Photocatalytic Annulation of Primary Amines to δ-Lactams: Access to Privileged (Spiro)piperidine Space

Piperidines are the most prevalent saturated nitrogen heterocycles in pharmaceuticals, yet efficient and general methods for accessing α-disubstituted and spirocyclic variants have remained a long-standing synthetic challenge. A broadly applicable annulation strategy from unprotected primary alkylamines would represent an important advance, enabling access to privileged piperidine scaffolds from the most accessible nitrogen feedstocks. Here we disclose a general photoredox/hydrogen atom transfer dual catalytic annulation that converts primary amines into α-mono- and α-disubstituted δ-lactams, versatile intermediates that provide streamlined access to diverse piperidines. The method proceeds under mild conditions, can be scaled to ∼100 g in continuous flow, and affords products capable of downstream modification. This work provides a broadly applicable solution to a challenging problem in heterocycle synthesis, expanding the structural space accessible to drug discovery.