Synlett, Table of Contents Synlett 2021; 32(07): 718-722DOI: 10.1055/a-1343-5203 letter Copper and N-Heterocyclic Carbene-Catalyzed Oxidative Amidation of Aldehydes with Amines Ashmita Singh , Anudeep Kumar Narula∗ Recommend Article Abstract All articles of this category Abstract A one-pot two-step oxidative process has been developed for the tert-butyl hydroperoxide mediated transformation of aldehydes and amines into amides catalyzed by copper(I) iodide and an N-heterocyclic carbene. The process is additive-free and does not require the amine to be transformed into its hydrochloride salts. The method is simple and practicable, has a broad substrate scope, and uses economical, feasible, and abundant reagents. Keywords KeywordsN-heterocyclic carbenes - copper catalysis - organocatalysis - aldehydes - amines - amides Full Text References References and Notes 1a Cupido T, Tulla-Puche J, Spengler J, Albericio F. Curr. Opin. Drug Discovery Dev. 2007; 10: 768 1b Bode JW. Curr. Opin. 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ChemistrySelect 2020; 5: 9417 27 Amides 3a–y; General Procedure An oven-dried Schlenk tube was charged with a solution of NHC precursor 1a (10 mol%) and CuI (10 mol%) in CH3CN (3 mL) under N2. NaH (10 mol%) was added, and the resulting mixture was stirred vigorously for about 20–30 min and then the appropriate aldehyde (2.5mmol) and amine (2.5mmol) were added to the flask together with TBHP (3 equiv). The mixture was refluxed for 6 h in an oil bath then cooled to r.t., filtered through a Celite pad, and washed with H2O. The organic portion was extracted with EtOAc, dried (Na2SO4), and purified by column chromatography (silica gel, EtOAc–hexane). 2,6-Difluoro-N-[2-(2-thienyl)ethyl]benzamide (4x) White solid; yield: 521 mg (78%); mp 152–153 °C. 1H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 1 H), 7.15 (dt, J = 5.1, 1.2 Hz, 1 H), 6.96–6.83 (m, 4 H), 6.19 (br s, 1 H), 3.71 (q, J = 6.3 Hz, 2 H), 3.14 (t, J = 6.7 Hz, 2 H). 13C NMR (101 MHz, CDCl3): δ = 161.32, 160.55, 141.04, 131.65, 127.22, 125.75, 124.20, 114.36, 111.95, 41.51, 29.85. LC-MS: m/z [M + H]+ calcd for C13H12F2NOS: 268.0512; found: 268.0509. Supplementary Material Supplementary Material Supporting Information
