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Abstract The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data‐guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity. 

Diverse amines and amino acids are now readily accessed from carboxylic acids, aldehydes, and amine precursors in a direct decarboxylative reaction enabled by a homogeneous triple catalytic system based on acridine photocatalysis. 

The reactivity of the sulfonyl group varies dramatically from nucleophilic sulfinates through chemically robust sulfones to electrophilic sulfonyl halides—a feature that has been used extensively in medicinal chemistry, synthesis, and materials science, especially as bioisosteric replacements and structural analogs of carboxylic acids and other carbonyls. Despite the great synthetic potential of the carboxylic to sulfonyl functional group interconversions, a method that can convert carboxylic acids directly to sulfones, sulfinates and sulfonyl halides has remained out of reach. We report herein the development of a photocatalytic system that for the first time enables direct decarboxylative conversion of carboxylic acids to sulfones and sulfinates, as well as sulfonyl chlorides and fluorides in one step and in a multicomponent fashion. A mechanistic study prompted by the development of the new method revealed the key structural features of the acridine photocatalysts that facilitate the decarboxylative transformations and provided an informative and predictive multivariate linear regression model that quantitatively relates the structural features with the photocatalytic activity.