Fe(III)-Catalyzed Cascade C-H Functionalization/cycloaddition of ortho-Alkynyl Arylhydrazides: Facial Access to 3,4-Disubstituted Cinnolines.

A synthetic protocol for the construction of 3,4-disubstituted cinnoline scaffolds was described, which allowed for the transformation of ortho-alkynyl arylhydrazides via iron-catalyzed cascade C-H functionalization/cycloaddition. Furthermore, the practical utility of this method had been validated by easily scale-up synthesis, substrates derived from bioactive molecules and versatile derivatization of the target products. Mechanistic studies revealed that the reaction possibly proceeds via twice iron-mediated single-electron transfer (SET) processes. Furthermore, the resulting 3,4-disubstituted cinnolines exhibited significant anti-inflammatory effects from LPS stimulation experiment.