[3+3] Cyclization Reaction Of Active Methylene Isocyanides With Cyclopropene Derivatives

Since the first isonitrile compound was reported,in the development process of nearly 160 years,isonitriles have been used as a general method for the synthesis of nitrogen-containing heterocycles due to their special structure.This method of constructing heterocyclic skeleton has been widely used in organic chemistry,pharmaceutical chemistry and polymer science.Active methylene isonitrile as an important functional isonitrile in isonitrile compounds has been developed for nearly60 years.Active methylene isonitrile was found to be acidic at the α-position,and the introduction of electron-withdrawing groups at the α-position significantly enhanced its α-acidity.Based on the enhancement of nucleophilicity at the reaction site of isonitrile,the study of one-step synthesis of heterocyclic ring from active methylene isonitrile was gradually developed.When the cyclopropenes were isolated from natural products and their structure was confirmed,scientists were attracted to this particular structure.After 100 years of development,a large number of studies have shown that cyclopropylenes may be the smallest unsaturated ring compounds in nature,and their unique structure determines that they have alkene or alkyne properties.In recent years,with the gradual improvement and increase of methods for the preparation of cyclopropene and its derivatives,a complete and effective synthetic route has been formed.This has contributed to the study of cyclopropylenes.Among them,the most recent research focuses on the ring-opening mode of cyclopropene(C-C and C=C bond fracture mode).It is a common reaction to synthesize nitrogen-containing five-memed ring provided by active methylene isonitrile.However,limited by the structure of active methylene isonitrile itself,studies on the synthesis of six-memed pyridines are relatively rare.In this paper,based on the research progress of active methylene isonitrile in the construction of nitrogen-containing heterocyclic compounds,and combined with the reaction characteristics of cyclopropene derivatives,the reaction model of active methylene isonitrile and cyclopropene derivatives is proposed to generate a series of pyridine derivatives.This reaction model provides a new method for the synthesis of 4-fluoropyridine and 4-hydroxy pyridine compounds from active methylene isonitrile via [3+3] ring.At the same time,it also enriches the application range of cyclopropylenes.