Asymmetric anti-Mannich-Type Reactions Using Designed Amino Acid Catalysts

Abstract

The development of catalysts for Mannich-type reactions that afford anti-products with excellent diastereo- and enantioselectivities is a significant challenge. We have developed pyrrolidine-derived catalysts bearing an acid group at the 3-position of the pyrrolidine for direct enantioselective anti-selective Mannich-type reactions of unmodified aldehydes or ketones with N-p-methoxyphenyl-protected alpha-imino esters. Reactions of aldehydes catalyzed by (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid and reactions of ketones catalyzed by (R)-3-pyrrolidinecarboxylic acid (or (R)-beta-proline) afforded anti-Mannich products in good yields with excellent diastereo- and enantioselectivities. The results indicate that the acid group on pyrrolidine ring of the catalyst has a significant role in directing the stereoselection of the catalyzed reaction.

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