Modular Synthesis of Substituted Lactams via a Deoxygenative Photochemical Alkylation-Cyclization Cascade of...

γ-Lactams are crucial scaffolds in many bioactive compounds and pharmaceutical agents, yet their synthesis featuring diverse γ- and N-substitution remains a significant synthetic challenge. Current methods often lack modularity and efficiency, particularly when targeting sterically hindered or highly functionalized analogues. Herein, we report a modular, three-step strategy for the systematic synthesis of γ- and N-substituted γ-lactams from readily available primary amines and carboxylic acids. The sequence includes deoxygenative activation of secondary amides using triflic anhydride, a photochemical silane-mediated radical alkylation, and intramolecular cyclization. The alkylation-lactamization cascade proceeds under additive-free, continuous-flow photochemical conditions, enabling rapid reaction times (20 min) and scalable operation. Compared to conventional N-alkylation approaches, this method broadens access to sterically hindered analogues and offers a valuable platform for medicinal chemistry applications.