Synthesis of α‐Ketoamides via Electrochemical Decarboxylative Acylation of Isocyanides Using α‐Ketoacids as an Acyl Source

Abstract

A catalyst‐, transition metal‐, oxidant‐free strategy for the synthesis of α‐ketoamides via an electrochemical decarboxylative acylation of isocyanides at room temperature with carbon dioxide as a sole by‐product was developed in this work. This is a simple, rapid and practical strategy under mild conditions for synthesizing highly functionalized α‐ketoamides with high atom economy.

Recent Advances in the Electrochemical Functionalization of Isocyanides

“…Almost simultaneously, Gong and co‐workers also unraveled an electrochemical acylation of isocyanides 1 for synthesizing α‐keto amides 22 using platinum plates as anode and cathode (Scheme 9). [26] Aryl isocyanides with electron‐withdrawing groups such as NO 2 or halogens were successfully transformed into the corresponding products 22 i – k with better yields than with benzyl isocyanide ( 22 l ). Aryl α‐keto acids with different substituents were viable substrates in the reaction ( 22 m – o ), while compared with the report in Scheme 7, aliphatic α‐keto acid failed to participate in this transformation.…”

“…can deliver an acyl radical 27, which undergoes radical addition with isocyanide 1 to give the imidoyl radical intermediate 28. The radical-radical cross-coupling of 28 with an iodine radical can also result in the intermediate 29, which is attacked by H 2 O to form the intermediate 30, followed by tautomerization to produce the final product α-keto amide 22.Almost simultaneously, Gong and co-workers also unraveled an electrochemical acylation of isocyanides 1 for synthesizing α-keto amides 22 using platinum plates as anode and cathode (Scheme 9) [26]. Aryl isocyanides with electron-withdrawing groups such as NO 2 or halogens were successfullyScheme 6.…”

I2‐Mediated Oxidative Amidation of Aryl Methyl Ketones: Synthesis of Primary α‐Ketoamides Using Ammonium Carbamodithioate as Amine Surrogate

“…α-Ketoamides and their derivatives are widely distributed in natural products, biologically active molecules, and pharmaceuticals. [1] Examples include RARγ agonists, [2] poststatin, [3] eurystatin A and B, [4] and protease inhibitors. [5] Moreover, α-ketoamides are used as valuable intermediates in organic synthesis, especially in the construction of heterocycles.…”

“…α‐Ketoamides and their derivatives are widely distributed in natural products, biologically active molecules, and pharmaceuticals [1] . Examples include RARγ agonists, [2] poststatin, [3] eurystatin A and B, [4] and protease inhibitors [5] .…”

“…1 H spectra were recorded in CDCl 3 or DMSO-d 6 on 500/600 MHz NMR spectrometers and resonances (δ) are given in parts per million relative to tetramethylsilane. Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constants (Hz) and integration 13.…”