Synthesis of new chiral keto alcohols by baker's yeast

Abstract

Fourteen chiral alpha- and beta-keto alcohols 2a-2r were synthesized by the asymmetric reduction of their corresponding diketones 1a-1r via baker's yeast. In addition, ten corresponding racemic cc-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral cc-keto alcohols 2i, 2j and chiral beta-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker's yeast for the first time. There are some studies in the literature where baker's yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (H-1 and C-13), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed. (C) 2014 Elsevier Ltd. All rights reserved.