过渡金属催化苯并-2,1-异噁唑的环化反应研究进展

Research on the transition metal-catalyzed annulations of anthranils

含氮杂环常见于天然产物、药物和材料分子中,也是人体内多种氨基酸和激素的主要结构单元.近年来,苯并-2,1-异噁唑作为有效的胺化试剂被广泛应用于胺化、环化反应中.尤其是过渡金属催化的苯并-2,1-异噁唑的胺化-环化反应,已经成为构建C—N键和合成含氮杂环的强有力工具,也引起越来越多研究者的兴趣和关注.本文概述了近年来过渡金属催化苯并-2,1-异噁唑环化反应的相关研究,并对该研究领域存在的问题和难点进行简要的展望.

Nitrogen containing heterocycles are important structures of many natural products and drugs,which are widely used in active drugs,herbicides,insecticides and other fields.In addition,nitrogen-containing heterocyclic compounds also play an indispensable role in human body,such as tryptophan,α-amino acid,neurotransmitter,serotonin,melatonin,etc.The synthesis and functionalization of nitrogen-containing heterocyclic compounds have attracted great attention due to their great influence and application in materials science,medicinal chemistry and agricultural chemistry.C—N bond is one of the most abundant and important chemical bonds in many natural products,drugs and materials.The efficient construction of C—N bond through the development of novel catalytic systems and amination reagents has attracted extensive attention of synthetic chemists.Benzo-2,1-isoxazole has become an important and versatile amination reagent because of its easy availability and good reactivity.It has been widely used in many types of amination cyclization reactions due to its rich and adjustable activity in transition metal catalysis.The structure of benzo-2,1-isoxazole satisfies the Hückel rule and is stable in general.However,benzo-2,1-isoxazole can be converted to aryl or ketene species by pyrolysis of N—O bond at relatively high temperature.The thermal decomposition of anthranils is generally controlled by the 3-substituted group of anthraquinone.The anthranils with no substituents at the 3-position give ketenes,while the anthranils with aryl substituents at the 3-position give aryl intermediates.In recent years,the development of transition metal catalysis(Au,Rh,Co,Cu,Ni,etc.)provides powerful tools for the activation of anthracene compounds,and enables these useful synthons to be transformed into highly active metal aryl nitrenes species for the rapid synthesis of various promising high-value nitrogen-containing molecules.Therefore,anthranils can be used as an efficient electrophilic amination reagent in transition metal catalyzed cross coupling reactions with organometallic reagents or C—H amination reactions.In addition,in the presence of gold catalyst,anthranils can be used as N-nucleophilic reagent to react with alkynes to formα-imino gold carbene complex in situ for further amination.Most importantly,anthranils contain five membered rings composed of electrophilic formyl group and nucleophilic amino group,which have good 1,3-dipolar properties.Therefore,the[4+3]and[4+2]cyclization reactions of various important anthranils rings have been successfully applied to the synthesis of nitrogen-containing heterocycles with different functional groups.In recent years,some research groups have developed transition metal Au,Cu,Rh and Sc catalyzed amination cyclization of benzo-2,1-isoxazole,mainly including cyclization with alkyne derivatives,diaryl iodides,aromatic amines,aromatic aldehydes,amidines and other compounds to generate nitrogen-containing heterocyclic compounds such as pyrazine,indole,pyrimidine,quinoline,etc.In view of the rapid development of the cyclization reactions involving benzo-2,1-isoxazole,the related reactions catalyzed by transition metals such as Au,Cu,Rh and Sc in recent years were summarized,and the reaction mechanism was emphatically introduced.It is hoped that this work can provide reference for researchers.