Copper(I)-Catalyzed Cycloaddition of 4-Bromosydnones and Alkynes for the Regioselective Synthesis of 1,4,5-Trisubstituted Pyrazoles

Abstract

Copper-catalyzed cycloaddition of alkynes with 4-bromosydnones provides a convenient, mild, and regioselective method for the synthesis of a wide range of bromopyrazoles. The broad functional group tolerance of the cycloaddition reaction and further palladium-catalyzed cross-coupling reactions allowed the preparation of polyfunctionalized 1,4,5-pyrazoles that are otherwise difficult to obtain by conventional methods.

Ultrafast Click Chemistry with Fluorosydnones

“…[9] In their work, sydnones were found to react more slowly than azides with cyclic alkynes, thereby limiting applicability as ab ioorthogonal ligation substrate.Atthe same time,wereported [10] that the presence of ah alogen in the 4-position has ab eneficial impact on the rate of the reaction, with the order of reactivity correlating with halogen electronegativity (Cl > Br > I). [11] With these data in mind, we aimed to develop anovel class of sydnones with the most electronegative element, fluorine,inthe 4-position. [11] With these data in mind, we aimed to develop anovel class of sydnones with the most electronegative element, fluorine,inthe 4-position.…”

Synthesis of [18F]Fluoroarenes by Nucleophilic Radiofluorination of N‐Arylsydnones

“…[19b,23] With these results in hand, the optimized reaction conditions were applied to aseries of diverse N-arylsydnones to establish the scope of the reaction. [19b] While sydnones are valuable precursors for the synthesis of functionalized pyrazoles [24] and biologically interesting molecules, [16c] their most popular utility in the last few years has been their role in bioorthogonal reactions. Several heterocycles,w hich are often problematic for metalmediated radiofluorination methods,u nderwent radiofluorination with high RCC to afford thiophene (15 a), benzofuran (16 a)and pyridine (17 a)derivatives.Ofparticular note is the successful preparation of ethyl 3-[ 18 F]fluorobenzofuran-2carboxylate 16 a in 45 %R CC which is,t ot he best of our knowledge,t he first report of an [ 18 F]benzofuran derivative.…”

Synthesis of aminopyrazoles from sydnones and ynamides

“…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. Although it is known that terminal sulfonyl ynamides are water sensitive, this was not a major concern during previous studies on metal-free systems, as the desired reactions outpaced any side-reactions.…”

“…1 Previously reported attempts to try to address these issues include the use of alkynylboronates 9,10 or copper promoters to direct the regioselectivity of the sydnone-alkyne cycloaddition reactions. [11][12][13] Due to the high interest towards new routes to fully functionalised pyrazoles, which are known to possess biological activities, 14,15 we were interested in expanding the scope of the sydnone-alkyne cycloaddition reaction to increase the tolerance for activated and electron-rich alkynes. To do so, we developed the synthesis of 4-aminopyrazoles from cycloaddition reactions between sydnones and ynamides, which have not been reported to date.…”