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First Evidence of Proline Acting as a Bifunctional Catalyst in the Baylis–Hillman Reaction Between Alkyl Vinyl Ketones and Aryl Aldehydes
Author(s) -
Gruttadauria Michelangelo,
Giacalone Francesco,
Lo Meo Paolo,
Mossuto Marculescu Adriana,
Riela Serena,
Noto Renato
Publication year - 2008
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.200701112
Subject(s) - chemistry , bifunctional , catalysis , methyl vinyl ketone , organic chemistry , alkyl , amine gas treating , ketone , aryl , organocatalysis , bifunctional catalyst , medicinal chemistry , enantioselective synthesis
Abstract Proline in the presence of sodium hydrogen carbonate has been found to be an effective catalyst for the Baylis–Hillman reaction between methyl or ethyl vinyl ketone and aryl aldehydes. Screening of several amine catalysts showed that an ionizable carboxylic function directly linked to the secondary amine catalyst plays an important role in the synthesis of the desired product in good yield. The data obtained has allowed us to suggest, for the first time, that proline, sarcosine, pipecolinic acid and homoproline may act as bifunctional catalysts via a bicyclic enaminolactone species as intermediate. Quantum‐mechanical calculations (PM3/COSMO and ab initio 3‐21G/COSMO) support this mechanism and give more insight into the role of hydrogen carbonate.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)