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(micro-Et)(micro-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(micro-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(micro-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.
Kondo
Yoshinori
Y
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki Aza Aoba 6-3, Sendai, Japan.
Morey
James V
JV
Morgan
Jacqueline C
JC
Naka
Hiroshi
H
Nobuto
Daisuke
D
Raithby
Paul R
PR
Uchiyama
Masanobu
M
Wheatley
Andrew E H
AE
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D003460:Crystallization; D018360:Crystallography, X-Ray; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011336:Probability; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
D009942:Organometallic Compounds; D011108:Polymers; D008094:Lithium; D015032:Zinc