Rh(?)-Catalyzed C-C ? Bond Functionalizations

C-C?bond functionalization provides a versatile transformation platform to assemble and reorganize complex molecular skeletons through via high atom-economic and step-economic chemical bond cleavage.However,it is very challengling to activate the C-C?bonds due to the steric hindrance effect caused by the dense distribution of chemical bonds around carbon atoms and the inert characteristics of carbon-carbon?bonds.Indoles are important aromatic heterocyclic compounds,which are widely used in the fields of biopharmaceuticals,synthetic chemistry,materials and so on.Therefore,the development of synthetic methodology of multifunctional indole derivatives has recently aroused wide concerns.The exploration of the C-C?bond activations and functionalizations from indolyl skeletons will provide a new approach to access complex organic molecxules,in which could be employed in pharmaceutical chemistry and other fields.The first part of this thesis was involved in an unprecedented Rh(?)-catalyzed unstrained aryl-ketone Csp~2-Csp~2?bond amination under the pyridine-chelation assistance.Different andolyl/alkyl ketones could efficiently react with sulfonylazides to assemble 2-aminoindolyl skeletons in good to excellent reaction conversions.This newly developed methodology enables a direct conversion of C2-acyl group to C2-arylsulfonylamido group in highly congested indole molecules via Csp~2-Csp~2?bond cleavage.The combination of experiments with DFT calculations about this transformation demonstrated that?-aryl elimination derived from enole-based cyclorhodiumates belonged to a key step,while the formation of rhodium nitrene was rate-limiting step.Subsequently,A Rh(?)-catalyzed?-carbon amination of?-arylalcohols with sulfonyl azides has been further explored based on a novel direct amination of ketones via Csp~2(aryl)-Csp~2(C=O)bond cleavage,in which?-aryl elimination derived from enol-based cyclometallation process play a key role in this carbon-carbon bond amination.Various indolyl/alkyl alcohols including cycloalkyl alcohols were allowed to react with sulfonyl azides to provide the 2-aminoindoles via the direct Csp~2(aryl)-Csp~3(alkyl)?bond cleavage.Mechanism studies demonstrated that hydroxyl group from alcohols and pyridinyl nitrogen played a key role to coordinate with Rh(?)catalysts for activating the Csp~2(indolyl)-Csp~3(alkyl)bonds.As we known,enols belong to unstable and highly active intermediates in many organic transformations,developing new organic reactions to assemble stable enols are therefore a challenging research project in synthetic chemistry.Encouraged by our previous progress and the existing C-C?bond activation strategies,we employed the diazocompounds as possible“enol”sources,and explored a Rh(?)-catalyzed Csp~2-Csp~3?bond carbenoid functionalization of?-(2-indolyl)alcohols with acceptor/acceptor diazo compounds.It was found that Rh(?)-catalyzed coupling reaction of?-indolyl alcohols with donor/acceptor diazo compounds provided a novel approach to assemble stable C2-enolated indole skeletons with high stereoselectivity Z-enolization via Csp~2-Csp~3?bond cleavage.The compatibility of this transformation with indole-fused cycloalkyl alcohols renders this reaction synthetic value for reorganizing the complex indole skeletons.