Upgrading ketone synthesis direct from carboxylic acids and organohalides

Abstract

The ketone functional group has a unique reactivity in organic chemistry and is associated with a number of useful reactions. Catalytic methods for ketone synthesis are continually being developed. Here, we report a photoredox, nickel and phosphoranyl radical synergistic cross-electrophile coupling of commercially available chemicals, aromatic acids and aryl/alkyl bromides. This allows for concise synthesis of highly functionalized ketones directly, without the preparation of activated carbonyl intermediates or organometallic compounds, and thus complements the conventional Weinreb ketone synthesis. Use of the appropriate photocatalyst, ligand amount and solvents can match the reaction rate required by any simple catalytic cycle. The practicality and synthetic robustness of the reaction are illustrated by the facile synthesis of complex ketones from readily available feedstock chemicals.

Decarboxylative Acylation of Carboxylic Acids: Reaction Investigation and Mechanistic Study

“…Thioesters containing heterocycles such as furan and thiophene are able to participate readily in this acylation, furnishing the desired products (3jj, 3kk). In view of our previous arylalkyl ketone synthesis routes [43][44] , the flexibility of the alkyl source is a useful addition.…”

Phosphorus Compounds as Precursors and Catalysts for Radical C−C Bond‐Forming Reactions

“…In 2020, Xie and co‐workers merged photochemical phosphine‐mediated deoxygenation of carboxylic acids with nickel catalysis to deliver a powerful method for the synthesis of aryl ketones [45] . This method uses an iridium photocatalyst to generate a phosphonium radical cation, which reacts with the carboxylate to give the acyl radical 89 (Scheme 20).…”

Nickel-Mediated Photoreductive Cross Coupling of Carboxylic Acid Derivatives for Ketone Synthesis

“…In the past few years, dual nickel-photoredox catalysis has been established as a greener alternative to palladium chemistry, permitting a plethora of transformations to form alkyl-aryl bonds, [12] ketones, [13] ethers [14] and other structural moieties under mild reaction conditions. [15] For ketone synthesis, several options exist in this context, starting from various compounds such as α-ketoacids, [16] secondary aliphatic carboxylic acids, [17] amides, [18] and aldehydes, [19] amongst others.…”

“…Xie et al used dual nickel-photoredox catalysis in combination with stoichiometric amounts of triphenyl phosphine to access ketones directly from aromatic carboxylic acids and alkyl/aryl bromides. [17] However, only aromatic carboxylic acids could be used which excludes purely aliphatic ketones from the product scope. The previously mentioned examples focus on the generation of acyl radicals and mostly employ aromatic acyl moieties with their additional resonance stabilization, which limits the accessibility of aliphatic ketones.…”