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Density Functional Study of Proline‐Catalyzed Intramolecular Baylis–Hillman Reactions
Author(s) -
Duarte Filipe J. S.,
Cabrita Eurico J.,
Frenking Gernot,
Santos A. Gil
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801624
Subject(s) - intramolecular force , polarizable continuum model , chemistry , density functional theory , imidazole , catalysis , computational chemistry , baylis–hillman reaction , imine , enamine , solvent effects , stereochemistry , solvent , organic chemistry
A rationalization of stereoselectivity : The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path (see scheme).The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods at the B3LYP/6‐31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6‐31++G(d,p)//B3LYP/6‐31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co‐catalyst, water is still important in the imidazole addition step, but is not present in the Baylis–Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis–Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.