Chiral amine catalyzed enantio- and diastereoselective Michael reaction in brine

Simple pyrrolidine-based chiral amines were synthesized and used for the Michael addition of different ketones to a variety of nitro-olefins in brine. The effect of different surfactants and acids on the yields and stereochemical outcome of the Michael adducts was studied in detail. Chiral amine 1g was found to catalyze the formation of Michael adducts with high enantioselectivity (up to >99%), diastereoselectivity [up to 98:2 (syn:anti)] and yield (up to 94%).

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(S)-2-(N-Phenylaminometh-1-yl)pyrrolidineC11H16N2[α]D20=+18.6 (c 0.72, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

((S)-2-(N-3-Nitrophenylaminometh-1-yl)pyrrolidineC11H15N3O2[α]D20=+16.7 (c 0.61, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(N-Naphth-1-ylaminometh-1-yl)pyrrolidineC15H18N2[α]D20=+17.9 (c 0.65, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(N-Cyclohexylaminometh-1-yl)pyrrolidineC11H22N2[α]D20=+14.45 (c 0.78, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

C10H20N2(S)-1-(Pyrrolidin-2-ylmethyl)piperidine[α]D20=+18.3 (c 0.84, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-1-Methyl-4-(pyrrolidin-2-ylmethyl)piperazineC10H21N3[α]D20=+17.5 (c 0.83, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-1-Methyl-4-(pyrrolidin-2-ylmethyl)piperazineC15H23N3[α]D20=+17.0 (c 0.77, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)