Lithium diisopropylamide-mediated enolizations: Solvent-dependent mixed aggregation effects

Li-6 and N-15 NMR spectroscopic investigations of lithium diisopropylamide- mediated ester enolization in THF, t-BuOMe, HMPA/THF, and DMPU/THF (HMPA = hexamethylphosphoramide, DMPU = 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrim idone) reveal substantial concentrations of mixed aggregates. While previou s quantitative rate studies revealed that the metalations by lithium diisop ropylamide (LDA) homonuclear dimers proceed at nearly solvent-independent r ates, the reactivities of the intermediate mixed aggregates are markedly lo wer and quite sensitive to the choice of solvent. The autoinhibition correl ates with the relative stabilities of the mixed aggregates. However, the re lative stabilities do not correlate in a simple fashion with the ligating p roperties of the solvent.