Ferrocene Ligands In Asymmetric Allylic Substitution Reaction

This thesis focused mainly on studying the role of planar chirality and the synthesis and application of novel ferrocene ligands.Planar chiral ferrocene compounds have been extensively used as ligands in asymmetric catalysis. The role of planar chirality has however been neglected more or less. Palladium-catalyzed allylic substitution reaction is one of the most important reactions in constructing C-C and C-hetero atom bonds. The asymmetric study was limited in the symmetrical 1,3-diphenyl allylic system. There were few successful examples on regioselectivity in reactions of unsymmetrically allylic derivatives, and enantioselectivities obtained with prochiral nucleophiles. In this thesis, it was intended to investigate the role of planar chirality and the design and synthesis of novel ligands.1. The role of planar chiralityThioether, selenide and phosphino-derivatives of ferrocenyl oxazolines were synthesized conveniently from ferrocenyl oxazolines with high diasteroselectivities (>99/1). All the ligands were found to be effective in palladium-catalyzed allylic alkylation with 7, and the highest ee was 99.3%. With P, N-ligands, palladium-catalyzed allylic amination of 7 was realized with ee values of 97.2%. By comparing the results with several pairs of diastereoisomeric ligands or ligands with only planar chirality, the ee and the absolute configuration of the products were found to be determined mainly by the central chirality, however, the matching of planar chirality with central chirality is very important in obtaining high enantioselectivity. The palladium complexes were synthesized and characterized by X-ray diffraction and solution NMR. The high ee of the product was caused by both kinetic and thermodynamic effects. The ee was low by using S, N-ligands with only planar chirality because of low diastereoselectivity during the complexation between S and Pd, with the formation of new chiral center on S-atom. For P, N-ligands with only planar chirality there were no such disturbance. When (Sp)-L37 (L43, L47) was used in the two model reactions, comparatively high enantioselectivities were obtained. In addition, higher enantioselectivity would be given when the groups on the oxazoline ring were less steric demanding. That is, substrate will be closer to the backbone of ferrocene. These results indicated that the planar chirality effected the asymmetric induction by the interaction between the substrate and the backbone of ferrocene, especially the nonsubstituted Cp-ring.2. Synthesis and application of planar chiral ferrocene modified bisphosphine pocket ligandsA series of planar chiral ferrocene modified bisphosphine pocket ligands were synthesized, which showed better induction effect with the aid of planar chirality. The ligand (R, R, Sp, Sp)-L49 was found to be very effective in the construction of quaternary carbon center through asymmetric allylic alkylation. Some non-codedα,α-disubstituted amino acids could be obtained with up to 75.3% ee through allylic alkylation with ketone imino esters. The enolates of simple ketone could also be used as nucleophile in the allylic alkylation reaction,α,α-disubstituted ketone was obtained with ee up to 95%. In many cases, the results were better than those with phenyl-derived ligands. In addition, L51 and L53 were synthesized and used in palladium-catalyzed allylic substitution of 7 (85% ee) and cycloalkenyl- acetates (61.8% ee), respectively.3. Synthesis and application of 1, 1'-ferrocene P, N-ligandsA new type of ferrocene based P, N-ligands has been synthesized conveniently with the aim for regio- and enantio-selective control in palladium-catalyzed allylic substitution. Using ligand (S, Sphos, R)-L66, highly regio- and enantio-selective palladium-catalyzed allylic alkylation of mono-substituted allylic acetates could be achieved for a very wide range substrate scope (up to b/1>99/1 and 97% ee). In many cases, better results could be achieved than those using other metals like W, Mo or Ir in terms of substrate scope, activity of the catalyst, yield, regioselectivity and enantioselectivity.In addition, these ligands were also effective in palladium-catalyzed allylic amination of monosubstituted allylic acetates, with ee up to 98.2% and high regioselectivity. It provided a practical method to synthesize chiral allylic amines. The free OH in the ligand was very important in selective control through the hydrogen bonding with benzylamine, which was proved by experimental results. Apart from the unsymmetrical substrates, the symmetrical allylic acetates were also used in allylic alkylation and amination reaction with these ligands, with ee up to 93% and 98% were obtained, respectively.