One-Pot Cascade Synthesis Of CF₃-Substituted Nitrogen-fused Polycyclic Pyrazolines

Cascade reaction(domino reaction,tandem reaction)is a chemical process for some complex structures,which contains two or more consecutive reactions.And each subsequent reaction can not occur until the chemical intermediates formed in the previous steps.With concurrent formation of several bonds in one process,cascade reacton can be utilized to provide a straightforward access to complex compounds,which meets atomic economy,green chemistry and operational simplicity.Therefore,the cascade reaction has great potential in the synthesis of natural products,pharmaceuticals and materials.Pyrazoline compounds are widely present in numerous nature products.And substituted pyrazolines have demonstrated a broad of biological activities,and been used widely in pharmaceuticals and agrochemicals such as antitumor,antibacterial,antifungal,antiviral,antiparasitic,anti-tubercular and insecticidal agents.They are also the key heterocyclic cores of some fluorescence probes for Cu(I),Cu(II),Al(III),Hg(II).Therefore,the construction of pyrazoline compounds bearing several different functionalitis is a challenging theme in organic synthetic chemistry.In the thesis,we developed one-pot cascade transformations involving [3 + 2] cycloaddition / Michael / aldol and [3 + 2] cycloaddition / double addition reactions of 2,2,2-trifluorodiazoethane with various α,β-unsaturated enones.This protocol provides a straightforward access to trifluoromethyl-substituted polycyclic pyrazolines with high chemo-,regio-,and diastereoselectivity.The relative configurations of the polycyclic pyrazolines were established by single-crystal X-ray analyses.Finally,based on the control experiment,we verified the key intermediate and proposed plausible mechanism for the cascade cycloaddition reactions.