Cr-Catalyzed Regio‑, Diastereo‑, and Enantioselective Reductive Couplings of Ketones and Propargyl Halides

Enantioconvergent reductive couplings of racemic alkyl
halides
with carbonyl compounds provide efficient access to valuable chiral
alcohols, especially those bearing vicinal stereocenters. However,
limited success has been achieved due to the challenging reactivity
and stereoselectivity control. Herein, we developed the Cr-catalyzed
asymmetric reductive coupling of racemic propargylic chlorides and
ketones, affording valuable chiral tertiary alcohols bearing vicinal
stereocenters. These reactions proceed efficiently under mild conditions
in a radical–polar crossover manner with good regio-, diastereo-,
and enantioselectivity control. Preliminary mechanistic studies, including
radical trapping, nonlinear effect, and UV–vis spectroscopy,
provide insights into the radical-involved catalytic cycle. DFT calculations
suggest that the regio- and stereoselectivity are determined by the
Zimmerman–Traxler-type ketone addition transition states under
Curtin–Hammett conditions.