Transition-Metal-Catalyzed Intramolecular Cross-Dehydrogenative-Coupling Of Ortho-Functionalized-2-Arylindoles

The transition-metal-catalyzed cross-dehydrogenative-coupling(CDC)reaction has proved a new and convenient way for the efficient construction of carbon-carbon bonds and carbon-heteroatom bonds.The cross dehydrogenation coupling reaction(CDC reaction)is highly attractive because both two coupling partners do not require pre-functionalization.The intermolecular CDC reactions,such as Fujiwara-Moritani alkylation,Sonogashira Alkynylation,Friedel crafts alkylation and so on,have become a significant tool in the construction different types of C-C bonds;and the intramolecular CDC reaction is a powerful method to synthesize cyclic compounds.The combination of intermolecular and intramolecular dehydrogenation coupling reaction,which has high atom economy,has become the front researchfield of polycyclic molecules synthesis.Polycyclic compounds with indole skeleton exist in many natural products or bioactive molecules,and their synthesis methods have received considerable attention by many organic chemists.In this dissertation,we investigated intramolecular dehydrogenation coupling reaction to synthesize fused-indole compounds from ortho-C-H functionalized 2-arylindole.The research content contains two aspects:(1)The intramolecular dehydrogenation coupling reaction of O-olefinated 2-phenylindole was inverstigated.The results show that the site selectivity of intramolecular dehydrogenation coupling reaction can be realized by selecting different catalysts:Pd(OAc)₂ favored 6-alkylidene-6H-isoindo[2,1-a]indoles via intramolecular C-H/N-H CDC reaction,while[Cp*Rh Cl₂]₂ led to 11H-benzo[a]carbazoles through intramolecular C-H/C-H CDC reaction.Moreover,the synthesis of 11H-benzo[a]carbazoles via sequential intermolecular ortho C-H/olefin coupling and intramolecular C3-H/olefin coupling from 2-phenylindoles and alkenes can be operated in one-pot.Additionally,a fused-pentacyclic ring could be efficiently synthesis in three steps from 2-phenyl-1H-indole via quadruple CDC reactions.(2)The intramolecular dehydrogenation coupling reaction of O-alkylated 2-phenylindole was inverstigated.The results show that O-alkylated 2-phenylindole undergoes intramolecular free radical cross dehydrogenation coupling reaction affording5H-Indeno[1,2-b]indole using manganese acetate(III)as a mediator.In this method,0.2mmol of 2-[2-(1H-indole-2-yl)-3-methyl-phenyl]-malonate dimethyl ester was used as the reaction substrate,dimethyl sulfoxide(2 m L)as the solvent,and the reaction was conducted for 20 hours under 3 equivalent Mn(OAc)₃·H₂O.This method provides a new way for the synthesis of indno[1,2-b] indoles.