Kinetics and Mechanism of the (-)-Sparteine-Mediated Deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine
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- 作者：Daniel J. Pippel ; Gerald A. Weisenburger ; Neil C. Faibish ; and Peter Beak
- 刊名：Journal of the American Chemical Society
- 出版年：2001
- 出版时间：May 30, 2001
- 年：2001
- 卷：123
- 期：21
- 页码：4919 - 4927
- 全文大小：251K
- 年卷期：v.123,no.21(May 30, 2001)
- ISSN：1520-5126
文摘
The (-)-sparteine-mediated asymmetric lithiation-substitution of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine ((E)-5) to afford 
-substituted enantiomerically enriched products 6 is reported. Thesolution structure for the lithiated intermediate 8·1 in these reactions was determined by heteronuclear NMRto be a configurationally stable, 
-lithio, 
1-coordinated monomer. This intermediate is proposed to exist astwo rotamers that are rapidly equilibrating on the NMR time scale; competitive electrophilic substitution ofeach conformation results in the formation of Z or E products. Kinetic measurements of the lithiation by insitu infrared spectroscopy provide pseudo-first-order rate constants for reactions with a variety of concentrationsof amine, (-)-sparteine, and n-BuLi. The reaction is first order in amine and zero order in 1:1 base-ligandcomplex. When the concentration of n-BuLi is varied independently of (-)-sparteine concentration, the reactionrate exhibits an inverse dependence on n-BuLi concentration. The deuterium isotope effect for the reactionwas determined to be 86 at -75 
C, a result consistent with C-H bond breaking in the rate-determining stepand indicative of tunneling. A reaction pathway involving a prelithiation complex is supported by kineticsimulations.
-substituted enantiomerically enriched products 6 is reported. Thesolution structure for the lithiated intermediate 8·1 in these reactions was determined by heteronuclear NMRto be a configurationally stable, -lithio, 1-coordinated monomer. This intermediate is proposed to exist astwo rotamers that are rapidly equilibrating on the NMR time scale; competitive electrophilic substitution ofeach conformation results in the formation of Z or E products. Kinetic measurements of the lithiation by insitu infrared spectroscopy provide pseudo-first-order rate constants for reactions with a variety of concentrationsof amine, (-)-sparteine, and n-BuLi. The reaction is first order in amine and zero order in 1:1 base-ligandcomplex. When the concentration of n-BuLi is varied independently of (-)-sparteine concentration, the reactionrate exhibits an inverse dependence on n-BuLi concentration. The deuterium isotope effect for the reactionwas determined to be 86 at -75 C, a result consistent with C-H bond breaking in the rate-determining stepand indicative of tunneling. A reaction pathway involving a prelithiation complex is supported by kineticsimulations.