Chemo- and Stereoselective Reduction of beta-Keto-alpha-oximino Nitriles by Using Baker's Yeast

Abstract

The baker's yeast mediated reduction of beta-keto-alpha-oximino nitriles 3 at 20 degrees C gave beta-hydroxy-alpha-oximino nitriles 4 in high yields with high enantiomeric purity [enantiomeric excess (ee) values >99%]. At room temperature, the same reaction afforded the product in a slightly lower yield. The beta-hydroxy-alpha-oximino nitriles 4 were obtained as single stereoisomers according to chiral GC-MS analyses and the H-1 and F-19 NMR spectra of the corresponding Mosher esters. The absolute stereochemistry of alcohol 4a was determined by hydrolysis of its oximino nitrile group followed by conversion into its corresponding alpha-hydroxy ester. The beta-hydroxy-alpha-oximino nitrile products were further submitted to oxime-and nitrile-selective transformations. This chemo- and stereoselective reduction can be used to generate important chiral building blocks.