Lithium Diisopropylamide-Mediated
Lithiation of 1,4-Difluorobenzene
under Nonequilibrium Conditions: Role of Monomer‑, Dimer‑,
and Tetramer-Based Intermediates and Lessons about Rate Limitation
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Abstract
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