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A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction
Author(s) -
Wang Bing,
Chen Guohong,
Liu Lingyan,
Chang Weixing,
Li Jing
Publication year - 2009
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.200900427
Subject(s) - chemistry , aldol reaction , cyclohexanone , thioamide , enantioselective synthesis , cyclopentanone , organic chemistry , catalysis , acetone , alcohol , enantiomeric excess , ketone , enantiomer , organocatalysis
A new prolinethioamide compound 4 , prepared from readily available natural amino acid L ‐proline and amino alcohol L ‐valinol, has been found to be an active catalyst for the direct aldol reaction of various aldehydes with acetone, cyclohexanone or cyclopentanone at 0 °C. Using only 2 mol% loading of this organocatalyst, the reaction could give high enantioselectivity with up to 96% enantiomeric excess for the reaction of 2‐nitrobenzaldehyde with acetone. And as for the cyclohexanone, the excellent diastereoselectivity ( anti/syn : 99/1) and enantioselectivity (99% ee ) could be achieved when reacted with 3‐nitrobenzaldehyde in water in the presence of this thioamide 4 . This structurally simple catalyst is a highly efficient prolinethioamide derivative, and the terminal hydroxy group in this catalyst is a primary alcohol which is different from the previously reported prerequisite secondary or tertiary alcohol of prolinamides. Our results suggest a new strategy in the design of diversiform organic catalysts for direct asymmetric aldol reactions and related transformations.

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