SOLVENT-DEPENDENT AND SUBSTRATE-DEPENDENT RATES OF IMINE METALATIONS BY LITHIUM DIISOPROPYLAMIDE - UNDERSTANDING THE MECHANISMS UNDERLYING K(REL)

Rate studies of the metalation of imines derived from cyclohexanone an d 2-methylcyclohexanone with lithium diisopropylamide (LDA) in tetrahy drofuran (THF), N,N,N',N'-tetramethylethylenediamine (TMEDA), and dime thylethylamine (DMEA) mixtures are described. The N-isopropylimines ap pear to metalate via a mechanism involving deaggregation of the LDA di mer to give reactive monomers without participation of additional dono r solvent. TMEDA functions as an eta1 ligand in both the starting LDA dimer and the rate-determining monomeric transition state as evidenced by analogous behavior with DMEA. Comparisons of the N-isopropylimine metalations with previously described rate studies of the isostructura l N,N-dimethylhydrazones provide no evidence that a Me2N-Li interactio n facilitates the metalation. Metalation of imines bearing pendant Me2 N moieties on the N-isopropyl groups appears to proceed by either of t wo mechanisms. In THF and THF/hexane mixtures, the monomer-based pathw ay completely dominates; a Me2N-Li interaction does not appear to be i mportant. In TMEDA/hexane mixtures and DMEA/hexane mixtures, dramatic rate accelerations are observed. Accompanying substantial changes in t he mathematical forms of the rate equations suggest that the metalatio ns proceed by double dissociation of R3N ligands with subsequent rate- limiting metalation by the solvent-free LDA dimer. Open dimers of LDA are suggested to be the critical reactive intermediates in a mechanism shown to constitute a complex-induced proximity effect (CIPE).