Copper-catalyzed Decarboxylative Cyclization For The Synthesis Of 2-Phosphorylmethyl Indoles

Phosphorus-containing heterocyclic compounds are an important class of organic compounds.Not only is it widely present in many natural or pharmacologically active natural products or drug molecules,but also used as useful intermediates for constructing many other heterocyclic compounds.Thus,the efficient synthesis of such compounds has been a significant research topic of organic chemists.Although plenty of protocols have been developed,many of them are synthetically tedious,and generally require harsh conditions,such as high temperature or an equivalent strong oxidizing agents.Therefore,the development of simple,inexpensive and green synthetic methods for phosphorus-containing compounds is of important research significance.In this thesis,by applying ethynyl benzoxazinones that were previously developed in our group,under mild conditions,we realized a copper-catalyzed,one-step synthesis of 2-phosphorylmethyl indoles.The possible reaction pathway was described as following:the reaction between ethynyl benzoxazinones and copper catalysts deliveres a copper-contained 1,4-dipole precursor after releasing carbon dioxide;then,the nucleophilic P(0)H compound attacks the Cy position of the Cu-allenylidene part of dipole intermediates followed with an intromolecular Michael addition,leading to the desired 2-phosphorylmethyl indoles.Through screening of a series of conditions,we found that the combination of Cul and nitrogen ligand(Pybox)was the best catalyst by using methanol as solvent and DIPEA as base.Under the optimal conditions,we examined the substrate scope for this copper-catalyzed decarboxylative cyclization.A series of 2-phosphorylmethyl indoles were obtained in 40-99%yields,which were identified by1H NMR,13C NMR,31P NMR,HRMS and so on.It is worth mentioning that when the reaction is performed with an alkynyl benzoxazinone substrate containing a quaternary carbon center,the 2,3-disubstituted phosphorus-containing compounds can be synthesized in 40%yield.In addition,we proposed a possible mechanism based on the proceeding literature and control experiments.This research has been published in Chemical Communications(2018,54,3154-3157).