Hydrazone-oxime Selectively Directed Redox-Neutral [4 + 2] Annulations Cascade with Alkynes and Iodonium Ylides to Build 1,1′-Biisoquinoline Mono-<i>N</i>-oxides
Chaoying Wen, Yuqin Wang, Yanyan Yang, Ya-Nan Tian, Jinhua Wang, Shiqing Li
Abstract
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.