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

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.

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

“…5b), possibly indicative of offcycle pathways, which is also observed in a previous report. 60 The reaction exhibits a zeroth-order dependence on the concentration of alkyl bromide (Fig. 5c), and first-order dependence on the concentration of both aryl boronic acid ( Fig.…”

Reductive radical-polar crossover: traditional electrophiles in modern radical reactions

“…In 2019, Baran and co-workers were able to facilitate a decarboxylative Nozaki-Hiyama-Kishi reaction via the RRPCO pathway (Scheme 11). 17 They used redox active esters (RAE) to generate an alkyl radical upon electron transfer from the chromium(II) species to the RAE. Following the principle of RRPCO, this radical is captured by the excess chromium(II) salt to form a Cr(III)-alkyl complex.…”

Photocatalytic carbanion generation from C–H bonds – reductant free Barbier/Grignard-type reactions

“…1f in 2 mL dry, degassed MeCN. 10,[10991][10992][10993][10994][10995][10996] This journal is © The Royal Society of Chemistry 2019 displaying the signicant inuence of steric hindrance. In terms of functional group tolerance, alkenes (3y), alkyl chlorides (3z), ethers (3aa), esters (3ab) and protected amines (3ac) are viable substrates.…”

“…9 However, these reactions produce stoichiometric amounts of metal salt waste 9c and require organohalide starting materials which oen have to be prepared. 10 In our previous report we aimed to overcome those drawbacks by using carboxylates to generate carbanionic intermediates in a photocatalytic reaction (Scheme 1b). 8g However, only aldehydes were efficient electrophiles and CO 2 was released as a stoichiometric by-product.…”