TY - JOUR
T1 - Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes
T2 - Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences
AU - Friedfeld, Max R.
AU - Shevlin, Michael
AU - Margulieux, Grant W.
AU - Campeau, Louis Charles
AU - Chirik, Paul J.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/3/16
Y1 - 2016/3/16
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.5b10148
DO - 10.1021/jacs.5b10148
M3 - Article
C2 - 26854359
AN - SCOPUS:84962493187
SN - 0002-7863
VL - 138
SP - 3314
EP - 3324
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 10
ER -