α-Alkylation And N-Methylation Of Alcohols Catalyzed By A Dinuclear Cp*Ir Complex

The construction of C-C bond and C-N bond is a necessary step to construct the carbon skeleton of organic matter,and it is also a core problem that must be solved in organic synthesis.Theα-alkylation of ketones and alcohols is a key reaction in the construction of C-C bond.The traditional synthesis method is add equivalent of base and toxic halogenated hydrocarbon with nucleophilic reagents to produce alkylates and equivalent of inorganic salt,which resulting in atom waste and environment pollution.Similarly,the N-methylation reaction is an important reaction for the construction of C-N bond,and the N-methylated structure of the product exhibits extremely high biological activity and pharmacological activity.The hydrogen autotransfer reaction allows the reaction to be carried out using alcohols that is difficult to activate as alkylating agents（methanol as methylating agent）,which represents the most promising synthetic method.We hope to develop a water-soluble transition metal catalyst forα-alkylation and N-methylation in the aqueous phase under milder conditions.The reaction of acetophenone with benzyl alcohol was used as the reference reaction,and the iridium catalyst[{Ir（Cp*）（Cl）}₂（thbpym）][Cl]₂ and the base（potassium hydroxide）was added under the air reflux condition with water as solvent successfully obtained the desired product.A series ofα-alkylated products were obtained by expanding various substituents under the same conditions.In addition,we successfully synthesized donepezil,a drug for the treatment of Alzheimer’s disease,using this catalytic system.The catalytic effect of this catalytic system on the N-methylation reaction in the aqueous phase was further explored.Using benzenesulfonamide and methanol as reaction templates,the optimal reaction conditions were explored and applied to the N-methylation of sulfonamides,anilines and aliphatic amines with methanol.In this paper,a water-soluble catalyst[{Ir（Cp*）（Cl）}₂（thbpym）][Cl]₂ containing4,4’,6,6’-tetrahydroxy-2,2’-bipyrimidine（thbpym）ligand was successfully used to catalyze theα-alkylation reaction of ketones with alcohols in aqueous phase,and to catalyze the N-methylation of amines and methanol in aqueous phase.The catalytic system is environmentally friendly,the byproduct only generates water without other wastes,so the atomic utilization rate is very high;using water replace organic as solvent is more environmentally friendly.Therefore,the catalytic system have a good application prospect.