title: Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences.
abstract: The asymmetric hydrogenation of cyclic alkenes lacking coordinating functionality with a C1-symmetric bis(imino)pyridine cobalt catalyst is described and has been applied to the synthesis of important substructures found in natural products and biologically active compounds. High activities and enantioselectivities were observed with substituted benzo-fused five-, six-, and seven-membered alkenes. The stereochemical outcome was dependent on both the ring size and exo/endo disposition. Deuterium labeling experiments support rapid and reversible 2,1-insertion that is unproductive for generating alkane product but accounts for the unusual isotopic distribution in deuterated alkanes. Analysis of the stereochemical outcome of the hydrogenated products coupled with isotopic labeling, stoichiometric, and kinetic studies established 1,2-alkene insertion as both turnover limiting and enantiodetermining with no evidence for erosion of cobalt alkyl stereochemistry by competing β-hydrogen elimination processes. A stereochemical model accounting for the preferred antipodes of the alkanes is proposed and relies on the subtle influence of the achiral aryl imine substituent on the cobalt catalyst.
authors: Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
authors: Max R
authors: MR
authors: Friedfeld
authors: Department of Process & Analytical Chemistry, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors: Michael
authors: M
authors: Shevlin
authors: Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
authors: Grant W
authors: GW
authors: Margulieux
authors: Department of Process & Analytical Chemistry, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors: Louis-Charles
authors: LC
authors: Campeau
authors: Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
authors: Paul J
authors: PJ
authors: Chirik