Study On The Copper-Catalyzed Cyclization Reaction Of Diazo Compounds With Tert-Butyl Nitrite And Alkynes

Isoxazoles are a kind of important aromatic heterocycles that widely occur in many bioactive natural products and pharmaceutical drugs as the privileged skeletons.In addition,these compounds are also important intermediates in organic synthesis and are widely used in the synthesis of many important heterocyclic compounds.Therefore,the synthesis and application of isoxazole compounds has attracted much interest.Among various methods of synthesizing isoxazole compounds,undoubtedly,[3+2] cycloaddition reaction of alkynes with nitrile oxides represents the most straightforward and efficient method to access isoxazolederivatives.However,many methods have limitations such as narrow substrate scope and poor stereoselectivity.Therefore,the development of new [3+2] cycloaddition reaction of alkynes with nitrile oxides,especially transition metal-catalyzed [3+2] cycloaddition reaction of terminal and internal alkynes with nitrile oxides,is highly desirable.Diazo compounds not only have high reactivity,but also have various reaction orientations in the fields of natural products,organic chemistry,and pharmaceutical molecules because of its multiple resonance forms.In this research area,the coupling reactions of metal carbine,generated by the interaction of diazo compounds and transition metals,with various nucleophiles have been widely reported,but the coupling reactions of these metal carbenes with radicals are rarely reported.Therefore,exploiting new coupling reaction between metal carbene and free radicals is important for the application of diazo compounds in organic synthesis.In this thesis,using metal carbene generated by the interaction of diazo compounds and copper as precursor together with developing a new method of isoxazoles as the core,a [3+2]cycloaddition reaction of alkynes with nitrile oxides was developed employing nitrile oxides generated in situ by coupling reaction of copper carbene and nitroso radical as a key intermediate.The reaction not only extends the coupling reaction of metal carbene with radicals,but also provides a new method of synthesizing 3,4-disubstituted and3,4,5-trisubstituted isoxazoles.This method has many advantages such as mild reaction conditions,wide substrate scope,simple operation and high regioselective.