Photochemical α-selective radical ring-opening reactions of 1,3-disubstituted acyl bicyclobutanes with alkyl halides: modular access to functionalized cyclobutenes

Abstract

Although ring-opening reactions of bicyclobutanes bearing electron-withdrawing groups, typically with β-selectivity, have evolved as a powerful platform for synthesis of cyclobutanes, its application in the synthesis of cyclobutenes remains underdeveloped....

Photoredox-Catalyzed Alkylarylation of N-Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles

“…6 Additionally, an exclusive αselective radical ring-opening reaction of BCBs for the synthesis of cyclobutenes has been established very recently. 7 In contrast, only two examples of radical-mediated twocomponent difunctionalization reactions of BCBs using the visible-light-induced photoredox catalysis have been reported by Deng et al 5f and Glorius et al, 8 respectively. Deng and coworkers have reported a general and mild photocatalytic twocomponent bromoallylation and alkylation of BCBs with allyl bromides as the bifunctional reagents (the allyl radical and under high regio-and syn-selectivity in which C−S σ-bond cleavage of partially unsaturated sulfur-containing bifunctional reagents in an overall strain-release-driven process enables the thio-alkynylation, -alkenylation, and -allylation of BCBs (Scheme 1c).…”

“…6 Additionally, an exclusive αselective radical ring-opening reaction of BCBs for the synthesis of cyclobutenes has been established very recently. 7 In contrast, only two examples of radical-mediated twocomponent difunctionalization reactions of BCBs using the visible-light-induced photoredox catalysis have been reported by Deng et al under high regio-and syn-selectivity in which C−S σ-bond cleavage of partially unsaturated sulfur-containing bifunctional reagents in an overall strain-release-driven process enables the thio-alkynylation, -alkenylation, and -allylation of BCBs (Scheme 1c). 8 Despite this noteworthy progress, the development of new radical strategies for strain-release-driven difunctionalization reactions of BCBs is still desirable.…”

“…Radical addition reactions of BCBs have also been investigated (Scheme c). − In this context, the common electrophilic radical intermediate ( Int-B ) adjacent to an electron-withdrawing group would be formed via a Giese-type addition. In most cases, the intermediate Int-B would be reduced followed by protonation − or undergo a back hydrogen atom transfer (HAT) path to afford hydrofunctionalization products.…”

“…Of note, light-driven metal-catalyzed radical-type hydrofunctionalization of BCBs has been reported, which provides an alternative and impressive mode of reactivity for BCBs . Additionally, an exclusive α-selective radical ring-opening reaction of BCBs for the synthesis of cyclobutenes has been established very recently . In contrast, only two examples of radical-mediated two-component difunctionalization reactions of BCBs using the visible-light-induced photoredox catalysis have been reported by Deng et al and Glorius et al, respectively.…”

“…In addition, tetracycle 3ma could be readily synthesized from N -methyl- N -(naphthalen-1-yl)­bicyclo­[1.1.0]­butane carboxamide 1m . Of note, the 1,3-disubsituted bicyclobutyl amides ( 1n and 1o ) were proven to be suitable substrates for the exclusive β-selective radical ring-opening reaction with alkyl bromide to afford 1,1,3,3-tetrasubstituted cyclobutanes ( 3na and 3oa ) containing synthetically challenging vicinal all-carbon quaternary centers with excellent diastereoselectivity. Remarkably, coupling of N -aryl bicyclobutyl amides 1o and 1p derived from drug molecules and alkyl halide proceeded efficiently to give the desired oxindole-bioactive molecule hybrids in up to 93% yield.…”