Our research program revolves around the theme of synthesis. There are two major activities -- 1) developing the tools, i.e., the reactions and reagents, and 2) creating the proper network of reactions to make complex targets of interest because of their biological activity or materials' properties readily available from simple starting materials.

One major activity in designing new reactions and reagents involves the development of "chemists' enzymes" -- non-peptidic transition metal-based catalysts that can perform chemo-, regio-, diastereo-, and especially enantioselective reactions. In doing so, attention must be paid to the question of atom economy to minimize waste, energy, and consumption of raw materials.

Synthetic efficiency raises the question of metal-catalyzed cycloadditions to rings other than six membered. A general strategy for a "Diels-Alder" equivalent for formation of five, seven, nine, etc. membered carbo- and heterocyclic rings is evolving. Designing Asymmetric catalysts for such cycloadditions enhance the synthetic utility becomes a major objective.

An exciting new direction derives from the molecular gymnastics acetylenes undergo in the presence of transition metals. Inventing atom economical addition reactions constitutes a major goal. Cycloisomerization to virtually all types of ring sizes and systems with particularly versatile juxtaposition of functionality become special goals. Alkylations by simple additions are becoming possible. Novel metal catalyzed [4+2] and [5+2] cycloadditions are being explored.

While palladium catalysts represent a major part of our effort, new opportunities for selectivity complementary to that obtained with palladium complexes appear possible with nickel, chromium, molybdenum, ruthenium, iron, and tungsten complexes and bimetallic complexes composed of two different metals. Of prime concern are 1) exploration of unusual oxidation states of metals for new types of reactivity and 2) asymmetric templates that create enantiomerically pure stereogenic centers.

Main group chemistry, especially involving silicon, tin, and sulfur, also offers many opportunities for new reaction design. For example, sulfur-containing substrates may function as either electrophiles or nucleophiles depending upon their chemical environment -- a duality that allows them to be dubbed "chemical chameleons." Rational design of novel catalysts for an asymmetric direct aldol condensation is an exciting thrust.

From these new synthetic tools evolve new synthetic strategies towards complex natural products. Targets include ß-lactam antibiotics, ionophores, steroid and related compounds (e.g., Vitamin D metabolites), alkaloids, nucleosides, carbohydrates, and macrolide, terpenoid, and tetracyclic antitumor and antibiotic agents.

1) "Total Synthesis of (+)-Amphidinolide A, Part 2: Structure Elucidation and Completion of the Synthesis," B.M. Trost, P.E. Harrington, J.D. Chisholm, S.T. Wrobleski, J. Am. Chem. Soc., 127, 13598 (2005)

2) "Divergent Enantioselective Syntheses of (-)-Galanthamine and (-)-Morphine," B.M. Trost, W. Tang, F.D. Toste, J. Am. Chem. Soc., 127, 14785 (2005)

3) "Alkyne Hydrosilylation Catalyzed by a Cationic Ruthenium Complex: Efficient and General trans Addition," B.M. Trost, Z.T. Ball, J. Am. Chem. Soc., 127, 17644 (2005)

4) "A Direct Catalytic Asymmetric Mannich-type Reaction via a Dinuclear Zinc Catalyst: Synthesis of Either anti- or syn- a-H ydroxy -b- Amino Ketones," B.M. Trost, J. Jaratjaroonphong, V. Reutrakul, J. Am. Chem. Soc., 128, 2778 (2006)

5) "Molybdenum-Catalyzed Asymmetric Allylation of 3-Alkyloxindoles: Application to the formal Total Synthesis of (-)-Physostigmine," B.M. Trost, Y. Zhang, J. Am. Chem. Soc., 128, 4590 (2006)

6) "New Nucleophiles for Palladium-Catalyzed Asymmetric Allylic Alkylation. Total Synthesis of Agelastatin A," B.M. Trost, G. Dong, J. Am. Chem. Soc., 128, 6054 (2006)

7) "Enantioselective Synthesis of a-tertiary Hydroxy Aldehydes by Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates," B.M. Trost, J. Xu, M.J. Reichle, Am. Chem. Soc., 129,, 282 (2007)

8) "Synthesis of Ring Expanded Bryostatin Analogue," B.M. Trost, H. Yang, O.R. Thiel, A.J. Frontier, C.S. Brindle, J. Am. Chem. Soc., 129, 2206 (2007)

9) "A Diosphenol Based Strategy for the Total Synthesis of (-)-Terpestacin," B.M. Trost, G. Dong, J.A. Vance, J. Am. Chem. Soc., 129, 4540 (2007)

10) "Application of the Ru-Catalyzed [5+2]Cycloaddition toward the Total Synthesis of (+)-Frondosin A," B.M. Trost, Y. Hu, D.B. Horne, J. Am. Chem. Soc., 129, 11781 (2007)

11) "Enantioselective Construction of Spirocyclic Oxindolic Cyclopentanes by Palladium Catalyzed Trimethylenemethane [3+2] Cycloaddition," B.M. Trost, N. Cramer, S.M. Silverman, J. Am. Chem. Soc., 129, 12396 (2007)