The Application Of Axially Chiral Ligands Based On Binaphthyl Skeleton In Lewis Acid Catalytic Asymmetric Reactions And Nitrogen-containing Bases Triggered Michael Type Reactions

The first, second and third part of this dissertation focused on the design and the synthesis of axially chiral ligands which based on binaphthyl skeleton, and their applications in Lewis acid catalytic asymmetric Friedel-Crafts alkylation, asymmetric vinylogous Mannich reaction and asymmetric Mannich type difluoromethylation. The fourth part of this dissertation focused on nitrogen-containing bases promoted aza-Michael type reaction of a series of hydrazones with activated alkynes.1 A series axially chiral mono-Schiff base type ligands and bis-Schiff base type ligands L1-L16 were rationally designed and successfully prepared from optical pure 1,1'-binaphthalenyl-2,2'-diamine (BINAM). We applied these chiral ligands in zinc(II) catalyzed asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes under mild conditions to give the corresponding adducts in good yields (up to 90% yield) and moderate enantioselectivities (up to 67% ee).2 We designed and synthesized a series of axially chiral phosphine-Schiff base type ligands L17-L27 from optical pure 1,1'-binaphthyl-2,2'-diol (BINOL), which was quite stable, easily available. Then these chiral ligands were applied in silver(â… )-catalyzed asymmetric Vinylogous Mannich reaction of aldimines with siloxyfuran in which moderate to good enantioselectivity (up to 81% ee) and good diastereoselectivities (anti/syn up to 99/1)have been achieved when L22 was utilized as the ligand and phenylmethanol was used as an additive. However, when we applied our catalytic system in the reaction of aldimineâ…¡-8j, which possessed an o-anisidine N-aryl group, with siloxyfuran, the corresponding adduct was obtained in 63% ee, less effective than the catalytic system developed by Hoveyda and co-workers.3 Based on the work developed above, firstly, an unexpected reaction of aldimines and difluoroenoxysilane promoted with Zn(OTf)2 was disclosed and the reaction gave the unexpected Mukaiyama-aldol adductsâ…¢-3 in excellent yields (up to 87%) with the addition of H2O.Secondly, we found that the reaction of hydrazones with difluoroenoxysilane catalyzed by zinc(II) proceeded smoothly to afford the Mannich type adduct in moderate to good yield under mild conditions. An unexpected monofluorination of hydrazone III-5v with difluoroenoxysilane III-2a was also disclosed in this part, and the corresponding product could be achieved in up to 41% yield. Then the first example of Lewis acid catalyzed asymmetric Mannich-type difluoromethylation of hydrazone III-5v with difluoroenoxysilane III-2a using chiral phosphine-oxazoline ligand has been reported, giving the adduct III-6a in up to 51% ee.Thirdly, in order to improving the enantioselectivity of this asymmetric Mannich-type difluoromethylations of hydrazones with difluoroenoxysilanes, we designed and synthesized a series of chiral phosphine-imidazoline type ligands L48-L53. When the reaction was carried out under 20 mol% of phosphine-imidazoline ligand L52 mixed with 10 mol% of Zn(NTf2)2, an excellent enantioselectivity (up to 96% ee) has been achieved with good yield (up to 88%).4 Several highly efficient nitrogen-containing base promoted aza-Michael type reactions of hydrazones to activated alkynes have been developed in this part of work. This aza-Michael addition reaction can be applied into different types of hydrazones, and the corresponding adducts were achieved in high yields under mild reaction conditions. Generally, the reactions are initiated by the deprotonation of NH, than the Michael addition of nucleophilic intermediate to activated alkynes leading to the formation of corresponding products.