Chelation-Based Stabilization of the Transition Structure in a Lithium Diisopropylamide Mediated Dehydrobromination: Avoiding the “Universal Ground State” Assumption

Abstract

Dehydrobrominations of (±)-2-exo-bromonorbornane (RBr) by lithium diisopropylamide (LDA) were investigated to determine the roles of aggregation and solvation. Elimination with LDA/n-BuOMe occurs by deaggregation of disolvated dimers via a monosolvated monomer transition structure (e.g., [i-Pr2NLi·n-BuOMe·RBr]‡). In contrast, elimination by LDA−THF displays THF concentration dependencies that are consistent with parallel reaction pathways involving both mono- and disolvated monomer transition structures. Elimination is markedly faster by LDA−DME than by LDA with monodentate ligands and follows a rate law consistent with a transition structure containing a chelated monomeric LDA fragment. A number of hemilabile amino ethers reveal the capacity of different coordinating functionalities to chelate. A protocol based upon kinetic methods affords the relative ligand binding energies in the LDA dimer reactants. Separating contributions of ground state from transition state stabilization allows us to attribute the stabilizing effects of chelation exclusively to the transition structure. The importance of chelating ligands in LDA-mediated dehydrobrominations, but not in previously studied reactions of LDA, sheds light on lithium ion chelation.