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 and 2-methylcyclohexanone with lithium diisopropylamide (LDA) in tetrahydrofuran (THF), N,N,N',N'-tetramethylethylenediamine (TMEDA), and dimethylethylamine (DMEA) mixtures are described. The N-isopropylimines appear to metalate via a mechanism involving deaggregation of the LDA dimer to give reactive monomers without participation of additional donor 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 isostructural N,N-dimethylhydrazones provide no evidence that a Me2N-Li interaction facilitates the metalation. Metalation of imines bearing pendant Me2N moieties on the N-isopropyl groups appears to proceed by either of two mechanisms. In THF and THF/hexane mixtures, the monomer-based pathway completely dominates; a Me2N-Li interaction does not appear to be important. In TMEDA/hexane mixtures and DMEA/hexane mixtures, dramatic rate accelerations are observed. Accompanying substantial changes in the mathematical forms of the rate equations suggest that the metalations 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).