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

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.