A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines

J Am Chem Soc. 2019 Apr 24;141(16):6726-6739. doi: 10.1021/jacs.9b02238. Epub 2019 Apr 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemical synthesis*
  • Alcohols / chemistry*
  • Amines / chemical synthesis*
  • Amines / chemistry*
  • Chemistry Techniques, Synthetic
  • Free Radicals / chemistry
  • Ketones / chemical synthesis*
  • Ketones / chemistry*

Substances

  • Alcohols
  • Amines
  • Free Radicals
  • Ketones