Premium
Proline‐Derived N ‐Sulfonylcarboxamides: Readily Available, Highly Enantioselective and Versatile Catalysts for Direct Aldol Reactions
Author(s) -
Berkessel Albrecht,
Koch Burkhard,
Lex Johann
Publication year - 2004
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200404126
Subject(s) - aldol reaction , chemistry , amide , enantioselective synthesis , proline , catalysis , amine gas treating , organocatalysis , substituent , organic chemistry , acetone , amino acid , combinatorial chemistry , biochemistry
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.