Palladium-Catalyzed C-H Activition For Silylation And Germanylation

Organosilicon compounds are widely used as coupling agents and intermediates in synthetic chemistry.Due to the natural abundance of silicon and their physical and pharmacological properties,they play an indispensable role in the materials and pharmaceutical industries.In recent decades,organosilicon compounds have received more and more attention,and it is imperative to develop new methods to synthesize silicon-containing compounds.Transition-metal-catalyzed C-H bond activation is a green and efficient synthesis strategy which is attractive due to its steps and atom economy.In this article,the silylation of aliphatic ketones,aromatic ketones,aliphatic aldehydes,and amine was carried out using the palladium-catalyzed C-H activation strategy.The main content is divided into the following four parts:The first part:the development of a palladium-catalyzed C(sp~3)-H silylation of aliphatic ketones using aminooxyamide auxiliary.This method is the first to realize theβ-position C-H silylation reaction of aliphatic ketones.Andβ-substituted silylated products were successfully synthesized using hexamethyldisilane as the silicon source.For the results of substrate expansion,the reaction tolerates a number of functional groups and shows good selectivity in silylatingβ-C(sp~3)-H bonds in the company of C(sp~2)-H bonds and acidicα-C(sp~3)-H bonds.The aminooxyamide auxiliary is readily removed to giveβ-silyl ketones.The success of the gram-scale experiment and the derivatization reaction of silylated products enhances the application value of this method.Subsequently,late-stage diversification of the organic molecule with drug activity using this protocol further improved the applicability of the substrate for theβ-silylation of aliphatic ketones.The second part:the development of a palladium-catalyzed method for selective ortho-C(sp~2)-H silylation of aromatic ketones using aminooxamide promoters,and ortho-substituted silylated products were obtained.There is a broad substrate scope of this method,and the reaction exhibits high selectivity.In the presence of other aromatic C-H bonds,such as benzyl,allyl C(sp~3)-H bonds and acidicα-C(sp~3)-H bonds,the ortho-C(sp~2)-H bond could be selectively monosilylated.The aminooxyamide auxiliary can be readily removed after the silylation reaction.The success of the gram-scale experiment further enhances the application value of this method.In the derivatization reaction,Si Me can be cut to form Si-I and then react with water to form Si OH.This is the first time that the conversion of trimethylsilane to silanol has been realized,and it is a practical method for the efficient synthesis of silanol.The third part:the development of palladium-catalyzed C(sp~3)-H silylation and germanylation of aliphatic ketones with hydrazine as auxiliary.The substrate scope of trimethylsilylation,dimethylphenylsilylation,and trimethylgermanylation of aliphatic ketones and aldehydes were explored.This is the first case that acethydrazine is used as an auxiliary group for C-H functionalization.In the derivatization reaction,the TMS group can be converted to silanol.Subsequently,late-stage diversification of the organic molecule with drug activity using this protocol was carried out,and the corresponding products can be obtained with a moderate yield,which shows the good substrate applicability in theβ-silylation reaction system.Finally,the reaction palladium intermediate(5,5)bicyclic palladium ring intermediate was synthesized to explore the reaction mechanism and understand the mechanism of C-H activation and silylation.The fourth part:The development of palladium-catalyzed alkylamine free(NH)-directed C(sp~2)-H silylation method,and the scope of morpholinone substrates was explored.The success of the silicidation product derivatization reaction further enhances the application value of this method.Finally,a reasonable reaction mechanism is put forward as a reference for explaining the whole process of the reaction.