Ir-catalyzed Alkylation Of Nitrogen-containing Heterocycles And Aromatic Ketones

The construction of carbon-carbon bonds is one of the most important transformations in organic synthesis,and considerable research efforts have been directed towards the development of new methods in this area.Importantly,transformations of this type provide access to a wide variety of organic compounds that can be used as synthetic building blocks in the fine chemical and pharmaceutical industries,as well as key intermediates in the preparation of drugs and functional materials.The classical methodology for the formation of carbon-carbon bonds involves cation-anion-based nucleophilic substitution reactions between organometallic reagents and organohalides.Recent progress in this area has culminated in the development of transition-metal-catalyzed cross-coupling reactions,which have provided several useful C-alkylation methods for introducing various aryl,vinyl,and alkyl groups.Notably,these reactions do not require organometallic or organohalide substrates and are therefore much more atom-economical and environmentally friendly than their predecessor.Many studies have shown that transition metal iridium catalysts are widely used in organic synthesis reactions.These catalysts have the advantages of high catalytic activity,mild reaction conditions,and no toxic and hazardous substances,which meet the requirements of green chemistry and atomic economy.Therefore,more and more researchers are applying transition metal iridium catalysts to the study of organic synthesis,especially in the research directions of constructing C-C bonds,C-N bonds,acceptors dehydrogenation,and transfer hydrogenation through hydrogen transfer reactions.Meanwhile,transition metal-iridium catalysis as a promising alternative to C-alkylation methods,hydrogen transfer process using alcohols represents a highly utilizable and environmentally benign process that uses alcohols as alkylating agents and water is generated as the only major by-product.Based on transition metal-ligand bifunctional metal-iridium catalysts,two synthetic methods were developed using a borrowed hydrogen strategy to select less toxic alcohols as raw materials,reducing or avoiding the formation of by-products and exploring more moderate reaction conditions.The main studies are as follows:Using a water-soluble metal-ligand bifunctional iridium catalyst[Cp*Ir（2,2’-bpy O）（OH）][Na],β-methylated secondary alcohols were synthesized by a methylation/transfer hydrogenation tandem reaction using phenylacetone and methanol,water as raw materials and methanol as hydrogen source.In this system,using a catalytic amount of the weak base Cs₂CO₃ can effectively avoid the formation of dimethylation by-products and is a method with mild reaction conditions and high atomic economy.Using a water-soluble metal-ligand bifunctional iridium catalyst[Cp*Ir（2,2’-bpy O）（OH）][Na],heterocyclic compounds（1,3-dimethylbarbituric acid,2-indolone）and alcohols were used as raw materials,and not only water was used as a solvent,but also an acceptor-free dehydrogenation process was achieved to synthesize alkylation products of heterocyclic compounds.The reaction conditions are mild,with good yields and substrate tolerance,and it is a method in accordance with green chemistry and atomic economy.