Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.

Structures 401 2. η 3 -η 1 -η 3 Isomerization 401 3. Apparent Allyl Exchange via Pseudorotation 403 4. Apparent Allyl Exchange via Ligand Dissociation 403 D. Steric InteractionssLigand vs Nucleophile 404 1. Stabilized Nucleophiles 404 2. Unstabilized Nucleophiles 405 III.

Enhancing the efficiency of the synthesis of complex organic products constitutes one of the most exciting challenges to the synthetic chemist. Increasing the catalogue of reactions that are simple additions or that minimize waste production is the necessary first step. Transition metal complexes, which can be tunable both electronically and sterically by varying the metal and/or ligands, are a focal point for such invention. Except for catalytic hydrogenation, such methods have been rare in complex synthesis and virtually unknown for C-C bond formation until the advent of cross-coupling reactions. These complexes may orchestrate a variety of C-C bondforming processes, important for creation of the basic skeleton of the organic structure. Their ability to insert into C-H bonds primes a number of different types of additions to relatively nonpolar rr-electron systems. Besides imparting selectivity, they make feasible reactions that uncatalyzed were previously unknown. The ability of these complexes to preorganize rr-electron systems serves as the basis both of simple additions usually accompanied by subsequent hydrogen shifts and of cycloadditions. The ability to generate "reactive" intermediates under mild conditions also provides prospects for new types of C-C bondforming reactions. While the examples reveal a diverse array of successes, the opportunities for new invention are vast and largely untapped.

Professor Trost's research interests include the invention and development of new synthetic reactions largely based upon catalysis using transition-metal complexes and their use to define strategies that result in the total synthesis of complex molecules largely of biological importance. Matthew L. Crawley was born in Suffern, NY, in 1976. He obtained his B.A. degree from Williams College with a double major in political economy and chemistry under the guidance of Professor J. Hodge Markgraf. In 1998 he started his graduate studies with Professor Barry M. Trost at Stanford University, where his work has focused on the development of asymmetric palladium-catalyzed reactions with application in total synthesis. After completion of his Ph.D. degree in the spring of 2003, he will join the Medicinal Chemistry department at Incyte Corporation in Delaware. Scheme 1. Catalytic Cycle in Palladium-Catalyzed Asymmetric Allylic Alkylations Figure 1. Palladium/ligand cartoon.

An important first step in making organic reactions more environmentally benign by design requires processes that are, to a first approximation, simple additions with anything else needed only catalytically. Since so few of the existing reactions are additions, synthesis of complex molecules requires the development of new atom-economic methodology. The prospect for such developments is probed in the context of ruthenium-catalyzed reactions. Using mechanistic reasoning, over 20 new processes of varying complexity have been designed and implemented. While some involved oxidation-reduction processes, most involved C-C bond-forming reactions.