On the kinetic and thermodynamic reactivity of lithium di(alkyl) amidozincate bases in directed ortho metalation

Yoshinori Kondo, James V. Morey, Jacqueline C. Morgan, Hiroshi Naka, Daisuke Nobuto, Paul R. Raithby, Masanobu Uchiyama, Andrew E.H. Wheatley

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

Sequential reaction of HTMP (= 2,2,6,6-tetramethylpiperidine) with nBuLi and Et 2Zn affords unsolvated polymer chains of EtZn(μ-Et)(μ-TMP)Li 6. The scope of this reagent in directed ortho metalation (DoM) chemistry has been tested by its reaction with N,N-diisopropylnaphthamide in THF to give EtZn(μ-C 10H 6C(O)N iPr 2-2) 2Li·2THF 7. Data reveal that 6 has undergone reaction with 2 equiv of aromatic tertiary amide and imply that it exhibits dual alkyl/amido basicity. DFT calculations reveal that direct alkyl basicity is kinetically disfavored and instead point to a stepwise mechanism whereby 6 acts as an amido base, liberating HTMP during the first DoM event. Re-coordination of the amine at lithium then incurs the elimination of EtH. Reaction of the resulting alkyl(amido)(arylamido)zincate with a second equivalent of N,N-diisopropylnaphthamide eliminates HTMP and affords 7. Both DoM steps involve the exhibition of amido basicity and each reveals a low kinetic barrier to reaction. Understanding of this reaction sequence is tested by treating 6 with N,N-diisopropylbenzamide in THF. On the basis of theory and experiment, the presence of THF solvent (in place of stronger Lewis bases) combined with the use of a sterically less congested aromatic amide is expected to encourage threefold, stepwise reaction. Isolation and characterization of the resulting tripodal zincate Zn(μ-C 6H 4C(O)N iPr 2-2) 3Li·THF 8 bears this out and suggests a significant new level of control in zincate-induced DoM chemistry through the combination of experiment and DFT studies.

Original languageEnglish
Pages (from-to)12734-12738
Number of pages5
JournalJournal of the American Chemical Society
Volume129
Issue number42
DOIs
Publication statusPublished - 2007 Oct 24

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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