CHEMISTRY OF LITHIUM AMIDES

Cornell University Ithaca, Ithaca NY

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Abstract

We will investigate structure-reactivity relationships in N-lithiated species by focussing upon three lithium amides: lithium 2,2,6,6-tetramethylpiperidide (LiTMP), lithium hexamethyldisilazide (LiHMDS), and lithium diisopropylamide (LDA). 6Li-15N double labelling spectroscopic methods have already provided aggregation and solvation states, relative free energies and enthalpies of solvation, and even mechanisms of ligand substitution. The spectroscopic investigations will support and augment the rate and mechanistic studies. We will emphasize the correlation of solvation energy, aggregate structure, and reactivity through detailed mechanistic and rate studies of four synthetically important reactions of lithium amides: (1) ketone enolization, (2) imine metallation, (3) epoxide and alkyl halide elimination, and (4) orthometallation. Additional recurring themes include: (1) develop hemi-labile ligands to control reaction rates and selectivities, (2) explore the scope and mechanism by which Lewis acids and related electrophilic additive influence reactivity, (3) establish the necessary mechanistic foundations to allow ligands (solvents) to be employed catalytically, and (4) determine how the intervention of lithium amide-LiX mixed aggregates influence reaction rates and mechanisms. Significant progress is assured by substantial preliminary results and the mechanistic transparency of these particular reactions. Overall, the lithium amides offer a promising opportunity to understand the complexities presented by organolithium chemistry.