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.