The advance of glycoscience hinges on efficient access to oligosaccharides and glycans of defined yet diverse configurations and connectivities. Synthesis of 1,2-cis glycosidic bonds remains synthetically challenging, and a general synthetic approach to achieving their high stereoselective construction that is applicable to every sugar type has yet to be developed despite over a century of intense research in carbohydrate chemistry. This deficiency hinders the development of automation in carbohydrate synthesis, despite some recent progress. A major part of my dissertation describes a working solution in addressing this long-standing challenge via an SN2 strategy featuring a directing group on the anomeric leaving group. Such a directing group is employed to promote the acceptor attack at the backend of the anomeric carbon-leaving group bond (hence realizing an SN2 process) upon gold activation. This unique approach makes the directing group “traceless” in the glycoside products and permits the strategy to be of general applicability as the installation of the directing group and hence the adaptation of the strategy is not limited to any specific sugar types. The strategy is successfully applied to the synthesis of a range of 1,2-cis-pyranosides and furanosides with good to excellent stereoselectivities.In addition, the dissertation describes a gold-catalyzed in situ access to 2-aminofurans. The highly electron-rich nature of this class of furans makes it difficult to prepare by other means but endows them with exceptional synthetic value. With bifunctional phosphine ligands specifically designed for cooperative gold catalysis, acetylenic amides are efficiently transformed into 2-aminofurans in a single step, which are further converted into functional products in one pot.

Over the past twenty years, asymmetric gold(I)-catalysis has remained challenging due to the inherent linear structure of gold(I) complexes. The Zhang group has made significant advances in addressing this challenge via the development of ligand-enabled cooperative homogeneous gold catalysis for the past decade. However, cumbersome ligand synthesis limits the scope of available ligands and hinders further exploration of asymmetric catalysis. In my graduate research, a new and divergent synthesis of chiral bifunctional binaphthyl-2-ylphosphines was developed. This method enables the rapid construction of a chiral bifunctional gold catalyst library, including 23 new catalysts. With this catalyst library, asymmetric dearomatization of naphthols and phenols was achieved to access chiral spiro carbocycles with excellent enantioselectivities. Furthermore, we developed enantioselective desymmetrization and parallel kinetic resolution of ethynylcyclobutanols, leading to the synthesis of chiral α-methylenecyclopentanones. Extending beyond asymmetric gold catalysis, we also introduced a gold-catalyzed stererospecific trans-hydrogenation of internal alkynes, facilitated by a key hydrosilane-Lewis base interaction.