Educational Background:

PhD, Columbia University, 1980 MPhil, Columbia University, 1980 MA, Columbia University, 1978 BS, Cornell University, 1977

Awards:

• Eli Lilly Young Faculty Fellowship • DuPont Young Faculty Fellow • Alfred P. Sloan Foundation Fellowhip • Arthur C. Cope Scholar Award • Journal of Organic Chemistry, Associate Editor

Research Description:

The importance of organolithium reagents in organic chemistry is indisputable. Reports of the effects of solvents, reaction temperatures, additives, internal coordinating functionalities, electrophile structures, and substituents on product distributions pervade the literature. Nevertheless, complexities resulting from aggregation and solvation render our understanding of the origins of the reactivities and selectivities limited at best. Our group investigates the structural and mechanistic basis of selectivity using a range of spectroscopic, kinetic, and computational methods. A number of projects are in collaboration with pharmaceutical process groups. Typical case studies are illustrated below.

We investigate organolithium selectivities in three stages. In the Stage I, the detailed coordination chemistry of the organolithium reagent is unraveled using a variety of one- and two-dimensional NMR spectroscopic methods. Efforts to determine aggregation states, solvation numbers, and other key structural features are not so unlike investigations of the coordination chemistry of the transition elements. Stage II involves detailed rate studies in which the key solvation and aggregation events leading to the rate limiting steps are revealed. Often times the observable aggregate is not the reactive species. In Stage III, semi-empirical and ab initio computational methods are exploited to obtain insights into the reaction coordinate and transition structures that are not available from the experimental methods. In the end, we learn to control the rates and selectivities of synthetically important organolithium reactions employing strategies and logic based on mechanism rather than empiricism.

Selected Publications:

McNeil, A. J.; Collum, D. B. Reversible Enolization of -Amino Carboxamides by Lithium Hexamethyldisilazide. J. Am. Chem. Soc. 2005, 127 5655.

Qu, B.; Collum, D. B. Addition of n-Butyllithium to an Aldimine: Role of Chelation, Aggregation, and Cooperative Solvation. J. Am. Chem. Soc. 2005, 127, 10820.

Ramirez, A.; Sun, X.; Collum, D. B. Lithium Diisopropylamide-Mediated Enolization: Catalysis by Hemilabile Ligands. J. Am. Chem. Soc. 2006, 128, 10326.

Singh, K.; Collum, D. B. Lithium Diisopropylamide-Mediated Ortholithiation and Anionic Fries Rearrangement of Aryl Carbamates: Role of Aggregates and Mixed Aggregates. J. Am. Chem. Soc. 2006, 13753.

Collum, D. B.; McNeil, A. J.; Ramirez, A. Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis. Angew. Chem., Int. Ed. 2007, 49, 3002.