Reviews and Accounts ARKIVOC 2012 (i) 432-490
Scheme 3. Mechanism of epoxide elimination to dienes.
2.2.9. Conversion of sulfonic acids to sulfonamides and activated sulfonate esters. The sulfonamide moiety is the basis of several groups of drugs and is of tremendous importance to medicinal chemistry.12 It comprises the largest class of antimicrobial agents and is found in other drugs including thiazide diuretics (including hydrochlorothiazide, metolazone, and indapamide, among others), loop diuretics (including furosemide, bumetanide, and torsemide), sulfonylureas (including glipizide, glyburide, among others), some COX-2 inhibitors (e.g., celecoxib), and acetazolamide. The group acts as a transition state mimetic of peptide hydrolysis and has been shown to be the critical pharmacophore for potent inhibitors of cysteine proteases. 13 These enzymes have been implicated in the degradative processing of peptides and proteins, and play key roles in a number of physiological processes including arthritis, Alzheimer’s disease, and apoptosis. Traditional methods for the generation of sulfonamides have used sulfonyl chlorides and nucleophiles such as amines. Unfortunately, sulfonyl chlorides are not amenable to long- term storage and are often difficult to handle. As an alternative route, Caddick described a general method for the preparation of sulfonamides whereby a sulfonic acid or its salt undergo activation with 1 (Table 9, Entries 1-6), followed by a rapid reaction with amines.14 The method also proved successful for the preparation of activated pentafluorophenol-sulfonate esters which have been established as stable replacement to sulfonyl chlorides. Thus, as depicted in Table 9, the exposure of various aromatic, aliphatic, and heterocyclic sulfonic acid salts 6 to reagent 1, followed by reaction of the resulting activated RSO2O+PPh3 complex with either allylamine or pentafluorophenol (PFPOH), afforded the coupled sulfonamides 7 and PFP sulfonate esters 8 in high yields. In addition, a number of functional groups are tolerated under the reaction conditions It is noted that metal salts of sulfonic acids are unsuitable substrates for this reaction as they lack good solubility and are generally hygroscopic. However, pyridine, tetrabutylammonium, or Page 445 ©ARKAT-USA, Inc.
