Synthetic and catalytic studies of some new chiral PN ligands and (S)-BINOL derivatives

Abstract

The importance of chirality, general methods of asymmetric synthesis and the .development of the use of homogenous asymmetric catalysts are briefly introduced. Earlier work (up to 1997) on the synthetic and catalytic studies of chiral PN ligands and BINOL are also reviewed. The objectives of the research were to (1) synthesize new chiral PN ligands and study the catalytic properties of their metal complexes; (2) prepare (S)-BINOL derivatives and study the electronic effect of these ligands on asymmetric epoxidation of chalcone, asymmetric diethylzinc addition of benzaldehyde and triethylaluminium addition of benzaldehyde. PNN tridentate ligand. 2-diphenylphosphino-6-[4'(S)-isopropyloxazolin-2'-yl]pyndine 67 was prepared from 6-chloropicolic acid 69, via incorporation of oxazoline moiety from (S)-valinol and substitution of the chloride with potassium diphenylphosphite. The ruthenium (I) and rhodium (I) complexes of this ligand were used as catalysts for the asymmetric hydrogenation of 2-(6'-methoxy-2'-naphthyl)propenoic acid 73 and methyl a-acetamidocinnamate 75 to give products with enantiomeric excesses (ee) up to 11.6 % and 9.1 % in moderate conversions. Modification of the ligand 67 to 2-(diphenylphosphino)methyl-6-[4'(S)-etriyloxazolin-2'-yl] pyridine 77 was not successful. PN bidentate ligand, 2-[l-(diphenylphosphino)-ethyl]pyridine 82a was prepared from racemic pyridyl alcohol rac-84a via substitution of its tosylate 85a with Li(BH3)PPh2. Both enantiopure isomers of 82a were obtained by chiral preparative HPLC. The ruthenium (I) and rhodium (I) complexes of this ligand were used as catalysts for the asymmetric hydrogenation of 1-phenyl-1-(N-acetamide)ethene 87, tiglic acid 89, and acetophenone 28 to give the best enantioselectivity as 38.6% ee (for tiglic acid 89). Transfer hydrogenation of acetophenone with the ruthenium complexes of 67 and (+)-82a gave only racemic alcohols in good conversions. Attempted synthesis of pyridylphosphine 82d was failed. BINOL derivatives, namely the (S)-H8-BINOL (S)-60, (S)-6,6'-dibromo-1,1'-bi-2-naphthol 96, the (S)-6,6'-dimethyl-1,1-bi-2-naphthol 97, the (S)-6,6'-dicyano-1,1'-bi-2-naphthol 98 and the (S)-6.6'-dimethoxy-1,1'-bi-2-naphthol 99 were prepared from BINOL (S)-53. (S)-7,7'-Dimethoxy-l,l'-bi-2-naphthol 107 was prepared from dihydroxynaphthalene 108. The lanthanum complexes of BINOL (S)-53 and its derivatives 96-99 were used as catalysts on the asymmetric epoxidation of chalcone 65 with excellent enantioselectivity (89-92 % ee) in moderate to good conversions. Ligands (S)-60 and 107 were also applied on the catalytic epoxidation reaction to give epoxide 66 with 40% ee and 86% ee, respectively, in moderate conversions. No significant electronic effect was observed on the asymmetric diethylzinc addition of benzaldehyde 114 (84-88 % ee for ligands 96-99, 77% ee for ligand 107) and triethylaluminium addition of benzaldehyde 114 (85-88 % ee) catalyzed by titanium complexes of BINOL (S)-53 and its derivatives 96-99 and 107. These results were in agreement with the simple molecular modeling calculation. The thesis concludes with an experimental section (32 pages), bibliography (171 references) and appendices (35 pages of NMR spectra and formula for the molecular modeling calculation).