Synthesis of β-Polychlorinated Alkynes Enabled by Copper-Catalyzed Multicomponent Reaction

Abstract

Functional molecules bearing polychlorinated moieties usually play versatile roles in organic synthesis and biochemistry. A copper-catalyzed multicomponent polychlorocarboalkynylation of alkenes presents an efficient and operationally simple approach for the synthesis of β-polychlorinated alkynes. Mechanistic experiments were conducted demonstrating that an in situ generated copper acetylide complex was the real catalyst and reactive intermediate during the copper-catalytic cycle. And enantioselective exploration demonstrated potential application for the synthesis of chiral β-polychlorinated alkynes.The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.2c01755.Detailed experimental procedures, characteristic data, and copies of NMR spectra of compounds. (PDF)

Trichloromethyl‐Radical‐Initiated Three‐Component Reaction of Alkenes with CHCl3 and Quinoxalinones

“…In 2021, Li developed a radical alkoxypolyhaloalkylation of styrenes with chloroform and alcohols (Scheme 1d) [9] . Recently, Zhao disclosed a copper‐catalyzed three‐component reaction of tetrachloromethane with alkenes and alkynes (Scheme 1e) [10] . Although the polychloroalkyl radical‐initiated difunctionalization of alkenes is capable of forming complex polychloroalkyl‐containing structures, multicomponent reactions, especially those reactions involving the late‐stage modification of bioactive structures are still highly demanded.…”

“…Adamantane acid, benzoic acid and acetic acid were not so effective (Table 1, entries [10][11][12]. Additionally, the reaction did not occur when NaH 2 PO 4 was used as additive (Table 1, entry 13).…”

Copper-catalyzed trichloromethylative carbonylation of ethylene

“…[26][27][28][29] However, examples of trichloromethylative difunctionalization of alkenes employing CCl 4 as a versatile trichloromethyl radical precursor under external oxidant-free conditions are still rarely reported. 30,31 On the other hand, amides and esters are powerful molecular backbones ubiquitous in compounds that display biological properties, [32][33][34][35] especially in complex molecules with a trichloromethyl group. In this context, divergent syntheses from simple and readily available substrates to obtain diverse trichloromethyl-containing carbonylated compounds have received much attention.…”