Work

Modular synthesis of functionalized azetidines through visible-light copper-catalyzed carboamination of 1,3-dienes with azabicyclo[1.1.0]butanes

Year: 2026

Type: article

Abstract: The strain-release reactivity of azabicyclo[1.1.0]butanes (ABBs) offers a powerful entry to substituted azetidines, yet modular access to highly functionalized, allylic amine-containing frameworks remains underdeveloped. Here, we report a visible-light copper-catalyzed four-component coupling that effects 1,4-carboamination of aryl-substituted 1,3-dienes, assembling azetidines bearing a quaternary carbon center from dienes, aryl amines, and electrophiles using ABBs. Synergistic copper/photoredox catalysis unites strain-release generation of an azetidinyl radical with allylic C-N bond formation, delivering densely functionalized azetidines bearing an allylic amine in a single, redox-neutral operation. The reaction proceeds with high 1,4-regioselectivity and broad functional-group tolerance across diverse anilines, ABBs, dienes, and electrophiles, and operates under mild conditions. Biorelevant complex-molecule diversification, scalability, and downstream derivatization underscore the synthetic utility of the platform, while DFT calculations trace the 1,4-selectivity to stabilizing noncovalent interactions that favor benzylic C-N coupling and steric repulsion that disfavors the competing pathway.

Source: Chemical Science

DOI: 10.1039/d6sc06133h

Authors: Yejin Koo, Dongwoo Lee, Jiyong Park, Sungwoo Hong

Institutions: Korea Advanced Institute of Science and Technology, Institute for Basic Science

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funders: Korea Advanced Institute of Science and Technology, Institute for Basic Science

Awards: G1412995995, G7112187481