Brønsted acid-catalyzed synthesis of sulfinamidines and sulfinimidate esters through electrophilic fluorination and substitution†

Abstract

In this work, we present an innovative Brønsted acid-catalyzed approach for the concurrent preparation of sulfinamidines and sulfinimidate esters from sulfenamides under one set of mild and metal-free conditions, employing electrophilic fluorination followed by nucleophilic substitution, achieving high yields of up to 97% after 12 hours at room temperature. This reaction method is enabled by CSA as the Brønsted acid catalyst, Selectfluor as the electrophilic fluorinating reagent, and readily available amines and alcohols as nucleophiles. The proposed mechanism involves initial fluorination of the sulfur atom, followed by nucleophilic attack. The protocol is easily scalable and compatible with various substrates. Our method allows for gram-scale preparation, and these S(iv) products can be further oxidized to S(vi) derivatives, expanding their potential applications in medicinal chemistry and beyond. Importantly, this method shows considerable potential for late-stage functionalization of drugs, demonstrating its promise in new drug discovery and development.