TY - JOUR
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.
N1 - Funding Information:
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.
Publisher Copyright:
©
PY - 2020/12/16
Y1 - 2020/12/16
N2 - 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).
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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U2 - 10.1021/jacs.0c11214
DO - 10.1021/jacs.0c11214
M3 - Article
C2 - 33259715
AN - SCOPUS:85097835289
SN - 0002-7863
VL - 142
SP - 20979
EP - 20986
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 50
ER -