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Cascade CuH-Catalyzed Conversion of Alkynes to Enantioenriched 1,1-Disubstituted Products

preprint
submitted on 09.04.2019 and posted on 09.04.2019 by De-Wei Gao, Yang Gao, Huiling Shao, Tian-Zhang Qiao, Xin Wang, Brittany Sanchez, Jason Chen, Peng Liu, Keary Engle
Enantioenriched α-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize α-aminoboronates via CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.

Funding

NIH-5R35GM125052-02

NIH-1R35GM128779

History

Email Address of Submitting Author

keary@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0003-2767-6556

Declaration of Conflict of Interest

No conflict of interest to declare.

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