Stereoselectivities of histidine-catalyzed asymmetric aldol additions and contrasts with proline catalysis: a quantum mechanical analysis
Related Experiment Video
Updated: May 23, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Yu-hong Lam1, K N Houk, Ulf Scheffler
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
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.
More Related Videos
Related Concept Videos
Base-Catalyzed Aldol Addition Reaction
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
Acid-Catalyzed Aldol Addition Reaction
Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Regioselectivity of Electrophilic Additions-Peroxide Effect

