Copper-Catalyzed Asymmetric Hydrosilylations And The Synthesis,Self-Assembly And Applicationsof Chiral Dipyridylphosphine Ligands

Chiral alcohols, amines and amino acid derivatives are important building blocks for the synthesis of structurally interesting and biologically active compounds. The metal-catalyzed asymmetric reduction is one of the most direct and effective methods leading to these valuable intermediates and has attracted great attention. As the asymmetric inductive ability of chiral ligands normally depends both on the reaction types and on the substrate kinds, how to design highly effective chiral ligands and catalysts via new concepts and strategies plays a key role in the asymmetric catalysis.This dissertation focused on the copper-dipyridylphosphine-catalyzed asymmetric hydrosilylation of simple ketones and the synthesis, self-assembly and applications of novel chiral diphosphine ligands possessing pyridine-based crown ether. The research results are summarized as followes:(1) Based on the previously reported Cu-catalyzed asymmetric hydrosilylation system (S)-Xyl-P-Phos/CuF2/PhSiH3, we started our research with optimizing the catalytic system in silanes, chiral ligands, copper salts, solvents, and so on. In the presence of a low-cost, non-toxic and air stable reductant polymethylhydrosiloxane (PMHS) as well as an easy-to-handle and inexpensive copper salt Cu(acac)2, the (S)-Xyl-P-Phos/Cu(acac)2/PMHS system displayed high efficiency in the asymmetric hydrosilylation of a broad scope of aryl and hetero-aromatic alkyl aketones under air atmosphere and mild conditions in good to excellent ee’s (up to97%).(2) The catalytic system,(S)-Xyl-P-Phos/Cu(acac)2/PMHS, was further applied to the asymmetric hydrosilylation of diaryl ketones and aryl alkyl ketone in large scale. Based on the extensive research about the effect of additives in reaction, we found that the low reactivity using PMHS could be activated by adding cetain amounts of base (such as t-BuONa) and alchnol (such as t-BuOH). In asymmetric hydrosilylation of diaryl ketones with the modified system the ee values of chiral diary methanol could be up to90%. The reaction on a21g substrate scale can be conveniently completed within a few hours without distinct drop in ee value even at a substrate-to-ligand (S/L) ratio of50,000. The present catalyst system features good air-stability, high reactivity, good to excellent enantioselectivity, cost efficiency, wide substrate scope and mild reaction conditions.(3)"Supramolecular asymmetric catalysis" is a challenging field in asymmetric catalysis. Based on our previous work, we tried to get the combination of molecular recongnization, self-assembly, and asymmetric catalysis. By introducing a tunable informative modularity to the dipyridylphosphine ligand, P-Phos, we designed and synthesized a chiral supramolecular ligand (-)-Xyl-P16C6-Phos via7synthesis steps using2,6-dichloropyridine as the starting material. The obtained ligand was characterized by1H NMR,13C NMR,31P NMR、HRMS and optical rotation.(4) We got the supramolecular complexes from the chiral dipyridylphosphine ligand,(-)-Xyl-P16C6-Phos, and various alkali ions (Li+、Na+、K+) with different diameters owing to the selective recognition and strong complexation between the crown ether and cations. By altering the solvent, molar ratio of the host and guests, temperature, and the counter-ions (such as PF6, BF4, and BArF), steric (for example, the dihedral angles) and electronic properties of the ligands and the corresponding Rh supramolecular catalysts could be efficiently tuned. From the analyses of H NMR and MS, we found that1:2complexes were formed between the ligand (-)-Xyl-P16C6-Phos and alkali ions (M=Li, Na, K).(5) The chiral supramolecular catalysts (-)-Xyl-P16C6-Phos-alkali-Rh were applied to the asymmetric hydrogenation of a-dehydroamino acid esters. Systematic investigations have been made on the effects of the alkali ions, the molar ratios of the host and guests, the counter-ions of alkali ions, solvents, and hydrogen pressure on the reaction activities and enantioselectivities. The optimized supramolecular catalysts provided excellent enantioselectivities (95-98%ee) in the asymmetric hydrogenation of an assortment of α-dehydroamino acid esters. Comparing to the non-assembled catalyst, the activity and enantioselectivity (up to24%enhancement of ee value) of the catalysts with alkali-assembly were greatly improved.(6) The application of supramolecular catalysts (-)-Xyl-P16C6-Phos-alkali-Rh in the catalytic asymmetric hydrogenation of α-aryl enamides was further investigated. The results indicated that the supramolecular catalysts’activities and enantioselectivities were greatly affected by the kind of alkali ions, the molar ratio of the host and guests, the counter-ion of alkali ions, solvents and hydrogen pressures. The ee values largely relied on the functional groups of substrates and up to93%ee was obtained. Comparing with the non-assembled catalyst, the enantioselectivity of catalysts with alkali-assembly was improved greatly (up to59%ee enhancement).