3+2]‐Cycloadditions of N‐Cyano Sulfoximines with 1,3‐Dipoles

Felix Krauskopf,Kari Rissanen,Carsten Bolm,Khai‐Nghi Truong

doi:10.1002/ejoc.202000335

Felix Krauskopf, Kari Rissanen + Show 2 more

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https://doi.org/10.1002/ejoc.202000335

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Abstract

Involving the cyano group of N‐cyano sulfoximines in [3+2]‐cycloaddition reactions with 1,3‐dipoles provides practical routes for the construction of 5‐membered heterocycles bearing sulfoximinoyl moieties. An ytterbium‐catalyzed cycloaddition utilizing hydrazonoyl chlorides was developed, as well as a reaction involving imidoyl chlorides proceeding without the aid of a catalyst. Following these protocols, a range of sulfoximines with N‐1,2,4‐triazolyl and N‐1,2,4‐oxadiazolyl substituents was prepared.

Highlights

Being structurally related to the ubiquitous sulfamoyl group, the sulfoximinoyl moiety has in turn found significant interest in pharmaceutical and agrochemical industry.[1,2] Possessing a potential stereogenic sulfur and an additional site for further functionalization at the nitrogen atom, sulfoximines can be used to increase structural diversity, enable additional bonding interactions or generally improve pharmacokinetic properties.[1a]
BSO,[3] Roniciclib,[1a] and Gö 4962[4] are examples for medicinal compounds, while Sulfoxaflor[5] is employed as pesticide (Figure 1)
N-cyano sulfoximines proved useful as intermediates towards NH-sulfoximines, as the N-cyano group can be cleaved under welldefined reaction conditions.[14a,14b] In light of the rich chemistry of related compounds such as cyanamide,[17] it is surprising that chemical modifications of the N-cyano group of N-cyano sulfoximines keeping both the carbon and the nitrogen atom in the resulting molecular framework have only scarcely been studied

Summary

Introduction

Being structurally related to the ubiquitous sulfamoyl group, the sulfoximinoyl moiety has in turn found significant interest in pharmaceutical and agrochemical industry.[1,2] Possessing a potential stereogenic sulfur and an additional site for further functionalization at the nitrogen atom, sulfoximines can be used to increase structural diversity, enable additional bonding interactions or generally improve pharmacokinetic properties.[1a] BSO,[3] Roniciclib,[1a] and Gö 4962[4] are examples for medicinal compounds, while Sulfoxaflor[5] is employed as pesticide (Figure 1). Three-component denitrogenative [3+2] cycloadditions led to N-imidazolyl sulfoximines 3 (Scheme 1, middle),[19] and third, heterocyclizations via N(N-hydroxy guanidinyl) intermediates afforded sulfoximines with N-1,2,4-oxadiazolyl substituents 4 (Scheme 1, bottom).[20,21]

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