Cyclic frameworks are fundamental structural backbones of pharmaceuticals, agrochemicals and functional materials. Skeletal ring expansion serves as a powerful skeleton-editing strategy that directly remodels existing cyclic structures and avoids tedious de novo synthesis. However, most established ring-expansion methodologies only enable single-atom insertion, lacking a versatile catalytic platform capable of sequential multi-atom insertion coupled with peripheral functionalization of the ring scaffold.

γ-Lactams, five-membered nitrogen heterocycles, exhibit prominent biological activity, yet conventional synthetic routes struggle to achieve efficient and selective diversification at the γ-position. Although radical ring-opening chemistry of aminocyclopropanes has been well-established, it has not been exploited to construct polysubstituted γ-lactams via tandem carbonylation and cyclization.

To address these persistent synthetic bottlenecks, the research group led by Professors Wen-Jing Xiao and Jia-Rong Chen at Central China Normal University established a tunable visible-light photocatalytic multicomponent platform utilizing iridium photocatalysts and organic photosensitizer 4CzIPN. Starting from aminocyclopropanes, carbon monoxide (CO) and various radical trapping reagents, the system proceeds through a photoredox-mediated radical cascade process to realize sequential single C and N atom [n+2] ring expansion, converting strained three-membered aminocyclopropanes into γ-lactams in a single operation.

Iridium photocatalysts efficiently drive two core transformations: Giese addition and Minisci heteroarylation. By simply switching photosensitizers, additives and radical acceptors, six types of peripheral γ-functionalization can be further achieved, including alkynylation, acylation, alkenylation and thiolation. The practicality of this methodology is validated via broad substrate scope screening, gram-scale synthesis and derivatization of pharmaceutical molecules. Comprehensive mechanistic insights are obtained through radical trapping experiments, in-situ EPR characterization and DFT theoretical calculations. This work delivers a modular new strategy for simultaneous skeleton editing and peripheral diversification of highly strained small rings.

The excited-state redox potential of Ir-1 and Ir-2 perfectly matches aminocyclopropane substrates, triggering single-electron oxidation to generate aminyl radical cations and rapidly drive three-membered ring cleavage. Compared with organic photosensitizer 4CzIPN, iridium complexes eliminate radical regeneration barriers and deliver drastically enhanced catalytic activity.

Iridium coordination complexes possess robust light and thermal stability, resisting catalyst deactivation under long-term blue light irradiation within sealed high-pressure CO reaction vessels.

The iridium catalytic center directs carbon radicals to preferentially capture CO, inhibiting undesired [3+2] cycloaddition side reactions, thus enabling highly selective sequential C/N dual-atom [n+2] ring expansion.

Iridium photocatalysts are compatible with buffer salts, protic acids and oxidants, and can synergize with organic photosensitizers to establish a universal catalytic platform supporting six categories of γ-position peripheral diversification.

Radical capture tests with PhSeSePh unambiguously detect the key alkylacyl radical intermediate via HRMS, verifying the radical cascade ring-opening-carbonylation pathway.

DMPO spin-trapping EPR measurements confirm the generation of carbon-centered radical intermediates under blue light irradiation; no EPR signal is observed under dark conditions, proving the photocatalytic radical mechanism.

Computational energy profiles reveal the thermodynamic favorability of 5-endo-trig cyclization over competitive 4-exo-trig cyclization. The transition state orbital interactions and bond length data quantitatively explain the high chemo- and regioselectivity of the ring-expansion cyclization step.