Rapid Synthesis Of Spiro-4-oxazolidinones

Spiro compounds are structurally stable and have two perpendicular planes,which are often seen in various natural products.Its rigid structure makes it less prone to racemization.Under certain circumstances,they can constitute chiral molecules and some spiroheterocyclic compounds also have special properties such as spiroconjugation or spiro-hyperconjugation which other organic materials do not have.Due to their unique structure features and properties,spiro-heterocyclic compounds have been widely used in many fields such as biomedicine,luminescent materials,and asymmetric catalysis.Its broad prospect in application,novel structure and potentially high biological activities make them attractive targets for organic synthesis chemists.At the same time,many oxazolidinone compounds are found in various spiro heterocyclic natural products and bioactive molecules.They have been shown to prosses potential antibacterial,anticancer,and antimigraine properties.The drug development and exploration of oxazolidinone compounds have shown their high application potential in the treatment of bacterial infections.Therefore,it is extremely important to develop a simple,effective,high-yield method for synthesizing oxazolidinone spiro heterocyclic compounds,which has very important practical and academic significance in the development of new drugs and functional materials.Thos thesis is based on the investigation of azaoxyallyl cations,using the ?-halo hydroxamates to generate azaoxyallyl cation intermediates in situ under the action of Br?nsted bases.The [3+2] cycloaddition reaction with benzofuranones generated spiro-4-oxazolidinones.In view of the importance of spiro-4-oxazolidinones,we further screened the reaction conditions.In search for the optimal conditions with the model reaction,various organic bases,inorganic bases,solvents were screened,and diisopropylamine was used as a base and hexafluoroisopropanol as a solvent,and the spiro-4-oxazolidinone product was obtained in nearly 100% at room temperature for 12 hours.The reaction is simple in operation,high in yield,adaptable to functional groups,and has a wide substrate scope.Even if the reaction is carried out on a gram scale,the yield was not affected.In addition,highly functionalized products could be efficiently obtained by structural modification of the exocyclic double bond in the product,such as the epoxidation and reduction with hydrogen of the double bond.In addition,we also used this reaction for the modification of natural products.Estrone could generate the corresponding spiro-4-oxazolidone product in our reaction system with high yield and close to 100% enantioselectivity,which proves that the reaction has a very high application potential in the modification of pharmaceutical intermediates and compounds with medicinal value.This study provides a simple and highly efficient method to further construct series of compounds with important physiological activities or pharmacological activities.On the other hand,the discovery and research of azaoxyallyl cations have only been reported in the last five years and is in a good time for further development.Utilizing its high reactivity and easy access,new ideas for the construction of many nitrogen-containing heterocyclic compounds can be provided.At the same time,the nitrogen-containing heterocyclic compounds involved in the synthesis of azaoxyallyl cations can also be tested for their biological activities.These functionalized oxazolidinone compounds not only enriches the compound library for drug screening,but also further extends the reaction scope involving the nitroxallyl cations.