Synthesis of CF₃-Substituted 1,6-Dihydropyridazines by Copper-Promoted Cascade Oxidation/Cyclization of Trifluoromethylated Homoallylic N-Acylhydrazines

Abstract

A highly efficient strategy for the construction of CF 3 -substituted 1,6dihydropyridazines has been developed by cascade oxidation/cyclization of trifluoromethylated N-acylhydrazines. The produced 1,6-dihydropyridazines could be easily transformed to 3-trifluoromethyl pyridazine derivatives. Some of the 1,6dihydropyridazines exhibited aggregation-induced emission (AIE). DFT calculations were conducted to explain the mechanism.

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

“…Among these fluorinated products, the trifluoromethylated homoallylic acylhydrazines were easily transformed to CF 3 - substituted pyrazolines and 1,6-dihydropyridazines via a cascade oxidation/cyclization with NXS or Cu(OAc) 2 . Notably, some of the resultant CF 3 -substituted 1,6-dihydropyridazines exhibited aggregation-induced emission [102,103] (Scheme 16).…”

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes

“…In our group, we are endeavoring on the development of efficient methods to construct fluorine-containing heterocycles and find that fluoroalkylated N -acylhydrazones and nitrile imines are versatile building blocks for the synthesis of various fluorine-containing heterocycles such as pyrazoles, pyrazolines, pyrazolidines, imidazolines, imidazolidines, dihydropyridazines, oxadiazoles, triazoles, and triazolines . However, difluoromethylated N -acylhydrazones have never been synthesized and used for the construction of difluoromethylated heterocycles.…”

Metal-Free Tandem Oxidative Cyclization for the Synthesis of 1,2-Dihydropyridazines and Pyrazoles

“…Dihydropyridazines and pyrazoles are important N-heterocycles and exist widely in natural products and pharmaceutically active compounds, and are used for selective inhibition of cyclooxygenase-2 (COX-2), and as spasmolytic, antimicrobial, antihypertensive, and anti-inflammatory agents . These two types of N-heterocycles also serve as versatile intermediates in organic synthesis . For these reasons, they have received much attention from synthetic and pharmaceutical chemists.…”