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

• Published in: Advanced science Vol. 11; no. 40; pp. e2407931 - n/a
• Main Authors: Gu, Fengyan, Lin, Binyan, Peng, Zhi‐Huan, Liu, Shijie, Wu, Yuanqing, Luo, Mei, Ding, Ning, Zhan, Qichen, Cao, Peng, Zhou, Zhi, Cao, Tao
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01-10-2024; John Wiley and Sons Inc; Wiley
• Subjects: Carbon; cyclopropenes; DFT calculations; heterocycles; late‐stage modifications; Ligands; Nitrogen; rhodium; ring transformation; late‐stage modifications; cyclopropenes; ring transformation; heterocycles; DFT calculations; rhodium
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202407931

In 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.
Taking advantage of the unique ring‐opening properties of cyclopropenes, a versatile and efficient approach toward benzo‐fused five‐membered oxa‐ and aza‐heterocycles from the same raw materials is reported. With this practical method, a potential PD‐L1 down‐regulator with a novel isobenzofuranone O‐alkyl oxime moiety is synthesized.