Molecular Oxygen‐Induced Transamidation of Unactivated Amides in Diethyl Carbonate in the Presence of a Palladium Catalyst

Abstract

Herein we disclose a palladium‐catalyzed procedure for the transamidation of structurally diverse amides with amines based on the use of molecular oxygen as palladium‐activating agent. The reaction, which is scalable and amenable for the preparation of enantioenriched compounds, is carried out in a bio‐degradable solvent often used as a fuel additive, diethyl carbonate. As a result of 10‐4 mol% of catalyst required, final products are isolated containing palladium impurities in a concentration of 0.1 ppm. Two kinetically different mechanistic pathways are proposed for this reaction on account of a number of experiments such as kinetic curves, TEM images, catalyst poisoning experiments, UPLC‐ESI‐MS identification of intermediates and EPR spectra of reaction crude.

Palladium Catalysis: Dependence of the Efficiency of C–N Bond Formation on Carboxylate Ligand and Metal Carboxylate or Carboxylic Acid Additive

“…SanMartina’s team 15 recently disclosed the Pd II -catalyzed transamidation of dimethylacetamide with benzylamine in the presence of carboxylic acids and azole ligands, notably L 1 and L 2 ( Scheme 5 a). In toluene with Pd(OAc) 2 /L 1 and 3.6 equiv of AcOH, CF 3 CO 2 H, or PhCO 2 H under oxygen atmosphere, less than 9% of N -benzylacetamide was isolated while 39% yield was obtained with t -BuCO 2 H. Lowering the amount of t -BuCO 2 H was detrimental to the efficiency, with only traces of N -benzylacetamide being produced using this procedure under RCO 2 H-free conditions.…”