Asymmetric Transfer Hydrogenation Of Quinoline Compounds Based On Cyclopentadienyl Chiral Bronsted Acid

Chiral 1,2,3,4-tetrahydroquinolines are important structural units and organic synthetic intermediates in a number of natural products and a wide variety of biologically-active compounds and pharmaceuticals.Because of the important applications in many areas of research and the development of new drugs,it is particularly important to develop a convenient,efficient method to obtain optically tetrahydroquinolines.Among of all reported methods,the directed asymmetric reduction of quinolones affords a highly efficient route for optically tetrahydroquino lines,whitc h includes asymmetric hydrogenation and asymmetric-transfer hydrogenation.The catalysts containing Ir,Ru and Rh with some chiral ligands have been widely investigaged in the asymmetric hydrogenation of quinolones,affording good to excellent enantioselectivities.Generally,a higher hydrogen pressure is desired,and it is noted that the operation is inconvenient because of the demanding of inert atmoesphere.Inadditionally,Ir,Ru,Rh are precious metal,although they can-effectively participate in the asymmetric hydrogenation cycle and obtain a highly enantioselective tetrahydroquinoline product,the expensive price and the latent contamination of product limited the application.Apart from asymmetric hydrogenation,the asymmetric transfer hydrogenation is much more convenient,it use hantzsch ester or formic acid/triethylamine system as the hydrogen source,therefore,has been attracted much attention because of its safety.For asymmetric transfer hydrogenation of quinolines,the chiral phosphoric acid has been used widely,affording excellent enantioselectivities in the asymmetric transfer hydrogenation of 2-substituted quinoline-derivatives.Athought the chiral phosphoric acid catalytic transfer hydrogenation of 3-aryl-substituted and 3-NHTs substituted quinolines have been studied recently.In a sharp contrast,the results were not good enough.This might be due to the two different control step on enantioselectivity.For 2-substituted quinolines there is a 1,2-hydrogen addition,which benefits the enantioselective control,but for the 3-substituted quinolones,the 1,2-hydrogen addition does not provide a chiral center,the enantioselectivity of the 3-substituted quinoline must be come from the proton transfer in a chiral environment,that is,the proton environment is important in the asymmetric transfer hydrogenation of 3-substituted quinolines.At present,asymmetric transfer hydrogenation mainly developed by the chiral transition metal complexes or chiral phosphor:ic acid as catalyst,the price is relatively expensive.Therefore,the development of a cheaper and readily available chiral bronsted acid catalyst is particularly important.In this thesis,We synthesized some chiral Bronsted acids based on cyclopentadiene structure according to the procedure developed by Lambert et al Building different chiral environments generated through the introduction of menthol,chiral borneol and isoparaffin.With these catalysts in hand,here:in,we report our results on the asymmetric reduction of 3-substituted quinolines.A sereris of reaction conditions,including reaction time,temperature,solvents,Hantzsch ester and the type of catalysts have been investigated.Under the optimized reaction conditions,it demonstrated that the substrates such as 3-aryl quinolones or 3-alkylquinolbnes can be enantioselective reduction smoothly,obtaining 1,2,3,4-tetrahydroquinolines with moderate enantioselectivity.Our results show that a chiral menthol-derivated catalyst gave a good chiral environment for better reaction yields and enantio selectivity in the asymmetric transfer hydrogenation of 3-aryl-substituted and allkyl-substituted quinoline compounds.In addition,for a comparison,we also carried out the asymmetric transfer hydrogenation of 2-substituted quinoline derivatives,to our suprised,changing 3-substituted quinolones to the anologus 2-substituted quinolines gave some higher yields but lower enantioselectivities under the conditions employed.This result is just the opposite of that of chiral phosphoric acid catalysis,which lays the foundation for the future development of the catalyst in other fields.