Replacing planar aromatic rings in drug molecules with C(sp³)-rich isosteric mimetics, such as bicyclo[n.1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid C(sp³)-rich isosteric mimetics of heteroaromatic rings are rare. Heterobicyclo[n.1.1]alkanes are promising in this regard, but the lack of modular synthetic methods has currently hindered their exploration. We envisioned that the strategic and selective insertion of different heteroatomic units to bicyclo[1.1.0]butanes could offer a highly modular platform to access diverse heterobicyclo[n.1.1]alkanes. Herein we report a photoredox-catalysed highly regioselective and chemoselective insertion of amidyl radicals to bicyclo[1.1.0]butanes, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows a geometric resemblance of these C(sp³)-rich heterobicyclic motifs with pyridine and pyrimidine derivatives, suggesting their potential as isosteric mimetics of such medicinally important heterocycles. Additionally, various downstream transformations demonstrate their utility as versatile building blocks in synthetic chemistry.

用富含 C（sp³） 的等位模拟物（如双环 [n.1.1] 烷烃）取代药物分子中的平面芳香环，可以显着改变其理化和药代动力学特性，通常会导致更高的临床成功率。然而，与苯环不同的是，杂芳环的结构刚性富含 C（sp³） 的等位模拟物很少见。杂双环[n.1.1]烷烃在这方面很有前途，但目前缺乏模块化合成方法阻碍了他们的探索。我们设想，将不同的杂原子单元战略性和选择性地插入双环[1.1.0]丁烷可以提供一个高度模块化的平台来获取不同的杂双环[n.1.1]烷烃。在此，我们报道了光氧化还原催化的酰胺自由基与双环[1.1.0]丁烷的高度区域选择性和化学选择性插入，提供了对 2-氧杂-4-氮杂双环[3.1.1]庚-3-烯的直接访问。出口向量分析显示这些富含 C（sp³） 的异双环基序与吡啶和嘧啶衍生物的几何相似性，表明它们可能作为此类医学上重要的杂环的等位模拟物。此外，各种下游转化证明了它们作为合成化学中多功能构建模块的实用性。