Dual Photoredox and Titanium Catalyzed Regioselective Allenylation of Aldehydes via Reductive Radical-Polar Crossover

Abstract

The direct reductive coupling of carbonyl compounds with propargyl halides is a powerful and reliable tool in the synthesis of α-allenols. However, stoichiometric metal reductants, harsh reaction conditions and a variety of additional additives are required in the traditional strategies. Additionally, the reactivity and regioselectivity control remains an elusive challenge. Herein, we developed the Ti-catalyzed regioselective reductive coupling of readily available aldehydes and racemic propargyl bromides to rapidly access a wide range of α-allenols. This method proceed efficiently in a reductive radical-polar crossover manner featuring mild conditions, excellent regioselectivity control, broad substrate scope, and eco-friendliness. Preliminary mechanistic studies support the radical-involved catalytic cycle. And the DFT calculations demonstrate that the regioselectivity is determined by the Zimmerman-Traxler-type transition states.