title: Stereoselectivity in (Acyloxy)borane-Catalyzed Mukaiyama Aldol Reactions.
abstract: The origin of diastereo- and enantioselectivity in a Lewis acid-catalyzed Mukaiyama aldol reaction is investigated using a combination of dispersion corrected DFT calculations and transition state force fields (TSFF) developed using the quantum guided molecular mechanics (Q2MM) method. The reaction proceeds via a closed transition structure involving a nontraditional hydrogen bond that is 3.3 kJ/mol lower in energy than the corresponding open transition structure. The correct prediction of the diastereoselectivity of a Mukaiyama aldol reaction catalyzed by the conformationally flexible Yamamoto chiral (acyloxy) borane (CAB) requires extensive conformational sampling at the transition structure, which is achieved using a Q2MM-derived TSFF, followed by DFT calculations of the low energy conformational clusters. Finally, a conceptual model for the rationalization of the observed diastereo- and enantioselectivity of the reaction using a closed transition state model is proposed.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Lab of Computational Chemistry and Drug Design, School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.|Department of Chemistry and Molecular Biology, University of Gothenburg , Kemigården 4, SE 412 96 Göteborg, Sweden.|Pharmaceutical Technology and Development, AstraZeneca , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Norrby
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Helquist
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001880:Boranes / Q000737:chemistry* / Q000302:isolation & purification; D002384:Catalysis; D006860:Hydrogen Bonding; D058116:Lewis Acids; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D001880:Boranes; D058116:Lewis Acids; C116609:3-hydroxybutanal