Copper(II) 2-Quinoxalinol Salen Type Ligands as Catalysts for C-H Oxidation Reactions

Abstract

C-H oxidation is a powerful tool that has changed the face of synthetic organic chemistry over the last several years. Here, we explore the oxidation of alkynes to α,β-acetylenic carbonyls using only 1 mol % of an inexpensive Cu(II) 2-quinoxalinol salen catalyst with tert-butyl hydroperoxide (TBHP) as the oxidant in 4 hours. These reactions proceed under mild conditions (70 °C) with excellent selectivity, producing yields as high as 78 %. The optimized conditions were used with a variety of alkyne substrates to prepare the desired α,β-acetylenic ketones. Further, we report the ability to do these reactions in aqueous systems using a sulfonated version of the 2-quinoxalinol salen with good yields, thus reducing the need for volatile organic solvents and promoting “green chemistry.” Next, we investigate the use of salen type ligand supports for copper in C-H oxidation catalysis. The oxidation of allylic, propargylic, and benzylic C-H bonds is explored. A series of different ligands were tested in an effort to optimize these C-H oxidations. Derivatives of salen were prepared by altering the aldehyde and diamine starting materials. Upon investigation, the Cu(II) 2-quinoxalinol complex produced the best overall yields. This catalyst can be easily prepared in 5 synthetic steps from abundant starting materials. Finally, oxidative Mannich reactions can be catalyzed using the Cu(II) 2-quinoxalinol salen catalyst and tert-butyl hydroperoxide as the oxidant. Coupling between tertiary amines and carbon-based nucleophiles was found to be highly efficient utilizing this method. Under mild conditions, a range of both cyclic and open chain tertiary amines were investigated as substrates, resulting in yields up to 98 %. A radical reaction mechanism was proposed proceeding through a single electron transfer as the rate determining step. This method provides one alternative to more expensive and/or toxic catalysts.