基于铑催化亲核环化/炔烃芳基化的3-烯基吲哚合成  

Rhodium catalyzed nucleophilic cyclization/alkyne arylationfor synthesis of 3-alkenylindoles

作　　者：李锦晨 叶智识 LI Jinchen;YE Zhishi(School of Chemistry,Dalian University of Technology,Dalian 116024,China)

机构地区：[1]大连理工大学化学学院,辽宁大连116024

出　　处：《大连理工大学学报》2024年第4期331-337,共7页Journal of Dalian University of Technology

基　　金：国家自然科学基金资助项目(22071014);辽宁省“兴辽英才计划”资助项目(XLYC1907036)。

摘　　要：3-烯基吲哚是一类重要的生物碱骨架,广泛存在于天然产物、药物及生理活性化合物.为发展高效且简洁的3-烯基吲哚合成方法,采用了铑催化亲核环化/炔烃芳基化串联反应.首先利用N-(2-(环丙基乙炔基)苯基)-4-甲基苯磺酰胺为模型底物,探索邻氨基苯乙炔类化合物胺铑化形成的3-吲哚铑中间体与模型底物另一分子中炔基的插入反应.通过金属前体、配体和溶剂等反应条件的系统优化,发现在以Rh(COD)_(2)BF_(4)为金属前体,4,5-二(二-叔丁基膦)-9,9-二甲基氧杂蒽(^(t)BuXantphos)为配体,四氢呋喃(THF)为溶剂,80℃下反应获得了94%的产率和24∶1的区域选择性.反应表明其具有优秀的底物普适性和良好的官能团兼容性,从中等到优秀的产率和从良好到优秀的区域选择性.机理研究表明磺酰基在反应中具有定位导向作用,不但促进3-吲哚铑中间体与炔烃插入反应,而且控制反应的区域选择性.3-Alkenylindole is a kind of important alkaloid skeleton,which widely exists in natural products,drugs and physiologically active compounds.To develop an efficient and simple method for the synthesis of 3-alkenylindole,a rhodium-catalyzed nucleophilic cyclization/alkyne arylation cascade reaction is used.Initially,N-(2-(cyclopropylethynyl)phenyl)-4-methylbenzenesulfonamide is chosen as the model substrate,and the insertion reaction of indol-3-yl rhodium intermediate formatted by aminorhodation of 2-alkynyl aniline compound with alkynes of another molecular in model substrate is studied.Through systematic optimization of reaction conditions such as metal precursor,ligand and solvent,it is found that in the presence of Rh(COD)_(2)BF_(4) as metal precursor,4,5-bis(di-tert-butylphosphino)-9,9-dimethylxanthene(^(t)BuXantphos)as ligand and tetrahydrofuran(THF)as solvent,at 80℃,the reaction affords 94%of yield and 24∶1 of regioselectivity.The protocol features broad range of substrates,good functional group compatibility,moderate to excellent yields,and good to excellent regioselectivities.The mechanism study shows that sulfonyl group plays an essential location role in the reaction,which not only promotes the insertion reaction of indol-3-yl rhodium intermediate with alkynes,but also controls the regioselectivity of the reaction.

关 键 词：环化 芳基化 3-烯基吲哚 铑 

分 类 号：O621.3[理学—有机化学]