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.
Itoh
Kennosuke
K
Institute of Advanced Material Study, CREST of JST (Japan Science and Technology), Kyushu University, 6-1 Kasugakoen, Kasuga 816-8580, Japan.
Kanemasa
Shuji
S