AN APPROACH TO BIS(AMINO ACID)S UTILIZING DIMETHYL 
2,4-BIS(DIAZO)-3-OXOGLUTARATE AND STUDIES OF 
TRIS(2,6-DIHYDROXYPHENYL)E, E = B, P. 
 
Except where reference is made to the work of others, the work described in this thesis is 
my own or was done in collaboration with my advisory committee. This thesis does not 
include proprietary or classified information. 
 
 
________________________________ 
Lirui Guan 
 
 
 
 
Certificate of Approval: 
 
_________________________                     _________________________ 
Edward J. Parish                                 Peter D. Livant, Chair 
Professor                                       Associate Professor 
Chemistry                                      Chemistry 
 
_________________________                      _________________________ 
Thomas E. Albrecht-Schmitt                        Stephen L. McFarland 
Associate Professor                               Dean 
Chemistry                                       Graduate School 
AN APPROACH TO BIS(AMINO ACID)S UTILIZING DIMETHYL 
2,4-BIS(DIAZO)-3-OXOGLUTARATE AND STUDIES OF 
TRIS(2,6-DIHYDROXYPHENYL)E, E = B, P. 
 
Lirui Guan 
 
A Thesis 
Submitted to 
the Graduate Faculty of 
Auburn University 
in Partial Fulfillment of the 
Requirements for the 
Degree of 
Master of Science 
 
 
 
 
 
Auburn, Alabama 
December 16, 2005 
 
iii
AN APPROACH TO BIS(AMINO ACID)S UTILIZING DIMETHYL 
2,4-BIS(DIAZO)-3-OXOGLUTARATE AND STUDIES OF 
TRIS(2,6-DIHYDROXYPHENYL)E, E = B, P. 
 
Lirui Guan 
 
 
Permission is granted to Auburn University to make copies of this thesis at its discretion, 
upon request of individuals or institutions and at their expense. The author reserves all 
publication rights. 
 
 
 
______________________________ 
Signature of Author 
 
 
 
______________________________ 
Date 
 
 
 
 
 
 
 
 
iv
THESIS ABSTRACT 
AN APPROACH TO BIS(AMINO ACID)S UTILIZING DIMETHYL 
2,4-BIS(DIAZO)-3-OXOGLUTARATE AND STUDIES OF 
TRIS(2,6-DIHYDROXYPHENYL)E, E = B, P. 
 
Lirui Guan 
 
Master of Science, December 16, 2005 
(B.S., Hunan Univeristy, 2001) 
 
84 typed pages 
Directed by Peter D. Livant 
 
When treated with a diazo transfer agent, dimethyl 3-oxoglutarate afforded a high 
yield of the bis(diazo) compound dimethyl 2,4-bis(diazo)-3-oxoglutarate, 33. The 
bis(diazo) compound, catalyzed by Rh
2
(OAc)
4
, reacted with an excess of O-benzyl 
carbamate, (CbzNH
2
), to give the product of double N-H insertion, 36, 
[MeO
2
C-CH(NHCbz)]
2
C=O. Thus in two steps one obtains a protected bis(amino acid). 
Compound 36 exhibits complex 
1
H and 
13
C NMR spectra, which may be rationalized by 
assuming 36 is predominantly enolic.  
Attempted removal of the Cbz protecting groups gave startling results. 
Hydrogenation of 36 over Pd/C led to dimethyl 2-carboxamidosuccinate, 44, 
 
v
MeO
2
CCH
2
CH(CONH
2
)(CO
2
Me), the structure of which was proven by x-ray 
crystallography.  
In other studies, tris(2,6-dimethoxyphenyl)boron was synthesized by literature 
procedures. Demethylation was attempted using AlCl
3
/toluene, and BBr
3
?SMe
2
. In both 
cases, resorcinol, the product of B-C bond cleavage was observed. 
Tris(2,6-dihydroxyphenyl)phosphonium chloride 63 was synthesized and its x-ray 
crystal structure was determined. It binds ethyl ether via a hydrogen bond. The three aryl 
rings adopt propeller symmetry, with torsion angles relative to the P-H direction of 20.5?, 
24.5?, and 30.8?. Compared to the average C-P-H angle of [Ph
3
PH]
+
 - 108.2?, the average 
C-P-H angle of 63 is smaller, namely 104.9?.
 
vi
ACKNOWLEDGMENT 
 
    I would like to thank Dr. Peter Livant who has been so helpful in my research here at 
Auburn University, Dr. Albrecht-Schmitt for assistance with X-ray crystallography and 
Dr. Parish for his help with the thesis. I also would like to give the thanks to my 
laboratory partners Mrs. Yuanping Jie, Mr. Hui Wang and Mr. Xiaoxun Li for their help in 
my research. Also thank to my wife for supporting my life. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
vii
Style manual or journal used: Journal of Organic Chemistry                         
Computer software used: Microsoft Word 2002 & Chem. Draw Ultra 7.0                 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
viii
TABLE OF CONTENTS 
LIST OF SCHEMES???????????????????????????x 
LIST OF FIGURES .......................................................................................................... xii 
LIST OF TABLES ........................................................................................................... xiii 
1. PART I. INTRODUCTION ??????????????????????...1 
 1.1. Introduction to Diazocarbonyl Compounds............................................................1 
 1.2. Diazo Transfer Reaction .........................................................................................2 
 1.3. Catalysts for Metal Carbene Transformations ........................................................5 
 1.3.1. Mechanism of catalytic diazo decomposition. Metal carbene  
generation and reactions..............................................................................6 
 1.3.2. Rhodium catalysts for diazo decomposition..................................................8 
 1.4. N-H insertion ..........................................................................................................9 
 1.4.1. Intermolecular N-H Reaction.......................................................................11 
 1.4.2. Intramolecular N-H Reaction.......................................................................13 
 1.5. Bisdiazo compounds .............................................................................................15 
 1.6. Diamino Dicarboxylic Acids.................................................................................16 
 1.7. Diaminoglutaric Acid and Its 3-substituted Derivatives.......................................18 
 1.7.1. Diaminoglutaric Acid...................................................................................19 
 
ix
 1.7.2. 3-Substituted Diaminoglutaric Acids...........................................................21 
2. PART I. RESULTS AND DISCUSSION?????????????????...25 
 2.1. Synthesis of Bisdiazocarbonyl Compounds..........................................................25 
 2.2. N-H insertion of Rh(II)-stabilized carbenoid from bis(diazo) 
compound into Cbz-NH
2
.......................................................................................28 
 2.3. N-H insertion of Rh(II)-stabilized carbenoid from bis(diazo)  
compound into Boc-NH
2
.......................................................................................36 
 2.4. Catalytic hydrogenolysis of N-H insertion reaction products...............................38 
3. PART II. INTRODUCTION ??????????????????????..43 
 3.1. Introduction to hypervalency ...............................................................................43 
 3.2. Hypervalent boron 10-B-5 species.......................................................................44 
 3.3. Hypervalent phosphorus 10-P-5 Species .............................................................46 
4. PART II. RESULTS AND DISCUSSION ?????????????????.48 
 4.1. Synthesis of tris(2,6-dimethoxyphenyl)borane....................................................48 
 4.2. Demethylation of tris(2,6-dimethoxyphenyl)borane, 56 .....................................48 
  4.2.1. Demethylation of 56 by aluminum trichloride ............................................49 
  4.2.2. Demethylation by BBr
3
.S(Me)
2
...................................................................49 
 4.3. Synthesis of tris(2,6-dihydroxyphenyl)phosphonium chloride 63.......................50 
5. EXPERIMENTAL .........................................................................................................55 
6. REFERENCES ..............................................................................................................61 
7. APPENDICES????????????????????????????69 
 
x
LIST OF SCHEMES 
1. Mechanism of diazo transfer reaction............................................................................3 
2. Mechanism for catalytic decomposition of diazo compounds.......................................7 
3. Mechanism for insertion reaction of metal carbenes ...................................................11 
4. A summary of Intramolecular N-H Reaction...............................................................14 
5. Bacterial peptidoglycan ...............................................................................................17 
6. The interaction of peptide and peptide receptor ..........................................................18 
7. Reported Synthesis route I to diaminoglutaric acid (DAG).........................................20 
8. Reported Synthesis route II to diaminoglutaric acid (DAG) .......................................20 
9. Minmin?s synthesis route to diaminoglutaric acid (DAG)...........................................21 
10. Introduce fluorine by diethylaminosulfur trifluoride (DAST).....................................22 
11. A proposal from compound 28 to 27 ...........................................................................23 
12. Mechanism of fluoroacylated amino acids as suicide inhibitors 
 of enzymatic decarboxylation reactions.....................................................................24 
13. A proposal synthesis to fluorine bis(amino acid).........................................................24 
14. Highly enolic compound 36.........................................................................................34 
15. Highly enolic compound 42.........................................................................................37 
16. Proposed mechanism for formation of 44....................................................................42 
 
xi
17. Some simple hypervalent molecules............................................................................43 
18. Three-center four-electron (3c-4e), hypervalent bonding scheme...............................44 
19. Some hypervalent compounds based on second row elements ...................................45 
20. A proposal to new 10-B-5 species 59 ..........................................................................46 
21. The progress of Hui Li of our laboratory in the synthesis of 61..................................47 
22. Synthesis of tris(2,6-dihydroxyphenyl)phosphonium chloride 63...............................51 
23. Several reports of structures of the type (Ar
3
PH)
+
.......................................................53 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xii
LIST OF FIGURES 
1. 
1
H spectrum of compound 33 ......................................................................................26 
2. 
13
C spectrum of compound 33 .....................................................................................27 
3. IR spectrum of compound 33.......................................................................................27 
4. 
1
H NMR spectrum of compound 36 ..................................................................... 29~30 
5. 
13
C NMR spectrum of compound 36 .................................................................... 31~33 
6. Model compound used to assign 
1
H NMR chemical shifts in 36 ................................35 
7. Model compound used to assign 
13
C NMR chemical shifts in 36 ...............................36 
8. X-ray structure of compound 44..................................................................................39 
9. Crystal structure of compound 63................................................................................52 
 
 
 
 
 
 
 
 
 
 
 
xiii
LIST OF TABLES 
1. Crystal parameters of compound 63 ............................................................................52 
2. Geometrical parameters of some phosphonium ions compared to those of 63 ...........54 
 
 
1
1?  PART I. INTRODUCTION 
1.1 Introduction to Diazocarbonyl Compounds 
The date of the first recorded synthesis of an ?-diazocarbonyl compound is from 
the work of Curtius
1,2
 on diazotization of natural ?-amino acids (ethyl diazoacetate was 
first synthesized in 1883 from glycine). The simple diazocarbonyl compounds became 
available only in the late 1920s with the work of Arndt and Eistert,
3-5
 and of Bradley and 
Robinson.
6
 Now, modern organic synthesis continues to benefit from the unique 
versatility of diazocarbonyl compounds in cyclopropanation, X-H insertion (X = C, N, O, 
S, Se, P, halogen), Wolff rearrangement, ylide formation with subsequent transformations, 
aromatic cycloaddition and substitution, and many other useful reactions.  
There are perhaps four principal reasons for the high level of activity in the diazo 
compound area. First, the enormous number of transformations that can occur with 
diazocarbonyl compounds makes them extremely versatile reactants. Second, 
methodology for their synthesis has continued to develop on a broad front, and there are 
now available well-tested, reliable procedures for the preparation of all the main classes 
of diazocarbonyl compounds. Third, the introduction in the 1970s of dirhodium(II) 
catalysts for diazocarbonyl decomposition opened up numerous new opportunities for 
highly chemoselective transformations that were largely inaccessible with 
 
 
2
conventionalcopper catalysts. Fourth, the ever-increasing demands for stereocontrol in 
the production of molecules of high enantiopurity have led to the introduction of chiral 
catalysts for asymmetric transformations of diazocarbonyl compounds.
7
 
The synthesis of diazoketones involves addition of an acyl chloride to ethereal 
diazomethane
3-5
 at or below 0 ?C (eq. 1). Numerous synthetic intermediates containing 
the diazoketone functional group have been obtained in this way. 
 
RCOCl   +   2 CH
2
N
2
RCOCHN
2
   +   CH
3
Cl   +   N
2
(1)
Et
2
O
0 ?C
 
 
1.2 Diazo Transfer Reaction 
Diazo transfer is now the standard route which is widely used to transfer a 
complete diazo group from a donor to an acceptor. Since the middle of the last century, 
sulfonyl azide compounds have been developed to serve as excellent diazo donors.
8
 The 
diazo group transfers to the ?-methylene position of a carbonyl compound by the simple 
diazo transfer procedure of direct exposure to tosyl azide in dry acetonitrile or ethanol 
using triethylamine as a base (eq. 2). 
 
H
3
C S N
3
O
O
R R'
O O
+
R R'
O O
N
2
(2)
Et
3
N
 
 
 
 
3
The mechanism of diazo transfer reaction has been developed by M. Regitz 
Saarbr?cken (Scheme 1).
9
 
OO
R
2
R
1
H H
:B
N
N
N
SO
2
R
+
?
OO
R
2
R
1
N H
N
N
SO
2
R
H-B
+
?
?  RSO
2
NH
?
OO
R
2
R
1
N
N
+
?
 
Scheme 1 
 
Although tosyl azide has been by far the most frequently employed diazo donor, 
and was used by Doering and DePuy in 1953 in their synthesis of 
diazocyclopentadiene,
10
 work in the Merck laboratories
11
 has raised doubts regarding the 
safety aspects of this reagent. With these worries, Merck chemists
11,12
 have examined 
sulfonyl azides 1 to 12 from the standpoint of utility, thermal stability, ease of handling, 
and safety. It was found that methanesulfonyl (mesyl) azide 1 was the most hazardous 
and dangerous diazo transfer reagent of the group. Compared to more dangerous transfer 
reagent, tosyl azide, p-acetamidobenzenesulfonyl azide (p-ABSA) 7 offers more safety, 
yield, and ease of manipulation in diazo transfer. This reagent is currently commercially 
available and has some advantage in safety and yield, and so it is used in our laboratory 
for the diazo transfer reactions. These diazo transfer reagents, 1 to 12, are very efficient, 
giving good yield (>80%) in various diazo transfer reactions. 
 
 
4
 
CH
3
SO
2
N
3
CH
3
SO
2
N
3
C
12
H
25
SO
2
N
3
SO
2
N
3
1 234
CO
2
H
SO
2
N
3
5
SO
2
6
N
3
HN
SO
2
N
3
7
CH
3
O
Cl
SO
2
N
3
8
Br
SO
2
N
3
9
SO
2
N
3
C
9
H
19
C
9
H
19
SO
2
N
3
11
n
SO
2
N
3
12
O
2
N
10
 
 
These diazo transfer reagents may be made from the corresponding sulfonyl 
chlorides (eq. 3).  
 
 
 
5
SO
2
Cl
HN CH
3
O
+ NaN
3
SO
2
N
3
HN CH
3
O
TBAB
a
CH
2
Cl
2
(3)
7
a
 tetrabutylammonium bromide
 
With a diazo transfer reagent such as 7, the ?-diazocarbonyl compound is readily 
formed. When the reaction site is activated by two flanking carbonyls, the diazo transfer 
reaction works even more successfully. For example, Hazen et al.
11
 employed the 
naphthalene-based diazo transfer reagent 4 in the high-yield synthesis of dimethyl 
diazomalonate, DDM (eq. 4). 
 
H
3
CO OCH
3
O O
+ 4
Et
3
N
CH
3
CN, 0 ?C
H
3
CO OCH
3
O O
(4)
N
2
DDM, 95%
 
 
1.3 Catalysts for Metal Carbene Transformations 
Diazo compounds are inherently unstable to acid-promoted decomposition. 
Transition metals, which act as Lewis acids, are therefore effective catalysts for diazo 
decomposition.
14
 The reactivities of diazocarbonyl compounds and alkyl/aryl diazo 
compounds are different. This may be rationalized on the basis of the pK
a
 values of the 
corresponding diazonium ions. As an example, diazomethane is the conjugate base of the 
methanediazonium ion (eq. 5), whose pK
a
 value
14
 of 10 suggests the driving force for the 
 
 
6
high reactivity of diazomethane towards Br?nsted acids, and, by extension, Lewis acids. 
 
CN
H
H
H
N
+
CNN
H
H
+
H
+
+ ?
(5)
 
 
In contrast, the pK
a
 values of diazonium ions derived from diazoesters (a) and 
diazoketones (b) have been estimated to be between -5 and -2, respectively.
15
 This is  
 
CNH
H
N
+
O
R
CNH
H
N
+
O
RO
ba
 
 
consistent with the much greater stability of diazoesters and diazoketones toward 
acid-promoted decomposition. So, various transition metals have been developed as 
diazo decomposition catalysts to afford more efficient reactivity in diazo decomposition 
reactions. 
 
1.3.1 Mechanism of catalytic diazo decomposition. Metal carbene generation and 
reactions 
Transition metal complexes that are effective catalysts for diazo decomposition 
are Lewis acids.
13
 Their catalytic activity depends on coordinative unsaturation at the 
 
 
7
metal center, which allows them to react as electrophiles with diazo compounds.
7
 In the 
generally accepted mechanism for catalytic decomposition of diazo compounds (Scheme 
2),
13,16-19
 electrophilic addition causes the loss of dinitrogen and production of a 
metal-stabilized carbene (14). Transfer of the electrophilic carbene entity to an 
electron-rich substrate (S:) regenerates the catalytically active L
n
M and completes the 
catalytic cycle.  
 
SCR
2
S:
L
n
M
L
n
MCR
2
14
N
2
R
2
CN
2
L
n
MCR
2
N
2
+
?
 
Scheme 2 
 
The activities of catalytically active transition metal compounds towards diazo 
decomposition are dependent on both the electrophilicity of the transition metal 
compound and on the stability of the diazo compound.
15
 Among diazocarbonyl 
compounds, those with two carbonyl groups flanking the diazo-bearing carbon are more 
stable toward transition metal-catalyzed decomposition than those with only one 
 
 
8
carbonyl group.
17
 Diazoesters are generally more stable than diazoketones, and 
diazoamides are more stable than diazoesters. This profile is a useful guide to 
determining the reaction conditions required to generate a metal carbene. For example, 
diazoacetoacetates and diazomalonates require higher temperatures for reactions with 
transition metal catalysts than do diazoacetates, which can undergo catalytic nitrogen loss 
at or below room temperature.
15 
 
Increasing reactivity
Z Y
O
N
2
O
Z
R
R'R
O
N
2
N
2Z,Y = R, OR, NR
2
R, R' = alkyl, aryl, H
Increasing stability
 
 
1.3.2 Rhodium catalysts for diazo decomposition 
Dirhodium(II) catalysts are the most effective and versatile for diazo 
decomposition.
7,16-20
 Dirhodium(II) tetraacetate (15) was first introduced by Teyssi? and  
 
 
9
Rh
O
O
O
O
O
O
O
O
Rh
CH
3
H
3
C
CH
3
CH
3
15
Rh
O
O
O
O
O
O
O
O
Rh
16
Rh
O
N
O
N
O
N
O
N
Rh
17
H
S
O
2
COOMe
 
 
co-workers in 1973. Control of reactivity and selectivity in such catalysts can be 
provided by varying the catalysts? bridging carboxylate (e.g. 16
21
) or carboxamide (e.g. 
17
22
) ligands (in the structures above, the ligand shown is repeated three more times). 
Rhodium acetate 15 was originally employed as a catalyst for diazo decomposition in the 
presence of aniline (eq. 6), namely, insertion of a metal-carbene into an N-H bond. The 
reaction afforded the desired product 18 in 70% yield.
23
 Compared to copper catalyst 
with much lower yield (<30% usually),
24
 the dirhodium catalyst offers the advantages of 
mild conditions and higher yield. 
  
NH
2
H
N
O
OCH
3
+ N
2
CHCO
2
CH
3
Rh
2
(OAc)
4
18, 70%
(6)
 
 
 
 
10
1.4 N-H insertion 
Metal carbenes derived from ?-diazocarbonyl compounds, e.g. 19, are highly 
electrophilic. They readily react with an available Lewis base (B:) to form a zwitterionic 
adduct (Scheme 3, in which B: is PhNH
2
). Catalytically generated electrophilic metal  
 
Rh
O
O
O
O
O
O
O
O
Rh
H
3
C
H
3
C
CH
3
CH
3
O
R
1
R
2
19
=
R
2
L
n
M
R
1
O
 
 
carbenes add to Lewis bases, characteristically heteroatom-substituted organic 
compounds, to form zwitterionic adducts 20, which can either dissociate to form 
rearranged products (or form a ?free? ylide) and the catalyst, or revert to the metal 
carbene and Lewis base. With catalytically generated metal carbenes, especially those of 
rhodium, the metal-carbon bond of the intermediate metal-stabilized ylide is generally 
weaker than the R
2
C-base bond, and the preferred cleavage is that of the metal-carbon 
bond. The ease with which catalytically generated metal carbenes transfer the carbene 
entity to a heteroatom of an organic base is the basis for the synthetic utility to this diazo 
decomposition methodology.
7
 
 
 
11
 
R
1
O
R
2
L
n
M
+ H
2
N-Ph
+?
20
R
2
NL
n
M
O R
1
H
H
Ph
O
R
1
R
2
N
H
H
Ph
+
?
- L
n
M
O
R
1
R
2
N
H
Ph
H
- L
n
M
 
Scheme 3 
 
1.4.1 Intermolecular N-H Reaction 
Insertion into N-H bonds by diazocarbonyl compounds attracted little attention as 
a synthetic route to ?-amino ketones or esters until 1978, when a bicyclic ?-lactam 
synthesis was published from the Merck laboratories.
25-27
 Since then the power of this 
reaction has been demonstrated dramatically, especially the intramolecular reaction 
leading to nitrogen heterocycles. As mentioned, the introduction of rhodium(II) catalysts 
for N-H insertion led to major improvements with reaction between EDA and aniline in 
the presence of rhodium(II) acetate furnishing in 70% yield the insertion product (eq. 
6).
28
  
Reactions are carried out either neat or in solution (benzene or ethylene glycol 
dimethyl ether). In a similar fashion, Landais and Planchenault
29
 used rhodium(II) 
acetate in benzene to bring about N-H insertion of aniline in an allylic amino ester 
 
 
12
synthesis (eq. 7). 
 
CO
2
Et
N
2
+
NH
2
Rh
2
(OAc)
4
benzene
CO
2
Et
HN
68%
(7)
 
 
N-H insertion with diazocarbonyl compounds is not limited to amino functions. 
Insertion reactions involving amides, ?-lactams, and carbamates are also known. Some 
examples are shown in eqs. 8,
30
 9,
31
 and 10.
30
 For the reaction in eq. 10 two different  
 
MeO
MeO
O
O
N
2
NH
2
O
EtO
OEt
Rh
2
(OAc)
4
CH
2
Cl
2
N
H
O
EtO
OEt
O
O
OMe
OMe
81%
+ (8)
 
F
3
C CO
2
Me
N
2
+
O
O
NH
2
Rh
2
(OAc)
4
O
O
NH
F
3
C CO
2
Me
85%
(9)
(= Cbz-NH
2
)
 
 
O
O
MeO
MeO
N
2
PhO
O
N
H
O
H
2
N
Rh
2
(OAc)
4
O
O
MeO
MeO
NH
O
HN
71%
+ (10)
O
O
Ph
 
 
 
 
13
N-H sites are available, one in the form of an amide and the other a carbamate. The 
former is preferred. 
 
1.4.2 Intramolecular N-H Reaction 
By far the most successful metal-catalyzed N-H insertion reactions have been 
intramolecular, leading to nitrogen heterocycles. Most recent studies, mainly by Rapoport 
and co-workers,
32 
have established that while five-membered formation is preferred 
kinetically in the intramolecular insertion, it is possible to construct four- to 
six-membered aza rings from simple, conformationally mobile acyclic diazoester 
precursors. Rhodium(II) acetate was used as catalyst throughout, and variations in 
solvent, temperature, and catalyst concentration were found to play a role in determining 
product distributions. A summary of the results is shown in Scheme 4. Cyclization to 
four- and five-membered rings containing N occurred efficiently and selectively (entries 
1 and 2). With the diazo compound in entry 3, the opportunity exists for both 
intramolecular C-H and N-H insertion. Finally, the diazo compound in entry 4 presented 
the option of five- and six-membered ring formation from C-H insertion and 
seven-membered heterocycle formation from N-H insertion. Thus the kinetic preference 
for five-membered ring formation completely overwhelms any tendency for N-H 
insertion. However, four-membered rings are also directly accessible with rhodium(II) 
catalysts.
33
 
 
 
14
 
O
N
2
CO
2
Me
NH
Cbz
N
O
CO
2
Me
Cbz
Rh
2
(OAc)
4
benzene
100%
< 1 >
Entry
O
N
2
CO
2
Me
Rh
2
(OAc)
4
benzene
100%
< 2 >
HN
Cbz
N
O
CO
2
Me
Cbz
O
N
2
CO
2
Me
Rh
2
(OAc)
4
benzene
< 3 >
HN
O
CO
2
Me
NH
Cbz
N
O
CO
2
Me
Cbz
Cbz
+
67 % < 5%
O
N
2
CO
2
Me
Rh
2
(OAc)
4
benzene
< 4 >
O
CO
2
Me
N
H
39%
Cbz
NH
Cbz
O
O Ph
Cbz   =
 
Scheme 4 
 
Seebach
34
 and McKervey
35
 and their collaborators have found that Boc- and 
Cbz-protected ?-aminodiazoketones derived from L-alanine, L-valine, and 
L-phenylalanine cyclize very efficiently to the azetidin-3-one derivatives (eq. 11). 
 
 
 
15
H
N
N
2
O
R
PG
PG = Boc, Cbz
R = Me, i-Pr, PhCH
2
(11)
Rh
2
(OAc)
4
N OPG
R
50 - 60%
 
 
1.5 Bisdiazo compounds 
The decomposition of bisdiazo compounds in rhodium(II) catalyst using in the 
synthesis is limited studied. Recently, the photochemistry of bisdiazo compounds was 
studied for the synthesis of highly strained compounds (eq. 12).
36 
 
N
2
O
N
2
h?
PhH
N
2
O
+
(12)O
 
 
Also, the intramolecular insertion reaction of bisdiazo compounds was 
established as a useful route to cyclic ethers, especially some medium-ring and large-ring 
compounds. Kulkowit and McKervey used Cu(II)(acac)
2
 in benzene to catalyze the 
intramolecular O-H insertion reaction of a bisdiazo ketone (eq. 13).
37
 
 
 
16
O
CHN
2
O
CHN
2
(CH
2
)
m
O
HO OH
n
O
O
n
O
O
O
(CH
2
)
m
+
m = 6, n = 1, 27% yield
m = 8, n = 3, 62% yield
m = 9, n = 3, 21% yield
(13)
 
 
1.6 Diamino Dicarboxylic Acids 
Amino acid research is a large and important field. Diamino dicarboxylic acids or 
bis(amino acid)s are characterized by two glycine residues that are connected by a spacer 
via the ?-carbons. They contain two asymmetric carbons, two chemically identical amino  
 
spacer
?
OOC
+
H
3
N
COO
?
NH
3
+
 
a bis(amino acid) 
 
and carboxylic groups. This character confers on bis(amino acid)s an important role in 
studying biosynthesis inhibitors, such as investigating the synergistic effect when 
bacterial infections result in an immune response.
38
 For example, bacterial peptidoglycan 
(Scheme 5) is a giant macromolecule consisting of linear heteroglycan chains 
cross-linked by short peptide chains. When studying the synergistic effect, pure muramyl 
peptides with different lengths of peptide chain are required. The bis(amino acid)s then 
 
 
17
function as cross-linkers in the peptidoglycan network. 
O
O
O
OH
O
HO
NHAc
HO NHAc
O
Me
O
HN
L-Ala
D-iso-Gln
DAA (AA)
n
D-Ala
D-Ala
D-Ala
DAA
D-iso-Gln
L-Ala
DAA = diamino acid or L-lysine
(AA)
n
 = n amino acids, with n = 0 - 5
 
Scheme 5 
 
Also, the use of diamino dicarboxylic acid derivatives for peptidomimetic drug 
design is becoming more commonplace.
39 
Recently, members of this class have been 
used as conformational constraints in order to mimic the secondary structures of peptides, 
such as ?-turns,
40
 and to stabilize a helical conformation.
41 
As most peptides are flexible 
and have many conformations in solution which is difficult to determine the activity of 
the peptide. The conformational constraints may be helpful in elucidating these structures 
by restricting the peptide to a particular conformation or closely related family of 
conformations.
42
 After being bridged or linked by a bis(amino acid), the peptide will be 
restricted to a particular conformation which will be associated with a receptor and a 
desired biological effect can be obtained (Scheme 6).
45(a)
 
 
 
18
DAA
DAA
bioactive
conformation
A
B
receptor
peptide-receptor complex
desired
biological
effect
+ alternative
receptor
undesired
biological
effect
+ peptidase
peptidase-peptide
complex
alternative 
receptor-
peptide complex
destruction of
the peptide
 
Scheme 6 
 
1.7 Diaminoglutaric Acid and Its 3-Substituted Derivatives 
Recently, much interest has been focused on the synthesis of unnatural and 
 
 
19
unusual ?-amino acids,
43
 since this class of compounds has an intrinsic biological activity. 
Such compounds can also modify biological potency and improve metabolic stability in a 
useful way when incorporated into medicinally important peptides.
44
 Meanwhile, the 
synthesis of the modified peptides based on the substitution of ?-amino acids by 
non-standard residues in order to control flexibility and to determine conformations or to 
change the bioavailability and the inhibitory activity of the peptide has attracted 
significant attention.
43(b),44,45
 In particular, the incorporation of ?-amino acids with a 
functional group that can act as a receptor ligand is of great interest. 
1.7.1 Diaminoglutaric Acid 
Glutaric acid is an important chemical messenger which is released in most of the 
excitatory synapses of mammalian central nervous systems.
46
 Several syntheses of 
differentially functionalized (2R,4S)- and (2R,4R)-diaminoglutaric acids (DAG) 21 and 
22 which was employed as a building block for peptidomimetics have been reported.
47
  
 
R
1
O OR
2
O
R
3
HN NHR
4
O
R
1
O OR
2
O
R
3
HN NHR
4
O
21 22
 
 
Scheme 7
47(d)
 and Scheme 8
47(f)
 summarize two reported routes to 21 and 22.  
 
 
20
N
O
Boc
CHO
P
CO
2
Me
NHCOPhEtO
O
EtO
t-BuO
?
K
+
N
O
Boc
NHCOPh
CO
2
Me
H
2
, Pd/C
isoPrOH
N
O
Boc
NHCOPh
CO
2
Me
+
N
O
Boc
NHCOPh
CO
2
Me
1. CSA, MeOH, rt
2. Jones oxidation
3. CH
2
N
2
, rt
MeO
2
C CO
2
Me
BocHN NHCOPh
MeO
2
C CO
2
Me
BocHN NHCOPh
+
23 24
CSA = camphorsulfonic acid
 
Scheme 7 
 
O
N
O
Ph
Ph
Boc
1. LiN(TMS)
2
2. PhSeBr
      84%
O
N
O
Ph
Ph
Boc
SePh
H
CO
2
Me
NHAc
n-Bu
3
SnH, AIBN
O
N
O
Ph
Ph
Boc
CO
2
Me
NHAc
O
N
O
Ph
Ph
Boc
CO
2
Me
NHAc
+
H
2
, Pd/C
THF,
reflux
HO
2
C CO
2
Me
BocHN NHAc
HO
2
C CO
2
Me
BocHN NHAc
+
25 26
 
Scheme 8 
The full syntheses are moderately lengthy. In work leading to his Ph. D. degree, 
Dr. Minmin Yang of our laboratory discovered that the N-H insertion reaction of diethyl 
2-diazoglutaconate was accompanied by a shift of the double bond (Scheme 9). This 
 
 
21
created the possibility for another diazotization/N-H insertion sequence. The net result 
was a concise high-yield synthesis of a bis(amino acid) derivative. When the final 
reduction was a hydrogenation over a chiral catalyst, partial control of stereochemistry 
was afforded.
47(g)
 
 
EtOOC COOEt
7
EtOOC COOEt
N
2
Cbz-NH
2
EtOOC COOEt
NH-Cbz
EtOOC COOEt
NH-CbzN
2
EtOOC COOEt
NH-CbzCbz-HN
EtOOC COOEt
NH-CbzCbz-HN
Cbz-NH
2
diethyl glutaconate
(diazo transfer)
7
(diazo transfer)Rh
2
(OAc)
4
(N-H insertion)
Rh
2
(OAc)
4
(N-H insertion)
[H]
Scheme 9 
 
1.7.2. 3-Substituted Diaminoglutaric Acids 
The incorporation of ?-amino acids with a functional group that can act as a 
receptor ligand, such as 3-substituted diaminoglutaric acids, has attracted interest as 
possible peptidomimetics. Our target 27 here is to introduce fluorine into the ??position 
of diaminoglutaric acid. 
 
 
22
MeOOC COOMe
NH-CbzCbz-HN
F
27
 
 
It has been known for some time that fluorine can have profound and unexpected results 
on biological activity.
48
 Once introduced, the high carbon-fluorine bond energy renders 
the substituent relatively resistant to metabolic transformations. The electronegativity of 
fluorine can have pronounced effects on the electron distribution in the molecule, 
affecting the basicity or acidity of neighboring groups, dipole moments within the 
molecule and the overall reactivity and stability of neighboring functional groups. As a 
consequence of the available electron density, fluorine can function as a hydrogen bond 
acceptor.
49
 Introduction of fluorine can be carried out successfully in the presence of 
various functional groups using diethylaminosulfur trifluoride (DAST) as a 
fluorodehydroxylation reagent (Scheme 10).
50
  
 
N
N
OMe
OMe
N
O
OH
O
Cbz
N
N
OMe
OMe
N
O
F
O
Cbz
Et
2
NSF
3
CH
2
Cl
2
 
Scheme 10 
 
We propose that the fluorine of 27 could be introduced this way (Scheme 11).  
 
 
23
MeOOC COOMe
NH-CbzCbz-HN
F
27
MeOOC COOMe
NH-CbzCbz-HN
OH
28
 
Scheme 11 
 
The importance of enzymatic decarboxylations of amino acids in biosynthetic 
pathways suggested the utility of specific inhibitors of the decarboxylation enzymes in 
studying these pathways.
49
 Fluoroacylated amino acids have been recognized as potent 
suicide inhibitors of enzymatic decarboxylation reactions.
51
 The enzymatic inactivation is 
thought to be dependent upon loss of fluoride from the intermediate base 29 formed 
between pyridoxal phosphate and the fluoroacyl amino acid. Loss of fluoride generates a 
reactive acceptor 30 which can add an enzyme bound nucleophilic functional group. The 
covalently bound enzyme 31 is no longer free to bind additional substrate (Scheme 12). 
This character gives the fluoro-substituted amino acids high biological potential to serve 
as inhibitors to disrupt polyamine synthesis, with important implications for various 
anti-biological agents.
49 
A short and easy synthesis route to our target compound 27 starting from cheap and 
commercial available compound 32 was developed as briefly shown in Scheme 13. The 
novel aspect of this proposed route is the use of bisdiazo compound 33 to introduce both 
amino nitrogens simultaneously by double N-H insertion. 
 
 
24
N
OH
CH
3
O
3
POCH
2
N
R
2
C
H
O
O
H
F
R
1
+
?
?
N
OH
CH
3
O
3
POCH
2
N
R
2
H
H
F
R
1
?
? F ?
N
OH
CH
3
O
3
POCH
2
N
R
2
H
H
R
1
+
?
enzyme
N
OH
CH
3
O
3
POCH
2
N
R
2
H
Henzyme
R
1
?
29
30 31
-CO
2
 
Scheme 12 
 
 
MeOOC COOMe
NH-CbzCbz-HN
F
27
MeOOC COOMe
NH-CbzCbz-HN
OH
28
MeOOC COOMe
NH-CbzCbz-HN
O
36
MeOOC COOMe
N
2
N
2
O
33
MeOOC COOMe
O
32
diazo
transfer
Cbz-NH
2
(double N-H
insertion)
-
OOC COO
-
NH
3
+
NH
3
+
F
 
Scheme 13 
 
 
25
2. PART I. RESULTS AND DISCUSSION 
2.1. Synthesis of Bisdiazocarbonyl Compounds. 
The bisdiazocarbonyl compound could be synthesized by diazo transfer from 
sulfonyl azide 7.
52
 Dropwise addition of aqueous sodium azide to a stirred solution of 
p-acetoamidobenzenesulfonyl chloride 13 in methylene chloride containing tetrabutyl-
ammonium bromide (TBAB) at 0 ?C, gave p-acetoamidobenzenesulfonyl azide (p-ABSA) 
7,
53
 as colorless crystals in 91.3% yield.  
 
SO
2
Cl
NHCOCH
3
+ NaN
3
(n-Bu)
4
N
+
 Br
?
CH
2
Cl
2
SO
2
N
3
NHCOCH
3
13 7, 91%
(14)
 
Compound 7 in acetonitrile was added dropwise to an acetonitrile solution of 
dimethyl 3-oxoglutarate 32 and triethylamine at 0 ?C, in hopes of preparing 33 (eq. 14). 
SO
2
N
3
NHCOCH
3
MeOOC COOMe
O
732
Et
3
N
CH
3
CN
MeOOC COOMe
O
N
2
N
2
33, 92%
+ (15)
 
 
 
26
The resulting yellow oil showed only one methyl ester peak in its 
1
H NMR 
spectrum (Figure 1). The peak at 74.2 ppm in the 
13
C NMR spectrum (Figure 2), and the 
strong peak at 2133 cm
-1
 in the IR spectrum (Figure 3) indicated that the C=N=N moiety 
was present in 33. Other peaks in the 
13
C NMR spectrum can be reasonably assigned as 
follows: 52.8 ppm, -CH
3
; 161.4 ppm, ester carbonyls; 174.5 ppm, ketone carbonyl. 
 
 
Figure 1. 
1
H spectrum of compound 33 
A possible reaction product, 34, is inconsistent with the IR results. It is also ruled 
out by the results of elemental analysis (calcd for C
7
H
6
N
4
O
5
 (33) %C, 37.18; %H, 2.67; 
%N 24.77: found %C, 37.15; %H, 2.69; %N, 24.53). 
NN
O
COOMeMeOOC
34
 
 
 
 
27
Thus the diazo transfer reaction afforded the hitherto unknown compound 
dimethyl 2,4-bis(diazo)-3-oxoglutarate 33 in excellent yield. (eq 15). 
 
Figure 2. 
13
C spectrum of compound 33 
 
 
Figure 3. IR spectrum of compound 33 
 
 
28
2.2. N-H insertion of Rh(II)-stabilized carbenoid from bis(diazo) compound 33 into 
Cbz-NH
2
. 
Benzyl carbamate (Cbz-NH
2
) 35, which was required for the N-H insertion 
reaction of dimethyl 2,4-bis(diazo)-3-oxoglutarate 33, was easily afforded by bubbling 
dry ammonia gas through a methylene chloride solution of benzyl chloroformate at 0 ?C 
(eq 16).  
 
O
O
Cl O
O
NH
2
0 ?C, CH
2
Cl
2
+ NH
3 (g)
(16)
35, 96%
 
 
Dimethyl 2,4-bis(diazo)-3-oxoglutarate 33 reacted with excess benzyl carbamate 
35 in refluxing methylene chloride, catalyzed by Rh
2
(OAc)
4
 (eq 17). After the reaction 
solution had refluxed for 1 h, the TLC showed bis(diazo) compound 33 was consumed.  
 
MeOOC COOMe
O
N
2
N
2
Rh
2
(OAc)
4
CH
2
Cl
2
MeO OMe
O O O
CbzHN NHCbz
Cbz-NH
2
+(17)(?)
33 3635
 
 
However, the purification of products was not smooth. The TLC exhibited a spot with a 
long tail when using 1:1 hexane:ethyl acetate as eluent. Trying various solvent systems, 
 
 
29
such as methylene chloride with ethyl acetate, chloroform with methanol, and methylene 
chloride with toluene, did not solve the separation problem. Fortunately, when the 
reaction mixture was passed though a silica gel chromatography column eluted with 1:1 
hexane:ethyl acetate, collecting all fractions before a yellow fraction on the column gave 
a mixture which could be separated by TLC using 5:1 hexane:ethyl acetate. Finally, a 
colorless oil was afforded by column chromatography in 63% yield. However, the 
1
H 
NMR spectra (Figure 4) showed four single peaks from 3.67~3.75 ppm which indicated 
four kinds of methyl groups of the methyl ester. Initially, we thought that the separated 
colorless oil was still a mixture. However the use of various solvent systems to attempt to 
separate this oil by TLC failed. The M+1 peak indicated on mass spectrum and elemental 
analysis of 36 were successful, which means the N-H insertion reaction occurred and the 
desired product was formed. Why did the NMR spectra show a mixture? 
 
 
Figure 4a. Partial 
1
H NMR spectrum of 36: OCH
3
 region. 
 
 
30
 
Figure 4b. Partial 
1
H NMR spectrum of 36: 4.7 ~ 6.0 ppm region. 
 
Figure 4c. Partial 
1
H NMR spectrum of 36: 7.0 ~ 8.2 ppm region. 
 
It is reasonable to assume that compound 36 is highly enolic (Scheme 14). In 
Scheme 14, the carbons are numbered only to distinguish one end of the molecule from 
the other. That is, the enol double bond might be between C2 and C3, which we denote 
with a suffix "a", or it might be between C3 and C4, which we denote with a suffix "b".  
 
 
31
Furthermore, geometrical (i.e. cis-trans) isomerism is possible for these enols. Thus, as 
 
Figure 5a. Partial 
13
C NMR spectrum of 36: 52.5 ~ 54.6 ppm region. A DEPT-135 
experiment showed all these peaks were from CH
3
/CH carbons. 
 
Figure 5b. Partial 
13
C NMR spectrum of 36: 67.1 ~ 68.4 ppm region. A DEPT-135 
experiment showed all these peaks were from CH
2
 carbons. 
 
 
32
 
Figure 5c. Partial 
13
C NMR spectrum of 36: 127.9 ~ 128.9 ppm region. A DEPT-135 
experiment showed all these peaks were from CH
3
/CH carbons. 
 
 
Figure 5d. Partial 
13
C NMR spectrum of 36: 134.3 ~ 136.2 ppm region. A DEPT-135 
experiment showed all these peaks were from quaternary carbons. 
 
 
 
33
 
Figure 5e. Partial 
13
C NMR spectrum of 36: 151.1 ~ 170.3 ppm region. A DEPT-135 
experiment showed all these peaks were from quaternary carbons. 
 
shown in Scheme 14, we have four possible forms of 36, namely E-36a, E-36b, Z-36a, 
and Z-36b. This explains the four methyl signals in the 3.67 ~ 3.75 ppm region of the 
1
H 
NMR. In Figure 4a, two methyl signals are marked with ? and two with *. The two ? 
peaks are equal in area, as are the two * peaks. Since "a" forms and "b" forms are equal 
in energy, K
eq
 = 1, i.e., there must be equal amounts of E-36a and E-36b, and equal  
 
 
34
MeO OMe
O O O
CbzHN NHCbz
MeO OMe
O O O
CbzHN NHCbz
MeO OMe
O O O
CbzHN NHCbz
H
H
CbzHN
OMe
O O
NHCbz
OMeO
NHCbz
MeO
OO
CbzHN
O OMe
H
H
1
2
3
4
5
1
1
2
3
4
5
2
1
2
3
4
5
3
4
5
1
2
3
4
5
36
E-36a
E-36b
Z-36b
Z-36a
 
Scheme 14 
 
amounts of Z-36a and Z-36b. The a ' b equilibrium in this solvent (CDCl
3
) at ambient 
probe temperature is apparently slow on the 400 MHz NMR timescale, so separate 
signals for a and b forms are observed. However, there is no reason to expect E and Z 
isomers to be present in equal amounts. From integration of ? peaks versus * peaks we 
find a 60:40 ratio. It is reasonable to speculate that the more abundant form is the E form, 
because the internal hydrogen bond in the E isomer appears stronger than that in the Z 
form, making the E form slightly more stable. 
To help assign the remainder of the peaks in the 
1
H and 
13
C NMR spectra, model 
compound 37 was used.
74
 It is shown in Figures 6 and 7 with E-36. 
 
 
 
35
BocHN
H
HN COOMe
H
O O
37
1
H chemical shifts
3.73
4.63
4.68
5.15
7.59
E - 36
COOMe
N
OH
HN COOMe
O O
a
b
c
d
e
f
f'
H
O
O
c'
H
e'
 
Figure 6. Model compound used to assign 
1
H NMR chemical shifts in 36. 
 
From Figure 6, we may predict the chemical shifts of the protons in compound 36. 
The peaks can be reasonably assigned as follows (note: the peaks came out pairs indicate 
the two diastereoisomers, E-36 and Z-36): 8.0 ppm (broad peaks), CbzNHC=C (Ha); 5.8 
ppm and 5.9 ppm, four peaks also indicate four kind of C=CCH (Hb) as the methyl ester 
groups; 5.1 ppm, OCH
2
Ph (Hc/Hc'); 4.8 ppm and 4.9 ppm (broad peaks), CbzNHCH 
(Hd); 7.2~7.5 ppm (multiple peaks), phenyl protons (He/He'); 3.6~3.7 ppm methyl 
groups (Hf/Hf'). 
We may also assign the 
13
C peaks of compound 36 regarding the model compound 
37 (Figure 7) as follows: 54.5 and 54.7 ppm, 53.3 ppm and 53.2 ppm, methyl group (Ca 
and Ca'); other peaks around 53 ppm, HNCH (Cb); 67.3~68.7 ppm, OCH
2
Ph (Cc and 
Cc'); 128~129 ppm, aromatic carbon (Cd and Cd'); 134.5 ppm and 134.7 ppm, 
NHC=COH (Ce); 136.2 ppm and 136.4 ppm, NHC=COH (Cf, due to the ?OH, the 
 
 
36
chemical shift is downfield); 151.6 ppm and 156.5 ppm, COOCH
2
Ph (Cg and Cg'); 
167.6 ppm and 167.8 ppm, CHCOOMe (Ch), 170.2 ppm and 170.5 ppm, C=CCOOMe 
(Ci).  
BocHN
H
HN COOMe
H
O O
52.5
48.9
67.4
153.2
121.6
129.7
165.2
37
13
C chemical shifts E - 36
COOMe
N
OH
HN COOMe
O O
a
b
c
d
e
f
H
O
O
c'
H
d'
g
g'
h
i a'
 
Figure 7. Model compound used to assign 
13
C NMR chemical shifts in 36. 
 
2.3. N-H insertion of Rh(II)-stablilized carbenoid from bis(diazo) compound 33 into 
Boc-NH
2
. 
The t-butyl carbamate (Boc-NH
2
) 40, which was required for the N-H insertion 
reaction of dimethyl 2,4-bis(diazo)-3-oxoglutarate 33, was easily afforded by bubbling 
dry ammonia gas through an ethanol solution of t-butyl dicarbonate 40 at 0 ?C.(eq 18)  
 
Boc
2
O +
CH
2
Cl
2
0 ?C
Boc =
O
t-BuO
Boc-NH
2
41, 96%40
(18)NH
3 (g)
 
 
 
37
Dimethyl 2,4-bis(diazo)-3-oxoglutarate 33 reacted with excess t-butyl carbamate 
41 in refluxing methylene chloride, catalyzed by Rh
2
(OAc)
4
. After the reaction solution 
had refluxed for 1 h, the TLC showed bis(diazo) compound 33 was completely consumed. 
Further purification by silica gel chromatography provided a colorless oil in 46% yield. 
As discussed in section 2.2, the N-H insertion reaction product 42 consists of two enol 
forms E-42 and Z-42. The NMR spectrum indicated the ratio of these two isomers was 
E-42: Z-42 = 67:33. 
 
MeO OMe
O O O
BocHN NHBoc
MeO OMe
O O O
BocHN NHBoc
MeO OMe
O O O
BocHN NHBoc
H
H
BocHN
OMe
O O
NHBoc
OMeO
NHBoc
MeO
OO
BocHN
O OMe
H
H
1
2
3
4
5
1
1
2
3
4
5
2
1
2
3
4
5
3
4
5
1
2
3
4
5
42
E-42a
E-42b
Z-42b
Z-42a
 
Scheme 15 
 
Finally, we were able to get bisprotected diamino dicarboxylic acids 36 and 42. 
Stereocontrol of the insertion products was impossible because of extensive enolization. 
Nevertheless, the successful double N-H insertion reaction of the new bisdiazo 
 
 
38
compound 33 reflects a further synthesis value on X-H (X = C, N, O, S, Se, P, halogen) 
insertion reactions. 
2.4. Catalytic hydrogenolysis of N-H insertion reaction products. 
Reduction of the ketone functionality of 36 and 42 to an alcohol (or CH
2
) was the 
next goal. First we tried the reaction shown in eq. 19, hoping to reduce the central 
"ketone" while simultaneously deprotecting the amines by hydrogenolysis of the Cbz 
groups. We hoped that hydrogenation of these two enols 36 and 42 over Pd catalysts 
would achieve that goal. The reported hydrogenations of similar enolic substances caused 
us to be optimistic. (eq. 21).
54
 The reaction was run in either methanol or 1,4-dioxane 
solvent. 
OH
CbzHN
MeOOC
CbzHN
COOMe
E-36
OH
MeOOC
CbzHN
CbzHN
COOMe
Z-36
H
2
Pd/C catalyst
MeOOC COOMe
OH
H
2
N NH
2
47
(19)
 
OH
BocHN
MeOOC
BocHN
COOMe
E-42
OH
MeOOC
BocHN
BocHN
COOMe
Z-42
H
2
Pd/C catalyst
MeOOC COOMe
OH
BocHN NHBoc
48
(20)
 
 
39
 
R
O HO
OR'
O
H
2
, Pt/Al
2
O
3
modifier
R
O OH
O
OR'
(21)
R = Me, t-Bu, Ph
R' = Et, H
modifier - HCd or HCn to improve the ee
HCd = 10,11-dihydrocinchonidine
HCn = 10,11-dihydrocinchonine
 
After hydrogenation under 40 psi H
2
, compound 36 yielded white crystals after 
purification. However, the 
1
H NMR spectrum gave an unexpected result. A doublet signal 
at 3.0 ppm coupled with triplet signal at 3.7 ppm indicated that there is a -CH
2
-CH- 
group in the structure which did not match any groups of compound 28. Fortunately, we 
were able to obtain the x-ray structure of this strange product 44 (Figure 8). The crystal 
structure data are included in Appendix A. 
 
Figure 8. X-ray structure of compound 44 
 
 
40
A big question came to our mind. Why would we get compound 44? We 
examined a sample of 36 by NMR after establishing the structure of 44 to check whether 
36 had decomposed or rearranged on storage. It had not. 
 
MeO OMe
O O O
CbzHN NHCbz
36
MeO OMe
O OH O
H
2
N NH
2
OMe
O
44
O
MeO
NH
2
O
H
2
, Pd/C
methanol
or dioxane
 
 
After searching the literature, we found a few examples which seemed to be 
related to the mechanism by which 44 is produced. Equation 22 illustrates the unusual 
formation of N-benzylamines during Cbz group hydrogenolysis.
67
 Equation 23
75
 is an 
example which illustrates the formation of a nucleophilic intermediate (in this case an 
enolate) during catalytic hydrogenation. These precedents support us to propose a 
mechanism for the hydrogenolysis of compound 36 on Pd/C catalyst (Scheme 18). 
 
N
Ms
NCbz
N
Ms
NH
N
Ms
NBn
+ (22)
10% Pd/C
H
2
 
 
 
41
O
H
O
O
CH
3
H
2
, Rh(COD)
2
OTf
Ar
3
P, K
2
CO
3
, THF
HO
CH
3
O
H
O
72%
(23)
 
 
We postulate that in several steps 49 is formed by routine deprotection of the 
"righthand" NHCbz group (as drawn in Scheme 16) and deprotection followed by C-N 
hydrogenolysis of the "lefthand" NHCbz group. The next step is similar to eq. 23 in 
which a nucleophilic species attacks a neighboring carbonyl carbon. Cyclopropane 50 
opens to relieve ring strain, giving 51 and hydroxide. Hydroxide adds to 51 in Michael 
fashion to give 52, which loses hydride (perhaps to 49), giving 53. This tautomerizes to 
44. This mechanism is highly speculative. 
 
 
 
42
NHCbz
O
OMeMeO
O OH
NH
2
O
OMeMeO
O OH
H
CbzHN H
?
MeO
O
H H
O
OMe
NH
2
HO
?
MeO
O
O
?
OMe
NH
2
HO
H
MeO
O
O
OMe
NH
2
HO
MeO
O
O
OMe
NH
2
O
- H
?
+ H
?
36 49 50
515253
44
H
2
Pd
MeO
O HO
NH
2
O
?
OMe
HH
- OH
?
 Scheme 16. Proposed mechanism for formation of 44 
 
We also tried Pd/C catalyzed hydrogenation of Boc-protected compound 42 
which won?t undergo the hydrogenolysis of Boc group. However, we only found the 
starting compound 42 instead of expected alcohol 48. 
 
H
2
Pd/C catalyst
MeOOC COOMe
OH
BocHN NHBoc
48
MeO OMe
O O O
BocHN NHBoc
42
X
 
 
           
 
43
3. PART II. INTRODUCTION 
3.1 Introduction to hypervalency. 
The concept of hypervalent molecules was established by J. I. Musher in 1969.
55
 
Hypervalent compounds are ions or molecules of the elements bearing more electrons 
than the octet within a valence shell (Scheme 17). According to Musher,
55
 there are 
essentially two ways to hold electrons beyond the octet within a valence shell: (1) make 
up a set of dsp
3
 or d
2
sp
3
 hybrid orbitals using higher-lying d orbitals or (2) make up 
highly ionic orbitals revising the basic idea of Lewis that a covalent bond is formed by a 
localized pair of two electrons. 
 
10-S-4                   10-P-5                   12-Xe-4
S:
F
F
F
F
P
Cl
Cl
Cl
Cl
Cl Xe
F
F
F
F
 
Scheme 17. Some simple hypervalent molecules 
 
Pimentel and Rundle,
56
 in 1951, laid the basis for new development in this area 
by proposing the idea of the three-center four-electron (3c-4e) bond, employing the 
molecular orbital theory. Owing to progress in computing and the efforts of many 
           
 
44
scientists, the idea of the 3c-4e bond has become supported and is presently widely 
accepted. 
The 3c-4e bond (Scheme 18) is an electron-rich, orbital-deficient bond and the 
nonbonding molecule orbital (NBMO) becomes HOMO while the antibonding orbital is 
the LUMO. Most hypervalent species will have a pseudo-trigonal bipyramidal geometry 
(TBP) that employs two types of bonding: hypervalent bonding to two apical ligands, 
and normal bonding to all equatorial ligands.
57
 
 
M
L L
L
L
MM
L
L
Occupied
Bonding
Occupied
Non-bonding
Unoccupied
Antibonding
 
Scheme 18. Three-center four-electron (3c-4e), hypervalent bonding scheme 
 
3.2 Hypervalent boron 10-B-5 species. 
During the period when the interest in hypervalent species grew, very few 
hypervalent compounds of second-row elements were isolated or even detected. Only 
boron, carbon and fluorine species have been made so far, and there are only a small 
number of examples of these compounds. Some examples are the first hypervalent 
10-B-5 boron compound 54 reported by Lee and Martin in 1984,
58
 hypervalent 10-C-5 
           
 
45
carbon compound 55 synthesized by Kin-Ya Akiba recently
59
 (Scheme 19) and first 
10-F-2 hypervalent fluorine species observed by Ault and Andrews in 1976,
60
 which was 
the highly unstable trifluoride anion F
3
- 
generated by simultaneous deposition of an 
argon/fluorine mixture with CsF, RbF or KF and detected at low temperature by Raman 
and infrared spectroscopy. 
 
B
O
O
N
+
F
3
C
F
3
C
CF
3
CF
3
R
=
Et
4
N
+
10-B-5                                               10-C-5
MeO C OMe
OMeMeO
+
B
2
F
7
?
54                                                      55
 
Scheme 19. Some hypervalent compounds based on second row elements. 
 
Recently, Wada et al.
61
 reported a synthesis route to tris(2,6-dimethoxyphenyl)-
borane 56 which let us set a program leading to a new 10-B-5 species 59 (Scheme 20). In 
this thesis, we report on progress toward this goal. 
 
           
 
46
OMe
OMe
+   n-butylLi
TMEDA
OMe
OMe
Li
BF
3
?OEt
2
benzene, reflux
OMe
OMe
B
3
demethylation
OH
OH
B
3
PCl
3
 or
ether, 0 ?C
 P(OPh)
3
56
60
59
O
O
O
P
O
O
B
+
+
=
P
O
58 5657
 
Scheme 20 
 
3.3 Hypervalent phosphorus 10-P-5 species. 
Phosphorus species 61 also attracted our interest (Scheme 23). It is formally an 
8-P-5 species that may exhibit a three-center two-electron (3c-2e) bond. An analogous 
compound, 65, was described recently.
72
 Compound 65 was found to be undergoing a  
 
O
O
O
B
O
O
N
?
B
O
?
?
?
?+
65a
3c-2e bond
O
O
O
B
O
O
N
B
O
O
O
O
B
O
O
N
B
O
equilibrating 8-N-4 species
65b 65c
 
dynamic equilibrium in solution. The x-ray crystal structure of 65 revealed an 
unsymmetrical B-N-B triad (i.e. 65b or 65c), with the "free" boron coordinated to a 
           
 
47
solvent THF molecule. It was of interest to see whether 61, the phosphorus analogue of 
65, would have a greater tendency than 65 to engage in three-center bonding.  
Hui Li of our laboratory has made progress in the synthesis of 61.
73
 We report 
herein our work directed at the completion of this synthesis. 
OMe
OMe
TMEDA
OMe
OMe
Li
ether, 0 ?C
5857
P(OPh)
3
THF, rt
38%
OMe
OMe
P
64
3
2. HCl
90%
OH
OH
PH
+
  Cl
?
63
3
deprotonation
OH
OH
P
62
3
n-BuLi
1. AlCl
3
,
    toluene
H
3
BO
3
 or
B(OCH
3
)
3
O
O
O
B
O
O
P
?
B
O
?
?
?
?+
61
(8-P-5)
 
Scheme 21 
 
 
 
 
 
           
 
48
4. PART II. RESULTS AND DISCUSSION 
4.1 Synthesis of tris(2,6-dimethoxyphenyl)borane 
Compound 56, ?
3
B (the 2,6-dimethoxyphenyl group is sometimes denoted as 
"?"), was prepared by the reaction of ?Li 58 and boron trifluoride diethyl etherate.
61
 To 
a solution of 1,3-dimethoxybenzene 57 and a catalytic amount of N,N,N?,N?-tetramethyl-
ethylenediamine (TMEDA) in diethyl ether was added a 2.5 M n-hexane solution of 
n-butyllithium at 0 ?C under nitrogen. To the suspension of ?Li 58 after precipitates 
formed was added boron trifluoride diethyl etherate in benzene. After reflux and 
recrystallization from THF, white crystals of ?
3
B 56 were obtained in 41% yield for both 
steps (eq. 24).   
 
OMe
OMe
+   n-butylLi
TMEDA
OMe
OMe
Li
BF
3
?OEt
2
benzene, reflux
OMe
OMe
B
3
ether, 0 ?C
58 5657
(24)
 
 
4.2 Demethylation of tris(2,6-dimethoxyphenyl)borane, 56. 
Many reagents have been utilized for demethylation of aryl methyl ethers as 
reported in the chemical literature. The most commonly used are hydrogen iodide (or 
           
 
49
bromide),
62
 boron tribromide,
63
 trimethylsilyl iodide,
64
 aluminum chloride,
65
 pyridinium 
hydrochloride,
65
 and sodium amide.
66
 In our research here, we have tried aluminum 
trichloride and boron tribromide so far.  
4.2.1 Demethylation of 56 by aluminum trichloride. 
To the fine suspension of ?
3
B 56 in toluene was added anhydrous AlCl
3
 under 
nitrogen. After reflux, water was added to hydrolyze the excess AlCl
3
. However, the 
white solid obtained proved to be resorcinol 66 by NMR spectrum (eq. 25). The 
unexpected decomposition indicates that the carbon-boron bonds in 56 were cleaved, 
although the demethylation still occurred. 
 
OMe
OMe
B
3
OH
OH
56                                                        66
(25)
AlCl
3
toluene, reflux
OH
OH
B
3
not formed
 
4.2.2 Demethylation by BBr
3
.
S(Me)
2
. 
BBr
3
 is another commonly used demethylation reagent which came to mind after 
AlCl
3
 failed to afford desired tris(2,6-dihydroxyphenyl)borane. To the solution of ?
3
B 56 
in methylene chloride was added a solution of BBr
3
.
S(Me)
2
 complex in methylene 
chloride at 0 ?C under nitrogen. The afforded mixture indicated that the demethylation 
only partially occurred and we still detect resorcinol in the product by NMR spectrum (eq. 
26). 
           
 
50
 
OMe
OMe
B
3
BBr
3
.
S(Me)
2
CH
2
Cl
2
, rt
OH
OH
56                                                        66
(26)+    partial demethylation products
 
 
The demethylation of 56 to target product could not be accomplished by either 
AlCl
3
 or BBr
3
. Because of the time limit, further investigation of the demethylation of 56 
has not been done yet. When choosing other demethylation reagents, the cleavage of the 
carbon-boron bond of ?
3
B 56 might be avoided by avoiding acidic conditions, which 
seem to promote C-B cleavage. 
4.3 Synthesis of tris(2,6-dihydroxyphenyl)phosphonium chloride 63. 
The synthesis of compound 63 has been well developed by Hui Li in his previous 
work in our laboratory
73
 as shown in Scheme 21. Tris(2,6-dimethoxyphenyl)phosphine 
64 can be prepared by adding the triphenyl phosphite to 58 which was the product of 
ortho-lithiation of 1,3-dimethoxybenzene 57 in THF. Further demethylation of 
tris(2,6-dimethoxyphenyl)phosphine 64 by anhydrous AlCl
3
 in toluene afforded a red 
solid. 
 
           
 
51
OMe
OMe
THF, 
0 ?C
OMe
OMe
Li
THF, r.t.
38%
OMe
OMe
P
3
OH
OH
P
+
HCl
-
3
2. HCl
     80%
57 58 64 63
(PhO)
3
P
n-BuLi
1. AlCl
3
    PhCH
3
 
Scheme 22 
 
By recrystallization from EtOEt/MeOH, a single crystal suitable for x-ray 
diffraction was obtained. The crystal was found to be a co-crystal with the ethyl ether, 
which was revealed by proton NMR. This indicated the hydrogen bond between 
compound 63 and solvent is strong which also was found that compound 63 associated 
with ethyl acetate from Hui Li?s research.
73
 A structure diagram is provided in Figure 9 
and crystal structure data are included in Appendix B. We are interested in the bond 
lengths and bond angles of phosphorus to the neighboring atoms which are indicated in 
Table 1. 
 
           
 
52
 
Figure 9. Crystal structure of compound 63 
 
 
Parameters 
Bond  
length (?)
Bond  
angle (?) 
Torsion  
angle (?) 
P(1)-C(13) 1.770(3)   
P(1)-C(7) 1.770(3) 
P(1)-C(1) 1.786(2)   
P(1)-H(1) 1.27(2) 
C(13)-P(1)-C(7)  114.84(12)  
C(13)-P(1)-C(1)  113.68(12)  
C(7)-P(1)-C(1)  112.37(12)
H(1)-P(1)-C(1)  104.7(11)  
H(1)-P(1)-C(7)  104.0(10) 
H(1)-P(1)-C(13)  106.0(11)  
H(1)-P(1)-C(1)-C(2)   30.8(11) 
H(1)-P(1)-C(7)-C(8)   20.5(11) 
H(1)-P(1)-C(13)-C(14)   24.5(11) 
Table 1. Selected Structural Parameters of 63 
           
 
53
 
PH
+
PH
+
OMe
OMe
MeO
FeCl
4
-
PH
+
OMe
OMe
MeO Fe
2
Cl
6
2-
H
P
Br
-
HO
3 3
3 2
67
68
69 70
2
 
Scheme 23 
 
The P(1), C(1), C(7) and C(13) formed an asymmetric pyramid with the equal 
length of P(1)-C(7) and P(1)-C(13). A search of the crystallographic literature revealed 
several reports of structures of the type (Ar
3
PH)
+
. The majority of crystal structures 
which were found involved the triphenylphosphonium ion, Ph
3
PH
+
, 67.
70
 Other more 
relevant examples were: tris(2,4,6-trimethoxyphenyl)phosphonium tetrachloroiron(III) 
68
68
, bis{tris(2,4,6-trimethoxylphenyl)phosphonium} bis[(?
2
-chloro)-dichloroiron] 69
69
, 
(2-hydroxyphenyl)diphenylphosphonium bromide 70
71 
(Scheme 25). Geometrical 
parameters of these phosphonium ions are compared to those of 63 in Table 2. 
           
 
54
Parameters 63 67
a
 68 69 70 
h (?) - 0.525(16) 0.481 0.541 0.542 
average P-C  
bond length (?) 
1.771(8) 1.786(8) 1.783(6) 1.791(7) 1.786(2)
P-H  
bond length(?) 
1.27(2) 1.351(6) 1.438 1.612 1.413 
average C-P-C  
bond angle (?)  
113.6(2) 110.7(5) 113.0(3) 111.3(2) 111.2(2) 
average C-P-H  
bond angle (?) 
104.9(4) 108.2(14) 105.7(4) 107.7(6) 107.4(7) 
a
 values are averages of all reported triphenylphosphonium ion structures 
Table 2. 
 
We first thought that the parameters of compound 63 would be similar to those of 
compound 70 because compound 70 has ?OH on its phenyl ring. However, from the 
Table above, the P-C bond length, C-P-C bond angle and C-P-H bond angle of compound 
63 are most close to compound 68. The P-H bond length of compound 63 is much less 
than either the average P-H bond length of triphenylphosphonium ion or the other 
triarylphosphonium ions.  
We have been able to synthesis tris(2,6-dihydroxyphenyl)phosphonium chloride 
63 and determine its structure. The next step is to deprotonate 63 by base (Scheme 21) 
which is a key step in the synthesis of compound 61 and the study of multicenter, perhaps 
hypervalent, bonding between the phosphorus and boron or other main group elements. 
 
           
 
55
5. EXPERIMENTAL 
General: Methylene chloride and acetonitrile were distilled over calcium hydride 
under nitrogen atmosphere. Reagents used in the syntheses were purchased from the 
Aldrich Chemical Company and were used without further treatment. 
Melting points were recorded on a capillary melting point apparatus and are 
uncorrected. NMR spectra were obtained at room temperature from Bruker AV-400 
spectrometer operating at 400 MHz for 
1
H and 100 MHz for 
13
C. TMS was used as 
internal standard. The results are presented as parts per million (ppm or ?) and coupling 
constants are reported in Hz. 
Mass spectral (MS) data were obtained using either a Finnegan 3300 or a VG 
7070E mass spectrometer using a solid probe. The results are presented in terms of 
intensity percentage relative to the base peak and probable fragmentation product. 
Elemental analysis was performed by Atlantic Microanalytical lab, GA. 
TLC was performed on Sorbent Technologies silica G TLC plates w/UV254. 
Preparative column chromatography employed Sorbent Technologies silica gel (60 ?, 
32-63 ?m). 
p-Acetoamidobenzenesulfonyl azide, 7.
52 
To a suspension of p-acetamido-
benzenesulfonyl chloride 13 (50.0 g, 0.214 mol) in 400 ml methylene chloride containing 
           
 
56
tetrabutylammonium bromide (0.200 g, 0.008 mmol) at 0 ?C was added dropwise a 
solution of sodium azide (16.0 g, 0.248 mol, in 50 mL H
2
O). The reaction was allowed to 
warm up to rt and was kept stirring at rt for 16 h. The organic layer was separated and 
washed with water (2 x 75 mL) and saturated aqueous sodium chloride (2 x 50 mL), 
dried over Na
2
SO
4
 and evaporated to give 46.9 g (91.3%) pure white solid, mp 107-110 
?C. 
1
H NMR (400 MHz, CDCl
3
): 2.25 (s, 3H), 7.80 (m, 2H), 7.89 (m, 2H), 8.04(br, 1H). 
13
C NMR (100 MHz, CDCl
3
): 25.0, 119.8, 129.2, 132.7, 144.2, 169.3. 
Dimethyl 2,4-bis(diazo)-3-oxoglutarate, 33. To a stirred solution of dimethyl 
3-oxoglutarate 34 (2.41 g, 13.9 mmol) and triethylamine (3.00 g, 29.7 mmol) in 45 mL 
acetonitrile at 0 ?C was added dropwise p-acetamidobenzenesulfonyl azide 7 (7.20 g, 
30.0 mmol) in 100 mL acetonitrile over 30 minutes. The reaction was allowed to warm to 
rt and stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated 
under reduced pressure. The residue was washed with ethyl acetate/hexanes (1:1), 
filtered, and the solvent was evaporated. Further purification by silica gel column 
chromatography (hexanes/ethyl acetate = 4:1) gave 2.86 g yellow oil (92%). 
1
H NMR 
(400 MHz, CDCl
3
): 3.83 (s). 
13
C NMR (100 MHz, CDCl
3
): 52.8, 74.2, 161.4, 174.5. IR 
(neat): 3004.6, 2956.0, 2133.3, 1719.0, 1601.2, 1433.9, 1321.4, 1192.3, 1126.2, 996.1, 
750.1, 763.1, 698.9. Anal. Calcd. for C
7
H
6
O
5
N
4
: C, 37.18; H, 2.67; N, 24.77. Found: C, 
37.15; H, 2.69; N, 24.53. 
Benzyl carbamate, 35. To a stirred solution of benzyl chloroformate (10.3 g, 
           
 
57
0.063 mol) in 200 mL methylene chloride was bubbled through dry ammonia gas at 0 ?C. 
Stopped bubbling while there was no more precipitation formed. Filtered the 
precipitation and the filtrate was evaporated under reduced pressure to give 9.10 g (99%) 
white crystals, mp 87-88 ?C. 
1
H NMR (400 MHz, CDCl
3
): 4.89 (br, 2H), 5.10 (s, 2H), 
7.36 (m, 5H). 
13
C NMR (100 MHz, CDCl
3
): 67.1, 128.3, 128.4, 128.8, 136.4, 157.0. 
Compound 36. To a stirred solution of dimethyl 2,4-bis(diazo)-3-oxoglutarate 33 
(0.300 g, 1.33 mmol) in 15 mL methylene chloride was mixed with benzyl carbamate 35 
(0.401 g, 2.66 mmol). A catalytic amount of rhodium(II) acetate (24 mg, 0.05 mmol) was 
added. The reaction set up was then immediately moved to a pre-heated oil bath at 42? . 
After refluxing for 3 h, the bis(diazo) compound was completely consumed. The reaction 
mixture was purified by silica gel column chromatography (first using hexanes/ethyl 
acetate = 1:1 washing out the fractions before yellow band. The afforded fractions were 
separated by hexanes/ethyl acetate = 5:1) gave 0.430 g (68%) colorless oil. 
1
H NMR 
(400 MHz, CDCl
3
): 3.67 (s, 3H), 3.71 (s, 3H), 4.96 (br, d, J = 3.2 Hz, 1H), 5.98 (d, J = 
10.3Hz, 1H), 7.95 (br, 1H) for one isomer; 3.73 (s, 3H), 3.75 (s, 3H), 4.79 (br, 1H), 5.82 
(d, J = 9.2 Hz, 1H), 8.17 (br, d, J = 1.2 Hz, 1H) for the other isomer, 5.15 (m, 5H, two 
CH
2
Ph, OH), 7.33 (m, 10H). 
13
C NMR (100 MHz, CDCl
3
): 52. 8, 53.2, 53.2, 53.3, 53.3, 
53.4, 128.1, 128.3, 128.3, 128.4, 128.7, 128.7, 128.7, 128.8, 128.92, 128.94, 129.03, 
129.03, 134.6, 134.7, 136.2, 136.4, 151.6, 156.2, 156.5, 167.6, 167.9, 170.2, 170.5. 
t-Butyl carbamate, 41. To a 50 mL saturated NH
3
-EtOH solution was added 
           
 
58
dropwise a solution of t-butyl dicarbonate 40 (21.3 g, 97.8 mmol) in 50 mL ethanol at 0 
?C. While stirring, the solution was bubbled through dry ammonia gas. Stopped bubbling 
while there was no more precipitation formed. Filtered the precipitation and the filtrate 
was evaporated under reduced pressure. Added 50 mL hexane. Boiled at 65 ?C for 30 
minutes. Cooled down to 0 ?C. Washed with hexane and dried to give 11.0 g (96%) white 
crystals, mp 106-108 ?C. 
1
H NMR (400 MHz, CDCl
3
): 1.45 (s, 9H), 4.67 (br, 2H). 
13
C 
NMR (100 MHz, CDCl
3
): 28.4, 79.8, 156.7. 
Compound 42. To a stirred solution of dimethyl 2,4-bis(diazo)-3-oxoglutarate 33 
(1.94 g, 8.58 mmol) in 100 mL methylene chloride was mixed with t-butyl carbamate 41 
(2.10 g, 17.9 mmol). A catalytic amount of rhodium(II)acetate (40 mg, 0.1 mmol) was 
added. The reaction set-up was then immediately moved to pre-heated oil bath at 42? . 
After refluxing for 3 h, the bisdiazo compound was completely consumed. The reaction 
mixture was purified by silica gel column chromatography (first using hexanes/ethyl 
acetate = 1:1 washing out the fractions before yellow band. The afforded fractions were 
separated by hexanes/ethyl acetate = 5:1) gave 1.59 g (46%) colorless oil. 
1
H NMR (400 
MHz, CDCl
3
): 1.44 (s, 9H), 1.48 (s, 9H), 3.74 (s, 3H), 3.75 (s, 3H), 4.90 (br, 1H), 5.06 
(dd, J
A 
= 10.4Hz, J
B 
= 4.00Hz, 1H), 5.71 (d, J = 10.4Hz, 1H), 7.68 (br, 1H) for one 
isomer; 1.45 (s, 9H), 1.49 (s, 9H), 3.74 (s, 3H), 3.78 (s, 3H), 4.69 (br, 1H), 5.14 (dd, J
A 
= 
9.1 Hz, J
B 
= 3.6 Hz, 1H), 5.55 (d, J = 9.2 Hz, 1H), 7.96 (br, 1H) for the other isomer. 
13
C 
NMR (100 MHz, CDCl
3
): 28.1, 28.1, 28.4, 28.4, 52.8, 53.0, 53.1, 53.2, 54.7, 54.8, 62.3, 
           
 
59
63.4, 80.3, 80.6, 83.6, 83.8, 128.4, 129.2, 150.0, 150.4, 155.6, 155.8, 168.0, 168.4, 170.8, 
170.9. 
Tris(2,6-dimethoxyphenyl)borane, 56.
61
 To a solution of 1,3-dimethoxybenzene 
57 (5.52 g, 40.0 mmol) and a catalytic amount of N,N,N?,N?-tetramethylethylenediamine 
(TMEDA, 0.2 mL) in diethyl ether (50 mL) was added a 2.5 M n-hexane solution of 
n-butyllithium (16 mL, 40 mmol) at 0 ?C under nitrogen. The mixture was stirred for 3 h 
to afford the precipitate of ?Li 58. To this suspension was added boron trifluoride 
diethyl etherate (1.89 g, 13.2 mmol) in benzene (50 mL) and the mixture was refluxed for 
4 h. 15 mL methanol was added at rt and the insoluble materials were recrystallized from 
THF to give 2.27 g (41%) white crystals of ?
3
B 56. m.p.: 234-235 ?C. 
1
H NMR (400 
MHz, CDCl
3
): 3.45 (s, 18H), 6.47 (d, J = 8.2 Hz, 6H), 7.18 (t, J = 8.2 Hz, 3H). 
13
C NMR 
(100 MHz, CDCl
3
): 56.8, 105.3, 130.3, 162.7. 
Tris(2,6-dimethoxyphenyl)phosphine, 64. To a solution of 1,3-dimethoxy-
benzene 57 (10.0 g, 72.5 mmol) in THF (40 mL) was added a 2.5 M n-hexane solution of 
n-butyllithium (30.5 mL, 76.3 mmol) at 0 ?C under nitrogen. After stirring at 0 ?C for 45 
minutes, a solution of triphenyl phosphite (6.75 g, 21.8 mmol) in THF (20 mL) was 
added dropwise. Then the stirring was continued overnight at rt. The reaction was 
quenched by adding a few mL methanol. Filtered the solid, washed with ether, combined 
the filtrate and the ether. Evaporate the solvent and wash the solid by water. The solid 
was recrystallized from acetone/water to give 3.61 g (37.5%) white crystals. m.p.: 
           
 
60
149-151 ?C. 
1
H NMR (400 MHz, CDCl
3
): 3.48 (s, 18H), 6.44 (dd, J
A 
= 8.2 Hz, J
B 
= 2.9 
Hz, 6H), 7.13 (t, J = 8.0 Hz, 3H). 
13
C NMR (100 MHz, CDCl
3
): 56.2, 104.5, 115.5, 128.7, 
162.5, 162.6. 
31
P NMR (162 MHz, CDCl
3
): -66.6. 
Tris(2,6-dihydroxyphenyl)phosphonium chloride 63. Anhydrous AlCl
3
 (810 
mg, 6.07 mmol) was added to a fine suspension of tris(2,6-dimethoxyphenyl)phosphine 
64 (442 mg, 1.00 mmol) in 15 mL dry toluene under nitrogen. The suspension was 
refluxed for 2 h and the stirred at rt overnight, which resulted in much gray-green 
precipitate. The reaction was quenched by slow addition of 15 mL 3 M HCl and the 
insoluble material changed color to pink. The stirring was continued until none of the 
precipitate stuck to the glass. The solid was collected by filtration and washed with 
diethyl ether, and dried on the vacuum line, which afforded 308 mg (80%) almost pure 
compound 63. Further purification can be achieved by recrystallization from Et
2
O/MeOH, 
mp 234 ?C. 
1
H NMR (400 MHz, DMSO-d
6
): 6.36 (dd, J = 5.6 Hz, 7.6 Hz, 6H), 7.22 (t, 
J= 8.1 Hz, 3H), 8.37 (d, J = 534 Hz, 1H), 10.63 (s, 6H). 
13
C NMR (100 MHz, DMSO-d
6
): 
93.2 (d, J= 102 Hz), 107.0 (d, J= 5.7 Hz), 136.3, 162.3. 
31
P NMR (162 MHz, DMSO-d
6
): 
-51.3 (d, J = 527 Hz). 
 
 
 
 
           
 
61
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69
APPENDICES 
 
           
 
70
Appendix A. Crystal structure data (CIF file) for compound 44. 
 
data_face  
  
_audit_creation_method            SHELXL-97  
_chemical_name_systematic  
;  
 ?  
;  
_chemical_name_common             ?  
_chemical_melting_point           ?  
_chemical_formula_moiety          ?  
_chemical_formula_sum  
 'C7 H11 N1 O5'  
_chemical_formula_weight          756.67  
  
loop_  
 _atom_type_symbol  
 _atom_type_description  
 _atom_type_scat_dispersion_real  
 _atom_type_scat_dispersion_imag  
 _atom_type_scat_source  
 'C'  'C'   0.0033   0.0016  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'H'  'H'   0.0000   0.0000  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'N'  'N'   0.0061   0.0033  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'O'  'O'   0.0106   0.0060  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
  
_symmetry_cell_setting            'orthorhombic'  
_symmetry_space_group_name_H-M    'P2(1)2(1)2(1)' 
  
loop_  
 _symmetry_equiv_pos_as_xyz  
 'x, y, z'  
 '-x+1/2, -y, z+1/2'  
           
 
71
 '-x, y+1/2, -z+1/2'  
 'x+1/2, -y+1/2, -z  
_cell_length_a                    5.0678(5)  
_cell_length_b                    11.2996(10)  
_cell_length_c                    16.1160(15)  
_cell_angle_alpha                 90.00  
_cell_angle_beta                  90.00  
_cell_angle_gamma                 90.00  
_cell_volume                      922.87(15)  
_cell_formula_units_Z             4 
_cell_measurement_temperature     193(2)  
_cell_measurement_reflns_used     9416  
_cell_measurement_theta_min       2.20 
_cell_measurement_theta_max       28.36 
  
_exptl_crystal_description        'prism'  
_exptl_crystal_colour             'colorless'  
_exptl_crystal_size_max           .700 
_exptl_crystal_size_mid           .100  
_exptl_crystal_size_min           .100  
_exptl_crystal_density_meas      'not measured'  
_exptl_crystal_density_diffrn     1.361  
_exptl_crystal_density_method     'not measured'  
_exptl_crystal_F_000              400  
_exptl_absorpt_coefficient_mu     0.117  
_exptl_absorpt_correction_type    'numerical'  
_exptl_absorpt_correction_T_min   0.95836  
_exptl_absorpt_correction_T_max   0.98905  
_exptl_absorpt_process_details    'SADABS'  
  
_exptl_special_details  
;  
 ?  
;  
  
_diffrn_ambient_temperature       193(2)  
_diffrn_radiation_wavelength      0.71073  
_diffrn_radiation_type            MoK\a  
_diffrn_radiation_source          'fine-focus sealed tube'  
_diffrn_radiation_monochromator   graphite  
_diffrn_measurement_device_type   'Bruker APEX'  
_diffrn_measurement_method        '0.3 wide w/ exposures' 
_diffrn_detector_area_resol_mean  0  
_diffrn_standards_number          'na'  
_diffrn_standards_interval_count  'na'  
_diffrn_standards_interval_time   'na'  
           
 
72
_diffrn_standards_decay_%         0  
_diffrn_reflns_number             9366  
_diffrn_reflns_av_R_equivalents   0.0321  
_diffrn_reflns_av_sigmaI/netI     0.0281  
_diffrn_reflns_limit_h_min        -6  
_diffrn_reflns_limit_h_max        6  
_diffrn_reflns_limit_k_min        -15  
_diffrn_reflns_limit_k_max        15  
_diffrn_reflns_limit_l_min        -21  
_diffrn_reflns_limit_l_max        20  
_diffrn_reflns_theta_min          2.20  
_diffrn_reflns_theta_max          28.36  
_reflns_number_total              2297  
_reflns_number_gt                 2042  
_reflns_threshold_expression      >2sigma(I)  
  
_computing_data_collection        'SMART'  
_computing_cell_refinement        'SMART,  SAINT' 
_computing_data_reduction         'SAINT'  
_computing_structure_solution     'SHELXS-97 (Sheldrick, 1990)'  
_computing_structure_refinement   'SHELXL-97 (Sheldrick, 1997)'  
_computing_molecular_graphics     'SHELXP-97 (Sheldrick, 1997)'  
_computing_publication_material   'SHELXCIF-97 (Sheldrick, 2000)' 
  
_refine_special_details  
;  
 Refinement of F^2^ against ALL reflections.  The weighted R-factor wR and  
 goodness of fit S are based on F^2^, conventional R-factors R are based  
 on F, with F set to zero for negative F^2^. The threshold expression of  
 F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is  
 not relevant to the choice of reflections for refinement.  R-factors based  
 on F^2^ are statistically about twice as large as those based on F, and R-  
 factors based on ALL data will be even larger.  
;  
  
_refine_ls_structure_factor_coef  Fsqd   
_refine_ls_matrix_type            full  
_refine_ls_weighting_scheme       calc   
_refine_ls_weighting_details  
 'calc w=1/[\s^2^(Fo^2^)+(0.0752P)^2^+0.0097P] where P=(Fo^2^+2Fc^2^)/3'  
_atom_sites_solution_primary      direct  
_atom_sites_solution_secondary    difmap  
_atom_sites_solution_hydrogens    geom  
_refine_ls_hydrogen_treatment     mixed  
_refine_ls_extinction_method      none  
_refine_ls_extinction_coef        ?  
           
 
73
_refine_ls_abs_structure_details  
 'Flack H D (1983), Acta Cryst. A39, 876-881'  
_refine_ls_abs_structure_Flack    0.3(12)  
_refine_ls_number_reflns          2297  
_refine_ls_number_parameters      118  
_refine_ls_number_restraints      0  
_refine_ls_R_factor_all           0.0476  
_refine_ls_R_factor_gt            0.0429  
_refine_ls_wR_factor_ref          0.1136  
_refine_ls_wR_factor_gt           0.1115  
_refine_ls_goodness_of_fit_ref    1.049  
_refine_ls_restrained_S_all       1.049  
_refine_ls_shift/su_max           0.001  
_refine_ls_shift/su_mean          0.000  
  
loop_  
 _atom_site_label  
 _atom_site_type_symbol  
 _atom_site_fract_x  
 _atom_site_fract_y  
 _atom_site_fract_z  
 _atom_site_U_iso_or_equiv  
 _atom_site_adp_type  
 _atom_site_occupancy  
 _atom_site_symmetry_multiplicity  
 _atom_site_calc_flag  
 _atom_site_refinement_flags  
 _atom_site_disorder_assembly  
 _atom_site_disorder_group  
C4 C -0.0009(4) 0.59200(13) 0.81987(10) 0.0319(3) Uani 1 1 d . . .  
O1 O 0.0052(3) 0.59020(10) 1.11748(7) 0.0391(3) Uani 1 1 d . . .  
C1 C 0.1480(3) 0.61401(12) 1.05091(10) 0.0269(3) Uani 1 1 d . . .  
C3 C 0.1634(3) 0.60757(13) 0.89644(10) 0.0279(3) Uani 1 1 d . . .  
H3A H 0.2089 0.6923 0.9030 0.033 Uiso 1 1 calc R . .  
H3B H 0.3299 0.5626 0.8903 0.033 Uiso 1 1 calc R . .  
O2 O 0.1083(3) 0.64643(14) 0.75549(7) 0.0491(4) Uani 1 1 d . . .  
C5 C -0.0324(6) 0.6382(2) 0.67762(12) 0.0630(6) Uani 1 1 d . . .  
H5A H 0.0646 0.6816 0.6347 0.094 Uiso 1 1 calc R . .  
H5B H -0.2088 0.6726 0.6840 0.094 Uiso 1 1 calc R . .  
H5C H -0.0484 0.5549 0.6614 0.094 Uiso 1 1 calc R . .  
C6 C 0.1031(4) 0.63393(17) 1.19590(11) 0.0452(4) Uani 1 1 d . . .  
H6A H -0.0179 0.6105 1.2404 0.068 Uiso 1 1 calc R . .  
H6B H 0.1153 0.7204 1.1938 0.068 Uiso 1 1 calc R . .  
H6C H 0.2782 0.6005 1.2066 0.068 Uiso 1 1 calc R . .  
O4 O 0.3522(3) 0.66760(13) 1.05216(8) 0.0478(4) Uani 1 1 d . . .  
C7 C 0.0245(3) 0.43010(11) 0.98115(9) 0.0224(3) Uani 1 1 d . . .  
           
 
74
O3 O -0.2041(3) 0.53906(16) 0.81592(8) 0.0559(4) Uani 1 1 d . . .  
C2 C 0.0179(3) 0.56488(11) 0.97361(8) 0.0227(3) Uani 1 1 d . . .  
H2A H -0.1696 0.5922 0.9713 0.027 Uiso 1 1 calc R . .  
O5 O 0.24075(19) 0.37986(9) 0.98167(9) 0.0345(3) Uani 1 1 d . . .  
N1 N -0.2005(2) 0.37440(11) 0.98872(9) 0.0295(3) Uani 1 1 d . . .  
H1A H -0.2028 0.2970 0.9946 0.035 Uiso 1 1 calc R . .  
H1B H -0.3495 0.4144 0.9880 0.035 Uiso 1 1 calc R . .  
  
loop_  
 _atom_site_aniso_label  
 _atom_site_aniso_U_11  
 _atom_site_aniso_U_22  
 _atom_site_aniso_U_33  
 _atom_site_aniso_U_23  
 _atom_site_aniso_U_13  
 _atom_site_aniso_U_12  
C4 0.0338(8) 0.0317(7) 0.0301(7) 0.0003(5) 0.0030(7) 0.0076(7)  
O1 0.0437(7) 0.0430(6) 0.0305(6) -0.0058(4) 0.0011(5) -0.0132(6)  
C1 0.0281(7) 0.0195(6) 0.0330(7) 0.0015(5) -0.0038(6) -0.0002(5)  
C3 0.0262(7) 0.0250(7) 0.0325(7) 0.0032(6) 0.0022(6) -0.0012(6)  
O2 0.0593(9) 0.0562(8) 0.0319(6) 0.0092(6) 0.0019(6) -0.0044(7)  
C5 0.0833(17) 0.0782(14) 0.0275(9) 0.0073(9) -0.0005(9) 0.0111(14)  
C6 0.0591(12) 0.0450(10) 0.0316(8) -0.0056(7) -0.0023(8) -0.0069(9)  
O4 0.0435(8) 0.0570(8) 0.0430(7) -0.0002(6) -0.0051(6) -0.0242(7)  
C7 0.0199(6) 0.0199(5) 0.0275(6) 0.0005(5) -0.0005(6) 0.0006(5)  
O3 0.0470(8) 0.0825(11) 0.0381(7) 0.0015(7) -0.0084(6) -0.0213(8)  
C2 0.0187(6) 0.0199(5) 0.0294(7) 0.0005(5) -0.0006(6) 0.0003(5)  
O5 0.0185(5) 0.0220(5) 0.0630(7) 0.0038(5) 0.0009(5) 0.0016(4)  
N1 0.0196(6) 0.0207(6) 0.0481(8) 0.0020(5) -0.0001(5) 0.0001(4)  
  
_geom_special_details  
;  
 All esds (except the esd in the dihedral angle between two l.s. planes)  
 are estimated using the full covariance matrix.  The cell esds are taken  
 into account individually in the estimation of esds in distances, angles  
 and torsion angles; correlations between esds in cell parameters are only  
 used when they are defined by crystal symmetry.  An approximate (isotropic)  
 treatment of cell esds is used for estimating esds involving l.s. planes.  
;  
  
loop_  
 _geom_bond_atom_site_label_1  
 _geom_bond_atom_site_label_2  
 _geom_bond_distance  
 _geom_bond_site_symmetry_2  
 _geom_bond_publ_flag  
           
 
75
C4 O3 1.193(2) . ?  
C4 O2 1.327(2) . ?  
C4 C3 1.499(2) . ?  
O1 C1 1.322(2) . ?  
O1 C6 1.445(2) . ?  
C1 O4 1.199(2) . ?  
C1 C2 1.515(2) . ?  
C3 C2 1.524(2) . ?  
O2 C5 1.446(3) . ?  
C7 O5 1.2344(16) . ?  
C7 N1 1.3079(18) . ?  
C7 C2 1.5281(17) . ?  
  
loop_  
 _geom_angle_atom_site_label_1  
 _geom_angle_atom_site_label_2  
 _geom_angle_atom_site_label_3  
 _geom_angle  
 _geom_angle_site_symmetry_1  
 _geom_angle_site_symmetry_3  
 _geom_angle_publ_flag  
O3 C4 O2 123.42(16) . . ?  
O3 C4 C3 125.63(15) . . ?  
O2 C4 C3 110.95(15) . . ?  
C1 O1 C6 116.90(14) . . ?  
O4 C1 O1 124.17(14) . . ?  
O4 C1 C2 125.06(14) . . ?  
O1 C1 C2 110.77(12) . . ?  
C4 C3 C2 111.45(13) . . ?  
C4 O2 C5 116.30(18) . . ?  
O5 C7 N1 123.51(11) . . ?  
O5 C7 C2 118.57(12) . . ?  
N1 C7 C2 117.90(12) . . ?  
C1 C2 C3 110.14(12) . . ?  
C1 C2 C7 106.87(11) . . ?  
C3 C2 C7 111.70(12) . . ?  
  
_diffrn_measured_fraction_theta_max    0.992  
_diffrn_reflns_theta_full              28.36  
_diffrn_measured_fraction_theta_full   0.992  
_refine_diff_density_max    0.372  
_refine_diff_density_min   -0.159  
_refine_diff_density_rms    0.049  
 
 
           
 
76
Appendix B. Crystal structure data (CIF file) for compound 63. 
 
data_p21n  
  
_audit_creation_method            SHELXL-97  
_chemical_name_systematic  
;  
 ?  
;  
_chemical_name_common             ?  
_chemical_melting_point           ?  
_chemical_formula_moiety          ?  
_chemical_formula_sum  
 'C22 H26 Cl O7 P'  
_chemical_formula_weight          468.85  
  
loop_  
 _atom_type_symbol  
 _atom_type_description  
 _atom_type_scat_dispersion_real  
 _atom_type_scat_dispersion_imag  
 _atom_type_scat_source  
 'C'  'C'   0.0033   0.0016  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'H'  'H'   0.0000   0.0000  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'O'  'O'   0.0106   0.0060  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'P'  'P'   0.1023   0.0942  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
 'Cl'  'Cl'   0.1484   0.1585  
 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'  
  
_symmetry_cell_setting            ?  
           
 
77
_symmetry_space_group_name_H-M    ?  
  
loop_  
 _symmetry_equiv_pos_as_xyz  
 'x, y, z'  
 '-x+1/2, y+1/2, -z+1/2'  
 '-x, -y, -z'  
 'x-1/2, -y-1/2, z-1/2'  
  
_cell_length_a                    8.9250(10)  
_cell_length_b                    17.926(2)  
_cell_length_c                    14.692(2)  
_cell_angle_alpha                 90.000(2)  
_cell_angle_beta                  100.157(2)  
_cell_angle_gamma                 90.000(2)  
_cell_volume                      2313.7(5)  
_cell_formula_units_Z             4  
_cell_measurement_temperature     193(2)  
_cell_measurement_reflns_used     ?  
_cell_measurement_theta_min       ?  
_cell_measurement_theta_max       ?  
  
_exptl_crystal_description        ?  
_exptl_crystal_colour             ?  
_exptl_crystal_size_max           ?  
_exptl_crystal_size_mid           ?  
_exptl_crystal_size_min           ?  
_exptl_crystal_density_meas       ?  
_exptl_crystal_density_diffrn     1.346  
_exptl_crystal_density_method     'not measured'  
_exptl_crystal_F_000              984  
_exptl_absorpt_coefficient_mu     0.274  
_exptl_absorpt_correction_type    ?  
_exptl_absorpt_correction_T_min   ?  
_exptl_absorpt_correction_T_max   ?  
_exptl_absorpt_process_details    ?  
  
_exptl_special_details  
;  
 ?  
;  
  
_diffrn_ambient_temperature       193(2)  
_diffrn_radiation_wavelength      0.71073  
_diffrn_radiation_type            MoK\a  
_diffrn_radiation_source          'fine-focus sealed tube'  
           
 
78
_diffrn_radiation_monochromator   graphite  
_diffrn_measurement_device_type   ?  
_diffrn_measurement_method        ?  
_diffrn_detector_area_resol_mean  ?  
_diffrn_standards_number          ?  
_diffrn_standards_interval_count  ?  
_diffrn_standards_interval_time   ?  
_diffrn_standards_decay_%         ?  
_diffrn_reflns_number             23442  
_diffrn_reflns_av_R_equivalents   0.0844  
_diffrn_reflns_av_sigmaI/netI     0.0826  
_diffrn_reflns_limit_h_min        -11  
_diffrn_reflns_limit_h_max        11  
_diffrn_reflns_limit_k_min        -23  
_diffrn_reflns_limit_k_max        23  
_diffrn_reflns_limit_l_min        -19  
_diffrn_reflns_limit_l_max        19  
_diffrn_reflns_theta_min          2.27  
_diffrn_reflns_theta_max          28.35  
_reflns_number_total              5738  
_reflns_number_gt                 3213  
_reflns_threshold_expression      >2sigma(I)  
  
_computing_data_collection        ?  
_computing_cell_refinement        ?  
_computing_data_reduction         ?  
_computing_structure_solution     'SHELXS-97 (Sheldrick, 1990)'  
_computing_structure_refinement   'SHELXL-97 (Sheldrick, 1997)'  
_computing_molecular_graphics     ?  
_computing_publication_material   ?  
  
_refine_special_details  
;  
 Refinement of F^2^ against ALL reflections.  The weighted R-factor wR and  
 goodness of fit S are based on F^2^, conventional R-factors R are based  
 on F, with F set to zero for negative F^2^. The threshold expression of  
 F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is  
 not relevant to the choice of reflections for refinement.  R-factors based  
 on F^2^ are statistically about twice as large as those based on F, and R-  
 factors based on ALL data will be even larger.  
;  
  
_refine_ls_structure_factor_coef  Fsqd   
_refine_ls_matrix_type            full  
_refine_ls_weighting_scheme       calc   
_refine_ls_weighting_details  
           
 
79
 'calc w=1/[\s^2^(Fo^2^)+(0.0831P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'  
_atom_sites_solution_primary      direct  
_atom_sites_solution_secondary    difmap  
_atom_sites_solution_hydrogens    geom  
_refine_ls_hydrogen_treatment     mixed  
_refine_ls_extinction_method      none  
_refine_ls_extinction_coef        ?  
_refine_ls_number_reflns          5738  
_refine_ls_number_parameters      288  
_refine_ls_number_restraints      0  
_refine_ls_R_factor_all           0.1032  
_refine_ls_R_factor_gt            0.0587  
_refine_ls_wR_factor_ref          0.1575  
_refine_ls_wR_factor_gt           0.1436  
_refine_ls_goodness_of_fit_ref    0.903  
_refine_ls_restrained_S_all       0.903  
_refine_ls_shift/su_max           0.076  
_refine_ls_shift/su_mean          0.009  
  
loop_  
 _atom_site_label  
 _atom_site_type_symbol  
 _atom_site_fract_x  
 _atom_site_fract_y  
 _atom_site_fract_z  
 _atom_site_U_iso_or_equiv  
 _atom_site_adp_type  
 _atom_site_occupancy  
 _atom_site_symmetry_multiplicity  
 _atom_site_calc_flag  
 _atom_site_refinement_flags  
 _atom_site_disorder_assembly  
 _atom_site_disorder_group  
P1 P 0.65162(7) 0.08868(4) 0.25817(5) 0.03365(19) Uani 1 1 d . . .  
Cl1 Cl 0.82487(8) 0.12525(4) 0.65688(5) 0.0484(2) Uani 1 1 d . . .  
O1 O 0.4273(2) -0.02282(10) 0.27741(15) 0.0565(6) Uani 1 1 d . . .  
H1A H 0.3615 -0.0546 0.2850 0.085 Uiso 1 1 calc R . .  
O2 O 0.4744(2) 0.22340(12) 0.17898(15) 0.0519(5) Uani 1 1 d . . .  
O3 O 0.8746(2) -0.02842(11) 0.28779(13) 0.0522(5) Uani 1 1 d . . .  
H3A H 0.9348 -0.0648 0.2963 0.078 Uiso 1 1 calc R . .  
O4 O 0.5780(2) 0.11216(11) 0.04688(13) 0.0524(5) Uani 1 1 d . . .  
H4A H 0.6159 0.1522 0.0701 0.079 Uiso 1 1 calc R . .  
O5 O 0.7826(2) 0.20697(10) 0.14906(12) 0.0457(5) Uani 1 1 d . . .  
H5B H 0.8002 0.2452 0.1196 0.069 Uiso 1 1 calc R . .  
O6 O 0.7182(3) 0.13404(12) 0.44566(14) 0.0638(6) Uani 1 1 d . . .  
H6A H 0.7381 0.1468 0.5015 0.096 Uiso 1 1 calc R . .  
           
 
80
O7 O 0.8237(3) 0.31142(13) 0.02966(16) 0.0811(8) Uani 1 1 d . . .  
C1 C 0.4502(3) 0.10155(14) 0.23108(17) 0.0336(6) Uani 1 1 d . . .  
C2 C 0.3575(3) 0.04219(15) 0.24746(19) 0.0412(6) Uani 1 1 d . . .  
C3 C 0.2019(3) 0.05056(16) 0.2328(2) 0.0530(8) Uani 1 1 d . . .  
H3B H 0.1387 0.0102 0.2442 0.064 Uiso 1 1 calc R . .  
C4 C 0.1383(3) 0.11798(17) 0.2014(2) 0.0538(8) Uani 1 1 d . . .  
H4B H 0.0308 0.1235 0.1917 0.065 Uiso 1 1 calc R . .  
C5 C 0.2254(3) 0.17673(16) 0.1841(2) 0.0452(7) Uani 1 1 d . . .  
H5A H 0.1792 0.2227 0.1625 0.054 Uiso 1 1 calc R . .  
C6 C 0.3814(3) 0.16895(14) 0.19835(18) 0.0366(6) Uani 1 1 d . . .  
C7 C 0.7235(3) 0.04039(14) 0.17002(17) 0.0350(6) Uani 1 1 d . . .  
C8 C 0.8257(3) -0.01864(14) 0.1955(2) 0.0408(6) Uani 1 1 d . . .  
C9 C 0.8724(4) -0.06228(17) 0.1298(2) 0.0564(8) Uani 1 1 d . . .  
H9A H 0.9419 -0.1020 0.1474 0.068 Uiso 1 1 calc R . .  
C10 C 0.8187(4) -0.0484(2) 0.0384(2) 0.0697(10) Uani 1 1 d . . .  
H10A H 0.8494 -0.0801 -0.0069 0.084 Uiso 1 1 calc R . .  
C11 C 0.7212(4) 0.01013(19) 0.0097(2) 0.0590(9) Uani 1 1 d . . .  
H11A H 0.6870 0.0195 -0.0542 0.071 Uiso 1 1 calc R . .  
C12 C 0.6750(3) 0.05442(15) 0.07568(19) 0.0427(7) Uani 1 1 d . . .  
C13 C 0.7529(3) 0.17063(14) 0.29833(17) 0.0372(6) Uani 1 1 d . . .  
C14 C 0.8077(3) 0.22225(14) 0.24043(18) 0.0389(6) Uani 1 1 d . . .  
C15 C 0.8841(3) 0.28535(16) 0.2765(2) 0.0519(8) Uani 1 1 d . . .  
H15A H 0.9213 0.3202 0.2371 0.062 Uiso 1 1 calc R . .  
C16 C 0.9059(4) 0.29722(18) 0.3701(2) 0.0621(9) Uani 1 1 d . . .  
H16A H 0.9584 0.3408 0.3949 0.075 Uiso 1 1 calc R . .  
C17 C 0.8537(4) 0.24782(19) 0.4291(2) 0.0580(8) Uani 1 1 d . . .  
H17A H 0.8704 0.2572 0.4938 0.070 Uiso 1 1 calc R . .  
C18 C 0.7772(3) 0.18478(17) 0.39356(19) 0.0460(7) Uani 1 1 d . . .  
C19 C 0.8840(6) 0.2144(3) -0.0659(3) 0.123(2) Uani 1 1 d . . .  
H19A H 0.8843 0.2013 -0.1306 0.185 Uiso 1 1 calc R . .  
H19B H 0.8186 0.1796 -0.0395 0.185 Uiso 1 1 calc R . .  
H19C H 0.9880 0.2116 -0.0308 0.185 Uiso 1 1 calc R . .  
C20 C 0.8277(6) 0.2881(3) -0.0612(3) 0.1070(16) Uani 1 1 d . . .  
H20A H 0.8928 0.3228 -0.0893 0.128 Uiso 1 1 calc R . .  
 
H20B H 0.7236 0.2908 -0.0979 0.128 Uiso 1 1 calc R . .  
C21 C 0.7751(12) 0.3857(3) 0.0364(4) 0.207(5) Uani 1 1 d . . .  
H21A H 0.7296 0.3834 0.0931 0.248 Uiso 1 1 calc R . .  
H21B H 0.8734 0.4117 0.0558 0.248 Uiso 1 1 calc R . .  
C22 C 0.7079(16) 0.4288(4) -0.0020(5) 0.321(8) Uani 1 1 d . . .  
H22A H 0.7102 0.4736 0.0364 0.481 Uiso 1 1 calc R . .  
H22B H 0.6026 0.4115 -0.0197 0.481 Uiso 1 1 calc R . .  
H22C H 0.7495 0.4405 -0.0578 0.481 Uiso 1 1 calc R . .  
H1 H 0.672(3) 0.0434(13) 0.3259(17) 0.038(7) Uiso 1 1 d . . .  
H2A H 0.434(4) 0.268(2) 0.175(3) 0.087(12) Uiso 1 1 d . . .  
  
           
 
81
loop_  
 _atom_site_aniso_label  
 _atom_site_aniso_U_11  
 _atom_site_aniso_U_22  
 _atom_site_aniso_U_33  
 _atom_site_aniso_U_23  
 _atom_site_aniso_U_13  
 _atom_site_aniso_U_12  
P1 0.0326(4) 0.0367(4) 0.0305(4) 0.0024(3) 0.0023(3) 0.0011(3)  
Cl1 0.0556(5) 0.0414(4) 0.0453(4) 0.0057(3) 0.0012(3) -0.0025(3)  
O1 0.0419(12) 0.0415(11) 0.0836(16) 0.0181(10) 0.0039(11) -0.0007(9)  
O2 0.0418(12) 0.0408(11) 0.0712(15) 0.0148(10) 0.0051(10) 0.0027(10)  
O3 0.0505(12) 0.0556(12) 0.0494(13) 0.0102(10) 0.0055(10) 0.0186(10)  
O4 0.0531(12) 0.0578(12) 0.0397(11) 0.0020(9) -0.0097(9) 0.0029(10)  
O5 0.0554(12) 0.0489(11) 0.0328(10) 0.0009(8) 0.0076(9) -0.0081(9)  
O6 0.0867(17) 0.0733(15) 0.0305(11) -0.0037(10) 0.0079(11) -0.0179(13)  
O7 0.143(2) 0.0575(14) 0.0476(14) 0.0038(11) 0.0293(15) -0.0024(15)  
C1 0.0291(13) 0.0396(14) 0.0313(13) -0.0001(11) 0.0034(10) -0.0001(11)  
C2 0.0372(15) 0.0430(15) 0.0425(16) 0.0030(12) 0.0049(12) 0.0039(12)  
C3 0.0363(16) 0.0519(18) 0.070(2) 0.0124(16) 0.0070(15) -0.0065(14)  
C4 0.0287(15) 0.065(2) 0.066(2) 0.0069(16) 0.0040(14) 0.0033(14)  
C5 0.0382(16) 0.0448(16) 0.0507(17) 0.0026(13) 0.0023(13) 0.0085(13)  
C6 0.0367(15) 0.0371(14) 0.0361(15) -0.0014(11) 0.0061(12) 0.0014(12)  
C7 0.0323(14) 0.0380(14) 0.0339(14) -0.0025(11) 0.0036(11) -0.0038(11)  
C8 0.0360(15) 0.0384(14) 0.0475(17) 0.0005(12) 0.0059(13) -0.0038(12)  
C9 0.057(2) 0.0498(18) 0.062(2) -0.0105(16) 0.0090(16) 0.0122(15)  
C10 0.080(2) 0.068(2) 0.062(2) -0.0288(19) 0.0163(19) 0.0061(19)  
C11 0.068(2) 0.070(2) 0.0361(17) -0.0135(15) 0.0017(15) -0.0012(17)  
C12 0.0402(16) 0.0461(16) 0.0398(16) -0.0035(13) 0.0015(12) -0.0048(13)  
C13 0.0336(14) 0.0424(15) 0.0336(14) -0.0030(11) 0.0002(11) 0.0014(11)  
C14 0.0337(14) 0.0454(15) 0.0361(15) -0.0017(12) 0.0019(12) 0.0021(12)  
C15 0.0575(19) 0.0466(17) 0.0491(18) -0.0012(14) 0.0022(15) -0.0121(14)  
C16 0.066(2) 0.0556(19) 0.057(2) -0.0094(16) -0.0087(17) -0.0156(17)  
C17 0.066(2) 0.066(2) 0.0353(17) -0.0080(15) -0.0083(15) -0.0064(17)  
C18 0.0445(17) 0.0567(18) 0.0346(16) -0.0012(13) 0.0006(13) -0.0006(14)  
C19 0.190(6) 0.109(4) 0.087(3) 0.007(3) 0.069(4) 0.058(4)  
C20 0.166(5) 0.103(4) 0.059(3) -0.002(2) 0.039(3) 0.012(3)  
C21 0.435(14) 0.100(4) 0.089(4) 0.018(3) 0.058(6) 0.115(7)  
C22 0.74(2) 0.151(7) 0.068(4) 0.010(4) 0.050(8) 0.196(11)  
  
_geom_special_details  
;  
 All esds (except the esd in the dihedral angle between two l.s. planes)  
 are estimated using the full covariance matrix.  The cell esds are taken  
 into account individually in the estimation of esds in distances, angles  
 and torsion angles; correlations between esds in cell parameters are only  
           
 
82
 used when they are defined by crystal symmetry.  An approximate (isotropic)  
 treatment of cell esds is used for estimating esds involving l.s. planes.  
;  
  
loop_  
 _geom_bond_atom_site_label_1  
 _geom_bond_atom_site_label_2  
 _geom_bond_distance  
 _geom_bond_site_symmetry_2  
 _geom_bond_publ_flag  
P1 C13 1.770(3) . ?  
P1 C7 1.770(3) . ?  
P1 C1 1.786(2) . ?  
O1 C2 1.358(3) . ?  
O2 C6 1.344(3) . ?  
O3 C8 1.360(3) . ?  
O4 C12 1.368(3) . ?  
O5 C14 1.349(3) . ?  
O6 C18 1.354(3) . ?  
O7 C21 1.409(6) . ?  
O7 C20 1.405(4) . ?  
C1 C2 1.395(4) . ?  
C1 C6 1.401(3) . ?  
C2 C3 1.376(4) . ?  
C3 C4 1.379(4) . ?  
C4 C5 1.359(4) . ?  
C5 C6 1.379(4) . ?  
C7 C8 1.404(4) . ?  
C7 C12 1.400(4) . ?  
C8 C9 1.364(4) . ?  
C9 C10 1.367(5) . ?  
C10 C11 1.381(5) . ?  
C11 C12 1.371(4) . ?  
C13 C14 1.402(4) . ?  
C13 C18 1.401(4) . ?  
C14 C15 1.378(4) . ?  
C15 C16 1.371(4) . ?  
C16 C17 1.377(4) . ?  
C17 C18 1.375(4) . ?  
C19 C20 1.420(5) . ?  
C21 C22 1.075(8) . ?  
  
loop_  
 _geom_angle_atom_site_label_1  
 _geom_angle_atom_site_label_2  
 _geom_angle_atom_site_label_3  
           
 
83
 _geom_angle  
 _geom_angle_site_symmetry_1  
 _geom_angle_site_symmetry_3  
 _geom_angle_publ_flag  
C13 P1 C7 114.84(12) . . ?  
C13 P1 C1 113.68(12) . . ?  
C7 P1 C1 112.37(12) . . ?  
C21 O7 C20 114.0(3) . . ?  
C2 C1 C6 118.7(2) . . ?  
C2 C1 P1 117.87(19) . . ?  
C6 C1 P1 123.39(19) . . ?  
O1 C2 C3 122.5(2) . . ?  
O1 C2 C1 117.3(2) . . ?  
C3 C2 C1 120.2(2) . . ?  
C2 C3 C4 119.5(3) . . ?  
C5 C4 C3 121.8(3) . . ?  
C4 C5 C6 119.3(3) . . ?  
O2 C6 C5 122.7(2) . . ?  
O2 C6 C1 116.7(2) . . ?  
C5 C6 C1 120.6(2) . . ?  
C8 C7 C12 118.2(2) . . ?  
C8 C7 P1 118.4(2) . . ?  
C12 C7 P1 123.2(2) . . ?  
O3 C8 C9 123.2(3) . . ?  
O3 C8 C7 116.2(2) . . ?  
C9 C8 C7 120.6(3) . . ?  
C10 C9 C8 119.6(3) . . ?  
C9 C10 C11 122.0(3) . . ?  
C12 C11 C10 118.5(3) . . ?  
O4 C12 C11 118.2(3) . . ?  
O4 C12 C7 120.7(2) . . ?  
C11 C12 C7 121.1(3) . . ?  
C14 C13 C18 118.5(2) . . ?  
C14 C13 P1 123.9(2) . . ?  
C18 C13 P1 117.6(2) . . ?  
O5 C14 C15 122.2(2) . . ?  
O5 C14 C13 117.1(2) . . ?  
C15 C14 C13 120.7(3) . . ?  
C16 C15 C14 119.1(3) . . ?  
C15 C16 C17 121.9(3) . . ?  
C18 C17 C16 119.3(3) . . ?  
O6 C18 C17 123.6(3) . . ?  
O6 C18 C13 115.8(3) . . ?  
C17 C18 C13 120.5(3) . . ?  
O7 C20 C19 113.1(4) . . ?  
C22 C21 O7 142.4(8) . . ?  
           
 
84
  
_diffrn_measured_fraction_theta_max    0.995  
_diffrn_reflns_theta_full              28.35  
_diffrn_measured_fraction_theta_full   0.995  
_refine_diff_density_max    0.465  
_refine_diff_density_min   -0.400  
_refine_diff_density_rms    0.057