TCFH–NMI\nKetone Synthesis Inspired by Nucleophilicity\nScales

<i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-Tetramethylchloroformamidinium\nhexafluorophosphate\n(TCFH) and <i>N</i>-methylimidazole (NMI) enable the facile\nand practical reaction of carboxylic acids with amines, alcohols,\nand thiols to form amides, esters, and thioesters. To develop a mild\nsynthesis of ketones with TCFH–NMI directly from carboxylic\nacids at room temperature, the Mayr nucleophilicity scale was used\nto compare the <i>N</i> values of competent nucleophiles\nto potential carbon-centered nucleophiles, identifying pyrroles and\nindoles as successful substrates when <i>N</i> ≥\n10.