Carboxylic acids are a common functional group in synthetic organic and biological chemistry, and they serve as accessible sites for further modification and structural tunability. Fluorofunctionalization is a highly desired transformation due to the distinct properties provided by the introduction of fluorine or fluorine-containing groups into a molecule of interest. However, convenient methodologies to perform the aforementioned transformation employing carboxylic acids as substrates are still sought after. Therefore, we present the deoxygenation-fluorofunctionalization of diverse carboxylic acids using a phosphorous-based reagent system to access acyl fluorides, trifluoromethyl and difluoromethyl ketones in excellent yields under mild conditions. The methodology exhibits remarkable chemoselectivity, tolerating a wide range of functional groups. The pluripotency of the acyloxyphosphonium intermediate is demonstrated by showing its reactivity towards diverse nucleophiles. In addition, late-stage functionalization of active pharmaceutical ingredients is shown.

Direct access to acyl fluorides and perfluoroalkyl carbonyl compounds from carboxylic acids using a phosphine-based deoxygenative reagent system

2019 Fall National Meeting

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