Highly Enantiomerically Enriched Secondary Alcohols via Epoxide Hydrogenolysis

In this article, we report the development of ruthenium-catalyzed
hydrogenolysis of epoxides to selectively give the branched (Markovnikov)
alcohol products. In contrast to previously reported catalysts, the
use of Milstein’s PNN-pincer-ruthenium complex at room temperature
allows the conversion of enantiomerically enriched epoxides to secondary
alcohols without racemization of the product. The catalyst is effective
for a range of aryl epoxides, alkyl epoxides, and glycidyl ethers
and is the first homogeneous system to selectively promote hydrogenolysis
of glycidol to 1,2-propanediol, without loss of enantiomeric purity.
A detailed mechanistic study was conducted, including experimental
observations of catalyst speciation under catalytically relevant conditions,
comprehensive kinetic characterization of the catalytic reaction,
and computational analysis via density functional theory. Heterolytic
hydrogen cleavage is mediated by the ruthenium center and exogenous
alkoxide base. Epoxide ring opening occurs through an opposite-side
attack of the ruthenium hydride on the less-hindered epoxide carbon,
giving the branched alcohol product selectively.