Research On N-heterocycle Synthesis Using Oxime Acetates As The Starting Materials

N-heterocyclic compounds widely exist in the research fields of pesticide,medicine and materials science.3H-pyrazolo[1,5-a]indol-4(3aH)-one skeleton is the core structure among many bioactive molecules,while multi-substituted pyridine derivatives,especially the trifluoromethyl pyridine compounds,are widely used in the medical chemistry.In view of N-heterocyclic compounds being significant practicality and application value,studies on synthetic methods of this kind of compounds are still a hotspot in organic synthesis.Although a large number of literature reports the research methods for the synthesis of nitrogen heterocycles,the efficient construction of N-heterocyclic compounds with high selectivity from cheap raw materials remains the target of researchers.This paper focuses on the synthetic methods of N-heterocyclic compounds under the transition metal catalysis or metal-free conditions to prepare 3H-pyrazolo[1,5-a]indol-4(3aH)-one compounds,2,4-diaryl pyridine derivatives and trifluoromethyl pyridine compounds using the oxime esters as the raw materials.The research content is as follows:1.The 3H-pyrazolo[1,5-a]indol-4(3aH)-one compounds was synthesized through the intermolecular cyclization catalyzed by copper salt under oxygen atmosphere using 2-substituted indoles and oxime esters as the raw materials.This method features advantages including low-cost copper catalyst,mild reaction conditions,high yield,wide substrate scope,broad functional-group tolerance.The by-products acetic acid and water are nontoxic to environment and the separation and purification of the desired products are easily handling.Oxime esters served as not only a source of "N" but also as an internal oxidant to initiate the aerobic oxidation and cyclization of indoles.This protocol provides a new entry to the synthesis of 3H-pyrazolo[1,5-a]indol-4(3aH)-one compounds.2.2,4-Diaryl pyridine derivatives have been efficiently and selectively prepared by the synergistic promotion of I2 and triethylamine using oxime esters and enals as the raw materials.The reaction is facile and the additives I2 and triethylamine used in this method are cheaply and readily available.The results from mechanistic experiments indicate that the reaction probably proceeds through a radical pathway.3.Mono-or di-trifluoromethyl pyridine derivatives,which are of important medical value,have been obtained using oxime esters and trifluoromethyl reagents as raw materials on the synergistic assistance of ammonium iodide and the reducing reagent Na2S2O4.On the meanwhile,the 2,3,4,6-tetrasubstituted trifluoromethyl pyridines were synthesized in one pot with the treatment of ammonium iodide and triethylamine using of oxime esters,aldehydes and trifluoromethyl reagents as the raw material.The method features the advantages including transition metal-free and simple conditions and high yield.It also represents a new protocol for the synthesis of trifluoromethyl pyridine derivatives.