Br(?)nsted Acid Synergistic With Titano-Lewis Acid Catalyzed Oxime Reaction And Its Application

Cooperative binary acid catalytic system with high activity and selectivity were developed,by employing titanocene dichloride combined with Br???nsted acids. This strategy addressed the following problems of organometallic titanocene Lewis acid complexes, which are sensitive to water and moisture, as well as inferior selectivity. Particularly, the first water-soluble organometallic titanocene Lewis acid complex was achieved in water medium and could be recycled in the reaction of indole and nitroalkene.Friedel-Crafts reaction of indole and nitroolefin in pure water, selective Friedel-Crafts reaction of indole and N-sulfonylimine and Cu-catalyzed Sonogashira reaction were involved to evaluate the activity of Bransted acid cooperated with titanocene, and the ability coordination of the its products. The corresponding catalytic mechanisms were studied by NMR, HR-MS and X-ray, analyzed the coordination chemistry of titanocene dichloride withBransted acids. The main contents are included as follows:?1? A novel water-soluble titanocene complex [Cp₂Ti?H₂O?₂]?O₃SC₆H₃-2-?OH?-CO₂H?₂·4H₂O ?I? was prepared in a large scale via a simple aqueous-organic two-phase method. This complex efficiently catalyzed the Friedel-Crafts reaction of indole and nitroolefin in water, affording the 96% yield of desired product. The proposed mechanism study revealed that the complex I was in equilibrium with anions [Cp₂Ti?H₂O?₂]2+??? and [Cp₂Ti??1-5-Hsal?]+?III?, and the real active catalytic species was recognized as III in base condition through the NMR titration. The catalyst can be recycled in aqueous solution for at least six times by the simple extraction procedure with the yields of 96%-82%. This study realized the water-soluble titancene Lewis acid applied to aqueous-phase catalysis for the first time, as well as the good recovery and reusability of the catalyst. These findings directly settled the concerns that titanocene Lewis acids are sensitive towards air and moisture, and difficult to use water as a medium.?2? A new strategy to control the selective Friedel-Crafts reaction of indoles and imines was developed by the ligands assisted titanocene dicholide to achieve tunable acidity and active sites. The results demonstrated that Cp₂TiCl2 and phenol catalyzed the mono-Friedel-Crafts reaction of indoles and N-sulfonyl aldimines with 91% yields and excellent selectivity of 95:5, whereas o-aminophenol significantly enhanced the activity of the titanocene catalyst and promoted the synthesis of bisindole with excellent yields up to 98% and selectivity of 98:2.An exquisite selectivity profile that is dictated by the mode of coordination between titanocene and ligand, which breaking the poor selectivity in organometallic titanocene Lewis acid.?3? From the perspective of the coordination chemistry, bisindoles ?BIMs? bearing two hard and strongly basic N-donor centers, making BIMs as versatile ligands for hard metal ion. In basis of that, highly modulated BIMs were examined to improve the activity of Cu-catalyzed Sonogashira reaction. Ligand screening experiments showed that BIMs could accelerate various copper salts including cuprous salts and cupric salts. Among these catalysts, the combination of BIMs ?10 mol-%? and CuCl ?5 mol-%? catalyzed the cross-couplings of a wide range of substituted aryl iodides and both alkyl-/aryl-substituted terminal alkynes with yields up to 99%. Theligand beared chlorobenzol unit greatly facilitated the proceeding of the cross-coupling reaction, which provided important evidence for the ?-electron ligand catalytic mechanism.