Hydrazone-oxime Selectively Directed Redox-Neutral [4 + 2] Annulations Cascade with Alkynes and Iodonium Ylides to Build 1,1′-Biisoquinoline Mono‑N‑oxides

• Published in: Organic letters Vol. 25; no. 15; pp. 2616 - 2621
• Main Authors: Wen, Chaoying, Wang, Yuqin, Yang, Yanyan, Tian, Ya-Nan, Wang, Jinhua, Li, Shiqing
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.04.2023; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; DESIGN; ORGANOCATALYSTS; AZIDES; O BOND; ISOQUINOLINES; EXCITED-STATE PROPERTIES; ALLYLATION; BOND ACTIVATION; KETIMINES; C-H FUNCTIONALIZATION
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.3c00590

Selective C–H activation of a molecule containing multiple directing groups is an important but challenging issue in organic chemistry. Herein, a combined directing group (hydrazone-oxime) selectively directed [4 + 2] annulation cascade to synthesize novel 1,1′-biisoquinoline mono-N-oxides has been developed. Owing to the subtle differences in electronic properties between hydrazone and oxime, the first C–H annulation with alkynes preferentially occurs at the hydrazone side to form 1-oximido isoquinolines, which then undergoes a second C–H annulation with iodonium ylides at the oxime side. The two [4 + 2] annulations work smoothly under redox-neutral conditions and can be performed in one pot, without utilization of stoichiometric external oxidants. Moreover, ESI-MS and DFT calculations have been conducted to corroborate the reaction mechanism. Such novel biisoquinoline skeletons can pave the way for future research prospects with synthetic value.