Glyoxylic Acid versus Ethyl Glyoxylate for the Aqueous Enantioselective Synthesis of alpha- Hydroxy-gamma-Keto Acids and Esters by the N-Tosyl-(S-a)-binam-L-prolinamide-Organocatalyzed Aldol Reaction

摘要

N-Tosyl-(S-a)-binam-L-prolinamide is an efficient catalyst for the aqueous aldol reaction between ketones and glyoxylic acid, as the monohydrate or as an aqueous solution, or a 50% toluene solution of ethyl glyoxylate. These reactions led to the formation of chiral alpha-hydroxy-gamma-keto carboxylic acids and esters in high levels of diastereo-and enantioselectivities (up to 97% ee), providing mainly anti aldol products. Only cyclopentanone and cyclohexane-1,4-dione afforded an almost 1: 1 mixture of the syn/anti-diastereoisomers; however, the reaction between 4-phenylcyclohexanone and ethyl glyoxylate gave the corresponding syn, syn-product as the major diastereoisomer.