The Collum group studies how aggregation and solvation dictate the reactivity and selectivity of organolithium compounds commonly used by synthetic chemists in both academia and the pharmaceutical industry. A combination of spectroscopic, kinetic, and computational methods bridge organic, organometallic, and analytical chemistry.
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.
Regioselective Lithium Diisopropylamide-Mediated Ortholithiation of 1-Chloro-3-(trifluoromethyl)benzene: Role of Autocatalysis, Lithium Chloride Catalysis, and Reversibility. Hoepker, A. C.; Gupta, L.; Ma, Y.; Faggin, M. F.; Collum, D. B. J. Am. Chem. Soc. 2011, 133, 7135.
Azaaldol Condensation of a Lithium Enolate Solvated by N,N,N’,N’ Tetramethylethylenediamine: Dimer-Based 1,2-Addition to Imines. De Vries, T. S.; Bruneau, A. M.; Liou, L. R.; Subramanian, H.; Collum, D. B. J. Am. Chem. Soc. 2013, 135, 4214.
Enediolate-Dilithium Amide Mixed Aggregates in the Enantioselective
Alkylation of Arylacetic Acids: Structural Studies and a Stereochemical Model. Ma, Y.; Stivala, C. E.; Wright, A. M.; Hayton, T.; Liang, J.; Keresztes, I.; Lobkovsky, E.; Collum, D. B.; Zakarian, Z. J. Am. Chem. Soc. 2013, 135, 16853.
Method of Continuous Variations: Applications of Job Plots to the Study of Molecular Associations in Organometallic Chemistry. Renny, J. S.; Tomasevich, L. L.; Tallmadge, E. H.; Collum, D. B. Angew. Chem., Int. Ed. 2013, 52, 11998.
Solution Structures of Lithium Amino Alkoxides Used in Highly Enantioselective 1,2-Additions. Bruneau, A. M.; Collum, D. B. J. Am. Chem. Soc. 2014, 53, 2885.