Unified and practical access to ɤ-alkynylated carbonyl derivatives via streamlined assembly at room temperature

Abstract

The development of a unified and straightforward method for the synthesis of ɤ-alkynylated ketones, esters, and amides is an unmet challenge. Here we report a general and practical protocol to access ɤ-alkynylated esters, ketones, and amides with diverse substitution patterns enabled by dual-catalyzed spontaneous formation of C sp3-sp3 and C sp3-sp bond from alkenes at room temperature. This directing-group-free strategy is operationally simple, and allows for the straightforward introduction of an alkynyl group onto ɤ-position of carbonyl group along with the streamlined skeleton assembly, providing a unified protocol to synthesize various ɤ-alkynylated esters, acids, amides, ketones, and aldehydes, from readily available starting materials with excellent functional group compatibility.

Ni-Catalyzed Regioselective 1,2-Dialkylation of Alkenes Enabled by the Formation of Two C(sp3)–C(sp3) Bonds

“…These reactions, still difficult to develop, intrinsically minimize the number of catalytically generated alkylmetal species prone to undergo β-H elimination. A few reports on alkene alkylarylation have also been disclosed (Scheme D), but these reactions mostly utilize tert -alkyl and perfluoroalkyl halides, and α-haloesters amenable to the formation of alkyl, difluoroalkyl, and α-alkoxycarbonylalkyl radicals . Reactions with these reagents bypass the generation of additional β-H–C­(sp 3 )–[M] intermediates …”

The Alkynylative Difunctionalization of Alkenes

“…Initially, the intermediate In 2019, Shu reported a copper-and visible-light catalyzed alkyl-alkynylation of alkenes at room temperature (Scheme 32). [77] They carried out radical trap experiments and radical clock experiments, and no desired products were obtained, suggesting that the catalytic process may involve a radical pathway. Moreover, the desired product 109 was In 2019, Tsui reported a silver-catalyzed trifluoromethylalkynylation of unactivated alkenes in the presence of BIOMe and NaOAc with EBX as the alkynylating reagent at room temperature (Scheme 33).…”

“…In 2019, Shu reported a copper‐ and visible‐light catalyzed alkyl‐alkynylation of alkenes at room temperature (Scheme 32). [77] They carried out radical trap experiments and radical clock experiments, and no desired products were obtained, suggesting that the catalytic process may involve a radical pathway. Moreover, the desired product 109 was obtained in 66 % yield using phenyethynyl copper as the catalyst, proving that alkynylcopper Int 72 is an intermediate in the catalytic cycle.…”