The Development And Apllication Of Synergistic Catalysis Strategy In Allylic Substitutions

In order to solve the problems in allylic substitutions,such as low catalytic activity,narrow substrate scope,and the stereocontrol of prochiral nucleophiles,this thesis describes the development and application of synergistic catalysis strategy in allylic substitutions.A concerted process using a Pd-catalyst,a pyrrolidine co-catalyst and a hydrogen-bonding solvent was firstly developed and used for the allylic alkylation of simple ketones with allylic alkyl ethers and allylic alcohols.An inter-bimetallic catalyst strategy was also developed and utilized for the asymmetric synthesis of non-proteinogenicα-alkyl-α-amino acid andα,α-dialkyl-α-amino acid.Part Ⅰ:C-O bond cleavage of allylic alkyl ether was realized in a Pd-catalyzed hydrogen-bond-activated allylic alkylation,using only alcohol solvents.This operationally trivial protocol does not require any additives and proceeds with high regioselectivity.The applicability of this transformation to a variety of functionalised allylic ether substrates was also investigated.Furthermore,this methodology can be easily extended to the asymmetric synthesis of enantiopure products（up to 99%ee）,which can be used for the synthesis of chiralγ-oxo-carboxylic acid and phenylacetic acid derivatives.Part Ⅱ:Allylic alcohols were directly used in Pd-catalyzed allylic alkylations of simple ketones under mild reaction conditions.The reaction proceeds smoothly at 20 ^oC through a concerted process using a Pd-catalyst,a pyrrolidine co-catalyst and a hydrogen-bonding solvent,not requiring any additional reagents.A preliminary attempt on the Pd-catalyzed asymmetric allylic alkylation of acetone was carried out with high yield and excellent enantioselectivity.A computational study suggested that methanol plays a crucial role in the formation of theπ-allylpalladium complex,by lowering the activation energy and stabilizing the resulting hydroxide.Finally,a catalytic cycle for the reaction under investigation has been proposed using DFT calculations.Part Ⅲ:The asymmetric allylation of amino acid derivatives has been accomplished through the synergistic combination of[Pd（η³-allyl）Cl]₂/mono-t Bu-Ru PHOX and Cu（OTf）₂/mono-t Bu-Ru PHOX catalysis.This inter-bimetallic catalyst strategy,in which both metal complexes are chiral and work in concert to control the configuration of the corresponding stereocenter,is most likely responsible for its high reactivity,as well as excellent enantioselectivities（94-99.3%ee）.By exploiting the present catalyst system,symmetrical 1,3-disubstituted allylic acetates were also successfully applied in asymmetric allylic alkylations with prochiral glycine-derived nucleophiles,to give allylated products in high yields and with excellent enantioselectivities.Part Ⅳ:The highly enantioselective allylic alkylation of aldimine Schiff base was completed with the above-mentioned cooperative bimetallic catalysis system,offering a reliable catalytic process for the asymmetric synthesis ofα,α-disubstitutedα-amino-acid derivatives.Direct stereoselective introduction of two different side chains to the glycine Schiff base with this catalyst system also provide an attractive and powerful strategy for the enantiopure creaction of the newly quarernary carbon center.This quaternization method is also highlighted by the short asymmetric synthesis of cell adhesion molecule BIRT-377,which is a potent inhibitor of the interaction between intercellular adhesion molecule-1（ICAM-1）and lymphocyte function-associated antigen-1（LFA-1）.In summary,this thesis highlights these benefits such as improved catalytic activity,wide substrate scope,increased selectivity,and cost efficiency,using the successful examples of synergistic catalysis in allylic substitutions.