One-Pot Tandem Oxidative Bromination and Amination of Sulfenamide for the Synthesis of Sulfinamidines

Abstract

The sulfinamidines as aza analogues of sulfinamides received limited attention from both organic chemists and pharmaceutical chemists. Herein, we present a tandem oxidative/nucleophilic substitution approach for the synthesis of sulfinamidines in high yield (up to 98%). This cascade reaction method is enabled by N-bromosuccinimide (NBS) as an oxidant and diverse readily available amines as nucleophiles without any additives or catalysts. Notably, this method is highly time-economical, safe to operate, and easy to scale up and has excellent functional group compatibility.

Hypervalent Iodine Mediated Synthesis of Sulfinamidines from Sulfenamides

“…12 Li described a tandem oxidative bromination and amination process of sulfenamides for constructing sulfinamidines (Scheme 1c). 13 While there are scattered reports on sulfinamidine synthesis, 14 developing an efficient method to complement existing approaches remains a practical and valuable pursuit in the field. 15 In our previous work, we reported on the hypervalent iodine-mediated synthesis of sulfonimidate esters derived from sulfenamides, demonstrating that the reaction proceeds through a ligand exchange process between alcohols and intermediate hypervalent iodine species.…”

“…The chemical yields referred are isolated products. 1 H NMR and 13 C { 1 H} NMR spectra were recorded on 400 MHz Bruker spectrometers. Chemical shifts of 1 H were reported in part per million relative to the TMS peak (δ 0.0).…”

“…Sulfenamides possess an S-NH bond and, due to their exceptional sulfur nucleophilicity, have garnered interest from several research groups recently . Li described a tandem oxidative bromination and amination process of sulfenamides for constructing sulfinamidines (Scheme c) . While there are scattered reports on sulfinamidine synthesis, developing an efficient method to complement existing approaches remains a practical and valuable pursuit in the field …”

Cu(II)-Catalyzed Aerobic Synthesis of Sulfinamidines from Sulfenamides

“…More recently, Li and co-workers described a tandem oxidative bromination and amination process of sulfenamides for constructing sulfinamidines (Scheme 1c). 14 This innovative method leverages the benefits of a tandem reaction sequence, allowing for the formation of the desired sulfinamidines in a single synthetic operation. Nevertheless, the requirement for stoichiometric amounts of brominating reagents raises concerns about the environmental impact and cost-effectiveness of this approach.…”

Expanding the Scope of Hypervalent Iodine Reagents in the Synthesis of Sulfinamides from Sulfenamides

“…12 Li described a tandem oxidative bromination and amination process of sulfenamides for constructing sulfinamidines (Scheme 1c). 13 While there are scattered reports on sulfinamidine synthesis, 14 developing an efficient method to complement existing approaches remains a practical and valuable pursuit in the field. In our previous work, we reported on the hypervalent iodine-mediated synthesis of sulfonimidate esters derived from sulfenamides, demonstrating that the reaction proceeds through a ligand exchange process between alcohols and intermediate hypervalent iodine species.…”