Rapid and Chemodivergent Synthesis of N-Heterocyclic Sulfones and Sulfides: Mechanistic and Computational Details of the Persulfate-Initiated Catalysis

Abstract

N-Heterocyclic sulfones and sulfides are key functional motifs in medicinal and agricultural chemistry and important building blocks in organic synthesis. Currently available methods produce N-heterocyclic sulfones in low yields and under harsh conditions. Here, we describe a rapid sulfone synthesis under ambient conditions that is initiated by persulfate with water as a cosolvent. The reaction has a broad scope and is readily expanded to the chemodivergent synthesis of symmetrical N-heterocyclic sulfones and sulfides. The products can be isolated by simple filtration. Our combined experimental and computational study suggests that the remarkable persulfate-initiated acceleration of the sulfone formation in the biphasic system that enables the otherwise sluggish reaction under ambient conditions is due to the combination of the previously unknown rapid acidification of the persulfate–sulfinate system, the self-catalysis of the reaction of sulfinic acid with halo-N-heterocycles, and the substantial acceleration of the reaction in the aqueous phase.