Proline-Derived N-Sulfonylcarboxamides: Readily Available, Highly Enantioselective and Versatile Catalysts for Direct Aldol Reactions

✍ Scribed by Albrecht Berkessel; Burkhard Koch; Johann Lex

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 224 KB
• Volume: 346
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.200404126

✦ Synopsis

Abstract

Proline catalysis of the asymmetric direct aldol reaction involves both the secondary amine function and the carboxyl group of the amino acid. N‐Sulfonylcarboxamides are known to be of similar acidity as carboxylic acids, and three N‐arylsulfonyl derivatives of L‐proline amide were synthesized as functionalized and versatile derivatives of L‐Pro. Their catalytic performance was evaluated in the direct aldol addition of acetone to 4‐nitrobenzaldehyde. Significantly improved reactivities and enantioselectivities were achieved in various solvents at low catalyst loadings (5–10 mol %) and at room temperature, with ees ranging up to 98%, whereas L‐proline itself afforded a maximum ee of 80% (in DMSO). Thus, N‐arylsulfonyl derivatives of proline amide represent a novel class of highly enantioselective catalysts for direct aldol reactions. Furthermore, the N‐arylsulfonyl substituent suggests possibilities for incorporation into larger catalyst assemblies (including immobilization) without affecting the catalytically active functional groups.