Applications Of 1, 1'-Bi-2-napthol (BINOL) And Its Derivatives In Asymmetric Alkynylzinc Additions And Enantioselective Fluorescence Recognition

Optically active 1,1'-bi-2-naphthol (BINOL) and its derivatives have been extensively used in asymmetric catalysis and chiral recognition. In the field of asymmetric catalysis, research of BINOL and its derivatives in the asymmetric alkynylzinc additons to aldehydes has attracted our particular attention because the resulting propargylic alcohols are versatile precursors to many organic molecules including natural products and pharmaceutical compounds. In the studies of chiral recognition, BINOL and its derivatives were the most extensively used as chiral receptors in enantioselective fluorescent recognition for organic molecules since these sensors can potentially provide a real time analytical tool for rapid chiral assay. Enantiomeric composition of organic molecules is of great significance in drug discovery and catalyst screening, especially in connection with the application of the high throughput combinatorial technique. In this dissertation, a new series of BINOLs derivatives were synthesized from material BINOL, applications of BINOL and its derivatives in asymmetric alkynylzinc additions and enantioselective fluorescence recognition were systematically studied, and a series of encouraging results were obtained.Up to date, there are two efficient systems for BINOL that catalyze highly enantioselective alkynylzinc addition to aldehydes: the BINOL/Ti (OiPr) 4/Me2Zn system discovered by Chan laboratory and the BINOL/Ti (OiPr) 4/Et2Zn system discovered by Pu laboratory. The method of Chan is only good for the reaction of aromatic aldehydes, and the system developed by Pu is the only one that exhibits high enantioselectivity for the reaction of aromatic, aliphatic andα,β-unsaturated aldehydes. In this dissertation, the first highly enantioselective addition of an alkynoate to aromatic aldehydes has been discovered for the synthesis of optically activeγ-hydroxy-α,β-acetylenic esters by Pu's system. This reaction is carried out at room temperature by using a substoichiometric amount of the chiral BINOL ligand in combination with Et2Zn and Ti(OiPr)4 in the presence of HMPA and it produces theγ-hydroxy-α,β-acetylenic esters with 85– 95% ee. The structures of the new propargylic alcohols are characterized by various methods including 1H NMR, 13C NMR, specific optical rotation and HRMS. The absolute configuration of stereogenic carbinol centers is determined to be S by careful 19F NMR analysis of (R)- and (S)-Mosher esters derivatives.We have synthesized the BINOL ligand that contains bulky 3,3'-tertiaryalkyl groups. This compound shows improved catalytic properties than the previously reported 3,3'-substituted BINOL ligands in the asymmetric alkyne addition to aromatic aldehydes. It can catalyze the phenylacetylene addition to aromatic aldehydes with high enantioselectivity without using Ti(OiPr)4 and a Lewis base additive. Several analogs have also been synthesized and their catalytic properties in the asymmetric alkyne addition to aldehydes have been studied. This study provides a better understanding of the mechanism of the asymmetric alkyne addition to aldehydes catalyzed by the 3,3'-substituted BINOL ligands.The tetrahydroxyl derivative of BINOL can be used to conduct the enantioselective recognition of chiral amino alcohols. In comparison with BINOL, the two additional hydroxyl groups of the tetrahydroxyl derivative have increased the binding of this compound with the amino alcohols and significantly improved the fluorescence quenching efficiency. The fluorescence quenching by the chiral amino alcohols was also found to be enantioselective. The fluorescence responses of the tetrahydroxyl derivative towards amino alcohols are compared with those of its analogs. It shows that the interaction of the central naphthyl hydroxyl groups of the tetrahydroxyl derivative with the substrates is responsible for the observed fluorescence quenching and the two additional alkyl hydroxyl groups increase the quenching efficiency.