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Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism

Gao, Yang and Hill, David E. and Hao, Wei and McNicholas, Brendon J. and Vantourout, Julien C. and Hadt, Ryan G. and Reisman, Sarah E. and Blackmond, Donna G. and Baran, Phil S. (2021) Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism. Journal of the American Chemical Society, 143 (25). pp. 9478-9488. ISSN 0002-7863. doi:10.1021/jacs.1c03007. https://resolver.caltech.edu/CaltechAUTHORS:20210625-220045705

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.1c03007DOIArticle
https://doi.org/10.26434/chemrxiv.14251787.v1DOIDiscussion Paper
ORCID:
AuthorORCID
Gao, Yang0000-0003-2320-2839
Hill, David E.0000-0002-7326-2509
Hao, Wei0000-0001-9493-6894
McNicholas, Brendon J.0000-0002-3654-681X
Vantourout, Julien C.0000-0002-0602-069X
Hadt, Ryan G.0000-0001-6026-1358
Reisman, Sarah E.0000-0001-8244-9300
Blackmond, Donna G.0000-0001-9829-8375
Baran, Phil S.0000-0001-9193-9053
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.
Funders:
Funding AgencyGrant Number
NIHGM-118176
NSFCHE-1740656
NSF2002158
Fujian Juhong Trade & Business Co. Ltd.UNSPECIFIED
NIH1S10OD025208
CaltechUNSPECIFIED
Dow Next Generation Educator FundUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Subject Keywords:Redox reactions, Aldehydes, Electrodes, Mixtures, Electrolysis
Issue or Number:25
DOI:10.1021/jacs.1c03007
Record Number:CaltechAUTHORS:20210625-220045705
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210625-220045705
Official Citation:Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism. Yang Gao, David E. Hill, Wei Hao, Brendon J. McNicholas, Julien C. Vantourout, Ryan G. Hadt, Sarah E. Reisman, Donna G. Blackmond, and Phil S. Baran. Journal of the American Chemical Society 2021 143 (25), 9478-9488; DOI: 10.1021/jacs.1c03007
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109585
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Jun 2021 22:24
Last Modified:14 Jul 2021 17:41

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