Skip to Content
MilliporeSigma
  • Regioselective lithium diisopropylamide-mediated ortholithiation of 1-chloro-3-(trifluoromethyl)benzene: role of autocatalysis, lithium chloride catalysis, and reversibility.

Regioselective lithium diisopropylamide-mediated ortholithiation of 1-chloro-3-(trifluoromethyl)benzene: role of autocatalysis, lithium chloride catalysis, and reversibility.

Journal of the American Chemical Society (2011-04-20)
Alexander C Hoepker, Lekha Gupta, Yun Ma, Marc F Faggin, David B Collum
ABSTRACT

Ortholithiation of 1-chloro-3-(trifluoromethyl)benzene with lithium diisopropylamide (LDA) in tetrahydrofuran at -78 °C displays characteristics of reactions in which aggregation events are rate limiting. Metalation with lithium-chloride-free LDA involves a rate-limiting deaggregation via dimer-based transition structures. The post-rate-limiting proton transfers are suggested to involve highly solvated triple ions. Autocatalysis by the resulting aryllithiums or catalysis by traces (<100 ppm) of LiCl diverts the reaction through di- and trisolvated monomer-based pathways for metalation at the 2 and 6 positions, respectively. The regiochemistry is dictated by a combination of kinetically controlled metalations overlaid by an equilibration involving diisopropylamine that is shown to occur by the microscopic reverse of the monomer-based metalations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Diisopropylamine, puriss. p.a., ≥99.0% (GC)
Supelco
Diisopropylamine, analytical standard
Sigma-Aldrich
Diisopropylamine, purified by redistillation, 99.95%
Sigma-Aldrich
Diisopropylamine, ≥99.5%
Sigma-Aldrich
Lithium diisopropylamide solution, 2.0 M in THF/heptane/ethylbenzene
Sigma-Aldrich
Lithium diisopropylamide, 97%
Sigma-Aldrich
Diisopropylamine, for synthesis
Sigma-Aldrich
Diisopropylamine, SAJ first grade, ≥98.0%