Chemoselective Deprotection of Sulfonamides Under Acidic Conditions: Scope, Sulfonyl Group Migration, and Synthetic Applications

Abstract

Chemoselective acidic hydrolysis of sulfonamides with trifluoromethanesulfonic acid has been evaluated as a deprotection method and further extended to more complex synthetic applications. In contrast to conventional troublesome sulfonamide hydrolysis, a near-stoichiometric amount of acid was found to be sufficient to bring about efficient deprotection of various neutral or electron-deficient N-arylsulfonamides, whereas electron-rich substrates provided sulfonyl group migration products. The deprotection method developed is fully selective for N-arylsulfonamides, and the possibility to discriminate among various different sulfonamides is demonstrated.

Domino Synthesis of 3‐Alkyliden‐2,3‐Dihydro‐4‐Quinolones

“…Very recently, it was described that chemoselective acidic hydrolysis of sulfonamides can be effected with trifluoromethanesulfonic acid (triflic acid) in a wide variety of examples of practical importance. [22] Those conditions, that involve the treatment of the sulfonamide with 2 equiv. of triflic acid in dichloroethane at room temperature for 12 h, were applied to substrate 5 c, affording the deprotected quinolone 6 in 71% yield (Scheme 3).…”

“…Finally, the deprotection of the sulfonamide moiety was attempted. Very recently, it was described that chemoselective acidic hydrolysis of sulfonamides can be effected with trifluoromethanesulfonic acid (triflic acid) in a wide variety of examples of practical importance . Those conditions, that involve the treatment of the sulfonamide with 2 equiv.…”

“…[22] Those conditions, that involve the treatment of the sulfonamide with 2 equiv. Very recently, it was described that chemoselective acidic hydrolysis of sulfonamides can be effected with trifluoromethanesulfonic acid (triflic acid) in a wide variety of examples of practical importance.…”

Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor

“…1 H NMR (400 MHz, CDCl 3 ) δ 6.99 (d, J = 8.5 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.51 (s br, 1H), 2.80 (s, 3H), 2.24 (s, 3H). 13 (13), 91 (41), 89 (10), 79 (12), 78 (15), 77 (26), 65 (25), 63 (16), 60 (12), 53 (11), 52 (18), 51 (26), 50 (16).…”

“…A light yellow solid was isolated in 71% yield (0.71 mmol, 207 mg). 1 (10), 116 (100), 111 (27), 90 (11), 89 (61), 75 (35), 63 (37), 51 (10), 50 (17). HRMS (ESI) m/z: [M + H] + calcd for C 14 H 11 ClNO 2 S 292.0194; found 292.0189.…”