Synthesis Of Nitrogen-containing Heterocycles Via ?-Halohydroxamates–Based [3+2] And [3+3] Cycloadditions

Nitrogen-containing heterocycles are widely distributed in nature and have important biological activities.They play an important role in the field of biochemistry and medicinal chemistry.Their synthesis has attracted wide attention from chemists.Cycloaddition reaction is a highly efficient and concise method for the synthesis of nitrogen-containing heterocycles.?-halohydroxamates are class of important building blocks for the construction of nitrogen-containing heterocycles.In this work,three different series of heterocycles bearing potential bioactivities were synthesized by using newly designed cycloaddition reactions of ?-halohydroxamates.The research contents are classified into the following three parts:I.Construction of 1,2,4-oxadiazinan-5-ones via [3+3] cycloaddition of ?-halohydroxamates with nitronesFirstly,we used model reaction of ?-halohydroxamate and nitrone to optimize the reaction conditions by screening solvents,bases and the ratio of the reactants.Then,with the optimized reaction conditions in hand,we extended the reaction scope of the [3+3] cycloadditions by diversifying ?-halohydroxamates and nitrones,and obtained 24 1,2,4-oxadiazinan-5-ones in the highest yield of 99%.Lastly,the chemical structure of target products was unambiguously determined by single crystal X-ray analysis.Moreover,we proposed the reaction mechanism for the corresponding [3+3] cycloaddition reaction.?.Construction of 2-iminothiazolidin-4-ones via [3+2] cycloaddition of ?-halohydroxamates and isothiocyanidesThe reaction conditions were optimized systematically by screening different factors such as solvents,bases and the ratio of the reactants.Under the optimized reaction conditions,the [3+2] cycloadditions efficiently furnished structurally diverse 2-iminothiazolidin-4-ones in moderate to excellent yields(25-99% yields).The structure of target products was determined by single crystal X-ray analysis.Also,we predicted the reaction mechanism for the formation of 2-iminothiazolidin-4-ones.?.Construction of 1,3,4-oxadiazin-6-imines via [3+3] cycloaddition of ?-halohydroxamates and hydrazonoyl chloridesFirst,we screened the effects of different solvents,inorganic bases,organic bases,the ratio of the reactants and temperatures on the model reaction.Next,under the optimal reaction conditions,we broadened the reaction scope of the [3+3] cycloaddition by diversifying ?-halohydroxamates and hydrazonoyl chlorides,and gained the desired 1,3,4-oxadiazin-6-imines in moderate to good chemical yields.Last,the chemical structure of the target products was determined by single crystal X-ray analysis.And we also assumed the reaction mechanism for the [3+3] cycloaddition of ?-halohydroxamates and hydrazonoyl chlorides by conducting DFT calculation.