A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines
- Shengyang,Ni
-
M. Padial, Natalia1
- Kingston, Cian1
- Vantourout, Julien C.1
- Schmitt, Daniel C.2
- Edwards, Jacob T1
- Kruszyk, Monika M.1
- Merchand, Rohan R.1
- Mykhailiuk, Pavel K.1
- Sanchez, Brittany B.3
- Yang, Shouliang4
- Perry, Matthew A.2
- Gallego, Gary M.4
- Mousseau, James J.2
- Collins, Michael R.4
- Cherney, Robert J.5
- Lebed, Pavlo S.6
- Chen, Jason S.3
- Qin, Tian1
- Baran, Phil S.1
- 1. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
- 2. Pfizer Medicinal Sciences, Eastern Point Road, Groton, Connecticut 06340, United States
- 3. Automated Synthesis Facility, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
- 4. Department of Chemistry, La Jolla Laboratories, Pfizer 10770 Science Center Drive, San Diego, California 92121, United States
- 5. Research & Development, Bristol-Myers Squibb Company, Rt. 206 & Province Line Road, Princeton, New Jersey 08543, United States
- 6. ChemBioCenter, Taras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, Ukraine
Description
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.