TCFH-NMI Ketone Synthesis Inspired by Nucleophilicity Scales
Johnson H Ho1, Grant H Miller1, Kasey K Chung1
1Department of Chemistry, Harvey Mudd College, 301 Platt Boulevard, Claremont, California 91711, United States.
Abstract:
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.
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