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.