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

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.