Photoinduced Copper-Catalyzed Enantioselective Alkylalkynylation of Alkenes via Polarity-Matched Hydrogen Atom Transfer.

Achieving precise chemo-, regio-, and stereoselective functionalization of C(sp3)-H bonds in inexpensive and readily accessible chemical feedstocks continues to pose a significant challenge in synthetic chemistry. However, while significant efforts have centered on substrates bearing hydridic C(sp3)-H bonds, enantioselective radical transformations of abundant feedstocks containing protic C(sp3)-H bonds remain underdeveloped. In this work, we report a photoinduced copper-catalyzed enantioselective three-component alkylalkynylation of alkenes with a wide range of chemical feedstocks, including acetonitrile, ketones, esters, amides, ethers, and amines. The reaction employs modified aryl iodides as hydrogen atom transfer (HAT) reagents, in which aryl radicals with tunable philicity could selectively abstract either protic or hydridic C(sp3)-H bonds based on the polarity-match effect. The resulting carbon-centered radicals then undergo sequential radical addition with alkenes, followed by copper-catalyzed asymmetric C(sp3)-C(sp) cross-coupling with terminal alkynes, furnishing various chiral alkynes with excellent chemo-, regio-, and stereoselectivities. This protocol offers a straightforward and mild method to access synthetically valuable chiral molecules directly from widely available chemical feedstocks, highlighting its efficiency and broad applicability.