3‐Carboxy‐/3‐Aminobicyclo[1.1.1]pentane‐Derived Sulfonamides and Sulfonyl Fluorides – Advanced Bifunctional Reagents for Organic Synthesis and Drug Discovery

A convenient approach to 1,3‐bifunctional sulfonyl fluorides, sulfonamides and sulfinates bearing a bicyclo[1.1.1]pentane unit attached to the sulfur atom and (protected) amino or carboxyl group is described. The method relied on photochemical decomposition of Barton [1‐hydroxypyridine‐2(1H)‐thione] esters of the corresponding carboxylic acids as the key step, followed by oxidation and cleavage of the 2‐pyridyl moiety. The title building blocks were obtained on a gram scale, and their utility was demonstrated by preparation of an isosteric analogue of classical sulfonamide anitibiotic sulfanilamide, as well as some other common chemical modifications. Synthesis of bifunctional bicyclo[1.1.1]pentane‐derived sulfonyl fluorides, sulfonamides, and sulfinates from the corresponding carboxylic acids is described, including an isosteric analogue of a classical sulfonamide antibiotic.