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

Y Kondo, J V Morey, J C Morgan, H Naka, D Nobuto, P R Raithby, M Uchiyama, A E H Wheatley

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90 Citations (SciVal)


Sequential reaction of HTMP (= 2,2,6,6-tetramethylpiperidine) with (BuLi)-Bu-n and Et2Zn affords unsolvated polymer chains of EtZn(mu-Et)(mu-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(mu-C10H6C(O)(NPr2)-Pr-j-2)(2)Li center dot 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,Ndiisopropylnaphthamide 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(mu-C6H4C(O)(NPr2)-Pr-j-2)(3)Li center dot 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
Issue number42
Publication statusPublished - 2007

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ID number: ISI:000250327000057


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