Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine.
The (-)-sparteine-mediated asymmetric lithiation-substitution of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine ((E)-5) to afford gamma-substituted enantiomerically enriched products 6 is reported. The solution structure for the lithiated intermediate 8.1 in these reactions was determined by heteronuclear NMR to be a configurationally stable, alpha-lithio, eta(1)-coordinated monomer. This intermediate is proposed to exist as two rotamers that are rapidly equilibrating on the NMR time scale; competitive electrophilic substitution of each conformation results in the formation of Z or E products. Kinetic measurements of the lithiation by in situ infrared spectroscopy provide pseudo-first-order rate constants for reactions with a variety of concentrations of amine, (-)-sparteine, and n-BuLi. The reaction is first order in amine and zero order in 1:1 base--ligand complex. When the concentration of n-BuLi is varied independently of (-)-sparteine concentration, the reaction rate exhibits an inverse dependence on n-BuLi concentration. The deuterium isotope effect for the reaction was determined to be 86 at -75 degrees C, a result consistent with C--H bond breaking in the rate-determining step and indicative of tunneling. A reaction pathway involving a prelithiation complex is supported by kinetic simulations.
Pippel
D J
DJ
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Weisenburger
G A
GA
Faibish
N C
NC
Beak
P
P
D000499:Allylamine / Q000031:analogs & derivatives / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry*; D003903:Deuterium; D007700:Kinetics; D008094:Lithium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011522:Protons; D013034:Sparteine / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
D003510:Cyclohexanes; C433063:N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine; D011522:Protons; D013034:Sparteine; D000499:Allylamine; D008094:Lithium; D003903:Deuterium