Müller S, Webber MJ, List B * Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
The Catalytic Asymmetric Fischer Indolization.
J. Am. Chem. Soc. 2011;
133: 18534-18537
Key words
Fisher indolization - ion exchange resins - spirocyclic phosphoric acids
Significance
The List group presents the first catalytic asymmetric Fischer indolization using newly developed spirocyclic phosphoric acid catalyst 1. The authors achieved an efficient catalyst turnover by the addition of a weakly acidic cation exchange
resin, which removes the generated ammonia. To show the synthetic utility of this reaction, the authors carried out a formal synthesis of the thromboxane receptor antagonist ramatroban starting from 2.0 mmol scale of 2, and the desired
intermediate 3 was obtained without loss of enantioselectivity.
Comment
The Fischer indolization, first reported over 120 years ago, remains one of the most important reactions in organic synthesis. However, a catalytic asymmetric version of this reaction was elusive. Possibly one of the main reasons for this is the
formation of ammonia, which poisons Brønsted acid catalysts during the reaction. Key to the success of described reaction has been the addition of an acidic ion exchange resin, which does not catalyze the reaction but efficiently removes ammonia.
The new methodology provides a scalable and efficient asymmetric Fischer indolization process under mild reaction conditions.
