Titanium-Promoted Acylation of Sulfonamides to N-Acylsulfonamide PPAR Antagonists

The direct acylation of sulfonamides by esters represents an attractive strategy in organic chemistry, being an interesting alternative to classical approaches to N-acylsulfonamides. Here is described a simple and effective method to obtain N-acylsulfonamides of pharmaceutical interest, in a reaction promoted by titanium(IV) chloride. This strategy was successfully applied to the synthesis of a peroxisome proliferator– activated receptor a antagonist with a benzenesulfonimide moiety, ensuring an excellent yield of product. The reaction was further studied to explore the behavior of different a-bromoesters and esters and the effects of para-substitution in the benzenesulfonamide moiety.