Synthesis Of Quinoline Derivatives By Titanocene/zirconocene Lewis Acid Combined With Metal (organic) Catalysis

Organometallic Lewis acids have been of fundamental interest due to their ubiquitous reactivity and selectivity in classic organic transformations.But the traditional Lewis acids have the limitation of the activity and stability different to balance and restricted appliacation.With regard to the above problems and the previous research in our laboratory,air-stable IVB metallocene were used as Lewis acid pre-catalyst,combination with other organic compounds or metals for efficient synthesis of quinoline.Mechanistic experiments including control experiment,in situ NMR and HRMS.The main contents are as follows:(1)An efficient strategy for synthesis of quinazoline derivatives in ethanol solution with titanocene dichloride as catalyst has been developed.1 mol%Cp2TiCl2 at 30?afforded 17 examples of quinazoline derivatives with yields of 95-98%in 7-12 minutes.Mechanistic experiments used in situ NMR and HRMS indicated that the coordination of ethanol to the titanocene moiety released the proposed catalytic species[Cp2Ti(OCH2CH3)2],m/z=270.9512.(2)A novel,simple,efficient and economic available organometallic surfactant-style catalyst is developed.This new amphipathic titanocene complex demonstrated superior activity for synthesis of quinolines derivatives from anilines use water as solvent.The catalyst could be easily scaled up for the gram scale,recovered directly by simple treatment and still exhibit over 90%yields after five cycles.The mechanistic studies including 1H NMR and HRMS analysis suggested that the coordination of 4-sulfophthalic acid to titanocene dichloride formed[Cp2Ti(OOC)2PhSO3H]as the catalytic active species.The catalytic complexes is identified as new organometallic surfactant which demonstrated highly efficient in synthesis of quinolines derivatives in water due to the cooperation of organometallic Lewis acid and Bronsted acid and the formation of emulsion during the reaction.(3)A new triple cooperative and relay catalysis system featuring the Mannich addition followed by C-C construction and oxydehydrogenation is described.The zirconocene dichloride and trimellitic acid synergic catalysis triggered the Mannich addition and C-C bond construction reactions,while CuO played relay catalysis for oxydehydrogenation.This novel strategy demonstrated superior activity for synthesis of substituted quinolines from commercially available anilines,aldehydes and ketones.The corresponding substituted quinolines were synthesized with 32 examples in 90-96%yields under mild reaction conditions.The novel zirconocene-Br(?)nsted acid complexes,generated in situ acting as active catalyst was validated from the mechanistic studies.(4)A palladium/titanocene cooperative and relay catalytic system for one-pot,four components synthesis of substituted quinolines via aryl iodides,alkyne,Fe(CO)5 and arylamine has been developed.Pd(OAc)2 and Cp2TiCl2 demonstrated good compatibility in this four-component cross-coupling reaction,afforded 35 examples of substituted quinolines with 90-97%yield.This simple procedure represents an interesting method for synthesis of substituted quinolines with good functional group compatibility.In addition,one-pot synthesis of substituted quinoline strategy could be easily scaled up for the gram scale.Mechanistic experiment via control experiment of catalytic active species elucidated that Pd(OAc)2 and xantphos can efficient catalyzed the carbonylative reaction of aryl iodides,Fe(CO)5 and alkyne,Cp2TiCl2 and terephthalic acid demonstrated superior activity for synthesis of substituted quinoline from arylamine and ynones.