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 stereo centers. 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.

Automated summary

We developed a calcium-catalyzed asymmetric reductive coupling reaction, which can efficiently synthesize valuable chiral tertiary alcohols with vicinal stereocenters by reacting propargylic chlorides and ketones. These reactions proceed in a radical-polar crossover manner under mild conditions, with good regio-, diastereo-, and enantioselectivity control.