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.
In
this investigation, an unprecedented transition-metal-free and
redox-neutral synthesis of sulfilimines was realized through the S-arylation
of readily obtainable sulfenamides employing diaryliodonium salts.
The pivotal step encompassed the resonance between bivalent nitrogen-centered
anions, engendered postdeprotonation of sulfenamides under alkaline
conditions, and sulfinimidoyl anions. The experimental outcomes demonstrate
that sulfinimidoyl anionic species function as efficacious nucleophilic
reagents, affording sulfilimines with notable to exceptional yields
and superlative chemoselectivity, all executed within a transition-metal-free
protocol and under exceptionally mild conditions.
In this investigation, an unprecedented transition-metal-free and redox-neutral synthesis of sulfilimines was realized through the S-arylation of readily obtainable sulfenamides employing diaryliodonium salts. The pivotal step encompassed the tautomerization between bivalent nitrogen-centered anions, engendered post-deprotonation of sulfenamides under alkaline conditions, and sulfinimidoyl anions. The experimental outcomes demonstrate that sulfinimidoyl anionic species function as efficacious nucleophilic reagents, affording sulfilimines with notable to exceptional yields and superlative chemoselectivity, all executed within a transition-metal-free protocol and under exceptionally mild conditions.
Sulfilimines are a class of bioisosteres with immense potential in medicinal chemistry, characterized by the presence of a tetravalent sulfur atom bearing one nitrogen and two distinct carbon substitutes. The conventional methods for synthesizing sulfilimines, relying on metal-catalyzed oxidative thioesters, suffer from a poor atomic economy and wastage of resources. To this end, we present a metal-free and redox-neutral approach for the first selective S-alkylation of sulfenamides under basic conditions to obtain sulfilimines. Our sustainable and efficient strategy involves sulfur-selective alkylation of easily accessible sulfenamides and commercially available halogenated hydrocarbons, leading to the successful synthesis of 60 sulfimides with high yields (36–99%) in a short reaction time. This novel approach not only offers a promising alternative to traditional methods but also expands the synthetic toolbox for the preparation of sulfilimines in medicinal chemistry.
Inhere, the first instance of copper-catalyzed oxidative amination of sulfenamides for the synthesis of sulfinamidines was documented. Employing air as the terminal oxidant, a variety of secondary and primary amines can be effectively transformed into their target products. This reaction boasts excellent chemoselectivity, mild conditions, straightforward operation, and broad substrate compatibility, which has significant implications for the fields of pharmaceuticals and organic synthesis.
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