Regioselective Lithium Diisopropylamide-Mediated Ortholithiation of 1-Chloro-3-(trifluoromethyl)benzene: Role of Autocatalysis, Lithium Chloride Catalysis, and Reversibility.
- Resource Type
- Article
- Authors
- Hoepker, Alexander C.; Gupta, Lekha; Yun Ma; Faggin, Marc F.; Collum, David B.
- Source
- Journal of the American Chemical Society. 5/11/2011, Vol. 133 Issue 18, p7135-7151. 17p.
- Subject
- *LITHIUM
*BENZENE
*AUTOCATALYSIS
*LITHIUM chloride
*CATALYSIS
*TETRAHYDROFURAN
- Language
- ISSN
- 0002-7863
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 regiochemistryis 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. [ABSTRACT FROM AUTHOR]