Enantioselective Friedel–Crafts type addition of indoles to nitro-olefins using a chiral hydrogen-bonding catalyst – synthesis of optically active tetrahydro-β-carbolines

Abstract

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-β-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.