Diastereoselective Alkylation of β-Amino Esters: Structural and Rate Studies Reveal Alkylations of Hexameric Lithium Enolates

Alkylation of β-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.