title: Goldilocks Catalysts: Computational Insights into the Role of the 3,3' Substituents on the Selectivity of BINOL-Derived Phosphoric Acid Catalysts.
abstract: BINOL-derived phosphoric acids provide effective asymmetric catalysis for many organic reactions. Catalysts based on this scaffold show a large structural diversity, especially in the 3,3' substituents, and little is known about the molecular requirements for high selectivity. As a result, selection of the best catalyst for a particular transformation requires a trial and error screening process, as the size of the 3,3' substituents is not simply related to their efficacy: the right choice is neither too large nor too small. We have developed an approach to identify and quantify structural features on the catalyst that determine selectivity. We show that the application of quantitative steric parameters (a new measure, AREA(θ), and rotation barrier) to an imine hydrogenation reaction allows the identification of catalyst features necessary for efficient stereoinduction, validated by QM/MM hybrid calculations.
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Jolene P
authors.initials: JP
authors.lastname: Reid
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goodman