Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences

• DOI: 10.1021/jacs.5b10148
• Publication Date: 2016-02-08T18:08:48Z
• Authors: Max R. Friedfeld; Michael Shevlin; Grant W. Margulieux; Louis-Charles Cam...; Paul J. Chirik
• Keywords: Alkene; Imine; Isotopic labeling; Alkane; Kinetic isotope effect; Asymmetric hydrogenation

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 important substructures found in natural products biologically active compounds. High activities enantioselectivities were observed substituted benzo-fused five-, six-, seven-membered alkenes. stereochemical outcome was dependent on both ring size exo/endo disposition. Deuterium labeling experiments support rapid reversible 2,1-insertion that unproductive for generating alkane product but accounts unusual isotopic distribution deuterated alkanes. Analysis hydrogenated coupled labeling, stoichiometric, kinetic studies established 1,2-alkene insertion as turnover limiting enantiodetermining no evidence erosion alkyl stereochemistry by competing β-hydrogen elimination processes. A model accounting preferred antipodes alkanes proposed relies subtle influence achiral aryl imine substituent catalyst.