Synfacts 2007(5): 0471-0471  
DOI: 10.1055/s-2007-968473
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of 3-Indolyl Methylamines (Gramines)

Contributor(s): Victor Snieckus, Wei Gan
Q. Kang, Z.-A. Zhao, S.-L. You*
Shanghai Institute of Organic Chemistry, P. R. of China
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Publication History

Publication Date:
24 April 2007 (online)


An enantioselective Friedel-Crafts reaction of indoles with imines to give gramine derivatives using the metal-free chiral phosphoric acid catalyst 1 is reported. In contrast to the results reported by Zhou (Org. Lett. 2006, 8, 1621-1624) who, using chiral Cu-complex catalysis for the synthesis of gramines, showed that enantioinduction is strongly dependent on electronic features of the starting indoles, the present work demonstrates high yields and high ee values using indoles with both EDGs and EWGs. However, for substituted benzaldimines, a slight drop in yields and ee was observed when EDGs are replaced by EWGs. For one example of an aliphatic imine, only moderate yield and ee were observed. Most of the reactions are completed within one hour under the given reaction conditions.