The increasing popularity of four-member rings in drug discovery has prompted the synthetic chemistry community to advance and reinvent old strategies to craft these structures. Recently, the strain-release concept has been used to build complex architectures. However, although there are many strategies for accessing small carbocyclic derivatives, the synthesis of azetidines remains underdeveloped. Here we report a photocatalytic radical strategy for accessing densely functionalized azetidines from azabicyclo[1.1.0]butanes. The protocol operates with an organic photosensitizer, which finely controls the key energy-transfer process with distinct types of sulfonyl imines. The radical intermediates are intercepted by the azabicyclo[1.1.0]butanes via a radical strain-release process, providing access to difunctionalized azetidines in a single step. This radical process is revealed by a combination of spectroscopic and optical techniques and density functional theory calculations. The power and generality of this method is illustrated with the synthesis of various azetidine targets, including derivatives of celecoxib and naproxen.

四元环在药物发现中越来越受欢迎，促使合成化学界推进和重新发明旧策略来制作这些结构。最近，应变释放概念已被用来构建复杂的架构。然而，尽管有许多获得小碳环衍生物的策略，但氮杂环丁烷的合成仍然不发达。在这里，我们报告了一种从氮杂双环[1.1.0]丁烷中获取密集官能化氮杂环丁烷的光催化自由基策略。该协议使用有机光敏剂，可通过不同类型的磺酰亚胺精细控制关键的能量转移过程。自由基中间体通过自由基应变释放过程被氮杂双环[1.1.0]丁烷拦截，从而一步获得双官能化氮杂环丁烷。这一根本过程是通过光谱和光学技术以及密度泛函理论计算的结合来揭示的。通过合成各种氮杂环丁烷靶标（包括塞来昔布和萘普生的衍生物），说明了该方法的功效和通用性。