Hypervalent Iodine-Mediated Synthesis of Sulfinimidate Esters from Sulfenamides

Abstract

In this study, we present a novel and efficient approach for the oxidative esterification of sulfenamides using phenyliodonium diacetate, enabling the synthesis of sulfinimidate esters and sulfilimines under mild and metal-free conditions, with yields reaching up to 99%. The protocol is readily scalable and compatible with a diverse range of substrates and functional groups, and we demonstrate its potential for late-stage functionalization of pharmacologically relevant molecules. Furthermore, we propose a plausible reaction mechanism to account for the observed sequence of events.

Overlooked aza-S(iv) motifs: synthesis and transformations of sulfinamidines and sulfinimidate esters

“…In 2023, Lu and coworkers reported the preparation of sulfinimidates from secondary N -acyl and N -aroyl sulfenamides. 40 A wide library of substrates could be efficiently transformed, including functionalized S -alkyl, S -aryl and S -heteroaryl sulfenamides 10 (Scheme 15). The protocol yielded the desired compounds 36 by reacting sulfenamides with primary or secondary alcohols in the presence of PhI(OAc) 2 as the oxidant.…”

Hypervalent Iodine Mediated Synthesis of Sulfinamidines from Sulfenamides

“…The sulfenamides were prepared following the literature procedure. 16 General Procedure for S-Amination of Sulfenamides. To a solution of a sulfenamides (0.15 mmol, 1.0 equiv) in toluene (3.0 mL) were added Na 2 CO 3 (23.9 mg, 0.225 mmol, 1.5 equiv) and amine (0.18 mmol, 1.2 equiv) at room temperature, and then PhI(OAc) 2 (72.5 mg, 0.225 mmol, 1.5 equiv) was added.…”

“…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 . Given that amines display higher nucleophilicity compared with alcohols, we postulate that they could engage in the ligand exchange process, forming an amine-associated hypervalent iodine species.…”

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

“…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. 15 Given that amines display higher nucleophilicity compared to alcohols, we postulate that they could engage in the ligand exchange process, forming an amine-associated hypervalent iodine species. This would then pave the way for subsequent reductive elimination steps, ultimately yielding sulfinamidines (Scheme 1d).…”