On the kinetic and thermodynamic reactivity of lithium Di(alkyl)amidozincate bases in directed ortho metalation
On the kinetic and thermodynamic reactivity of lithium Di(alkyl)amidozincate bases in directed ortho metalation
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DOI：
10.1021/ja072118m
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发表时间：
2007-10-24
影响因子：
15
通讯作者：
Wheatley, Andrew E. H.
中科院分区：
文献类型：
--
作者：
Kondo, Yoshinori;Morey, James V.;Wheatley, Andrew E. H.
HTMP（= 2,2,6,6-四甲基哌啶）与(BuLi)-Bu-n和Et2Zn依次反应得到EtZn(mu-Et)(mu-TMP)Li 6的未溶剂化聚合物链。通过与N，N-二异丙基萘酰胺在THF中反应得到EtZn(mu-C10H6C(O)(NPr2)-Pr-j-2)(2)Li中心点2thf7，考察了该试剂在定向邻位金属化（DoM）化学中的作用范围。结果表明，6与2个等量的芳叔酰胺发生反应，具有烷基/酰胺双碱度。DFT计算表明，直接烷基碱度在动力学上是不利的，而是指向了一个循序渐进的机制，其中6作为氨基碱，在第一次DoM事件中释放HTMP。然后，胺在锂上的重新配位导致EtH的消除。生成的烷基（氨基）（芳基氨基）锌酸盐与第二等价物N， ndi异丙基萘酰胺反应可消除HTMP，并提供7。DoM的两个步骤都涉及到氨基碱度的展示，并且每个步骤都显示出低的反应动力学屏障。通过在THF中用N，N-二异丙基苯酰胺处理6来测试对该反应序列的理解。在理论和实验的基础上，THF溶剂的存在（代替较强的Lewis碱）与空间上较少拥挤的芳酰胺的使用相结合，有望促进三步反应。通过实验和DFT相结合的研究，得到了锌酸盐Zn(mu-C6H4C(O)(NPr2)-Pr-j-2)(3)Li中心点thf8的分离和表征，证实了这一点，并提出了锌酸盐诱导DoM化学控制的重要新水平。
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.