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Multistep Continuous Flow Synthesis of Isolable NH 2 ‐Sulfinamidines via Nucleophilic Addition to Transient Sulfurdiimide
Author(s) -
Andresini Michael,
Carret Sébastien,
Degennaro Leonardo,
Ciriaco Fulvio,
Poisson JeanFrançois,
Luisi Renzo
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202202066
Subject(s) - transient (computer programming) , nucleophile , chemistry , continuous flow , nucleophilic addition , medicinal chemistry , physics , organic chemistry , computer science , mechanics , catalysis , operating system
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 NH 2 ‐sulfinamidines by nucleophilic attack of organometallic reagents to in situ prepared N ‐(trimethylsilyl)‐ N ‐trityl‐λ 4 ‐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.