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

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.

Synthesis of Tetrahydro-indolones through Rh(III)-Catalyzed [3 + 2] Annulation of Enaminones with Iodonium Ylides

“…Nevertheless, to the best of our knowledge, these major advances in Rh­(III)-catalyzed annulation of enaminones focused on the C­(sp 2 )–H bond functionalization process occurring only on aryl ortho -carbon, and the C­(sp 2 )–H bond functionalization process on the alkenyl fragment of enaminones remains challenging, probably as a result of the strong π-coordinating ability of the CC bond having some inhibitory effect on the C–H bond activation process of the catalyst and the alkenyl C–H activation being more sensitive to steric hindrance . As a continuation of the development in Rh­(III)-catalyzed C–H activation of iodonium ylides and our work on developing enaminone chemistry for heterocycle synthesis, herein, we are interested in describing a new synthetic strategy for the synthesis of tetrahydro-indolones via a Rh­(III)-catalyzed [3 + 2] annulation reaction from simple and readily available enaminones with iodonium ylides (Scheme h). Meanwhile, the C­(sp 2 )–H bond functionalization process is chemoselectively achieved on the alkenyl fragment of enaminones.…”