Synthesis And Catalytic Performance Of Chiral Ferrocenyl P,N, P,N,N And P,P Ligands

This thesis is concerned with the synthesis of chiral ferrocenyl P,N, P,N,N and P,Pligands and their application in asymmetric catalysis. The synthesis of all compoundsdescribed herein starts from the available precursor (R)-Ugi′s amine18, which possessestwo special properties, that is, diastereoselective ortho-lithiation and the other one whichallows a further stereospecific SN1-type reaction of the dimethylamino moiety occurs withretention of configuration.1. Synthesis of P-chiral and non P-chiral PPFA analoguesPPFA analogues are very important1,2-disubstituted ferrocene derivatives, as a very prototypical example of a planar-chiral compound, PPFA is not only the frst ligand withplanar chirality but also proved to be very effective ligand for a variety of catalyticasymmetric transformations. Diastereoselective ortho-lithiation and subsequent in situtrapping with an electrophilic R2PCl has become a standard methodology for thepreparation of chiral ferrocene-based phosphines. But this methodology largely dependson the amounts of R2PCl reagents, considering the inconvenience and cost, we have todesign a new route to avoid the limitations. A series of non-P-chiral PPFA compounds109-115were prepared according to the new synthetic route.If reaction conditions and amounts of the organometallic reagent could be strictlycontrolled, we can synthesize P-chiral PPFA analogues according to the new route. Thesame as the non-P-chiral PPFA compounds, dichlorophosphine108should be preparedfirstly, then reacted with equimolar amount organometallic reagent below-78°C andfinally with another equimolar amount organometallic reagent below-78°C to afford asingle diastereomer PPFA. The diastereoselectivity might reduce at higher temperature.P-chiral PPFA analogues116-122were synthesized in moderate yields. 2. Synthesis and application of novel chiral ferrocenyl P,N,N ligandsThere are two methods to prepare P,N,N ligands starting from PPFA:1) After reactionof PPFA with Ac2O, followed by treatment with a large excess ofpyridin-2-ylmethanamine to form target compounds.2) PPFA were transformed tocorresponding primary amine PPFA-NH2, reductive amination of PPFA-NH2withpicolinaldehydes resulted in formation of P,N,N ligands in high isolated yields. Althoughthe first method has fewer steps, considering the expensive and uncommon reagents, wesynthesized P,N,N ligands according to the second method. The substituent groups on theP-phenyl and pyridine rings played a significant role on the reaction enantioselectivity onthe basis of performance of ligands129-132and134-136. All P,N,N ligands were appliedin the Ir-catalyzed asymmetric hydrogenation of aromatic ketones. The iridium complexesof these ligands catalyzed asymmetric hydrogenation of aromatic ketones in up to87%ee.3. Synthesis and application of new Josiphos ligandsThe Josiphos ligands arguably constitute one of the most versatile and successful ligandfamilies, second probably only to the BINAP ligands. The two phosphine groups can beintroduced in consecutive steps with very high yields, a variety of ligands are readilyavailable with widely differing electronic and steric properties. Josiphos are not only theefficient ligands of functional olefins, but they also perform excellently in asymmetrichydrogenation of imines. Prochiral substrates164,166and168could be enantioselectivehydrogenated to afford the corresponding optically products in good isolated yields andmoderate to good enantioselectivities, especially the iridium complexes of152catalyzed asymmetric hydrogenation of2-methyl-quinoxaline168in up to79.2%ee when using I2as an additive.The key step for the technical process of (S)-metolachlor is the asymmetrichydrogenation of an imine intermediate made possible by an iridium ferrocenyldiphosphine catalyst system.(RC,SFc)-Xyliphos12is the key ligand. We explored akilogram scale production process of (RC,SFc)-Xyliphos12.