title: Stereoselectivities of histidine-catalyzed asymmetric aldol additions and contrasts with proline catalysis: a quantum mechanical analysis.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Lam
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Ulf
authors.initials: U
authors.lastname: Scheffler
authors.forename: Rainer
authors.initials: R
authors.lastname: Mahrwald
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011392:Proline / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000447:Aldehydes; D002264:Carboxylic Acids; D007093:Imidazoles; D006639:Histidine; D002244:Carbon; C029899:imidazole; C116609:3-hydroxybutanal; D011392:Proline