Stereoselective Synthesis of Trisubstituted Alkenes via Copper Hydride-Catalyzed Alkyne Hydroalkylation
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nihms-1925492.pdf
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Accepted version
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1.22 MB
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Author(s)
Kutateladze, Dennis A
Mai, Binh Khanh
Dong, Yuyang
Zhang, Yu
Liu, Peng
Buchwald, Stephen L
Date Issued
August 4, 2023
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Stereoselective Synthesis of Trisubstituted Alkenes via Copper Hydride-Catalyzed Alkyne Hydroalkylation. Dennis A. Kutateladze, Binh Khanh Mai, Yuyang Dong, Yu Zhang, Peng Liu, and Stephen L. Buchwald. Journal of the American Chemical Society 2023 145 (32), 17557-17563.
Version
Author's final manuscript
Abstract
Alkenes are ubiquitous in organic chemistry, yet many classes of alkenes remain challenging to access by current synthetic methodology. Herein, we report a copper hydride-catalyzed approach for the synthesis of Z-configured trisubstituted alkenes with high stereo- and regioselectivity via alkyne hydroalkylation. A DTBM-dppf-supported Cu catalyst was found to be optimal, providing a substantial increase in product yield compared to reactions conducted with dppf as the ligand. DFT calculations show that the DTBM substitution leads to the acceleration of alkyne hydrocupration through combined ground and transition state effects related to preventing catalyst dimerization and enhancing catalyst–substrate dispersion interactions, respectively. Alkyne hydroalkylation was successfully demonstrated with methyl and larger alkyl tosylate electrophiles to produce a variety of (hetero)aryl-substituted alkenes in moderate to high yields with complete selectivity for the Z stereochemically configured products. In the formation of the key C–C bond, computational studies revealed a direct SN2 pathway for alkylation of the vinylcopper intermediate with in situ-formed alkyl iodides.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
10.1021/jacs.3c06479
