N-Thiophosphoryl imines: convenient substrates in the aza-Henry reaction

In the presence of 1,1,3,3-tetramethylguanidine (TMG), N-diethoxythiophosphorylimines 1 and N-diphenylthiophosphinoylimines 2 exhibited good reactivity in the aza-Henry reaction. The corresponding products were obtained in excellent chemical yields under mild conditions. Moreover, the asymmetric version of the N-thiophosphoryl imine 1-based aza-Henry reaction was also realized with ee values up to 87% by employing Takemoto’s thiourea as the catalyst.

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1-((1R,2R)-2-(Dimethylamino)cyclohexyl)-3-(diphenylphosphorothioyl)thioureaC21H25N3PS2[α]D20=-44.9 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R,R)

(R)-O,O-Diethyl 2-nitro-1-phenylethylphosphorothioamidateC12H19N2O4PSEe = 85%[α]D20=-18.0 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 2-nitro-1-p-tolylethylphosphorothioamidateC13H21N2O4PSEe = 86%[α]D20=-5.6 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 1-(2-methoxyphenyl)-2-nitroethylphosphorothioamidateC13H21N2O5PSEe = 84%[α]D20=-23.0 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 1-(3-methoxyphenyl)-2-nitroethylphosphorothioamidateC13H21N2O5PSEe = 87%[α]D20=-10.0 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 1-(4-methoxyphenyl)-2-nitroethylphosphorothioamidateC13H21N2O5PSEe = 87%[α]D20=-4.7 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 1-(2-chlorophenyl)-2-nitroethylphosphorothioamidateC12H18ClN2O4PSEe = 82%[α]D20=-5.0 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 2-nitro-1-(2-(trifluoromethyl)phenyl)ethylphosphorothioamidateC13H18F3N2O4PSEe = 87%[α]D20=-10.4 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(R)-O,O-Diethyl 1-(3-fluorophenyl)-2-nitroethylphosphorothioamidateC12H18FN2O4PSEe = 83%[α]D20=-5.6 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (R)

(S)-O,O-Diethyl 1-(furan-2-yl)-2-nitroethylphosphorothioamidateC10H17N2O5PSEe = 77%[α]D20=-18.6 (c 1.0, CHCl3)Source of chirality: (1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (S)