Metal Pd-catalyzed N-arylation Of NH-sulfoximines And Aryl Bromides In Aqueous Micelles

Due to its unique physicochemical and biological properties,N-aryl sulfoximines have a wide range of applications in synthetic chemistry,medicinal chemistry and many other fields.N-aryl sulfoximines are important and versatile chiral auxiliaries,ligands and catalysts in asymmetric synthesis.In agrochemistry,sulfoximine is a new and unique insect control agent such as sulfoxaflor.In medicinal chemistry,N-aryl sulfoximines are an important component of many biologically active drugs and have outstanding performance in drug molecules such as inhibitors(anti-cancer,anti-asthma,anti-HIV and antimicrobial).So far,there have been many reports on the synthesis of N-aryl sulfoximines.These synthesis methods can be roughly divided into three categories:1)transition metal catalysis,commonly used metal catalysts including Pd,Cu,Fe,Ni,etc.;2)nonmetallic catalysts Metal catalysis;3)Photocatalysis;4)Electrocatalysis.Due to its wide range of substrates and high catalytic activity,transition metal-catalyzed C-N bond coupling to synthesize N-aryl sulfoximines is still the most commonly used method.The synthesis of the above-mentioned N-aryl sulfoximines is carried out in organic solvents,and the amount of metal catalyst is relatively high,and the reaction time is relatively long,resulting in high reaction cost and great pollution to the environment.With the development of green chemistry,how to make full use of resources,reduce the emission of chemical pollutants,and improve the atomic economy has become the theme of the development of the times.The application of N-aryl sulfoximines in drug molecules has been a wide concern by chemists,so the improvement of their synthetic methods is imminent.Using water as a solvent to realize chemical transformation conforms to the basic principles of green chemistry and has become one of the important research directions of green chemistry.Compared with organic solvents,water is less harmful to the environment,inexpensive and has a high safety factor.However,most organic compounds have low solubility in water,which makes the organic synthesis of water phase difficult.To solve the solubility problem of organics,surfactants can be added to the aqueous phase,which forms micelles in the self-aggregation of the aqueous phase.The hydrophobic inner core of micelles can function as "nano-microreactors",which is conducive to the selfconcentration of organic reactants in these "nanoreactors",thereby increasing the local reaction concentration,improving the reaction efficiency,and shortening the reaction time.That is the "micelle effect".Therefore,this thesis designed and studied the Pdcatalyzed coupling reaction of NH-sulfoximine and aryl bromide in aqueous phase in micelles.By screening the type and amount of catalyst,type of base,reaction temperature,reaction time and other conditions,the optimal reaction conditions were finally determined:1 equiv.NH-sulfoximine,1 equiv.aryl bromide,0.5 mol%tBuXPhos-Pd-G3,1.5 equiv.(0.3 mmol)NaOH,1 mL 2wt%TPGS-750-M/H2O,80℃,0.1 MPa N2 for reaction.Under the condition of micellar catalysis,the reaction time is greatly shortened,and the reaction can be completed in only 15 min,and the substrate has wide applicability and high yield.A total of 28 kinds of N-aryl sulfoximine compounds are obtained.In this paper,the above N-aryl sulfoximine compounds were tested and characterized by melting point,low-resolution mass spectrometry or high-resolution mass spectrometry,hydrogen nuclear magnetic resonance(1H NMR),and carbon spectrum(13C NMR).In conclusion,this thesis provides a new method for the synthesis of N-aryl sulfoximine and bissulfoximine products,which is environmentally friendly,and has a short reaction time and a wide range of substrates.