Cu‐Promoted Sydnone Cycloadditions of Alkynes: Scope and Mechanism Studies

Abstract

Cu-salts have been found to promote the cycloaddition reaction of sydnones and terminal alkynes, providing significant reduction in reaction times. Specifically, the use of Cu(OTf)2 is found to provide 1,3-disubstituted pyrazoles whereas simply switching the promoter system to Cu(OAc)2 allows the corresponding 1,4-isomers to be produced. The mechanism of the Cu-effect in each case has been investigated by experimental and theoretical studies, and they suggest that Cu(OTf)2 functions by Lewis acid activation of the sydnone whereas Cu(OAc)2 promotes formation of reactive Cu(I)-acetylides.

Exploiting Synergistic Catalysis for an Ambient Temperature Photocycloaddition to Pyrazoles

“…Pyrazole‐containing molecules are prevalent within the medicinal and agrochemical industries, and have been traditionally accessed by cycloaddition or condensation strategies . Work within our laboratory has sought to establish sydnone cycloadditions with alkynes as a versatile platform for the synthesis of pyrazole containing molecules . While this transformation demonstrates a broad scope and is tolerant of a range of functionalities, there remain a number of associated challenges relating to reaction regiocontrol, as well as the requirement for elevated temperatures and prolonged reaction times.…”

A Mild and Regiospecific Synthesis of Pyrazoleboranes

“…Beginning with the nature of the sydnone N‐substituent, we were pleased to find that both aromatic and aliphatic groups were tolerated, providing the corresponding pyrazoles 4 – 7 in high yield (entries 1–4). This methodology is therefore especially well suited to the cycloaddition of N‐alkyl sydnones, which are typically less stable and less reactive than the N‐aryl analogues and often perform poorly in cycloadditions . To further demonstrate the versatility of the chemistry, the cycloaddition scope with respect to the alkynyl trifluoroborate salts was undertaken (entries 5–9).…”

Synthesis of aminopyrazoles from sydnones and ynamides

“…A popular approach is the use of Lewis acids, since via coordination to the sydnone, the reaction is favoured and the regioselectivity of the pyrazole products can be affected. 12,45 The use of copper promoters has also been shown to affect regioselectivity and facilitate the cycloaddition reaction, commonly referred to as a Cu-mediated Sydnone Alkyne Cycloaddition (CuSAC). 11,13 Based on these reports, we decided to undertake a screening of readily available copper catalysts and study their effect on the cycloaddition between ynamides and sydnones.…”