Work

Remote difunctionalization of alkenes through a photocatalytically triggered radical clock and α-carbonyl carbocation generation

Year: 2025

Type: article

Abstract: The 1,5-difunctionalization of alkenes can precisely introduce functional groups at specific positions and create chiral centers, which is crucial for the development of complex drug molecules and functional materials. Here we show a photocatalytic, remote 1,5-difunctionalization of alkenes to achieve the synthesis of α,ε-difunctionalized γ,δ-unsaturated amides or esters. This three-component reaction of the amides or esters bearing a free radical clock moiety at α-carbon with Umemoto reagents (UR) and O/F/Cl-nucleophiles is initiated through an addition of CF3 radical generated in situ by the photocatalytic fragmentation of UR to the double-bond, triggering off the radical clock and generating α-carbonyl radicals. The subsequent photocatalytic oxidation of the resulting α-carbonyl radicals to corresponding α-carbonyl carbocation enabled an unusual α-nucleophilic addition to amides or esters, thus realized the remote difunctionalizations. This regiospecific and umpolung strategy affords a rapid access to biologically important Cα-tetrasubstituted amides or esters which were usually constructed through several-step transformations. Cα-tetrasubstituted amides and esters are biologically important but are typically constructed through several-step transformations. Here, the authors report the synthesis of α,ε-difunctionalized γ,δ-unsaturated amides and esters via a photocatalyzed three-component remote 1,5-difunctionalization of alkenes using a tandem CF3 radical addition/radical clock cleavage approach with Umemoto reagents.

Source: Communications Chemistry

DOI: 10.1038/s42004-025-01695-9