Synthesis of γ-Oxo-α-amino Acids via Radical Acylation with Carboxylic Acids

Abstract

Herein we present a highly efficient, light-mediated, deoxygenative protocol to access g-oxo-a-amino acid derivatives. This radical methodology employs photoredox catalysis, in combination with triphenylphosphine, to generate acyl radicals from readily available (hetero)aromatic and vinylic carboxylic acids. This approach allows for the straightforward synthesis of g-oxo-aamino acids bearing a wide range of functional groups (e.g. Cl, CN, furan, thiophene, Bpin) in synthetically useful yields (~ 60% average yield). To further highlight the utility of the methodology, several deprotection and derivatization reactions were carried out.

Enantioselective Radical Hydroacylation of α,β-Unsaturated Carbonyl Compounds with Aldehydes by Triplet Excited Anthraquinone

“…Various acyl radical precursors have been developed, such as α-keto acids, carboxylic acids, anhydrides, acyl chlorides, acyl silanes, 4-acyl-1,4-dihydropyridines, and acyl oximes . However, beyond all that, inexpensive and readily available aldehydes are the especially attractive ones due to the highly atom-economical property .…”

Nanocellulose as Convenient Reaction Media for the FeCl3 Mediated Mechanochemical Synthesis of 3-Acylchromones

“…21 During the same time, a photoredox acylation approach for the synthesis of γ-oxo-α-amino acid derivatives has also been reported which employed photoredox catalysis in combination with triphenylphosphine to generate acyl radicals from the readily available (hetero)aromatic and vinylic carboxylic acids. 22 Nevertheless, the aforementioned methods suffer from one or other drawbacks such as the use of expensive transition metals, photocatalysts, hazardous and toxic additives or ligands, the requirement of an inert atmosphere, high temperatures, and prolonged reaction times. It is thus necessary to develop an alternative acylation strategy using cheap and nontoxic catalysts as well as biocompatible reaction media to accomplish one of the main principles of Green Chemistry.…”

Eosin-Y/Cu(OAc)2-catalyzed aerobic oxidative coupling reactions of glycine esters in the dark

“…5 A few protocols to synthesize γ-carbonyl amino acids have been documented. 6 Given their multipurpose applications, the development of greener and step economical methods to synthesize them from readily available starting materials is the need of the hour. We surmised that the oxidative coupling of glycine ester derivatives with β-keto acids would offer easy access to γ-carbonyl α-amino acid derivatives.…”