Direct organocatalytic asymmetric Mannich-type reactions in aqueous media: one-pot Mannich-allylation reactions

Abstract—The first direct organocatalytic asymmetric Mannich-type reactions in aqueous media are demonstrated herein. L-Proline-catalyzed reactions in aqueous media to provide -formyl substituted -amino acid derivatives with excellent diastereoselectivities (dr up to 19:1, syn/anti) and high enantioselectivities (ee between 72 and>99%). These conditions provided for the development of novel one-pot asymmetric syntheses of cyclic -allyl substituted -amino acid derivatives (ee up to>99%). This was accomplished by combining the proline-catalyzed Mannich-type reactions with indium promoted allylations in aqueous media. © 2003 Elsevier Science Ltd. All rights reserved. Mannich-type reactions are among the most important carboncarbon bond-forming reactions in organic chemistry. They provide for the creation of structurally diverse nitrogen containing compounds from simple and readily available starting materials.1 The increasing demand of today’s pharmaceutical industry for opti-cally active nitrogen containing molecules has driven the development of asymmetric versions of the Man-nich reaction.2 Recently, the first Lewis acid-catalyze