Copper‐Catalyzed C(sp²)–C(sp³) Cross‐Dehydrogenative Coupling of Quinones with Cyclic Alkanes: One‐Step Access to Parvaquone and its Analogs

Abstract

A copper-catalyzed direct cross coupling reaction of quinones with cycloalkanes in the presence of TBHP was developed. This methodology allows the direct installation of cycloalkyl groups with medium and large-sized rings on 1,4-naphthoquinones, anthracene-1,4-dione, or 1,4-benzoquinones. Based on this new protocol, the one-pot synthesis of the antimalarial drug, parvaquone, was achieved.

Menadione: a platform and a target to valuable compounds synthesis

“…In a work published by Baral and co-workers, the unprecedented Csp 2 –Csp 3 alkylation of menadione ( 10 ) with medium and large-size cyclic alkanes was achieved by the combination of copper(II) triflate and tert -butyl hydroperoxide ( Scheme 35 ) [ 147 ]. The products 107a – d were obtained in 58–64% yield range.…”

Direct C−H Radical Alkylation of 1,4‐Quinones

“…[32] In 2016, Lee's group described a direct copper-catalyzed cycloalkylation using tert-butyl hydroperoxide (TBHP) as hydrogen-abstraction agent starting from cycloalkanes. [33] Finally, Wang's team extended their benzylation method to the direct alkylation of quinones using tert-butyl peroxybenzoate 19 (TBPB) and bismuth(III) trifluoromethanesulfonate as catalyst. [34] Remarkably, they showed that TBPB 19 could act as a radical methyl donor allowing the radical methylation of numerous bismuth-activated quinones in good yields (Scheme 12, Pathway A).…”

“…At the end of the 20 st century, Chuang's group studied a direct manganese‐mediated alkylation of various 1,4‐naphthoquinones with malonates [32] . In 2016, Lee′s group described a direct copper‐catalyzed cycloalkylation using tert ‐butyl hydroperoxide (TBHP) as hydrogen‐abstraction agent starting from cycloalkanes [33] . Finally, Wang's team extended their benzylation method to the direct alkylation of quinones using tert ‐butyl peroxybenzoate 19 (TBPB) and bismuth(III) trifluoromethanesulfonate as catalyst [34] .…”

Recent Advances in Direct Functionalization of Quinones

“…Despite the manganese(III)‐mediated oxidative free radical reactions, the metal catalyzed radical reactions were efficient methods for the assembly of substituted quinones as well. In 2016, a copper‐catalyzed cross‐dehydrogenative coupling (CDC) reaction was developed by Lee and co‐workers . Cycloalkanes were applied as alkylating agents in the presence of tert ‐butylhydroperoxide (TBHP) as terminal oxidant (Scheme ).…”