Electroreductive Olefin-Ketone Coupling

Pengfei Hu; Byron K. Peters; Christian A. Malapit; Julien C. Vantourout; Pan Wang; Jinjun Li; Lucas Mele; Pierre Georges Echeverria; Shelley D. Minteer; Phil S. Baran

doi:10.1021/jacs.0c11214

Electroreductive Olefin-Ketone Coupling

Pengfei Hu, Byron K. Peters, Christian A. Malapit, Julien C. Vantourout, Pan Wang, Jinjun Li, Lucas Mele, Pierre Georges Echeverria, Shelley D. Minteer^*, Phil S. Baran^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).

Original language	English (US)
Pages (from-to)	20979-20986
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	142
Issue number	50
DOIs	https://doi.org/10.1021/jacs.0c11214
State	Published - Dec 16 2020

Funding

Financial support for this work was provided by NIH (GM-118176), NSF (CCI Phase 1 grant 1740656 and Phase II grant 2002158), George E. Hewitt Foundation (P.H.), and Swedish Research Council (Vetenskapsrådet, VR 2017-00362, B.K.P.). Authors are grateful to Dr. D.-H. Huang and Dr. L. Pasternack (Scripps Research) for assistance with nuclear magnetic resonance (NMR) spectroscopy, to Dr. J. Chen, B. Sanchez, and E. Sturgell (Scripps Automated Synthesis Facility) for assistance with HPLC, HRMS, and LCMS, to Dr. J. R. Gage, Dr. Y. Hsiao, and Dr. E. Zhang (Asymchem Inc.) for assistance with scale-up reaction.

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.0c11214

Cite this

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title = "Electroreductive Olefin-Ketone Coupling",

abstract = "A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).",

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T1 - Electroreductive Olefin-Ketone Coupling

AU - Hu, Pengfei

AU - Peters, Byron K.

AU - Malapit, Christian A.

AU - Vantourout, Julien C.

AU - Wang, Pan

AU - Li, Jinjun

AU - Mele, Lucas

AU - Echeverria, Pierre Georges

AU - Minteer, Shelley D.

AU - Baran, Phil S.

PY - 2020/12/16

Y1 - 2020/12/16

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AB - A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).

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Electroreductive Olefin-Ketone Coupling

Abstract

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ASJC Scopus subject areas

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