11 research outputs found
Solution Structures of Lithium Amino Alkoxides Used in Highly Enantioselective 1,2-Additions
Lithium
ephedrates and norcarane-derived lithium amino alkoxides
used to effect highly enantioselective 1,2-additions on large scales
have been characterized in toluene and tetrahydrofuran. The method
of continuous variations in conjunction with <sup>6</sup>Li NMR spectroscopy
reveals that the lithium amino alkoxides are tetrameric. In each case,
low-temperature <sup>6</sup>Li NMR spectra show stereoisomerically
pure homoaggregates displaying resonances consistent with an <i>S</i><sub>4</sub>-symmetric cubic core rather than the alternative <i>D</i><sub>2<i>d</i></sub> core. These assignments
are supported by density functional theory computations and conform
to X-ray crystal structures. Slow aggregate exchanges are discussed
in the context of amino alkoxides as chiral auxiliaries
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