Copper(Ⅱ)-Catalyzed Cyclization Of Exocyclic α,β-Unsaturated Cycloketones With Amidines For The Synthesis Of Spiroiminazolines

Imidazoline derivatives are a kind of nitrogen-containing heterocyclic compounds,which are widely used in organic synthesis,coordination chemistry,biomedicine,multi-functional materials and other fields.As a member of imidazoline derivatives,spiroimidazoline compounds are found in many natural products as well as biologically,pharmacologically and medically active molecules.Therefore,the synthesis of spiroimidazoline compounds has been attracting broad attention from organic and pharmaceutical chemists.At present,there are many reports about spiroimidazoline compounds,and most of these synthetic methods exhibit enough efficiency.But there are still some drawbacks including complicated steps of the reaction,harsh conditions,expensive or scarce catalyst,low atomic economy,environment pollution and so on.In view of these points,herein we have succesffully developed a novel method for the synthesis of spiroimidazoline compounds.In this thesis,three kinds of spiroimidazoline compounds were synthesized by cheap and safe CuBr₂-catalyzed tandem cyclization of exocyclicα,β-unsaturated cycloketones with amidines.The details are as follows:（1）The CuBr₂-catalyzed cyclization of indanediones with amidines was studied,and the reaction conditions were systematically explored.Under the optimized reaction condition,24 indandione-spiroimidazolines were efficiently synthesized.（2）The CuBr₂-catalyzed cyclization of barbituric acids with amidines was investigated.Under the optimal reaction condition,24babiturate-spiroimidazolines were efficiently synthesized.（3）The CuBr₂-catalyzed cyclization ofα,β-unsaturated pyrazolones with amidines was studied.Under the optimal reaction,26pyrazolone-spiroimidazolines were obtained.In the above three reaction systems,all kinds of substrates have good applicability to functional groups and good yields,regardless of electron-withdrawing groups and electron-donating groups.All the products were characterized by ¹H NMR and ¹³C NMR,and the stereostructures were identified by single crystal diffraction of the representative products.In addition,we proposed the reaction mechanism and made a series of control experiments to verify the rationality of the reaction mechanism.The present method has the following advantages:cheap and easily available catalysts,mild reaction conditions,simple treatment,good atom economy（water as the sole byproduct）and high yields.Moreover,this protocol can still exhibit high efficiency even in gram-scale reaction,which makes it potentially practicable.This method provides a new alternative to the synthesis of novel spiroimidazoline compounds.