Azaaldol Condensation of a Lithium Enolate Solvated
by <i>N,N,N′,N′</i>-Tetramethylethylenediamine: Dimer-Based 1,2-Addition to Imines
- Publication date
- Publisher
Abstract
The lithium enolate of <i>tert</i>-amylacetate solvated
by <i>N,N,N′,N′</i>-tetramethylethylenediamine
(TMEDA) is shown to be a doubly chelated dimer. Adding the dimeric
enolate to 4-fluorobenzaldehyde-<i>N</i>-phenylimine affords
an N-lithiated β-amino ester shown to be monomeric using <sup>6</sup>Li and <sup>15</sup>N NMR spectroscopies. Rate studies using <sup>19</sup>F NMR spectroscopy reveal reaction orders consistent with
a transition structure of stoichiometry [(ROLi)<sub>2</sub>(TMEDA)<sub>2</sub>(imine)]<sup>⧧</sup>. Density functional theory computations
explore several possible dimer-based transition structures with monodentate
and bidentate coordination of TMEDA. Supporting rate studies using <i>trans-N,N,N′,N′</i>-1,2-tetramethylcyclohexanediamine
showing analogous rates and rate law suggest that TMEDA is fully chelated