Development of Practical Synthetic Tools Using Copper and Gold Catalysis

Abstract

The use of transition metal catalysis in the synthesis of complex organic molecules has dramatically expanded the role of synthetic chemistry across a broad spectrum of applications including drug discovery, chemical biology, and materials science. This is due in large part to the development of practical, transition-metal-catalyzed techniques for: 1) the construction of synthetically challenging molecular structures and 2) the selective activation of strong bonds. Our contribution in the first area has focused on the functionalization of C-C multiple bonds using copper and gold catalysts. I will begin by discussing the development of a convenient method for the asymmetric synthesis of cyclic ethers containing highly-substituted stereocenters: complex structures which are found in a wide variety of natural products. Our efforts in the second area have been directed at C-O bond activation using copper catalysts. I will describe our investigation of the copper-catalyzed reduction of alkyl triflates, and how this technique was applied in a new approach to the selective deoxygenation of primary alcohols that offers significant advantages over traditional methods. Finally, I will present an extension of this strategy to the copper-catalyzed reduction of primary and secondary halides which proceeds through a non-radical mechanism.