Journal of the American Chemical Society, Vol.125, No.51, 15893-15901, 2003
Lithium 2,2,6,6-tetramethylpiperldide-mediated alpha- and beta-lithiations of epoxides: Solvent-dependent mechanisms
Lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-mediated alpha- and beta-lithiations of epoxides are described. LiTMP displays a markedly higher reactivity than does lithium diisopropylamide, consistent with literature reports. Detailed rate studies of LiTMP/THF and LiTMP/Me2NEt mixtures reveal similar rates but significant mechanistic differences. LiTMP-mediated alpha-lithiation of cis-cyclooctene oxide with subsequent oxacarbenoid formation and transannular C-H insertion proceeds via monosolvated dinners in both THF and Me2NEt. LiTMP-mediated beta-lithiation of 2,3-dimethyl-2-butene oxide affords the corresponding allylic alcohol via a monosolvated monomer in THF and a monosolvated dimer in Me2NEt. We discuss how the solvent-dependent aggregation of LiTMP markedly influences the rate profile. The reaction transition structures are examined with density functional computations.