Expanding the Potential of Heteroaryl Vinyl Sulfones

Abstract

The easily available vinyl sulfone 3 showed great potential for new applications in several fields such as organic synthesis and bioconjugate formation. This was demonstrated by performing a systematic assessment of its reactivity in Michael, radical, and cycloaddition reactions. Heteroaryl vinyl sulfone 3 presented excellent output in terms of reactivity and selectivity, proving superior to phenyl vinyl sulfone 1 and with clear advantages over bis-sulfone 2. This behavior might be due to the conformational and orbital control exerted by the tetrazole unit according to DFT calculations. Moreover, some alternative transformations to the Julia-Kocienski olefination on the obtained products are also described.

Modular radical cross-coupling with sulfones enables access to sp 3 -rich (fluoro)alkylated scaffolds

“…First, they tolerate powerful anionic chemistry (α-alkylation and fluorination) for functional elaboration before the cross-coupling event (Fig. 1, A and B) (10,11); second, when attached to unsaturated systems, they enable facile cycloadditions and Michael/Giese-type additions (12); and last, their stability and crystallinity allow for convenient manipulation.…”

“…Because of the well-studied reactivity of vinyl sulfones in cycloaddition chemistry, 7 was treated with cyclo-hexadiene in a Diels-Alder reaction and subsequently cross-coupled to afford [2.2.2]-bicycle 51 . Compound 7 is known to react with dienes under mild and more selective conditions than those of acrylates or the corresponding phenyl vinyl sulfone (12).…”

“…Reagents such as 7 and 11 open up distinct possibilities for stepwise, successive RCC chemistry because the PT-sulfone is known to enhance the rate of Giese-type radical additions (12). A variety of olefin- and carboxylic acid-derived radicals could be smoothly intercepted with 7 or 11 followed by desulfonylative RCC in order to generate structures that in some cases would be challenging to otherwise procure (27, 28).…”

Sulfones: A New Functional Group for Modular Radical Cross-Coupling

“…Notably, both electron-rich and electron-deficient heterocyclic organozinc reagents are competent coupling partners in this reaction manifold, as exemplified by indole 22 and pyridine 23. To assess the disclosed method relative to the prior state of the art in the cross-coupling of unacti-vated alkyl sulfones, a direct comparison of substrates (24)(25)(26)(27)(28)(29)(30) previously evaluated under Fe catalysis was conducted. The conditions reported herein compared favorably in all cases to literature-reported yields and allowed access to compounds that were previously inaccessible via a desulfonylative cross-coupling route.…”

“…Reagents such as 7 and 11 open up unique possibilities for stepwise, successive RCC chemistry as the PT-sulfone is known to enhance the rate of Giese-type radical additions. 30 Indeed it was found that a variety of olefin-and carboxylic acid-derived radicals could be smoothly intercepted with 7 or 11 followed by desulfonylative RCC to generate structures that in some cases would be quite challenging to otherwise procure. 42,43 For example, 66 is prepared in the literature using an elegant deborylative cyclization; 44 the current modular approach starts with commercial cyclohexenyl boronic ester followed by olefin RCC and then desulfonylative RCC.…”