?X+Y?Study On The Reaction Of Ring Synthesis Of Multi-heteroatom Heterocyclic Compounds

In this article,two new methods were developed for [X+Y] Synthesis of oxazidiazepine derivatives and isoxazole derivatives with hetero heterocyclic compounds.In the first part,an efficient synthesis of 1,2,4-oxadiazinan-5-ones via [3+3] cycloaddition of in situ generated aza-oxyallyl cations with nitrones has been developed.The protocol is featured with easy operation,excellent yields,excellent diastereo-control,broad substrate scope and good functional group tolerance.Firstly,the reaction conditions were selected and optimized from three aspects: the solvent,the base,and the reaction temperature.Finally,the optimal reaction conditions for the reaction were determined: anhydrous acetonitrile as the solvent,heating to 50? and under the basic conditions of sodium carbonate.A total of more than 30 products were synthesized,and the products were identified by MS,NMR,X-Ray,and Noesy.The generality of the reaction was also studied.The results show that the reaction has good universality and good yield(Up to 98%).Based on this,the possible reaction mechanism was introduced.The reaction may be formed by first removing one molecule of hydrogen halide by ?-haloamide under the basic conditions to form nitrogen-oxyallyl cation A.At the same time,nitrone formed 1,3-dipolar intermediate B in organic solvents.Immediately after the oxygen anion on the nitrone nucleophile attacks the nitrogen-oxyallyl cation.Finally,the nitrogen anion underwent an intramolecular nucleophilic attack to produce the target product.Due to the presence of chiral sites in the target product,the presence of isomers was considered.The isoform configuration(3R,6S configuration)was determined by the single crystal diffraction pattern and the two-dimensional hydrogen spectrum of the related products.In the second part,a new method was developed for synthesis of 3-phenyl-5-benzoyl-dihydroisoxazole derivatives under the basic conditions of ?-Bromo ketoxime and sulfuryllide in dry dichloromethane solvent and sodium carbonate.In the same way,the reaction conditions were selected and optimized from three aspects: the solvent,the base,and the reaction temperature.The optimal reaction conditions for this reaction were also set: dichloromethane was used as a solvent under the alkaline conditions of sodium carbonate,and the reaction proceeded smoothly at room temperature.A total of 20 products were synthesized,and the products were identified by MS and NMR.The generality of the reaction was also studied.The results show that the reaction has good universality and good yield,up to 90%.Based on this,the possible reaction mechanism was introduced.The reaction may be achieved through the removal of a molecule of hydrogen bromide by ?-bromohydrazine under alkaline conditions to form nitrosoethylene intermediate A.Simultaneously,sulfuryllide also removed a molecule of hydrogen bromide to form an intermediate B with a negative center under alkaline conditions.The negative center of intermediate B had a nucleophilic attack on nitrosoethylene.Through the removal of a molecule of dimethyl sulfide by electron transfer,the final cyclization achieved the desired product.