α-chloroacetone as a donor in the BINAM-L-prolinamide organocatalyzed aldol reaction:: application to the enantioselective synthesis of α,β-epoxy ketones

Recoverable (S-a)-BINAM-L-prolinamide in combination with benzoic acid catalyzed the direct aldol reaction between alpha-chloroacetone and several aldehydes in different solvents, including water. It is possible to obtain mainly one of the isomers with good regio-, diastero-, and enantioselectivity by choosing the appropriate solvent and reaction conditions. Thus, alpha-chloroacetone mainly gives the anti-aldol isomer in DMF/H2O with up to 97% ee. The crude a-chloro-p-hydroxy ketones obtained are transformed stereo specifically into the corresponding enantioenriched trans-alpha,beta-epoxy ketones derivatives with up to 97% ee through an S(N)2 displacement reaction by treatment with Et3N. (c) 2007 Elsevier Ltd. All rights reserved.