On the Kinetic and Thermodynamic Reactivity of Lithium Di(alkyl)amidozincate Bases in Directed Ortho Metalation

Sequential reaction of HTMP (= 2,2,6,6-tetramethylpiperidine) with nBuLi and Et2Zn 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-C10H6C(O)NiPr2-2)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-C6H4C(O)NiPr2-2)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.