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

Abstract

Abstract Light‐driven decarboxylative cross‐coupling has emerged as a pivotal platform for constructing C(sp 3 )–C(sp 2 ) 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.