Decarboxylative C_sp³–N Bond Formation by Electrochemical Oxidation of Amino Acids

Abstract

Decarboxylative C sp 3 −N coupling reactions have been developed through electrochemical oxidation of amino acids. The reaction proceeds via anodic oxidative decarboxylation of carboxylic acids to form stabilized carbocations, which are trapped by azoles or amides to construct C−N bonds. This method avoids the preactivation of carboxylic acids and the use of expensive transition-metals and external chemical oxidants.

Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

“…However, they typically require the use of solvent‐quantities of the nucleophile (including water, alcohols, carboxylic acids, and nitriles), and are often limited to α‐heteroatom‐substituted, benzylic as well as tertiary acids, since the second oxidation step is favorable only when stabilized carbocations are formed as intermediates. Some of these seemingly inherent limitations have recently been overcome by intricate choice of heteroatom nucleophiles [109–111] and/or additives (e. g. Ag salts), [112] as detailed below, and this reaction type has shifted into the focus of the attention of method developers.…”

A Decarboxylative C(sp3)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

“…[10] Another decarboxylative C(sp 3 )À N formation has been developed through electro-chemical oxidation of amino acids, which expanded from the intramolecular to the intermolecular reaction (Scheme 1c). [11] However, the pre-activation of carboxylic acids is still required for the decarboxylation via a metal catalysis and/or photochemistry condition. The poor availability of starting materials is another drawback.…”

Advances in Electrochemical Decarboxylative Transformation Reactions

“…In 2019, the Wang group developed a new electrochemical decarboxylative Csp 3 −N bond formation methodology using amino acids [37] . The Csp 3 −N coupled products were obtained at constant current electrolysis of I=7 mA in an undivided cell equipped with a graphite anode and a nickel cathode (Scheme 13).…”