This program has as its objectives the discovery, development, and application of selective catalytic reactions of use in organic synthesis. In particular, the focus of our research is on catalytic reactions that generate optically active products from achiral or racemic starting materials. We seek to identify catalysts for asymmetric reactions of broad synthetic utility, to elucidate the reaction mechanisms of these reactions, and to illustrate their utility through their application in the efficient synthesis of useful building blocks and complex targets. We have developed highly effective transition metal, main group metal, and organic catalyst systems for asymmetric synthesis. Cooperative reactivity between catalyst reactive sites has been identified asa powerful strategy for stereochemical control of nucleophile-electrophile reactions. Many of the reactions we plan to investigate rely on the design of catalyst systems that effect dual activation of reacting partners within a chiral framework. Our aim is to discover chiral frameworks,which we have coined "privileged chiral ligands", that display high enantioselectivity across a broad range of mechanisms. In addition, we seek catalyst systems that display extraordinary generality across a range of substrate combinations. Our efforts to this point have revealed that such breadth of scope is not only possible, but quite common. Through careful screening and design of new catalystsand investigation of their reaction mechanisms, we seek to elucidate the basis of these surprising generality phenomena in asymmetric catalysis. Ultimately, we anticipate that these studies will not only lead to catalystsfor valuable organic reactions, but also lay the principles that will allow rational design of new, broadly effective catalysts. During the coming grant period, our efforts will be directed toward the discovery of enantioselective additions of carbon-centerednucleophiles to epoxides, imines, alkylhalides, and a,(3-unsaturated carbonyl systems. The generation of chiral (handed) compounds efficiently and in pure form stands as one of the most important challenges in synthetic chemistry, partly due to the difficulty of the challenge, and partly due to the prevalence of chirality in Nature. This program aims to impact public health through the development of catalysts that will find widespread application for the practicalsynthesis of pharmaceuticals and other biologically important compounds.