Synthesis Of Chiral Compounds Derived From Amino Acids And Their Application To Asymmetric C-C Bonds Formation

This thesis is focused on the study of the synthesis of chiral ligands based on natural amino-acids and their application to the catalytic asymmetric carbon-carbon bond formation.Although chiral amino-alcohol ligands have been successfully applied to various kinds of catalytic asymmetric reactions, few examples of the synthesis of chiral multi-dentate ligands, such as tri- or tetra-dentate from amino acids, and their application to asymmetric reactions have been reported. In particular, the chiral phase transfer catalysts (PTC) have been almost limited to Cinchona alkaloid, such as Cinchonine (CN), Quinine (QN) and related compounds. Besides, it is significant to explore new types of small organo-molecule catalyzed intermolecula asymmetric aldol reactions, and there are certain rooms for developing new donor-acceptor system of this kind of reactions. In this dissertation, we reported the syntheses of some new chiral ligands and their application to enantioselective carbon-carbon bonds' forming reactions.Firstly, tridentate chiral ligands (1a¹f) were synthesized from natural amino-acids and the structures were confirmed by means of spectural and elemental analyses. Particularly, the structure of amino-alcohol ligand 1d, which possesses two pyrrolyl rings in the molecule, was given in details by investigation through ¹H NMR, ¹³C NMR, ¹H-¹H cosy, ¹³C-¹H Cosy and X-Ray diffraction on single crystal. From these results, configurations of the chiral centres were confirmed, the geometry of the molecule was elucidated. These amino-alcohols ligands could be applied to enantioselective addition ofdiethylzinc to aldehydes, high yields and moderate ee values were achieved. Two of them (le^lf) were shown to be effective catalysts for some direct aldol reactions.Secondly, a series of 2,2,2-trifluoro-l-arylethanone were synthesized. The direct asymmetric aldol addition of aliphatic methyl ketones to these activated 2,2,2-trifluoro-l-arylethanones was then investigated using Z,-proline as the organocatalyst. It was shown that 2,2,2-trifluoro-l-phenylethanone and its analogures substituted with electron-withdrawing group (F, Cl) can smoothly react with aliphatic methyl-ketones affording optically active /?-trifiuoromethyl-/?-hydroxy ketones in excellent yields (almost quantitative) with moderate enantioselectivities (up to 64 % ee), without formation of any dehydrated product.Some chiral organic molecules structurally related to proline were also tested as catalysts for the aldol reaction of this donor-aceptor system. It was found that proline is still the best chiral organocatalyst at present for the reaction mentioned above. In order to find the absolute configuration of the adducts, an attempt to transform the aldol adduct 2-hydroxy-4-oxo-2-phenyl-pentanenitrile into the Mosher's acid, was made. Unfortunately, it was unsuccessful. Further continuous research on this subject is necessary. Thorough studies of these reactions manifested that there were several factors which affected the results of the reactions and gave us some new ideals for designing new aldol addition reaction systems.Thirdly, an efficient, convenient, and universally applicable method of preparing C2-symmetric 1,4-Diazabicyclo[2.2.2]octane (DABCO) derivatives from amino acid esters, was successfully developed. This method has the advantages of short synthetic route, high yield and easy-to-operate. The structural feature of this kind of compounds is that they all have a rigid core of bicyclo[2.2.2]octane ring system, similar to that of cinchona alkaloid such as cinchonine, cinchonidine, quinine, and quinidine. and they distinguish themselve from cinchona alkaloids by the fact that the bicyclic ring core in the molecule is a diaza system, and substituted symmetrically, and hence the molecule is C2-symmetric. Bearing this structural feature, this kind of compounds might be useful precursor of efficient phasetransfer catalysts, which were previously not reported in the literature. In order to discriminate the two stereoisomers 20a and 20a', one of them (20a) was analyzed by single crystal X-ray diffraction. In the attempt to prepare chiral quaternary ammonium salts from the DABCO derivatives mentioned above, no pure product was isolated and identified.