title: Lithium 2,2,6,6-tetramethylpiperidide-mediated alpha- and beta-lithiations of epoxides: solvent-dependent mechanisms.
abstract: 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/Me(2)NEt 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 dimers in both THF and Me(2)NEt. 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 Me(2)NEt. We discuss how the solvent-dependent aggregation of LiTMP markedly influences the rate profile. The reaction transition structures are examined with density functional computations.
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
authors.forename: Sean H
authors.initials: SH
authors.lastname: Wiedemann
authors.forename: Antonio
authors.initials: A
authors.lastname: Ramírez
authors.forename: David B
authors.initials: DB
authors.lastname: Collum
mesh_terms: D004852:Epoxy Compounds / Q000737:chemistry*; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D012997:Solvents; D013816:Thermodynamics
chemical_list: D004852:Epoxy Compounds; D009942:Organometallic Compounds; D010880:Piperidines; D012997:Solvents; D008094:Lithium