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Nickel-Catalyzed Site- and Stereoselective Reductive Alkylalkynylation of Alkynes

preprint
revised on 12.11.2020, 13:44 and posted on 16.11.2020, 05:43 by Yi Jiang, Jiaoting Pan, Tao Yang, Joel Jun Han Lim, Yu Zhao, Ming Joo Koh
Development of a catalytic multicomponent reaction by orthogonal activation of readily available substrates for the streamlined difunctionalization of alkynes is a compelling objective in organic chemistry. Alkyne carboalkynylation, in particular, offers a direct entry to valuable 1,3-enynes with different substitution patterns. Here, we show that the synthesis of stereodefined 1,3-enynes featuring a trisubstituted olefin is achieved by merging alkynes, alkynyl bromides and redox-active N-(acyloxy)phthalimides through nickel-catalyzed reductive alkylalkynylation. Products are generated in up to 89% yield as single regio- and E isomers. Transformations are tolerant of diverse functional groups and the resulting 1,3-enynes are amenable to further elaboration to synthetically useful building blocks. With olefin-tethered N-(acyloxy)phthalimides, a cascade radical addition/cyclization/alkynylation process can be implemented to obtain 1,5-enynes. The present study underscores the crucial role of redox-active esters as superior alkyl group donors compared to haloalkanes in reductive alkyne dicarbofunctionalizations.

Funding

Ministry of Education of Singapore Academic Research Fund Tier 1: R-143-000-B57-114

Ministry of Education of Singapore Academic Research Fund Tier 2: R-143-000-A94-112

History

Email Address of Submitting Author

chmkmj@nus.edu.sg

Institution

National University of Singapore

Country

Singapore

ORCID For Submitting Author

0000-0002-2534-4921

Declaration of Conflict of Interest

The authors declare no competing financial interests.

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