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

Abstract

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.

Cr-Catalyzed Asymmetric Cross Aza-Pinacol Couplings for β-Amino Alcohol Synthesis

“…According to these mechanistic studies as well as previous reports, ,, a mechanistic catalytic cycle is proposed in Figure e. The reaction was initiated by inner-sphere single electron transfer from Cr II / L1 to phenylsulfonimide 2 , generating an α-amino radical intermediate A .…”

Visible-Light-Induced Stoichiometric Coupling of Alkylarenes and Trifluoromethyl Ketones

“…Based on the above mechanistic investigations and literature precedents, 7,8,15 the possible mechanism for this visible-light catalyzed benzylation is outlined in Scheme 4. Irradiation of the Ir III complex initiates the reaction, which generates a longlived triple excited *Ir III complex (τ = 557 ns).…”

“…6 Consequently, numerous efforts have been directed toward the development of powerful strategies for synthesizing trifluoromethyl alcohols through transition-metal and Lewis catalysis in the past few decades (Scheme 1b). 7 These reports are still restricted by high loading metal catalysts, strong bases, and high temperature. In 2019, Barker and co-workers 8 reported the nucleophilic addition of benzylboronic acid pinacol ester to trifluoromethyl ketones, constructing benzyl-substituted trifluoromethyl alcohols in moderate to good yields (Scheme 1c).…”