0.542458 39 1 0 8.138955 1.380478 -1.204440 40 7 0 0.488734 -1.607859 0.402085 41 1 0 0.562698 -2.426307 1.002107 42 1 0 0.041997 -1.877375 -0.480201 43 8 0 -1.892952 -1.334865 -1.456267 44 8 0 -1.570121 -1.438572 2.265571 45 6 0 -2.743607 -1.201169 2.983526 46 1 0 -2.782758 -1.869184 3.861288 47 1 0 -2.826600 -0.167490 3.364447 48 1 0 -3.656887 -1.397947 2.391752 49 6 0 -2.841125 -5.341066 -0.607535 50 6 0 -3.987326 -4.330970 -0.436402 51 6 0 -3.446977 -2.897745 -0.344082 52 6 0 -2.696595 -2.517662 -1.626748 53 6 0 -1.760609 -3.612861 -2.070925 54 6 0 -1.816878 -4.866403 -1.609137 55 1 0 -2.345152 -5.515343 0.360348 56 1 0 -4.669675 -4.412257 -1.294469 57 1 0 -4.264813 -2.186115 -0.171901 58 1 0 -2.434389 -0.646863 -1.021206 59 1 0 -1.016839 -3.325810 -2.813476 60 1 0 -1.097334 -5.601198 -1.969890 61 1 0 -2.758396 -2.799913 0.505118 62 1 0 -4.575328 -4.572726 0.456421 63 1 0 -3.234332 -6.319267 -0.916933 64 1 0 -3.424454 -2.323355 -2.434193 --------------------------------------------------------------------- 7TS8 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 116 1 29 0 -1.291632 0.477067 -0.660176 2 6 0 5.354223 -2.923294 -0.097908 3 6 0 3.228035 -2.039023 -0.096320 4 6 0 3.758392 -0.715644 -0.112261 5 6 0 5.863932 -1.573682 -0.106625 6 1 0 1.475920 -3.263301 -0.133399 7 6 0 1.830979 -2.239131 -0.100463 8 6 0 2.868378 0.382295 -0.128152 9 6 0 1.509006 0.167382 -0.127105 10 6 0 0.965921 -1.155589 -0.102364 11 1 0 3.276215 1.388520 -0.140744 12 6 0 -1.091625 -2.294446 0.222991 13 6 0 -2.500707 -2.465018 0.224465 14 6 0 -3.415257 -1.409499 -0.126283 15 6 0 -3.005814 -3.737418 0.621947 16 6 0 -4.821887 -1.701369 -0.067445 17 6 0 -4.352616 -4.008520 0.671705 18 1 0 -2.288106 -4.512683 0.886701 19 6 0 -5.242023 -2.957865 0.316522 20 1 0 -6.313143 -3.155313 0.351176 21 1 0 -0.512807 -3.150454 0.581230 22 7 0 -0.443194 -1.214645 -0.144526 23 8 0 -3.052391 -0.215608 -0.474728 24 6 0 -5.790992 -0.608755 -0.432554 25 1 0 -5.665987 0.264895 0.218411 26 1 0 -5.619392 -0.253697 -1.455527 27 1 0 -6.825717 -0.957071 -0.352790 28 6 0 -4.890862 -5.357767 1.083154 29 1 0 -5.483675 -5.818614 0.282127 30 1 0 -4.079990 -6.049316 1.334241 31 1 0 -5.546082 -5.281658 1.960787 32 7 0 4.058710 -3.129489 -0.094187 33 7 0 5.109142 -0.508238 -0.115860 34 8 0 7.208051 -1.427864 -0.106799 35 1 0 7.377945 -0.467612 -0.115249 36 6 0 6.296904 -4.092301 -0.093831 37 1 0 5.722982 -5.021004 -0.088772 38 1 0 6.950531 -4.072581 -0.974063 39 1 0 6.953097 -4.064487 0.784296 40 7 0 0.538820 1.226883 -0.174135 41 1 0 0.783330 1.961883 -0.836472 42 1 0 0.376234 1.701278 0.729296 43 8 0 -0.491481 2.860688 1.979803 44 8 0 -1.669949 2.130079 -1.367478 45 6 0 -2.894479 2.453880 -1.958879 46 1 0 -2.927799 2.195431 -3.033896 117 47 1 0 -3.748983 1.950840 -1.479917 48 1 0 -3.074302 3.542045 -1.888652 49 6 0 0.931582 5.979945 -0.460482 50 6 0 -0.494308 6.155881 0.086032 51 6 0 -1.060877 4.821290 0.589085 52 6 0 -0.199407 4.258641 1.725333 53 6 0 1.273545 4.353073 1.419378 54 6 0 1.776313 5.112723 0.440353 55 1 0 0.897262 5.531294 -1.465589 56 1 0 -0.475604 6.882271 0.910742 57 1 0 -2.091783 4.955594 0.944944 58 1 0 -1.424089 2.715694 1.748534 59 1 0 1.929345 3.761853 2.057272 60 1 0 2.853542 5.125338 0.275327 61 1 0 -1.097464 4.080603 -0.222175 62 1 0 -1.148008 6.574343 -0.687504 63 1 0 1.415158 6.957681 -0.590779 64 1 0 -0.407619 4.808622 2.658322 --------------------------------------------------------------------- 8 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.072897 0.247366 -0.887574 2 6 0 -6.349160 -0.101442 0.327157 3 6 0 -4.071652 0.152846 0.103011 4 6 0 -3.940903 -1.208217 -0.299538 5 6 0 -6.186976 -1.477509 -0.077534 6 1 0 -3.092110 2.017702 0.443386 7 6 0 -2.931398 0.979804 0.174400 8 6 0 -2.659010 -1.708984 -0.618457 9 6 0 -1.556868 -0.888705 -0.534073 10 6 0 -1.673656 0.476322 -0.127033 11 1 0 -2.565919 -2.746328 -0.926162 12 6 0 -0.377252 2.393136 0.412500 13 6 0 0.743329 3.259858 0.354689 14 6 0 1.943732 2.931028 -0.368018 15 6 0 0.639863 4.515412 1.022667 16 6 0 2.988375 3.916712 -0.411229 17 6 0 1.650331 5.446482 0.989765 18 1 0 -0.278335 4.731984 1.566757 19 6 0 2.820596 5.113686 0.253521 20 1 0 3.628829 5.843390 0.213552 118 21 1 0 -1.238339 2.774640 0.967310 22 7 0 -0.465318 1.202392 -0.135017 23 8 0 2.134858 1.808831 -0.988104 24 6 0 4.240861 3.593040 -1.180920 25 1 0 4.729320 2.696462 -0.781482 26 1 0 4.013321 3.374007 -2.230900 27 1 0 4.952122 4.424304 -1.143984 28 6 0 1.546312 6.777402 1.694891 29 1 0 1.640857 7.615837 0.992512 30 1 0 0.584588 6.881570 2.207694 31 1 0 2.337669 6.899986 2.445936 32 7 0 -5.299865 0.681176 0.407834 33 7 0 -5.038478 -2.018174 -0.382640 34 8 0 -7.306798 -2.231718 -0.138946 35 1 0 -7.022771 -3.119925 -0.424512 36 6 0 -7.711417 0.438467 0.655249 37 1 0 -7.627362 1.490666 0.933966 38 1 0 -8.388969 0.341028 -0.201366 39 1 0 -8.167126 -0.121955 1.480304 40 7 0 -0.224537 -1.326442 -0.862863 41 1 0 -0.200202 -1.868852 -1.725654 42 1 0 0.208614 -1.923714 -0.130562 43 8 0 1.682205 -2.421476 0.849628 44 8 0 2.427746 -0.989821 -1.220178 45 6 0 3.754244 -0.616650 -1.488369 46 1 0 4.363236 -1.522278 -1.643132 47 1 0 3.837227 -0.004315 -2.399078 48 1 0 4.212659 -0.038996 -0.668415 49 6 0 4.660812 -5.445719 0.568020 50 6 0 4.395903 -4.828955 1.951906 51 6 0 3.656958 -3.490026 1.826537 52 6 0 2.290018 -3.677448 1.152731 53 6 0 2.406711 -4.552561 -0.076082 54 6 0 3.462522 -5.328593 -0.341583 55 1 0 5.523104 -4.951110 0.092933 56 1 0 3.785694 -5.524431 2.545451 57 1 0 3.519631 -3.014481 2.804331 58 1 0 2.184079 -1.962082 0.105352 59 1 0 1.564244 -4.517624 -0.766149 60 1 0 3.480124 -5.913573 -1.260935 61 1 0 4.250178 -2.797630 1.212936 62 1 0 5.338936 -4.697910 2.496171 63 1 0 4.949135 -6.501369 0.669339 64 1 0 1.603204 -4.154121 1.868388 --------------------------------------------------------------------- 119 9 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 2.365379 -0.010639 -0.199102 2 6 0 -1.885342 0.157494 -0.238553 3 6 0 -1.232820 -1.144287 0.256769 4 6 0 0.230619 -1.232857 -0.195451 5 6 0 1.055590 -0.071611 0.376176 6 6 0 0.329647 1.244950 0.219844 7 6 0 -0.971657 1.347445 -0.071963 8 1 0 -2.163660 0.060846 -1.300435 9 1 0 -1.272912 -1.172512 1.354585 10 1 0 0.685679 -2.185879 0.096556 11 1 0 2.249039 0.216698 -1.136266 12 1 0 0.941871 2.136301 0.350968 13 1 0 -1.417435 2.334236 -0.195620 14 1 0 0.275730 -1.180626 -1.294074 15 1 0 -1.799104 -2.013008 -0.099526 16 1 0 -2.829281 0.338353 0.293945 17 1 0 1.250817 -0.256102 1.441747 --------------------------------------------------------------------- 10 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 1.289297 -1.688267 -0.036604 2 6 0 -5.430383 1.537636 0.345196 3 6 0 -3.281986 0.750586 0.084950 4 6 0 -3.778674 -0.536910 -0.271944 5 6 0 -5.905497 0.225791 -0.025994 6 1 0 -1.562424 1.964373 0.458132 7 6 0 -1.891340 0.981265 0.140014 8 6 0 -2.859786 -1.568397 -0.572078 9 6 0 -1.507551 -1.322756 -0.515736 10 6 0 -0.995192 -0.032273 -0.167928 11 1 0 -3.244604 -2.547536 -0.841722 12 6 0 1.036965 1.206463 -0.145724 13 6 0 2.442611 1.388070 -0.090163 14 6 0 3.377100 0.289801 -0.042037 15 6 0 2.928269 2.729392 -0.109199 120 16 6 0 4.779325 0.611007 -0.011405 17 6 0 4.269565 3.024838 -0.073882 18 1 0 2.197881 3.536429 -0.148530 19 6 0 5.177582 1.930701 -0.024628 20 1 0 6.245075 2.147883 0.002614 21 1 0 0.444214 2.121176 -0.238729 22 7 0 0.408800 0.054161 -0.114404 23 8 0 3.041454 -0.960038 -0.040271 24 6 0 5.764330 -0.526301 0.036408 25 1 0 5.597421 -1.155795 0.918326 26 1 0 5.649670 -1.184796 -0.832751 27 1 0 6.793864 -0.155257 0.060625 28 6 0 4.785462 4.443526 -0.085273 29 1 0 5.441131 4.628678 -0.946184 30 1 0 3.963312 5.164973 -0.133560 31 1 0 5.371697 4.667979 0.815485 32 7 0 -4.141371 1.773630 0.394441 33 7 0 -5.122906 -0.776370 -0.322341 34 8 0 -7.244562 0.049160 -0.060286 35 1 0 -7.392402 -0.879081 -0.320317 36 6 0 -6.403499 2.632129 0.675868 37 1 0 -5.854838 3.539954 0.933833 38 1 0 -7.067803 2.835828 -0.172468 39 1 0 -7.047238 2.343652 1.515339 40 7 0 -0.507283 -2.329360 -0.796526 41 1 0 -0.434443 -2.528253 -1.794618 42 1 0 -0.665667 -3.216753 -0.317509 43 8 0 1.542315 -3.391896 0.559874 44 6 0 2.766136 -3.895551 1.001632 45 1 0 2.595763 -4.707555 1.730330 46 1 0 3.372019 -4.325128 0.181810 47 1 0 3.392817 -3.137361 1.500235 --------------------------------------------------------------------- 1TS11,12 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -1.200810 -1.427701 -0.464240 2 6 0 5.676640 1.384269 -0.087090 3 6 0 3.475380 0.707619 -0.008230 4 6 0 3.879910 -0.649401 0.151290 5 6 0 6.059230 0.000339 0.083860 6 1 0 1.838260 2.072099 -0.231870 121 7 6 0 2.103720 1.034349 -0.063120 8 6 0 2.892810 -1.655521 0.262830 9 6 0 1.561820 -1.313151 0.212590 10 6 0 1.143820 0.041279 0.054700 11 1 0 3.204140 -2.687871 0.389410 12 6 0 -0.814910 1.382179 0.184010 13 6 0 -2.206680 1.666449 0.093000 14 6 0 -3.193020 0.665129 -0.209400 15 6 0 -2.610690 3.011089 0.334860 16 6 0 -4.565820 1.079929 -0.266680 17 6 0 -3.930090 3.401799 0.277530 18 1 0 -1.838950 3.743009 0.566020 19 6 0 -4.890840 2.402469 -0.029160 20 1 0 -5.939750 2.692289 -0.078990 21 1 0 -0.177910 2.219449 0.477510 22 7 0 -0.253140 0.220589 -0.040470 23 8 0 -2.921450 -0.591531 -0.418970 24 6 0 -5.617430 0.049219 -0.585600 25 1 0 -5.611580 -0.766971 0.147010 26 1 0 -6.615550 0.497549 -0.594200 27 1 0 -5.438870 -0.413111 -1.564350 28 6 0 -4.361500 4.827679 0.526040 29 1 0 -5.062560 4.895429 1.367800 30 1 0 -3.503130 5.467459 0.753920 31 1 0 -4.872560 5.252089 -0.347690 32 7 0 4.406590 1.708389 -0.131020 33 7 0 5.205320 -0.981661 0.196230 34 8 0 7.381090 -0.258671 0.123960 35 1 0 7.485840 -1.222051 0.240920 36 6 0 6.726480 2.449249 -0.214350 37 1 0 6.248930 3.423009 -0.339720 38 1 0 7.368490 2.473249 0.674110 39 1 0 7.380150 2.253509 -1.072490 40 7 0 0.493840 -2.286671 0.308830 41 1 0 0.277130 -2.491141 1.287650 42 1 0 0.761140 -3.174101 -0.116110 43 8 0 -1.734550 -2.939511 -1.297900 44 8 0 -3.647950 -4.325681 0.414820 45 6 0 -3.369190 -3.562651 1.521600 46 1 0 -2.425940 -3.829261 2.026170 47 1 0 -3.401750 -2.485041 1.297560 48 1 0 -4.195200 -3.751541 2.237910 --------------------------------------------------------------------- 11 C 1 Standard orientation: 122 --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -1.320290 -1.921576 0.171316 2 8 0 -1.603361 -3.557840 0.807821 3 6 0 5.248143 1.614351 0.245887 4 6 0 3.132555 0.725049 0.055011 5 6 0 3.680410 -0.560416 -0.225633 6 6 0 5.775134 0.302234 -0.047024 7 1 0 1.365993 1.886730 0.372559 8 6 0 1.733868 0.900963 0.110215 9 6 0 2.803396 -1.644733 -0.456523 10 6 0 1.443283 -1.448928 -0.403661 11 6 0 0.877588 -0.165704 -0.124234 12 1 0 3.227806 -2.620744 -0.673694 13 6 0 -1.208093 0.977872 -0.142246 14 6 0 -2.617835 1.098804 -0.082081 15 6 0 -3.499960 -0.040037 0.014662 16 6 0 -3.166126 2.414858 -0.155129 17 6 0 -4.916744 0.216451 0.038366 18 6 0 -4.519058 2.647497 -0.124836 19 1 0 -2.474532 3.252900 -0.231179 20 6 0 -5.375211 1.514074 -0.026505 21 1 0 -6.451493 1.682711 -0.002616 22 1 0 -0.657996 1.911072 -0.293537 23 7 0 -0.526280 -0.142328 -0.053655 24 8 0 -3.108144 -1.270266 0.058514 25 6 0 -5.845736 -0.963836 0.135702 26 1 0 -6.891660 -0.641540 0.155880 27 1 0 -5.705555 -1.646774 -0.710471 28 1 0 -5.641125 -1.552825 1.037278 29 6 0 -5.102265 4.038242 -0.191350 30 1 0 -5.764850 4.158174 -1.058542 31 1 0 -5.699937 4.268939 0.700247 32 1 0 -4.315610 4.795935 -0.267926 33 7 0 3.950766 1.799767 0.292234 34 7 0 5.032705 -0.747805 -0.273237 35 8 0 7.119761 0.179053 -0.082230 36 1 0 7.305259 -0.756631 -0.285213 37 6 0 6.177142 2.766346 0.498608 38 1 0 6.837697 2.557439 1.348461 39 1 0 6.826772 2.943334 -0.366891 40 1 0 5.593177 3.665390 0.704480 41 7 0 0.488259 -2.518145 -0.616629 42 1 0 0.800642 -3.401065 -0.214626 123 43 1 0 0.326675 -2.683874 -1.611561 --------------------------------------------------------------------- 11 C 1 open shell singlet (broken symmetry) Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 -1.321057 -1.925220 0.158739 2 8 0 -1.631368 -3.583944 0.753504 3 6 0 5.240713 1.617626 0.257645 4 6 0 3.128814 0.721872 0.056977 5 6 0 3.681699 -0.561266 -0.224215 6 6 0 5.772969 0.307794 -0.036159 7 1 0 1.357674 1.876826 0.373081 8 6 0 1.729335 0.893254 0.107977 9 6 0 2.808971 -1.647972 -0.459967 10 6 0 1.448017 -1.456453 -0.412032 11 6 0 0.877796 -0.175771 -0.132327 12 1 0 3.236874 -2.622449 -0.676996 13 6 0 -1.205923 0.968255 -0.161498 14 6 0 -2.613356 1.099064 -0.092908 15 6 0 -3.498375 -0.033712 0.034772 16 6 0 -3.156598 2.416252 -0.183188 17 6 0 -4.913799 0.228081 0.073478 18 6 0 -4.508132 2.654354 -0.140734 19 1 0 -2.462671 3.249866 -0.282587 20 6 0 -5.367474 1.526256 -0.010178 21 1 0 -6.442634 1.700070 0.024190 22 1 0 -0.650474 1.895769 -0.325366 23 7 0 -0.527492 -0.154405 -0.065583 24 8 0 -3.107980 -1.263231 0.095879 25 6 0 -5.845672 -0.946455 0.205264 26 1 0 -6.889951 -0.619594 0.234195 27 1 0 -5.720002 -1.645288 -0.630141 28 1 0 -5.630625 -1.519810 1.114445 29 6 0 -5.087294 4.045744 -0.226168 30 1 0 -5.759950 4.151784 -1.087375 31 1 0 -5.673233 4.295192 0.668142 32 1 0 -4.298995 4.798929 -0.326497 33 7 0 3.942568 1.798705 0.299661 34 7 0 5.034773 -0.744165 -0.267229 35 8 0 7.118048 0.189010 -0.066518 36 1 0 7.307411 -0.745654 -0.270678 37 6 0 6.165041 2.772000 0.516490 124 38 1 0 6.823234 2.563191 1.368197 39 1 0 6.817185 2.953177 -0.346250 40 1 0 5.577427 3.668652 0.722420 41 7 0 0.494786 -2.525294 -0.627039 42 1 0 0.802550 -3.408254 -0.221424 43 1 0 0.334404 -2.693140 -1.621747 --------------------------------------------------------------------- 12 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 0.575017 0.000209 -0.012882 2 1 0 0.871214 -0.007846 1.057348 3 1 0 1.014774 0.911965 -0.451469 4 1 0 1.014129 -0.906015 -0.463614 5 8 0 -0.793778 0.000080 -0.008121 --------------------------------------------------------------------- 2,12TS14,15 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 2.104349 0.208368 -0.862662 2 6 0 -2.280219 -0.461156 -0.514978 3 6 0 -1.059778 -1.360241 -0.256985 4 6 0 -0.285572 -0.903092 0.987135 5 6 0 0.177715 0.540857 0.817116 6 6 0 -0.841081 1.447955 0.258377 7 6 0 -1.960426 1.001252 -0.346562 8 1 0 -2.676659 -0.638350 -1.524372 9 1 0 -1.375744 -2.405228 -0.155017 10 1 0 -0.928061 -0.974497 1.878480 11 1 0 0.683422 0.949925 1.700256 12 1 0 -0.659479 2.519008 0.328927 13 1 0 -2.688411 1.718778 -0.722735 14 1 0 1.085417 0.499679 -0.005018 15 1 0 0.574534 -1.559230 1.165950 16 1 0 -0.380718 -1.308985 -1.117199 17 1 0 -3.102183 -0.727470 0.170342 125 18 6 0 3.233046 -0.114798 -0.113271 19 1 0 4.030132 -0.350442 -0.838041 20 1 0 3.599754 0.714866 0.515157 21 1 0 3.101101 -1.009661 0.519589 --------------------------------------------------------------------- 14 C s Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.108186 -0.694320 1.274119 2 6 0 0.502718 -1.305691 0.000000 3 6 0 -0.108186 -0.694320 -1.274119 4 6 0 -0.108186 0.809006 -1.218098 5 6 0 -0.098409 1.478107 0.000000 6 6 0 -0.108186 0.809006 1.218098 7 1 0 -1.141713 -1.062139 1.400211 8 1 0 1.582547 -1.108573 0.000000 9 1 0 0.437306 -1.045154 -2.160460 10 1 0 -0.098916 2.567160 0.000000 11 1 0 -0.139485 1.370009 2.148664 12 1 0 -1.141713 -1.062139 -1.400211 13 1 0 0.374759 -2.394745 0.000000 14 1 0 0.437306 -1.045154 2.160460 15 1 0 -0.139485 1.370009 -2.148664 --------------------------------------------------------------------- 15 C s Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 0.046868 -0.757690 0.000000 2 6 0 0.046868 0.660853 0.000000 3 1 0 -0.437012 1.086274 0.893285 4 1 0 1.094153 0.974885 0.000000 5 1 0 -0.437012 1.086274 -0.893285 6 1 0 -0.876287 -1.051030 0.000000 --------------------------------------------------------------------- 2,11TS13,14 C 1 Standard orientation: 126 --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 0.910958 -0.591486 -0.956359 2 6 0 -6.210046 0.452720 0.966887 3 6 0 -4.008634 0.405867 0.292871 4 6 0 -4.260475 -0.746515 -0.507316 5 6 0 -6.437934 -0.710570 0.142926 6 1 0 -2.555302 1.801377 1.011957 7 6 0 -2.709965 0.954481 0.352498 8 6 0 -3.196763 -1.319319 -1.241767 9 6 0 -1.939512 -0.765871 -1.173684 10 6 0 -1.672862 0.391967 -0.377060 11 1 0 -3.396749 -2.196025 -1.850871 12 6 0 0.018419 2.023662 -0.019514 13 6 0 1.341415 2.533141 0.011408 14 6 0 2.489128 1.763615 -0.404554 15 6 0 1.509916 3.883665 0.439036 16 6 0 3.770633 2.419146 -0.377575 17 6 0 2.740247 4.493696 0.475410 18 1 0 0.623122 4.436319 0.746435 19 6 0 3.860608 3.725839 0.052473 20 1 0 4.842784 4.197632 0.065770 21 1 0 -0.769972 2.731521 0.253330 22 7 0 -0.328835 0.807040 -0.368729 23 8 0 2.441726 0.538559 -0.818009 24 6 0 4.977144 1.641447 -0.831658 25 1 0 5.878883 2.261267 -0.800674 26 1 0 5.142034 0.758161 -0.203264 27 1 0 4.842884 1.267898 -1.853516 28 6 0 2.923255 5.919453 0.936609 29 1 0 1.965696 6.375075 1.209156 30 1 0 3.580803 5.979762 1.813800 31 1 0 3.377316 6.542448 0.154928 32 7 0 -5.012337 0.983683 1.027023 33 7 0 -5.510477 -1.294526 -0.566846 34 8 0 -7.694284 -1.206957 0.122250 35 1 0 -7.673921 -1.981611 -0.469852 36 6 0 -7.335742 1.057126 1.755410 37 1 0 -6.966860 1.921705 2.310527 38 1 0 -8.153850 1.368998 1.095245 39 1 0 -7.759303 0.327528 2.455846 40 7 0 -0.798864 -1.307543 -1.880312 41 1 0 -0.784961 -1.019239 -2.859550 42 1 0 -0.766106 -2.326167 -1.860363 127 43 8 0 1.607482 -2.246005 -1.082388 44 6 0 3.792487 -4.236119 2.318617 45 6 0 3.408616 -4.694725 0.901889 46 6 0 4.213090 -3.936822 -0.163420 47 6 0 3.958226 -2.435408 -0.049501 48 6 0 3.965168 -1.929494 1.343951 49 6 0 3.894871 -2.734319 2.419174 50 1 0 3.059621 -4.607621 3.049145 51 1 0 3.553007 -5.778028 0.803106 52 1 0 5.287662 -4.140414 -0.031578 53 1 0 4.591052 -1.838711 -0.715798 54 1 0 4.010632 -0.850487 1.482925 55 1 0 3.919665 -2.301376 3.418914 56 1 0 2.860612 -2.260177 -0.503257 57 1 0 3.942156 -4.283921 -1.167160 58 1 0 2.343919 -4.490605 0.731361 59 1 0 4.753856 -4.687523 2.616413 --------------------------------------------------------------------- 2,11TS13,14 C 1 open shell singlet (broken symmetry) Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 29 0 0.952545 -0.602388 -1.069722 2 6 0 -6.098583 0.681946 0.957713 3 6 0 -3.903905 0.553993 0.272276 4 6 0 -4.208263 -0.571203 -0.547954 5 6 0 -6.379404 -0.455115 0.113301 6 1 0 -2.392466 1.875418 1.007991 7 6 0 -2.583345 1.046615 0.335320 8 6 0 -3.172431 -1.175066 -1.296913 9 6 0 -1.892883 -0.676280 -1.224107 10 6 0 -1.573144 0.455090 -0.409561 11 1 0 -3.410855 -2.031929 -1.920235 12 6 0 0.187468 2.004056 -0.009851 13 6 0 1.529087 2.457542 0.028302 14 6 0 2.640168 1.656853 -0.427824 15 6 0 1.759204 3.780767 0.510682 16 6 0 3.950615 2.252094 -0.379058 17 6 0 3.015573 4.332925 0.564570 18 1 0 0.899429 4.358743 0.846903 19 6 0 4.099944 3.533880 0.104618 20 1 0 5.102196 3.960585 0.133904 21 1 0 -0.568593 2.730155 0.302587 128 22 7 0 -0.213309 0.817080 -0.405257 23 8 0 2.535652 0.455430 -0.892687 24 6 0 5.117846 1.438035 -0.870175 25 1 0 6.050679 2.006761 -0.802225 26 1 0 5.230360 0.514034 -0.290656 27 1 0 4.970804 1.127205 -1.911118 28 6 0 3.264498 5.728636 1.083129 29 1 0 2.329975 6.213866 1.383124 30 1 0 3.930498 5.723064 1.955982 31 1 0 3.739947 6.363443 0.323978 32 7 0 -4.879202 1.160222 1.021992 33 7 0 -5.480624 -1.064542 -0.611672 34 8 0 -7.655823 -0.896784 0.089739 35 1 0 -7.671527 -1.660279 -0.516834 36 6 0 -7.194376 1.318741 1.762591 37 1 0 -6.786896 2.156190 2.332097 38 1 0 -8.000891 1.677486 1.112052 39 1 0 -7.646022 0.594642 2.451076 40 7 0 -0.780354 -1.252743 -1.950914 41 1 0 -0.786784 -0.983091 -2.935528 42 1 0 -0.763353 -2.271850 -1.912702 43 8 0 1.608547 -2.268001 -1.304048 44 6 0 2.944658 -4.204851 2.490054 45 6 0 2.686321 -4.734297 1.069528 46 6 0 3.766850 -4.249559 0.093135 47 6 0 3.781032 -2.722346 0.041633 48 6 0 3.697355 -2.082574 1.380958 49 6 0 3.325388 -2.744714 2.489766 50 1 0 2.055551 -4.355922 3.119057 51 1 0 2.629858 -5.830187 1.079054 52 1 0 4.752804 -4.618583 0.416885 53 1 0 4.610398 -2.324453 -0.555479 54 1 0 3.935185 -1.021884 1.443747 55 1 0 3.299312 -2.222439 3.445966 56 1 0 2.825702 -2.406230 -0.579507 57 1 0 3.586128 -4.653063 -0.909703 58 1 0 1.719021 -4.359095 0.711965 59 1 0 3.745101 -4.789613 2.973673 --------------------------------------------------------------------- 13 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 129 1 29 0 1.323196 -1.899009 0.097644 2 6 0 -5.260015 1.617971 0.259015 3 6 0 -3.145268 0.728596 0.059037 4 6 0 -3.693938 -0.558395 -0.213413 5 6 0 -5.788049 0.304727 -0.025626 6 1 0 -1.378319 1.893409 0.358417 7 6 0 -1.746419 0.905617 0.104002 8 6 0 -2.817758 -1.643728 -0.442639 9 6 0 -1.456771 -1.449523 -0.398933 10 6 0 -0.891791 -0.161654 -0.133206 11 1 0 -3.241874 -2.621955 -0.649372 12 6 0 1.188845 0.992279 -0.163253 13 6 0 2.599195 1.124302 -0.093147 14 6 0 3.490674 -0.002034 0.044942 15 6 0 3.135424 2.443258 -0.185300 16 6 0 4.902963 0.270596 0.090639 17 6 0 4.485682 2.692062 -0.137432 18 1 0 2.436864 3.272102 -0.292232 19 6 0 5.350716 1.571286 0.002889 20 1 0 6.424796 1.751092 0.041298 21 1 0 0.634133 1.922304 -0.317178 22 7 0 0.514337 -0.130888 -0.076574 23 8 0 3.107046 -1.235334 0.114818 24 6 0 5.844087 -0.895675 0.233014 25 1 0 6.886187 -0.561251 0.252674 26 1 0 5.640345 -1.457769 1.152241 27 1 0 5.720180 -1.606095 -0.592933 28 6 0 5.054231 4.087663 -0.227503 29 1 0 4.260312 4.833630 -0.337243 30 1 0 5.632438 4.347746 0.668853 31 1 0 5.731197 4.194534 -1.085244 32 7 0 -3.962435 1.804049 0.296955 33 7 0 -5.046736 -0.745875 -0.252171 34 8 0 -7.133191 0.180535 -0.052444 35 1 0 -7.318312 -0.756190 -0.250916 36 6 0 -6.187895 2.770766 0.512914 37 1 0 -5.602854 3.670715 0.711829 38 1 0 -6.842747 2.944470 -0.349324 39 1 0 -6.843317 2.565143 1.367547 40 7 0 -0.498438 -2.511532 -0.610789 41 1 0 -0.411534 -2.759910 -1.596725 42 1 0 -0.713274 -3.367801 -0.099671 43 8 0 1.608307 -3.592867 0.686823 44 1 0 2.525233 -3.710550 0.974767 --------------------------------------------------------------------- 130 O 2 D ?h Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 0.000000 0.000000 0.607259 2 8 0 0.000000 0.000000 -0.607259 --------------------------------------------------------------------- 16 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 2.140517 -0.314116 -0.254179 2 6 0 0.992166 -1.331498 -0.325953 3 6 0 -0.070601 -1.026902 0.736016 4 6 0 -0.647926 0.376111 0.557720 5 6 0 0.383914 1.414861 0.231135 6 6 0 1.636735 1.099433 -0.116573 7 1 0 2.801072 -0.542392 0.597974 8 1 0 0.526697 -1.282577 -1.318287 9 1 0 -0.895344 -1.746487 0.705721 10 1 0 0.072857 2.455205 0.292647 11 1 0 2.350853 1.899925 -0.306588 12 1 0 0.372298 -1.084995 1.739843 13 1 0 1.376542 -2.350110 -0.201609 14 1 0 2.776946 -0.390151 -1.145762 15 1 0 -1.252076 0.663660 1.423760 16 8 0 -1.611260 0.378942 -0.581688 17 8 0 -2.731074 -0.245119 -0.262899 --------------------------------------------------------------------- 16TS17 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -2.244386 0.050862 -0.171634 2 6 0 -1.464553 -1.170557 0.340516 3 6 0 -0.069606 -1.236614 -0.306232 4 6 0 0.695335 0.066375 -0.075620 5 6 0 -0.083655 1.306035 0.041654 131 6 6 0 -1.427153 1.311838 -0.055833 7 1 0 -2.542772 -0.104660 -1.221288 8 1 0 -1.356896 -1.095966 1.430030 9 1 0 0.527092 -2.060534 0.094885 10 1 0 0.479534 2.221353 0.203382 11 1 0 -1.960122 2.259747 -0.005907 12 1 0 -0.189290 -1.411174 -1.383818 13 1 0 -2.016681 -2.094029 0.131729 14 1 0 -3.181268 0.168360 0.387559 15 1 0 1.557743 0.180923 -1.051310 16 8 0 1.812160 -0.005643 0.770804 17 8 0 2.718686 0.001687 -0.423599 --------------------------------------------------------------------- 17 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 2.247656 -0.711840 0.082087 2 6 0 0.963480 -1.461333 -0.301059 3 6 0 -0.268101 -0.828754 0.361154 4 6 0 -0.368485 0.660874 0.073614 5 6 0 0.897294 1.399725 -0.079605 6 6 0 2.090207 0.778482 -0.051229 7 1 0 2.529314 -0.942418 1.122949 8 1 0 0.843600 -1.426792 -1.391763 9 1 0 -1.205530 -1.305873 0.060923 10 1 0 0.811884 2.476713 -0.196404 11 1 0 3.000716 1.372375 -0.123441 12 1 0 -0.195743 -0.934190 1.455650 13 1 0 1.040725 -2.518488 -0.024556 14 1 0 3.092812 -1.049280 -0.531217 15 1 0 -2.955606 0.155291 -0.039924 16 8 0 -1.448750 1.247870 0.011389 17 8 0 -3.593060 -0.604152 -0.116638 --------------------------------------------------------------------- 18 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -1.819134 0.093660 0.131885 132 2 6 0 -1.075866 -1.163638 -0.342485 3 6 0 0.328718 -1.243373 0.271427 4 6 0 1.143295 0.022378 0.017904 5 6 0 0.380531 1.289621 -0.051952 6 6 0 -0.960786 1.326041 0.025528 7 1 0 -2.743244 0.236084 -0.443072 8 1 0 -1.652489 -2.063132 -0.098050 9 1 0 0.974024 2.195331 -0.147430 10 1 0 -1.471135 2.288807 0.014823 11 1 0 -0.988027 -1.130393 -1.436480 12 1 0 -2.140484 -0.025425 1.179885 13 1 0 0.898714 -2.099017 -0.103304 14 1 0 0.251538 -1.365250 1.363325 15 8 0 2.361320 0.001858 -0.080443 --------------------------------------------------------------------- OH C ?v Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 0.000000 0.000000 0.109192 2 1 0 0.000000 0.000000 -0.873537 --------------------------------------------------------------------- 19 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.234792 1.048359 -0.125309 2 6 0 -1.466709 1.548379 0.017308 3 6 0 -2.713047 0.699627 0.029619 4 6 0 -2.391705 -0.789378 0.226386 5 6 0 -1.212913 -1.211854 -0.658452 6 6 0 0.051898 -0.426042 -0.302203 7 1 0 -1.598966 2.625079 0.123877 8 1 0 0.791189 -0.548333 -1.111703 9 1 0 -2.119513 -0.967713 1.273412 10 1 0 -3.276379 -1.400317 0.011419 11 1 0 -1.452519 -1.032449 -1.715616 12 1 0 -0.999942 -2.280852 -0.547474 13 1 0 0.626935 1.717053 -0.113344 14 8 0 0.584114 -1.010648 0.900774 133 15 1 0 1.218696 -0.382300 1.278914 16 1 0 -3.390969 1.053865 0.818263 17 1 0 -3.259701 0.850739 -0.915758 18 8 0 3.652136 0.040962 -0.663644 19 8 0 3.421848 0.363521 0.484609 --------------------------------------------------------------------- 19TS20 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 0.228488 0.900438 -0.784107 2 6 0 1.405248 1.443879 -0.393723 3 6 0 2.400229 0.671285 0.431062 4 6 0 2.222239 -0.841121 0.218652 5 6 0 0.765553 -1.277101 0.452483 6 6 0 -0.229034 -0.394905 -0.294182 7 1 0 1.662213 2.452695 -0.709068 8 1 0 -1.177835 0.088669 0.666194 9 1 0 2.508609 -1.085015 -0.812134 10 1 0 2.889397 -1.403453 0.881664 11 1 0 0.549946 -1.253902 1.530255 12 1 0 0.606774 -2.310376 0.126947 13 1 0 -0.454625 1.460215 -1.421227 14 8 0 -1.118202 -1.121291 -1.068708 15 1 0 -1.913322 -0.566130 -1.215621 16 1 0 3.420818 0.975478 0.166991 17 1 0 2.281217 0.919503 1.498694 18 8 0 -2.219883 0.429370 1.125525 19 8 0 -3.053105 0.405354 0.131457 --------------------------------------------------------------------- 20 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 0.003171 -0.516203 -0.768518 2 6 0 -0.992962 -1.471576 -0.540416 3 6 0 -2.204386 -1.120395 0.279209 4 6 0 -2.521266 0.384770 0.179875 5 6 0 -1.289576 1.251070 0.496639 6 6 0 -0.078785 0.775769 -0.251695 134 7 1 0 -0.897130 -2.465531 -0.966096 8 1 0 1.612524 -0.917887 0.589250 9 1 0 -2.855770 0.605746 -0.841528 10 1 0 -3.345858 0.648201 0.851812 11 1 0 -1.081283 1.241993 1.578721 12 1 0 -1.473012 2.301685 0.237531 13 1 0 0.850484 -0.766794 -1.408409 14 8 0 0.903241 1.705887 -0.378565 15 1 0 1.736175 1.255854 -0.625931 16 1 0 -3.070889 -1.709101 -0.047490 17 1 0 -2.045593 -1.389213 1.338573 18 8 0 2.589108 -0.958370 0.784014 19 8 0 3.141799 -0.075713 -0.040075 --------------------------------------------------------------------- 21 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.354804 1.249470 -0.078779 2 6 0 1.032223 1.346736 -0.002864 3 6 0 1.872971 0.114703 0.196102 4 6 0 1.161008 -1.143217 -0.336802 5 6 0 -0.277827 -1.259411 0.199026 6 6 0 -1.014823 0.034171 0.025346 7 1 0 1.512354 2.318819 -0.060227 8 1 0 1.123973 -1.088949 -1.432252 9 1 0 1.730093 -2.043815 -0.078463 10 1 0 -0.264941 -1.542251 1.264403 11 1 0 -0.822150 -2.058497 -0.320190 12 1 0 -0.946673 2.156574 -0.213814 13 8 0 -2.377137 -0.098308 -0.006728 14 1 0 -2.774801 0.784245 -0.087570 15 1 0 2.846776 0.228801 -0.298417 16 1 0 2.099971 -0.023169 1.268178 --------------------------------------------------------------------- OOH C s Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 8 0 0.055873 0.720103 0.000000 135 2 8 0 0.055873 -0.611635 0.000000 3 1 0 -0.893969 -0.867745 0.000000 --------------------------------------------------------------------- 22 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.362405 1.329448 0.113969 2 6 0 -1.681895 1.249656 -0.082699 3 6 0 -2.428651 -0.048481 -0.256559 4 6 0 -1.581869 -1.261229 0.159770 5 6 0 -0.160471 -1.139421 -0.402767 6 6 0 0.510862 0.113574 0.167918 7 1 0 -2.267905 2.167151 -0.113039 8 1 0 -1.526870 -1.311541 1.254174 9 1 0 -2.048891 -2.190422 -0.185371 10 1 0 -0.194264 -1.059576 -1.496464 11 1 0 0.453957 -2.011299 -0.151069 12 1 0 0.137706 2.280945 0.272685 13 8 0 1.039412 -0.048001 1.433051 14 1 0 1.881203 -0.533301 1.293579 15 1 0 -3.361295 -0.014475 0.321731 16 1 0 -2.738066 -0.144047 -1.309742 17 8 0 1.677054 0.418806 -0.789477 18 8 0 2.769908 -0.201394 -0.404108 --------------------------------------------------------------------- 22TS23 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.294574 -1.194932 -0.487624 2 6 0 -1.557056 -1.363278 -0.056934 3 6 0 -2.413708 -0.233129 0.449077 4 6 0 -1.895377 1.129294 -0.035107 5 6 0 -0.381269 1.256592 0.209063 6 6 0 0.369620 0.112640 -0.451727 7 1 0 -2.000382 -2.357305 -0.085820 8 1 0 -2.102561 1.230450 -1.108209 9 1 0 -2.424194 1.944057 0.471961 10 1 0 -0.187405 1.234714 1.288946 136 11 1 0 0.015381 2.198631 -0.180856 12 1 0 0.284715 -2.018525 -0.895873 13 8 0 1.322891 0.359212 -1.294485 14 1 0 2.282001 0.232953 -0.690969 15 1 0 -3.452726 -0.385811 0.130575 16 1 0 -2.433173 -0.261614 1.550778 17 8 0 1.729179 -0.295432 1.073075 18 8 0 2.829495 -0.071362 0.441282 --------------------------------------------------------------------- 23 C 1 Standard orientation: --------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z --------------------------------------------------------------------- 1 6 0 -0.058830 -0.799839 0.059159 2 6 0 -1.184990 -1.537754 0.083285 3 6 0 -2.570520 -0.952750 0.083463 4 6 0 -2.581427 0.493595 -0.431044 5 6 0 -1.471159 1.323193 0.228287 6 6 0 -0.107676 0.668246 0.090540 7 1 0 -1.102704 -2.623695 0.109240 8 1 0 -2.426307 0.484916 -1.517718 9 1 0 -3.558030 0.956973 -0.253116 10 1 0 -1.668363 1.422723 1.307385 11 1 0 -1.410493 2.337947 -0.176220 12 1 0 0.932093 -1.249409 0.040583 13 8 0 0.914496 1.359187 0.053319 14 1 0 2.504852 0.703139 -0.040354 15 1 0 -3.237679 -1.583453 -0.517416 16 1 0 -2.969960 -0.997388 1.110288 17 8 0 3.253163 -1.002464 -0.057334 18 8 0 3.430367 0.315789 -0.089085 --------------------------------------------------------------------- 137 References (1) Anastas, P. 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