The (-)-sparteine-mediated asymmetric lithiation-substitution of (
E)-
N-Boc-
N-(
p-methoxyphenyl)-3-cyclohexylallylamine ((
E)-
5) to afford
![](/images/gifchars/gamma.gif)
-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,
![](/images/gifchars/alpha.gif)
-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
![](/images/entities/deg.gif)
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.