Photocatalytic Carboxylate to Sulfinamide Switching Delivers a Divergent Synthesis of Sulfonamides and Sulfonimidamides

sulfinamides, sulfonamides, and sulfonimidamides are in-demand motifs in medicinal chemistry, yet methods for the synthesis of alkyl variants that start from simple, readily available feedstocks are scarce. In addition, bespoke syntheses of each class of molecules are usually needed. In this report, we detail the synthesis of these three distinct sulfur functional groups, using readily available and structurally diverse alkyl carboxylic acids as the starting materials. The method harnesses alkyl radical generation from carboxylic acids using acridine photocatalysts and 400 nm light with subsequent radical addition to sulfinylamine reagents, delivering sulfinamide products. Using the N-alkoxy sulfinylamine reagent t-BuO-NSO as the radical trap provides common N-alkoxy sulfinamide intermediates, which can be converted in a divergent manner to either sulfonamides or sulfonimidamides, by treatment with sodium hydroxide, or an amine, respectively. The reactions are scalable, tolerate a broad range of functional groups, and can be used for the diversification of complex biologically active compounds.

Automated summary

This study presents a new method for the synthesis of sulfinamides, sulfonamides, and sulfonimidamides using readily available alkyl carboxylic acids as starting materials. The method utilizes acridine photocatalysts and light to generate alkyl radicals, which are then added to sulfinylamine reagents to obtain the desired products. The method is scalable, compatible with various functional groups, and can be used for the diversification of complex biologically active compounds.