Rh(Ⅲ)-Catalyzed Csp~2-Csp~3 Bond C-2 Carbonylethylation Of Indoles

The transition metal-catalyzed C-Cσbond functionalization is an effective strategy to efficiently and quickly construct new C-C/C-X（X=C,N or O）bonds.However,due to the high thermodynamic stability of C-Cσbonds and steric hindrance derived from congested chemical bonds around these bonds,transition metal-catalyzed C-Cσbond activation is very challenging.On the other hand,indole compounds,especially 2-carbonylindole compounds,are the core skeletons of many natural products and biologically active molecules.Meanwhile,such compounds could also be converted into more complex indole-fused compounds.Therefore,the development of transition metal-catalyzed carbonylethylation of Csp²-Csp³σbond at the C-2 position of indoles has important scientific significance and practical value.Based on previous C-2 functionalization reactions of indole,Rh（Ⅲ）-catalyzed ligand-assisted indole/alkyl alcoholic C-Cσbond activation has been explored.This method provides a simple approach to 2-carbonylethyl compounds through the coupling reaction of C-Cσbonds with alcohols.The optimization of reaction conditions shows that[Cp*Rh Cl₂]₂/Ag₂CO₃ catalytical system enables the carbonylethylation of 2-indolyl alcohols with allylic alcohols.This transformation can tolerate a broad range of function groups.All kind of allylic alcohols can efficiently react with N-（2-pyridyl）indolylalkyl alcohol to furnish different 2-carbonylethylindoles with good to excellent yields.Electron-donating groups on the aromatic ring of indolyl skeleton can be efficiently converted into 2-carbonylethyl indoles while the reaction conversion of electron-withdrawing indolyl alcohols was lower.It should be noted that various alkyl chain length from alkyl alcohols have low impact on this reaction.More importantly,indole-fused cycloalcohols also smoothly underwent Csp²-Csp³ bond cleavage/carbonylethylation to furnish the corresponding 2-carbonylethylindoles in acceptable yields.All the structures of desired products were characterized by ¹HNMR,¹³CNMR,HR-MS and IR spectrum.Mechanism studies demonstrated that Rh（Ⅲ）-catalyzed Csp²-Csp³σbond carbonylethylation at C-2 position of indole involvesβ-aryl group elimination ofα-indole alcohol to form the corresponding cyclometallated rhodium（Ⅲ）complexes,followed by migration insertion,β-hydrogen elimination and enol/ketone isomerization to form 2-carbonylethylindoles.