基于铑催化亲核环化/炔烃芳基化的3-烯基吲哚合成OA北大核心CSTPCD

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)2BF4 as metal precursor,4,5-bis(di-tert-butylphosphino)-9,9-dimethylxanthene(tBuXantphos)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.