Titanium-Promoted Acylation of Sulfonamides to <i>N</i>-Acylsulfonamide PPARα Antagonists

<div><p></p><p>The direct acylation of sulfonamides by esters represents an attractive strategy in organic chemistry, being an interesting alternative to classical approaches to <i>N</i>-acylsulfonamides. Here is described a simple and effective method to obtain <i>N</i>-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 α antagonist with a benzenesulfonimide moiety, ensuring an excellent yield of product. The reaction was further studied to explore the behavior of different α-bromoesters and esters and the effects of <i>para</i>-substitution in the benzenesulfonamide moiety.</p></div