Ring Transformation of Cyclopropenes to Benzo‐Fused Five‐Membered Oxa‐ and Aza‐Heterocycles via a Formal [4+1] Cyclization

• DOI: 10.1002/advs.202407931
• Publication Date: 2024-08-29T10:34:18Z
• Authors: Fengyan Gu; Binyan Lin; Zhi‐Huan Peng; Shijie Liu; Yuanqing Wu; Mei Luo; Ning Ding; Qichen Zhan; Peng Cao; Zhi Zhou; Tao Cao
• Keywords: heterocycles; late‐stage modifications; ring transformation; Science; cyclopropenes; rhodium; Q; DFT calculations; Research Article; 0104 chemical sciences

AbstractIn the context of the growing importance of heterocyclic compounds across various disciplines, numerous strategies for their construction have emerged. Exploiting the distinctive properties of cyclopropenes, this study introduces an innovative approach for the synthesis of benzo‐fused five‐membered oxa‐ and aza‐heterocycles through a formal [4+1] cyclization and subsequent acid‐catalyzed intramolecular O‐ to N‐ rearrangement. These transformations exhibit mild reaction conditions and a wide substrate scope. The applications in the late‐stage modification of complex molecules and in the synthesis of a potential PD‐L1 gene down‐regulator, make this method highly appealing in related fields. Combined experimental mechanistic studies and DFT calculations demonstrate Rh(III)‐mediated sequential C─H coupling/π‐allylation/dynamically favorable O‐attack route.