以7-氮杂吲哚为内在导向基...—H官能化研究进展（英文）_袁成.pdf

有机化学有机化学 Chinese Journal of Organic Chemistry REVIEW *Corresponding author.E-mail: Received May 20,2022;revised June 29,2022;published online August 10,2022.Project supported by the Qing Lan Project of Jiangsu Province.江苏省高校青蓝工程资助项目.156 http:/sioc- Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences Chin.J.Org.Chem.2023,43,156170 DOI:10.6023/cjoc202205034 综述与进展综述与进展 以 7-氮杂吲哚为内在导向基团的 N-芳基 CH 官能化研究进展 袁 成 潘长多*(江苏理工学院化学化工学院 江苏常州 213001)摘要摘要 内在导向基团是底物中固有的官能团,同时也是产物中的核心结构单元.因此,在 CH 官能化反应中,内在导向基团无需事先引入以及事后脱除.在过渡金属催化的 N-芳基-7-氮杂吲哚的 N-芳基 CH 官能化反应中,7-氮杂吲哚往往作为内在的导向基团,借助CH官能化的反应策略,在N-芳基的邻位引入各种官能团.对过渡金属催化7-氮杂吲哚作为内在导向基的 N-芳基 CH 官能化的最新研究进展进行了概述.关键词关键词 7-氮杂吲哚;内在导向基;CH 活化;过渡金属催化 Recent Advances in the N-Aryl CH Functionalization Using 7-Azaindole as Intrinsic Directing Group Yuan,Cheng Pan,Changduo*(School of Chemistry and Chemical Engineering,Jiangsu University of Technology,Changzhou,Jiangsu 213001)Abstract The intrinsic directing group is a functional group in the substrates and also serves as an essential component in products.Thus,the preinstallation and removal of directing groups are avoided.7-Azaindole has been used as intrinsic direct-ing group for the N-aryl-CH functionalization of N-aryls under the catalysis of transition metals.Utilizing the CH func-tionalization strategy,numerous functional groups were installed into the ortho-position of N-aryls of the corresponding N-aryl-7-azaindoles.In this review,the recent achievements on the transition-metal catalyzed N-aryl ortho-CH functionali-zation directed by 7-azaindole are summarized.Keywords 7-azaindole;intrinsic directing group;CH activation;transition-metal catalyzed In the past few decades,CH functionalization has be-come one of the most popular hotspots of research due to its high efficiency,simple operation,high atom economy and environmentally benign nature.1 In this field,directed CH activation,which shows excellent site selectivity is one of the most powerful approaches for the construction of CC and CX bonds from inert CH bonds.2 However,there are various directing groups which cannot be removed or require some additional steps for their removal,thereby it limits the structural diversity of the products and lowers the step economy.These limitations are overcome by transient directing group strategy which coordinate themselves to any pre-existing moiety in the molecule and get released after reaction.The traceless directing group strategy features with functionalization of the substrates and removal of the directing groups in one pot is another wise choice.Moreo-ver,intrinsic directing group strategy is also one efficient method to overcome such limitations,since the intrinsic directing group is a functional group that already existed in the substrates and serves as an essential component in products,thus there is no requirement for additional instal-lation or removal steps.For example,sulfonamide,-car-boline amides,imidazole,purine,2H-indazole were widely used as the intrinsic directing group for CH functionali-zation.3 7-Azaindole,a bioisostere of indole,displays a wide range of biological activities,and has been found in a large number of drug molecules and candidate drugs.4 With the tremendous progress in medicinal chemistry,a variety of 7-azaindole derivatives have been prepared and evaluated in clinical trials.For example,vemurafenib,GSK1070916,decernotinib and BMS378806 are currently on the market or under the clinical phase(Figure 1).5 In addition,N-phenyl-7-azaindole derivatives also have a diverse bioac-tivity profile including anticancer,antiproliferative,anti-diabetic,and NHE inhibitory activities(Figure 1).6 Given the broad utilizations of 7-azaindoles in medicinal chemis-try,there emerged many studies on the CH functionali-Chinese Journal of Organic Chemistry REVIEW Chin.J.Org.Chem.2023,43,156170 2023 Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences http:/sioc- zation of 7-azaindoles.For example,efficient functional group modifications at the C(2)or C(3)position of azain-doles under the catalysis of transition metals have been described.7 Besides,7-azaindole could be used as an in-trinsic directing group to facilitate the functionalization of C(sp2)H in N-aryl moiety of N-aryl-7-azaindoles.In re-cent years,researches on the 7-azaindole-directed N-aryl CH alkenylation,cyclization,amidation,amination,cy-anation,alkynylation,nitration,etc.have been developed.The purpose of this review is to provide an essay on the advances of transition-metal catalyzed 7-azaindole-directed N-aryl CH functionalizations(Figure 2).2 Carbon-carbon bond formation by 7-azaindole-directed N-aryl CH functional-ization 2.1 N-Aryl CH alkenylation of N-aryl-7-azaindoles In 2016,Dongs group developed a rhodium(III)-catalyzed CH alkenylation of N-aryl-7-azaindoles with electron-donating olefins(Scheme 1).8 Variously substi-tuted vinyl acetates and allyl acetates were used as cou-pling partners,providing the dehydrogenative Heck-type(DHR)pro