title: Oxyanion hole stabilization by C-H···O interaction in a transition state--a three-point interaction model for Cinchona alkaloid-catalyzed asymmetric methanolysis of meso-cyclic anhydrides.
abstract: Oxyanion holes are commonly found in many enzyme structures. They are crucial for the stabilization of high-energy oxyanion intermediates or transition states through hydrogen bonding. Typical functionalities found in enzyme oxyanion holes or chemically designed oxyanion-hole mimics are N-H and O-H groups. Through DFT calculations, we show that asymmetric methanolysis of meso-cyclic anhydrides (AMMA) catalyzed by a class of cinchona alkaloid catalysts involves an oxyanion hole consisting of purely C-H functionality. This C-H oxyanion hole is found to play a pivotal role for stabilizing the developing oxyanion, via C-H···O hydrogen bonds, in our newly proposed three-point interaction transition-state model for AMMA reactions, and is the key reason for the catalyst to adopt the gauche-open conformation in the transition state. Predicted enantioselectivities of three cinchona alkaloid catalysts, namely DHQD-PHN, DHQD-MEQ, and DHQD-CLB, based on calculations of our transition-state model, agree well with experimental findings.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Ming Wah
authors.initials: MW
authors.lastname: Wong
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D004951:Esterification; D006859:Hydrogen / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry*; D011812:Quinuclidines / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000812:Anhydrides; D002930:Cinchona Alkaloids; D011812:Quinuclidines; D002244:Carbon; D006859:Hydrogen; D010100:Oxygen