Synthesis Of Nitrogen-containing Heterocycles Via Oxazolones–Based [3+2] Cycloadditions

Nitrogen-containing heterocycles constitutes a family of biologically and medicinally important molecules,and have found many significant applications in the drug development.These heterocycles can be constructed via the cycloaddition reactions concisely and efficiently.As the synthetically useful and important building blocks,under the different reaction conditions,oxazolones show the varying chemical behaviours in the cycloaddition.In this work,we newly designed two types of oxazolone-based [3+2] cycloadditions to prepare structurally diverse heterocycles possessing potential biological activities.Significantly,these research works enriched the synthetical methodology of isoxazolidinones and 1,2,4-triazole indolinones,and afforded the facile protocols to obtain structurally various heterocycles.This thesis involves the following two parts:1.Construction of isoxazolidinone via [3+2] cycloaddition of oxazolones with nitronesInitially,by using a model reaction between oxazolone with nitrone,we optimized the reaction conditions in terms of additives,solvents and substrates ratios at room temperature.Under the optimal reaction condition(oxazolones/nitrones/ TMSCl=1.2/1/2 in DCM at room temperature),we widened the reaction scope of the [3+2] cycloaddition by using structurally different oxazolones and nitrones.The conducted [3+2] cycloadditions worked well and provided the desired isoxazolidinones in 72%->99% chemical yields with >20:1 distereoselectivities.The chemical structure and relative configuration of target molecules was confirmed firmly via single-crystal X-ray structure analysis.Moreover,we hypothesized the reaction mechanism for the tandem nucleophilic addition of oxazolones with nitrones.2.Synthesis of 1,2,4-triazole indolinones through [3+2] cycloaddition between oxazolones and diazooxindolesAt the beginning,we screened additives,solvents,substrates ratios and temperatures to optimize the reaction conditions by using the model reaction between oxazolone and diazooxindole.With the optimal reaction condition in hand(oxazolones/diazooxindoles/DIPEA=1.3/1/0.5 in MeCN at room temperature),we broaden the reaction scope by choosing the structurally different substrates.Generally,the established [3+2] cycloadditions proceeded readily to furnish 1,2,4-triazole indolinones in up to 98% chemical yield.Moreover,the chemical structure of target molecules was clearly identified by single-crystal X-ray structure analysis.Also,the [3+2] cycloaddition tandem mechanism of oxazolones with diazooxindoles was proposed to interpret the formation of the desired compounds.