Synthesis of novel chiral bipyrimidine diphosphine and aminoalcohol ligands and their application in asymmetric catalysis

252 p. : ill. ; 30 cm.PolyU Library Call No.: [THS] LG51 .H577P ABCT 2003 ChenPalladium-catalyzed asymmetric allylic alkylation (AAA) is one of the most powerful tools for the sterically controlled introduction of carbon-carbon and carbon-heteroatom bond formation. In this thesis work, a novel chiral atropisomeric diphosphine ligand, 5,5'-bis(diphenylphosphino)- 1,1',3,3'-tetramethyl-4,4'- bipyrimidine-2,2',6,6'-( 1H, 1'H,3H,3'H)-tetrone (PM-Phos) was developed, whose palladium complex exhibited good to excellent enantioselectivity in catalytic asymmetric allylic alkylation. PM-Phos is the first bipyrimidine-type diphosphine ligand. The synthetic highlight includes an interesting "halogen-dance" reaction, a crucially modified Ullmann coupling procedure and an unexpected methyl group rearrangement. With the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with malonates as a model reaction, the asymmetric induction properties of PM-Phos was preliminarily tested. In this reaction, the optimal nucleophile was dimethyl malonate, the optimal solvent was CH₂Cl₂ and the optimal base was NaOAc. The catalytic activity of the PM-Phos palladium complex was excellent especially at room temperature. The enantioselectivity was fair at room temperature, but good at 0 ℃ and almost excellent at a lower temperature (up to 95% ee at -40 ℃). Another part of this thesis work is the synthesis of novel chiral amino alcohol ligands. With L-valine as starting material, new amino alcohol ligands with two stereogenic centers, i.e., 1R- [2'-(6'-methoxynaphthyl)] -2S-amino-3 -methylbutan-1-ol (4-6a) and 1R- [2'-(6'-methoxynaphthyl)] -2S-pyrrolidinyl-3 -methylbutan-1-ol (4-8), were synthesized. The enantioselective borane reduction of acetophenone catalyzed by the amino alcohols 4-6a provided high ee's (up to 97%). The enantioselective diethylzinc addition to aldehydes catalyzed by the N,N-cycloalkylated amino alcohol 4-8 also afforded the corresponding chiral secondary alcohols with good to excellent ee's (up to 98%). The third part of this thesis work is based on chiral ruthenium-complex catalysts recycled by ion exchangers and their application in asymmetric hydrogenation. The ruthenium complex of P-Phos was an excellent catalyst for the asymmetric hydrogenation of β-ketoesters. After the reaction, the catalyst was separated easily by a column packed with silica gel-based ion exchanger and was used in the subsequent recycling runs of the reaction with a slight loss of enantioselectivity and activity. This result indicates that the special nitrogen-containing feature of P-Phos favors the stability and recyclability of its ruthenium complex catalyst in asymmetric hydrogenation.Department of Applied Biology and Chemical TechnologyPh.D., Dept. of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2003