Enantioselective Michael additions of nitromethane by a catalytic double activation method using chiral Lewis acid and achiral amine catalysts

Reactions of nitromethane with 1-(2-alkenoyl)-3,5-dimethylpyrazoles can be effectively catalyzed by R,R-DBFOX/Ph·Ni(ClO4)2·3H2O and achiral amine bases, each in a catalytic loading of 10 mol %, to give 1-(3-substituted 4-nitrobutanoyl)-3,5-dimethylpyrazoles in high chemical yields. Excellent enantioselectivities up to 98% ee have been achieved. The nitro moiety can be easily reduced on Raney nickel at atmospheric pressure, followed by concurrent cyclization, to give enantiomers of 4-substituted 2-pyrrolidinone derivatives after usual workup. This method can be successfully applied to a short step synthesis of (R)-(-)-rolipram. Copyright © 2002 American Chemical Society.