Electrochemical Cleavage of Sulfonamides: An Efficient and Tunable Strategy to Prevent β-Fragmentation and Epimerization

Abstract

The electrochemical reduction of sensitive sulfonamides is described. The addition of a benzoyl group on the nitrogen atom facilitates the reductive cleavage of sulfonamides preventing β-fragmentation and epimerization. This strategy was successfully applied to the cyclopropylamine and to α-amino stannanes.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…In a follow-up study, they discovered that by introducing a benzoyl group on the sulfonamide nitrogen—the reduction potential of the sulfonamide may be lowered (absolute value) considerably, allowing deprotection to occur without β -fragmentation (Figure 48D, bottom). 858 Notably, an α -stannane group was also found to survive the reaction conditions; minimal epimerizations were observed when this method was applied to chiral amines. Cathodic conditions were also utilized by Médebielle and co-workers to remove a sulfone group in a nucleoside derivative through the cleavage of the C(sp 3 )–S bond.…”

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…140 Indeed, the related partial conversion of N-benzyl-N-cyclopropyl phenylsulfonamide into a ring-opened product, N-benzyl-N-propylamine, upon reductive desulfonation performed electrochemically, is proposed to proceed via the formation of an Ncyclopropylaminyl radical. 142,143 Using lithium aluminium hydride as the metallating agent, the imine function generated is reduced and the final product is an amine. 60 Examples are displayed in Scheme 46.…”

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 7.59−7.57 (m, 3H), 7.46 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.00 (d, J = 8.5 Hz, 2H), 3.16 (s, 3H), 1.30 (s, 9H). 13 (20), 162 (45), 147 (24), 146 (25), 141 (11), 132 (21), 118 (12), 91 (21), 78 (11), 77 (100), 51 (42) The Journal of Organic Chemistry m/z 323 (M + , 1), 182 (66), 181 (26), 180 (28), 167 (85), 166 (14), 152 (15), 115 (11), 77 (100), 51 (54), 50 (11). HRMS (ESI-TOF + ) m/z: [M + H] + calcd for C 19 H 18 NO 2 S 324.1053; found 324.1077.…”