Constrcution Of Multifunctional Full-substituted Benzoxazolidine (Azole) Derivatives From Tetraynes And Pyrroline Nitrogen Oxide

Benzoxazolidine structures which could be widely found in drug molecules and natural products have important value in organic synthesis.Benzyne intermediates have high reactivity due to its unique structure and are easily captured by a variety of reagents,which are often used to construct multifunctional aromatic compounds.Based on the previous study of our research group,we tried to synthesize benzoxazolidine derivatives in one pot by using benzyne intermediates formed by tetrayne substrates through hexadehydro-Diels-Alder(HDDA)reaction and pyrroline nitrogen oxide,and exploring the reaction of tetrayne substrates with other reagents containing nitrogen and oxygen.The main research contents including the following two parts:1.Tetraynes with 5,5-dimethyl-1-pyrroline N-oxide to construct benzoxazolidine derivativesThe reaction of benzynes formed by tetraynes with different substituents(p-F,p-Cl,p-Me,p-OCH3,p-Et,p-iPr)and 5,5-dimethyl-1-pyrroline nitrogen oxides to synthesize a series of polycyclic products were explored.A series of tetrayne substrates with different substituents were prepared under the protection of argon.Then the tetrayne substrate and 5,5-dimethyl-1-pyrroline nitroxide were reacted in acetonitrile to synthesize benzoxazolidine derivatives in one step.The cyclization reaction was atom economy since it could be carried out without any additives or catalysts.Density Functional Theory(DFT)calculation showed that during the cyclylation of benzene intermediate through 1,3-dipole cycloaddition reaction and C=N+-O-,there was a ring opening process after the formation of unstable five-member heterocyclic product to generate the final product.2.Tetraynes with 2-phenyl-4,4,5,5-tetramethylimidazoline-3-Oxide-l-Oxyl to construct benzoxazolidine azole derivativesThe reaction of benzyne precursor formed by tetrayne with different substituents and 2-phenyl-4,4,5,5-tetramethylimidazoline-3-Oxide-1-Oxyl were explored to synthesize a series of novel benzo polycyclic products.Firstly,as in the previous part,a series of tetrayne substrates with different substituents were prepared under the protection of argon.Secondly,the tetrayne substrates and 2-phenyl-4,4,5,5-tetramethylimidazoline-3-Oxide-1-Oxyl were reacted in the absence of metal catalysts and the benzisoxoxane azole derivatives were synthesized in one step.Finally,the reaction might underwent a free radical process and the formation of the isoxazole ring was promoted by an unexpected cleavage of the two C-N bonds.The benzyne intermediate formed by the HDDA reaction can be captured by trapping agent immediately.In this process,no catalysts or additives are required and can be used to construct multiple chemical bonds in one step.Benzyne intermediates generated by thermal cyclization broaden the application of aryne reactions to a certain extent.All the new compounds in this paper had been characterized by NMR,HRMS and IR,and some compounds were also confirmed by X-ray single crystal structure analysis.