syn-Selective Difunctionalization of Bicyclobutanes Enabled by Photoredox-Mediated C–S σ-Bond Scission

Abstract

Given the importance of cyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely forge and manipulate ring systems in synthetic chemistry. In this field, the intermolecular synthesis of densely substituted cyclobutanes with precise diastereocontrol under simple reaction conditions remains a challenge. Herein, a photoredox strategy for the difunctionalization of bicyclo[1.1.0]­butanes (BCBs) under high regio- and syn-selectivity is disclosed. 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 under mild conditions and demonstrates the generality of this protocol. Mechanistic studies suggest that the intermediacy of cyclic distonic radical cations might be key for the efficient scission of C–S σ-bonds and the origin of diastereoselectivity.

Strain-enabled radical spirocyclization cascades: rapid access to spirocyclobutyl lactones and – lactams

“…7 Bicyclobutane (BCB), the smallest fused strained hydrocarbon with a ring-strain of 64 kcal mol −1 , gained significant attention in recent years not only due to its unique structural features but also its ability to unlock strategies through strain release to synthetically challenging compounds either via single-electron or two-electron pathways. 8 For example, the stained carbon–carbon bond of BCB derivatives participates in various difunctionalization, 6 c ,9 carbene insertion, 10 or cycloaddition reactions, 11 leading to highly valuable carbocycles and heterocycles, which are bioisosteres of (hetero)arenes (Scheme 1B). 12 Despite the growing number of synthetic strategies using BCBs, reports on strain-enabled radical spirocyclization cascades haven't been studied to date.…”

Oxidative sulfonylarylation of strained C–C σ-bonds for the synthesis of 3-spirocyclic oxindoles initiated by insertion of sulfur dioxide

“…11 b Very recently, Glorius and co-workers disclosed an elegant photoredox-mediated difunctionalisation reaction of bicyclo[1.1.0]butanes with sulfur-containing bifunctional reagents with high regio- and diastereoselectivities (Scheme 1B). 15 Even though such an inspiring advancement has been made, the desire for novel radical-type difunctionalisation reactions of BCBs and access to new three-dimensional scaffolds bearing cyclobutane motifs continues to drive the development of new reaction platforms.…”

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

“…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.…”

“…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. Deng and co-workers have reported a general and mild photocatalytic two-component bromoallylation and alkylation of BCBs with allyl bromides as the bifunctional reagents (the allyl radical and bromine radical precursors) in a metal, additive-free manner using 2-isopropylthioxanthone photocatalyst (Scheme c) .…”

“…Deng and co-workers have reported a general and mild photocatalytic two-component bromoallylation and alkylation of BCBs with allyl bromides as the bifunctional reagents (the allyl radical and bromine radical precursors) in a metal, additive-free manner using 2-isopropylthioxanthone photocatalyst (Scheme c) . Meanwhile, Glorius and co-workers have employed [Acr-Mes 2 ] + [ClO 4 ] − photocatalyst for the two-component photoredox difunctionalization of bicyclo[1.1.0]­butanes (BCBs) 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 c) …”