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Advances towards Highly Active and Stereoselective Simple and Cheap Proline‐Based Organocatalysts
Author(s) -
Giacalone Francesco,
Gruttadauria Michelangelo,
Agrigento Paola,
Lo Meo Paolo,
Noto Renato
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000913
Subject(s) - chemistry , aldol reaction , cyclohexanone , organocatalysis , enamine , cyclopentanone , catalysis , acylation , proline , stereoselectivity , organic chemistry , combinatorial chemistry , enantioselective synthesis , amino acid , biochemistry
Ten 4‐acyloxy‐ L ‐prolines were screened as catalysts at loadings of 2–0.1 mol‐% for the direct asymmetric aldol reaction in water by using variable amounts of water. Among them, a new catalyst, the L ‐proline carrying a trans ‐4‐(2,2‐diphenylacetoxy) group, and a catalyst previously synthesized by us, the L ‐proline carrying a trans ‐4‐(4‐phenylbutanoyloxy) group, were found to be excellent catalysts for the aldol reaction between cyclohexanone or cyclopentanone and substituted benzaldehydes when employed in only 1 and 0.5 mol‐%,respectively, at room temperature without additives. For such catalysts, high turnover numbers were obtained, which are among the highest values obtained for enamine organocatalysis. Finally, these catalysts can be synthesized by direct O ‐acylation from inexpensive molecules and successfully used in scaled‐up reactions.