2 research outputs found
Azaaldol Condensation of a Lithium Enolate Solvated by <i>N,N,N′,N′</i>-Tetramethylethylenediamine: Dimer-Based 1,2-Addition to Imines
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
Lithium Diisopropylamide-Mediated Lithiation of 1,4-Difluorobenzene under Nonequilibrium Conditions: Role of Monomer‑, Dimer‑, and Tetramer-Based Intermediates and Lessons about Rate Limitation
Lithiation
of 1,4-difluorobenzene with lithium diisopropylamide
(LDA) in THF at −78 °C joins the ranks of a growing number
of metalations that occur under conditions in which the rates of aggregate
exchanges are comparable to the rates of metalation. As such, a substantial
number of barriers vie for rate limitation. Rate studies reveal that
rate-limiting steps and even the choice of reaction coordinate depend
on subtle variations in concentration. Deuteration shifts the rate-limiting
step and markedly alters the concentration dependencies and overall
rate law. This narrative is less about ortholithiation per se and
more about rate limitation and the dynamics of LDA aggregate exchange