Study On Cyclization/Difluoromethylation Of Hydrazones

N-Tosylhydrazone is easy to prepare and has stable properties,which not only exists as a skeleton structure in natural active molecules,but also as an important synthon to construct a series of active molecules with medicinal value or monomer functional molecules in the field of materials science.Therefore,the development of new reactions involving N-tosylhydrazones with high efficiency and selectivity under mild conditions has always been a research hotspot in the field of organic synthetic chemistry and has important research significance.Cyclic compounds are widely found in various natural products and functional molecules.The development of green and efficient methods for constructing various types of cyclic compounds has attracted much attention,especially the synthesis of the smallest cycloalkane,three-membered ring.And the cycloaddition reaction,which exhibits a relatively high chemical,regio-and stereoselectivity,has attracted much attention as one of the most effective methods for building cyclic compounds.On the other hand,fluorine-containing compounds that account for more and more weight in agrochemicals,pharmaceuticals,and functional materials which make fluorine chemistry as one of the key research areas for scientific researchers.This includes how to introduce difluoromethyl into the target molecules to achieve the modification of the structure and properties of the original molecules.Based on previous investigations,the development of a simple and efficient transformation process via simple and readily available N-tosylhydrazones to build cyclic and fluorine-containing compounds is of great significance.At the same time,new ideas for the synthesis of N-tosylhydrazones as raw materials have been expanding.The specific research content of this topic is as follows:In the second chapter,we studied the base-mediated synthesis of adjacent quaternary carbons aminocyclopropanephosphonates by the use of N-tosylhydrazones and dehydrophosphoramidate as substrates via [3 + 2] cycloaddition and denitrification.Under basic conditions without metal participation,the cyclopropane structure bearing amino and phosphate groups and two quaternary carbons was successfully built in one step.The construction of two adjacent C4 potential chiral centers and successful separation of the two configurations afforded convenience for the subsequent transformations,in which the products were converted to the corresponding coupling products and phosphoramidite derivatives by Suzuki coupling reactions and acidification reactions,respectively.In the third chapter,we mainly studied the difluoromethylation of N-tosylhydrazones with bromodifluoromethyltrimethylsilane as the difluoromethyl source under the co-promotion of base and phase transfer catalysts.At the same time,the construction of C-N bond was realized,and a series of N-difluoromethyl disubstituted N-tosylhydrazone compounds synthesized with good functional group tolerance and wide substrates scope,which can be converted into a series of useful molecules.