TY - JOUR
T1 - A Radical Approach to Anionic Chemistry
T2 - Synthesis of Ketones, Alcohols, and Amines
AU - Ni, Shengyang
AU - Padial, Natalia M.
AU - Kingston, Cian
AU - Vantourout, Julien C.
AU - Schmitt, Daniel C.
AU - Edwards, Jacob T.
AU - Kruszyk, Monika M.
AU - Merchant, Rohan R.
AU - Mykhailiuk, Pavel K.
AU - Sanchez, Brittany B.
AU - Yang, Shouliang
AU - Perry, Matthew A.
AU - Gallego, Gary M.
AU - Mousseau, James J.
AU - Collins, Michael R.
AU - Cherney, Robert J.
AU - Lebed, Pavlo S.
AU - Chen, Jason S.
AU - Qin, Tian
AU - Baran, Phil S.
N1 - Funding Information:
Financial support for this work was provided by NIH (GM-118176) and Pfizer. We gratefully thank the China Scholarship Council (CSC, S.N.), the Marie Skłodowska-Curie Global Fellowships (749359-EnanSET, N.M.P) within the European Union research and innovation framework programme (2014-2020), the Department of Defense (NDSEG fellowship to J.T.E.), Bristol-Myers Squibb (Graduate Fellowship to J.T.E.), Vividion (Graduate Fellowship to R.R.M.), and the Fulbright Scholar Program (P.K.M.). We would like to thank Enamine Ltd. for providing samples of several acids. We are grateful to Dr. Dee-Hua Huang and Dr. Laura Pasternack (Scripps Research) for assistance with NMR spectroscopy and Mr. Andrew Badwal (Pfizer) for high-throughput purification. We also thank Stephen Harwood (Scripps Research) for helpful advice and David Hill and Prof. Donna Blackmond (both Scripps Research) for assistance with the mechanistic studies.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/4/24
Y1 - 2019/4/24
N2 - Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other carboxylic derivatives (to produce ketones), imines (to produce benzylic amines), or aldehydes (to produce alcohols). The reactions are uniformly mild, operationally simple, and, in the case of ketone synthesis, broad in scope (including several applications to the simplification of synthetic problems and to parallel synthesis). Finally, an extensive mechanistic study of the ketone synthesis is performed to trace the elementary steps of the catalytic cycle and provide the end-user with a clear and understandable rationale for the selectivity, role of additives, and underlying driving forces involved.
AB - Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other carboxylic derivatives (to produce ketones), imines (to produce benzylic amines), or aldehydes (to produce alcohols). The reactions are uniformly mild, operationally simple, and, in the case of ketone synthesis, broad in scope (including several applications to the simplification of synthetic problems and to parallel synthesis). Finally, an extensive mechanistic study of the ketone synthesis is performed to trace the elementary steps of the catalytic cycle and provide the end-user with a clear and understandable rationale for the selectivity, role of additives, and underlying driving forces involved.
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U2 - 10.1021/jacs.9b02238
DO - 10.1021/jacs.9b02238
M3 - Article
C2 - 30943023
AN - SCOPUS:85064987381
SN - 0002-7863
VL - 141
SP - 6726
EP - 6739
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 16
ER -