The formation of amide bonds represents one of the most widely investigated transformations in synthetic organic chemistry. Although myriad methods and reagents exist for this transformation, research on robust and general methods for challenging substrates is relatively limited. In this presentation, the development of an amide bond formation using the readily available reagents N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI) will be described. This combination allows for access to highly reactive acyl imidazolium ions which can accomplish challenging couplings of hindered carboxylic acids with non-nucleophilic amines in high yields, and in many cases, with complete retention of adjacent stereogenic centers. The reagent delivers high reactivity similar to acid chlorides with the ease of use of modern coupling reagents like HATU or T3P.

TCFH-NMI: Direct access to n-acyl imidazoliums for challenging amide bond formations

2019 Fall National Meeting

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