Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Several cinchona based squaramide catalysts were applied to the asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yields and enantioselectivities. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.

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3-((3,5-Bis(trifluoromethyl)benzyl)amino)-4-(((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)amino)cyclobut-3-ene-1,2-dioneC33H30F6N4O3[α]D22=-65.0 (c 1.0, DMSO)Source of chirality: 9-Amino-(9-deoxy)-epi-quinineAbsolute configuration: (1S,2S,4S,5R)

3-(Benzylamino)-4-(((1S)-((2S,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methyl)amino)cyclobut-3-ene-1,2-dioneC31H34N4O3[α]D22=-77.0 (c 1.0, DMSO)Source of chirality: 9-Amino-(9-deoxy)-epi-hydroquinineAbsolute configuration: (1S,2S,4S,5R)

3-(Benzylamino)-4-(((1S)-((2S,4S,5S)-5-ethynylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methyl)amino)cyclobut-3-ene-1,2-dioneC31H30N4O3[α]D22=-84.0 (c 1.0, DMSO)Source of chirality: 9-Amino-(9-deoxy)-10,11-didehydroepi-quinineAbsolute configuration: (1S,2S,4S,5S)

(S)-4-(Diethoxyphosphoryl)-4-nitropentanoic acid 2-methoxyphenyl esterC16H24NO8P[α]D22=-1.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(2-Methyl-5-oxopyrrolidin-2-yl)-phosphonic acid diethyl esterC9H18NO4P[α]D22=+1.0 (c 1.25, CHCl3)Source of chirality: (S)-4-(Diethoxyphosphoryl)-4-nitropentanoic acid 2-methoxyphenyl esterAbsolute configuration: (S)