Design and synthesis of chiral cyclometalated oxazoline-based gold(III) complexes for asymmetric catalysis and supramolecular assembly in aqueous media

Abstract

Gold catalysis exhibited exceptional reactivity, great selectivity, and high functional group compatibility in a variety of organic transformations, which has been developed rapidly in recent decades. Compared to the extensively studied asymmetric gold(I) catalysis, the development of asymmetric gold(III) catalysis is still in its infancy. Several pioneering works have highlighted the potential of using chiral gold(III) complexes as effective catalysts in enantioselective transformations. In spite of these advances, literature examples with enantioselectivity above 90% ee are limited. Therefore, the development of new chiral gold(III) complexes is of significant interest to achieve high enantioselectivity in asymmetric gold catalysis. On the other hand, amphiphilic design of gold(III) complexes was independently reported showing the self-assembling abilities of the cyclometalated gold(III) complexes and was highly responsive to slight changes in molecular structure and resulting supramolecular nanostructures. However, compared with the well-developed organic amphiphiles, the luminescent properties, cytocompatibilities and chiral supramolecular assembly of gold(III) amphiphile systems are yet unknown. In chapter 1, the scientific background of homogeneous gold catalysis, chemistry of gold(I) and gold(III) complexes, development of asymmetric catalysis and our previous works on development of gold(III) complexes were introduced. In addition, the introduction of supramolecular chemistry and luminescent properties of self-assembled metal complexes were described. In chapter 2, a new synthetic strategy for the development of optically pure C,O-chelated oxazoline-based BINOL/gold(III) complexes through diastereomeric resolution was reported. Using inexpensive enantiopure BINOL as the chiral resolving agent, the diastereomers of the chiral BINOL/gold(III) complexes could be easily resolved and purified through simple filtration in high yield. Moreover, the gram scale optical resolution of enantiopure chiral gold(III) dichloride complexes was established. Besides, the gold(III)-mediated chiral resolution of BINOL derivatives was demonstrated to afford optically active BINOLs in good to excellent yields (overall 77 – 96%) with high optical purity up to 99% ee. In addition, the catalytic activity of this new class of C,O-chelated oxazoline-based BINOL/gold(III) complexes was examined which achieved asymmetric carboalkoxylation of ortho-alkynylbenzaldehydes in excellent enantioselectivity up to 99% ee. In chapter 3, an advanced supramolecular assembly system of luminescent amphiphilic C^N-chelated alkynyl gold(III) complexes with biocompatibility in aqueous media was demonstrated. The amphiphilic nature of the gold(III) complexes arising from the hydrophilic charged quaternary ammonium ion connected with the hydrophobic cyclometalated gold(III) core by an alkyl-linker improved the aqueous solubility. The alkynyl ligands as the strong σ-donor greatly enhanced the ambident luminescent properties of these gold(III) amphiphiles. Moreover, these gold(III) amphiphiles self-assembled into nanostructures in aqueous media showing high aspect ratio. The reversible supramolecular assembly transformation was observed by changing the packing parameters through counterion exchange process. Cytocompatibilities of gold(III) amphiphiles in aqueous media was studied showing limited cytotoxicity at low concentration. In chapter 4, the first example of the chiral cyclometalated gold(III) amphiphile (GA) was demonstrated with supramolecular assembly in aqueous media. The amphiphilicity of the chiral oxazoline gold(III) complex arise from connected the hydrophobic gold(III) core to a hydrophilic charged quaternary ammonium ion with an alkyl-linker which improved the aqueous solubility. The chirality was transferred from the chiral oxazoline moiety to the resulting supramolecular nanostructures. The counterion induced supramolecular transformations were demonstrated by the addition of D-, L-, or racemic-campionsulfonates. Cytocompatibility of GA in aqueous media was shown with limited cytotoxicity.