Multistep Continuous Flow Synthesis of Isolable NH2-Sulfinamidines via Nucleophilic Addition to Transient Sulfurdiimide

The growing interest in novel sulfur pharmacophores led to recent advances in the synthesis of some S(IV) and S(VI) motifs. However, preparation and isolation of uncommon primary sulfinamidines, the aza-analogues of sulfinamides, is highly desirable. Here we report a multistep continuous flow synthesis of poorly explored NH2-sulfinamidines by nucleophilic attack of organometallic reagents to in situ prepared N-(trimethylsilyl)-N-trityl-łambda4-sulfanediimine (Tr−N=S=N−TMS). The transformation can additionally be realized under mild conditions, at room temperature, via a highly chemoselective halogen-lithium exchange of aryl bromides and iodides with n-butyllithium. Moreover, the synthetic potential of the methodology was assessed by exploring further manipulations of the products and accessing novel S(IV) analogues of celecoxib, tasisulam, and relevant sulfinimidoylureas.

Références

Titre
Multistep Continuous Flow Synthesis of Isolable NH2-Sulfinamidines via Nucleophilic Addition to Transient Sulfurdiimide
Type de publication
Article de revue
Année de publication
2022
Revue
Chemistry – A European Journal
Volume
28
Pagination
asap
Soumis le 30 août 2022