Enantioselective Friedel-Crafts type addition of indoles to nitro-olefins using a chiral hydrogen-bonding catalyst--synthesis of optically active tetrahydro-beta-carbolines.
The enantioselective Friedel-Crafts addition of indoles to nitro-olefins using chiral hydrogen-bonding bis-sulfonamides as the catalysts has been developed. The reactions, in the presence of only 2 mol% catalyst, generally proceed in high yields and with enantioselectivities up to 64% ee, and the enantiomeric excess can be improved to >98% ee by recrystallization. Various synthetic transformations of the Friedel-Crafts adducts are demonstrated: the nitro group can easily be reduced to the corresponding amine and the product obtained can undergo a stereocontrolled Pictet-Spengler cyclization to give, for example, enantiopure tetrahydro-beta-carbolines. The X-ray structure of the chiral bis-sulfonamides has been determined and based on these structures the mechanism for the stereoselectivity in the reaction is discussed.
Zhuang
Wei
W
Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Hazell
Rita G
RG
Jørgensen
Karl Anker
KA