Bidirectional Elongation Strategy Using Ambiphilic Radical Linchpin for Modular Access to 1,4-Dicarbonyls via Sequential Photocatalysis

Organicmolecules that can be connected to multiple substratesby sequential C-C bond formations can be utilized as linchpinsin multicomponent processes. While they are useful for rapidly increasingmolecular complexity, most of the reported linchpin coupling methodsrely on the use of organometallic species as strong carbon nucleophilesto form C-C bonds, which narrows the functional group compatibility.Here, we describe a metal-free, radical-mediated coupling approachusing a formyl-stabilized phosphonium ylide as a multifunctional linchpinunder visible-light photoredox conditions. The present method usesthe ambiphilic character of the phosphonium ylide, which serves asboth a nucleophilic and an electrophilic carbon-centered radical source.The stepwise and controllable generation of these radical intermediatesallows sequential photocatalysis involving two mechanistically distinctradical additions, both of which are initiated by the same photocatalystin one pot with high functional group tolerance. The methodology enablesa bidirectional assembly of the linchpin with two electronically differentiatedalkene fragments and thus offers rapid and modular access to 1,4-dicarbonylcompounds as versatile synthetic intermediates.

Automated summary

Organic molecules that can be connected to multiple substrates by sequential C-C bond formations can be used as linchpins in multicomponent processes. In this study, a metal-free, radical-mediated coupling approach using a formyl-stabilized phosphonium ylide as a multifunctional linchpin under visible-light photoredox conditions is described. This approach allows for the bidirectional assembly of the linchpin with two electronically differentiated alkene fragments, providing rapid and modular access to 1,4-dicarbonyl compounds as versatile synthetic intermediates.