Research On The Application Of Supported Organometallic Catalysts In The Preparation Of Aromatic Alcohols In Continuous Flow

Flow chemistry is an interdisciplinary subject that combines microreaction techniques with chemical synthesis,also known as "continuous flow chemistry." Because of its high safety,fast heat and mass transfer rate,short production process and on-line purification,it is conducive to the industrial production of products.In the past 20 years,although continuous flow chemistry has achieved significant results in the production of large quantities of chemicals in the petrochemical industry,it is still a relatively new quantitative synthesis and screening technology in the field of drug synthesis,especially in the laboratory research and development stage.It poses a major challenge for organic synthetic chemists.In recent years,our research group has reported a series of solid-phase catalysts supported by mesoporous inorganic and organosilicon materials as carriers and applied to the Asymmetric transfer hydrogenation(ATH)reaction of ketones.These catalysts all exhibit good catalytic performance: mild conditions,and the resulting chiral alcohol can be used as an important raw material or intermediate in the fields of chemical medicine and the like.In this paper,the main advantages of continuous flow chemistry are used to immobilize the supported catalyst in the X-Cube packed bed reactor to catalyze the Asymmetric transfer hydrogenation reaction of aryl ketones,and explore the potential and theoretical basis of its application to industrial production.Based on the above basis,this paper is mainly divided into two parts.(1)The application of supported chiral organometallic ruthenium catalysts in the continuous flow of Asymmetric reduction reaction: Using post-grafting strategy,three different types of chiral quinone/diamine functionalized supported chiral organometallic ruthenium catalysts were obtained by coordination with the corresponding organometallic ruthenium on chiral diamine functionalized silicon materials(Two two-dimensional hexagonal mesoporous silicon(SBA-15 and PMO types)and one spherical mesoporous inorganic silicon).The catalytic performance of asymmetric hydrogen transfer reduction of acetophenone under continuous flow system was studied by filling the above three types of catalysts in an X-Cube reactor,Through the screening of reaction temperature,co-solvent and other factors,the comparative analysis of the test results shows that the PMO type catalyst with two-dimensional hexagonal structure has high reaction performance and high stability,and can continuously obtain up to 96% within 11 h.Yield and 97% enantioselective chiral phenylethyl alcohol.(2)The application of a combination of supported organometallic carbene palladium catalysts and chiral organometallic ruthenium catalysts in a continuous flow of coupling/reduction tandem reactions: Co-polycondensation of a carbene palladium functional silicon source with an ethyl bridged silicon source to obtain a PMO type supported organic carbene palladium catalyst having a two-dimensional hexagonal structure;Optimizing the coupling reaction of the carbene palladium catalyst in the X-Cube packed bed reactor,and obtaining the optimized reaction conditions of the continuous flow of the aromatic ketone and the arylboronic acid;Optimizing the ATH reaction of the supported organometallic ruthenium/diamine catalyst in the X-Cube packed bed reactor,and obtaining the optimized reduction reaction conditions of the continuous flow of the biaryl ketone compound;The two supported catalysts are combined to optimize the reaction conditions of the two catalysts in the coupling reaction and the ATH reaction,thereby realizing the preparation of chiral biphenylethanol efficiently,and can be prepared within twelve hours.Chiral phenylethyl alcohol with up to 96% yield and 97% enantioselectivity was continuously obtained.