Copper-Catalyzed Site-Selective C(sp²)–H Alkynylation of Allenes

Abstract

Conjugated allenynes serve as prominently featured structural units in various natural products. However, the absence of an efficient and adaptable synthesis has hindered their broader application in synthetic endeavors and biological investigations. In terms of atom-and step-economy, there is an urgent need for an efficient strategy with a broader substrate scope compared to previous reports. Herein, we report a copper-catalyzed allenic C(sp 2 )−H alkynylation of an array of allenes with exceptional site selectivity. While the alkynylation of aliphatic C(sp 3 )−H bonds has been extensively studied, radical-mediated regioselective alkynylation of allenyl C(sp 2 )−H bonds via direct hydrogen atom transfer (HAT) from the C(sp 2 )−H bond of allenes remains an unresolved challenge in synthetic chemistry. This difficulty arises from inherent issues such as the addition of radical intermediates to allenes or alkynes and the regioselectivity of the HAT process. Our protocol addresses these challenges and demonstrates a broader substrate scope, tolerance toward various functional groups, including active sp 3 C−H bonds such as benzyl groups and ethers, and results in a high diversity of products.