Development of Catalysts and Ligands for Enantioselective Gold Catalysis

• Published in: Accounts of chemical research Vol. 47; no. 3; pp. 889 - 901
• Main Authors: Wang, Yi-Ming, Lackner, Aaron D, Toste, F. Dean
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.03.2014
• Subjects: Alkadienes - chemistry; Carbon; Carbon-carbon composites; Catalysis; Catalysts; Formations; Gold; Gold - chemistry; Ligands; Methane - analogs & derivatives; Molecular Structure; Organic Chemistry Phenomena; Organogold Compounds - chemical synthesis; Organogold Compounds - chemistry; Organophosphorus Compounds - chemistry; Phosphines - chemistry; Rendering; Stereoisomerism; Transformations
• ISSN: 0001-4842; 1520-4898; 1520-4898
• DOI: 10.1021/ar400188g

During the past decade, the use of Au(I) complexes for the catalytic activation of C–C π-bonds has been investigated intensely. Over this time period, the development of homogeneous gold catalysis has been extraordinarily rapid and has yielded a host of mild and selective methods for the formation of carbon–carbon and carbon–heteroatom bonds. The facile formation of new bonds facilitated by gold naturally led to efforts toward rendering these transformations enantioselective. In this Account, we survey the development of catalysts and ligands for enantioselective gold catalysis by our research group as well as related work by others. We also discuss some of our strategies to address the challenges of enantioselective gold(I) catalysis. Early on, our work with enantioselective gold-catalyzed transformations focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, the careful choice of the weakly coordinating ligand (or counterion) was necessary to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In general, these tactics enhance the steric influence around the reactive gold center beyond the two-coordinate ligand environment. The use of binuclear complexes allowed us to use the second gold center and its associated ligand (or counterion) to exert a further steric influence. In a similar vein, we employed a chiral anion (in place of or in addition to a chiral ligand) to move the chiral information closer to the reactive center. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, we also developed a new class of mononuclear phosphite and phosphoramidite ligands to supplement the previously widely utilized phosphines. However, we needed to judiciously design the steric environment to create “walls” that enclose the gold center. We also successfully applied these same considerations to the development of binuclear carbene ligands for gold. Finally, we describe the design of bifunctional urea–monophosphine ligands used in a gold-catalyzed three-component coupling.