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