Three-Component Alkene Difunctionalization Enabled by Continuous-Flow Generation of the NCF3 Anion
Year: 2026
Type: preprint
Abstract: Multicomponent alkene difunctionalization provides an efficient route to molecular complexity by forging multiple bonds in a single operation. Although radical-polar crossover chemistry has greatly expanded the scope of these transformations, the use of highly reactive fluorinated nucleophiles remains largely unexplored because of their limited accessibility and poor stability. Here, we report the first three-component alkene difunctionalization employing the NCF3 anion as the nucleophilic reaction partner. The key to this transformation is the on-demand generation of the NCF3 anion in continuous flow, followed by its direct merger with visible-light photoredox catalysis. This strategy enables the coupling of a diverse range of radical precursors with styrenes and the flow-generated NCF3 anion through the sequential combination of radical and polar reactivities under mild photochemical conditions. The protocol accommodates extensive variation of the radical precursor, the alkene component and the NCF3 anion itself, and is applicable to the late-stage diversification of pharmaceuticals and agrochemicals. More broadly, this work demonstrates how continuous-flow generation of reactive intermediates can unlock multicomponent reaction manifolds that remain inaccessible using conventional batch methods.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7213471848