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Stereoselectivities of Histidine-Catalyzed Asymmetric Aldol Additions and Contrasts with Proline Catalysis: A Quantum Mechanical Analysis

Author:
Lam, Yu-hong, Houk, K. N., Scheffler, Ulf, Mahrwald, Rainer
Source:
Journal of the American Chemical Society 2012 v.134 no.14 pp. 6286-6295
ISSN:
1520-5126
Subject:
aldehydes, catalytic activity, enantiomers, histidine, hydrogen bonding, models, proline, stereochemistry
Abstract:
Quantum mechanical calculations reveal the origin of diastereo- and enantioselectivities of aldol reactions between aldehydes catalyzed by histidine, and differences between related reactions catalyzed by proline. A stereochemical model that explains both the sense and the high levels of the experimentally observed stereoselectivity is proposed. The computations suggest that both the imidazolium and the carboxylic acid functionalities of histidine are viable hydrogen-bond donors that can stabilize the cyclic aldolization transition state. The stereoselectivity is proposed to arise from minimization of gauche interactions around the forming C–C bond.
Agid:
5385042