Synthesis of conformationally restricted sulfonamides via radical cyclisation

Merging Cross-Metathesis and Radical Cyclization: A Straightforward Access to 4-Substituted Benzosultams

“…22 We therefore expected that the cyclization mode might be strongly dependent of the substitution of the double bond (Scheme 2). It is important to point out that, even before our first attempts to perform this reaction, the plausibility of the radical process was supported by a result obtained by Ganguly and co-workers, 23 who found that the diallylic 24 underwent an initial 7-endo-trig cyclization to give products 8 and 9a/9b. This preliminary study was based on the use of tributylstannane as a radical-chain promoter.…”

Conformational Restriction: An Effective Tactic in ‘Follow-On’-Based Drug Discovery

“…Conformationally restricted sulfonamide 48 was found to be a potent HIV-1 protease inhibitor in Merck & Co. research team (Figure 7) [50,51]. x-ray crystallography demonstrated that the conformationally restricted sulfonamide can bind to a similar pocket in protease as approved drugs such as darunavir.…”

Formation of Five- and Six-Membered Heterocyclic Rings under Radical Cyclization Conditions

“…Parsons and Wright developed 48 a synthetic route to potentially bioactive bis-pyrrolidines in good to excellent yields by sequential radical addition and cyclization of diallylamines using either hypophosphorous acid or a bisphosphinothioate. Ganguly and co-workers isolated 49 some benzannulated six-membered sultams from the reaction mixtures while working on the synthesis of benzannulated seven-and eight-membered sultams by tri(nbutyl)tin hydride and AIBN meadiated radical cyclization.…”

“…However, the attempt to synthesize analogues of 2-phenyl-3-aroylbenzo [b]thiophene (tubulin polymerization inhibitors) failed. Ganguly and co-workers reported 49 the formation of the pyrrolidine ring of 3-methyl 1-(phenylsulfonyl)indoline by tri(n-butyl)tin hydride and AIBN mediated radical cyclization of N-allyl-N-(2-bromophenyl)benzenesulfonamide in refluxing toluene. However, the reactions of substrates such as N-allyl-N-aryl-or N-allyl-N-benzyl-2bromobenzenesulfonamides under similar conditions afforded the six-and seven-membered heterocyclic rings.…”