Enantioselective Decarboxylative Acylation of α-Hydroxy Acids with Carboxylic Acids via Photoredox/Nickel Dual Catalysis.

Light-driven decarboxylative cross-coupling has emerged as a pivotal platform for constructing C(sp)-C(sp) bonds in organic synthesis and medicinal chemistry. However, using two structurally dissimilar carboxylic acids as a feedstock to form chiral α-oxygenated ketones remains a considerable challenge due to side reactions such as decarboxylative reduction and homocoupling. Herein, we report for the first time a photoredox/nickel dual-catalyzed enantioselective decarboxylative acylation of α-hydroxy acid derivatives and aliphatic carboxylic acids, enabling efficient access to enantioenriched α-oxygenated ketones. This method exhibits a broad substrate scope, good functional group tolerance, high chemoselectivity, and excellent enantioselectivity (up to 99% e.e.). The advantage of this reaction is that it eliminates the need for metal reductants and the use of precious metal photocatalysts and utilizes renewable feedstocks. The use of a coiled-tube continuous-flow photoreactor can shorten the illumination time by half and obtain results comparable to those of a batch reaction. Furthermore, preliminary mechanistic experiments support a pathway in which photocatalytic decarboxylation generates α-oxy alkyl radical species, and the Ni(I)-alkyl intermediate activates the in situ-formed mixed anhydride followed by reductive elimination to give the product in enantiomerically pure form.