Synthesis Of Novel Axially P, N Ligands And Their Applications To Asymmetric Catalysis

This thesis mainly focused on design, synthesis axially chiral P, N ligands with electron-deficient biphenyl backbone, and their applications to asymmetric reaction.Part 1. The research of Cu(Ⅰ)/Ag(Ⅰ) catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylide and their reaction mechanismA series of chiral P, N ligands were synthesized. We initially investigated the asymmetric 1,3-dipolar cycloaddition between azomethine ylides and dimethyl maleate in the presence of Cu(Ⅰ)/L-2a complex which showed high activity. We envisioned that the enantioselectivities could be further improved through the introduction of substituents into the corresponding 3,3’-position of the TF-BIPHAM backbone, meanwhile, the variation of the steric and electronic effects of the substituents on the phosphorus atom play a crucial role in the asymmetric catalytic reactions. Both perfect endo selectivity and enantioselectivity (>99%) were observed for glycine imino esters with L-2h as chiral ligand. High yield, enantioselectivity (97% ee) and fast reaction rate remained even when the reaction was performed as low as 0.1 mol% of catalyst loading. Under the optimized experimental condition, we tested a variety of azomethine ylides reacted with dimethyl maleate to afford the exclusively endo-products in high yields (85-99%) and excellent enantioselectivities (> 99%). The reaction between azomethine ylides derived from alanine, phenylglycine, phenylalanine, leucine, tryptophan and dimethyl maleate could also give excellent stereo-and enantio-control products with a quaternary stereocenter at the 2-position, it is of great importance and synthetic potential. The absolute configuration of the product was determined by NMR spectra and optical rotation comparisons with the data of the corresponding known compounds. Moreover, we tested the nonlinear effect and other dipolarophiles. On the basis of disclosed experimental results, we tentatively proposed a possible transition state model to elaborate the synergetic mechanism. This work provided an important understanding for other asymmetric catalytic reactions.To further validate the mechanism, we tested the reaction of vinyl phenyl sulfone and Azomethine ylides, which afforded the completely endo-products in accordance with our initial assumption. In conclusion, the present work provided a practical synthesis of optically active pyrrolidine derivatives in an environmentally benign manner.Part 2 Cu(Ⅰ)-catalyzed asymmetric Mannich reaction of benzophenone imine glycine estersAn array of novel electron-deficient axially chiral P, N-ligands were found to be of high reactivities on the Cu(Ⅰ)-catalyzed Mannich reaction of benzophenone imine glycine esters with N-tosylimines. High diastereoselectivities and enantioselectivities could be achieved.The steric and electronic effects and the size of the esters were play very important role in the reactions. Among different benzophenone imine glycine alkyl esters, the methyl ester substrate gave good to excellent stereoselectivities. We established the optimized conditions after screening studies, when we used L-2a as chiral ligand, the anti isomers were obtained as the major products with the diastereoselectivities up to 96:4 and the enantioselectivities up to 97%. We also tentatively proposed a possible transition state model to illustrate the reaction mechanism. In conclusion, the present work provided an efficient practical strategy to prepare biologically significantα,β-diamino acid derivatives and analogues.