Flow chemistry-assisted visible light-induced radical addition of β-amino iodides with enones en route to efficient construction of cis-2,6-piperidines

Abstract

A visible light-induced radical coupling of β-amino iodides and enones has been developed. This transformation offers efficient access to 1,5-amino ketones (25 examples, 71–96% yield), which serve as versatile precursors for the construction of cis-2,6-disubstituted piperidines. By integrating continuous-flow chemistry, the process becomes amenable to scale-up, affording higher yields and shorter reaction times compared to conventional batch reactions in flasks. The synthetic utility of this methodology was demonstrated through concise and symmetric total syntheses of cis-2,6-piperidine alkaloids, including H₃ receptor agonists and (–)-6-epi-porantheridine.