TCFH-NMI Ketone Synthesis Inspired by Nucleophilicity Scales.

N,N,N',N'-Tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI) enable the facile and practical reaction of carboxylic acids with amines, alcohols, and thiols to form amides, esters, and thioesters. To develop a mild synthesis of ketones with TCFH-NMI directly from carboxylic acids at room temperature, the Mayr nucleophilicity scale was used to compare the N values of competent nucleophiles to potential carbon-centered nucleophiles, identifying pyrroles and indoles as successful substrates when N ≥ 10.