Subscribe to RSS
DOI: 10.1055/s-0030-1258781
Entropy-Controlled Asymmetric Catalysis
Contributor(s):Benjamin List, Olga LifchitsTokyo University of Agriculture and Technology, Japan
Entropy-Controlled Catalytic Asymmetric 1,4-Type Friedel-Crafts Reaction of Phenols Using Conformationally Flexible Guanidine/Bisthiourea Organocatalyst
Angew. Chem. Int. Ed. 2010, 49: 7299-7303
Publication History
Publication Date:
21 October 2010 (online)
Key words
Friedel-Crafts reaction - conformationally flexible catalysts - guanidine/bisthiourea catalysis - entropy control
Significance
Sohtome, Nagasawa, and colleagues report an enantioselective Friedel-Crafts reaction of phenols and nitroolefins using their recently developed flexible guanidine/bisthiourea catalyst 3. Extensive catalyst development allowed the authors to achieve very good enantio- and chemoselectivity in the reaction, which is normally prone to cascade processes. Kinetic studies based on the Eyring equation revealed an unprecedented mode of enantiodifferentiation based solely on entropic control. This type of activation is equally efficient over a wide range of temperatures and the entropy term can be presumably tuned by changing the reaction conditions.
Comment
In contrast to most organocatalysts, which are rigid, the authors employed a conformationally flexible bifunctional organic molecule. The observation that increased temperature led to better enantioselectivity prompted the authors to examine the activation parameters of the reaction. Kinetic studies revealed that, regardless of concentration, the reaction was mainly entropically controlled and became entirely independent of enthalpy (and reaction temperature) at sufficiently low concentration. Further insight into the link between the observed kinetics and the molecular mechanism is expected for this conceptually intriguing catalysis mode.