Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism
Abstract
One of the most oft-employed methods for C–C bond formation involving the coupling of vinyl-halides with aldehydes catalyzed by Ni and Cr (Nozaki–Hiyama–Kishi, NHK) has been rendered more practical using an electroreductive manifold. Although early studies pointed to the feasibility of such a process, those precedents were never applied by others due to cumbersome setups and limited scope. Here we show that a carefully optimized electroreductive procedure can enable a more sustainable approach to NHK, even in an asymmetric fashion on highly complex medicinally relevant systems. The e-NHK can even enable non-canonical substrate classes, such as redox-active esters, to participate with low loadings of Cr when conventional chemical techniques fail. A combination of detailed kinetics, cyclic voltammetry, and in situ UV–vis spectroelectrochemistry of these processes illuminates the subtle features of this mechanistically intricate process.
Additional Information
© 2021 American Chemical Society. Received: March 21, 2021; Published: June 15, 2021. Financial support for this work was provided by NIH (GM-118176), NSF (CCI Phase 1 grant 1740656 and Phase II grant 2002158), and Fujian Juhong Trade & Business Co. Ltd (Y.G.). We thank Eisai for their generous donation of compounds S24, S25, S26, S27, 53, 56, and L*. The authors are grateful to Dr. Dee-Hua Huang and Dr. Laura Pasternack (Scripps Research) for assistance with the nuclear magnetic resonance (NMR) spectroscopy and to Dr. Jason Chen, Brittany Sanchez, and Emily Sturgell (Scripps Automated Synthesis Facility) for assistance with the HPLC, HRMS, and LCMS analysis. Glovebox for anaerobic procedures provided through NIH grant 1S10OD025208. R.G.H. acknowledges financial support from Caltech and the Dow Next Generation Educator Fund. Additional support was provided by the Beckman Institute Laser Resource Center supported by the Arnold and Mabel Beckman Foundation. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms-1767398.pdf
Submitted - electrochemical-nozaki-hiyama-kishi-coupling-scope-applications-and-mechanism.pdf
Supplemental Material - ja1c03007_si_001.pdf
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Additional details
- PMCID
- PMC8720499
- Eprint ID
- 109585
- Resolver ID
- CaltechAUTHORS:20210625-220045705
- GM-118176
- NIH
- CHE-1740656
- NSF
- 2002158
- NSF
- Fujian Juhong Trade & Business Co. Ltd.
- 1S10OD025208
- NIH
- Caltech
- Dow Next Generation Educator Fund
- Arnold and Mabel Beckman Foundation
- Created
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2021-06-25Created from EPrint's datestamp field
- Updated
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2022-07-12Created from EPrint's last_modified field