title: Stereoselectivity in Asymmetric Catalysis: The Case of Ruthenium-Catalyzed Ketone Hydrogenation.
abstract: The ruthenium-catalyzed asymmetric hydrogenation of simple ketones to generate enantiopure alcohols is an important process widely used in the fine chemical, pharmaceutical, fragrance, and flavor industries. Chiral diphosphine-RuCl2-1,2-diamine complexes are effective catalysts for the reaction giving high chemo- and enantioselectivity. However, no diphosphine-RuCl2-1,2-diamine complex has yet been discovered that is universal for all kinds of ketone substrates, and the ligands must be carefully chosen for each substrate. The procedure of finding the best ligands for a specific substrate can be facilitated by using virtual screening as a complement to the traditional experimental screening of catalyst libraries. We have generated a transition state force field (TSFF) for the ruthenium-catalyzed asymmetric hydrogenation of simple ketones using an improved Q2MM method. The developed TSFF can predict the enantioselectivity for 13 catalytic systems taken from the literature, with a mean unsigned error of 2.7 kJ/mol.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Kemigården 4, SE-412 96 Göteborg, Sweden.|Pharmaceutical Development, Global Medicines Development, AstraZeneca , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Elaine
authors.initials: E
authors.lastname: Limé
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556 United States.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Lundholm
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556 United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Forbes
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556 United States.|Lab of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest
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 Molecular Biology, University of Gothenburg , Kemigården 4, SE-412 96 Göteborg, Sweden.|Pharmaceutical Development, Global Medicines Development, AstraZeneca , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Norrby