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Stereodivergent Alkyne Hydrofluorination Using a Simple Practical Reagent

preprint
revised on 21.03.2020 and posted on 23.03.2020 by Rui Guo, Xiaotian Qi, Hengye Xiang, Paul Geaneoates, Ruihan Wang, Peng Liu, Yiming Wang
Vinyl fluorides play an important role in drug development as they serve as bioisosteres for peptide bonds and are found in a range of biologically active molecules. The discovery of safe, general and practical procedures to prepare vinyl fluorides remains an important goal and challenge for synthetic chemistry. Here we introduce an inexpensive and easily-handled reagent and report simple, scalable, and metal-free protocols for the regioselective and stereodivergent hydrofluorination of alkynes to access both the E and Z isomers of vinyl fluorides. These conditions were suitable for a diverse collection of alkynes, including several highly-functionalized pharmaceutical derivatives. Mechanistic and DFT studies support C–F bond formation through a vinyl cation intermediate, with the (E)- and (Z)-hydrofluorination products forming under kinetic and thermodynamic control, respectively.

Funding

Computational Models for Reactivity and Selectivity in Transition Metal-Catalyzed Olefin Functionalization

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

yimingw@pitt.edu

Institution

University of Pittsburgh

Country

U.S.A.

ORCID For Submitting Author

0000-0001-6414-0908

Declaration of Conflict of Interest

The authors declare no competing interests.

Version Notes

Corrected important error in figure 1 of manuscript and updated the supporting information.

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Read the published paper

in Angewandte Chemie International Edition

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