Diastereoselective alkylation of beta-amino esters: structural and rate studies reveal alkylations of hexameric lithium enolates.
Alkylation of beta-amino ester enolates proceeds with high diastereoselectivity. Single crystal, powder, and solution X-ray diffraction studies of the enolate show that the racemic enolate forms prismatic hexamers. 6Li NMR spectroscopic studies on partially racemic enolates reveal complex mixtures of homo- and heterochiral hexamers. An implicit fit of the aggregate populations to the Boltzmann distribution provides the free energy differences and equilibrium constants for the ensemble. Rate studies show that enolate alkylation occurs directly from the hexamer with participation by THF. A mechanism based on the alkylation of a ladder-like aggregate is proposed.
McNeil
Anne J
AJ
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Toombes
Gilman E S
GE
Gruner
Sol M
SM
Lobkovsky
Emil
E
Collum
David B
DB
Chandramouli
Sithamalli V
SV
Vanasse
Benoit J
BJ
Ayers
Timothy A
TA
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D004952:Esters; D009942:Organometallic Compounds; D008094:Lithium