Enantioselective synthesis of 2-amino-4H-pyrans via the organocatalytic cascade reaction of malononitrile and α-substituted chalcones

An organocatalytic cascade reaction of malononitrile and α-substituted chalcones has been developed for the synthesis of chiral multisubstituted 2-amino-4H-pyran derivatives. A series of chiral primary/tertiary amines and cinchona alkaloids were examined as the catalysts. Quinine was found to be the most efficient catalyst in the absence of any additive. The α-substitutents of the chalcones had a siginificant effect on the yield and the enantioselectivity. A number of multisubstituted 2-amino-4H-pyrans were obtained in excellent yields and enantioselectivities.

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(S)-2-Amino-4-(4-bromophenyl)-5,6-diphenyl-4H-pyran-3-carbonitrileC24H17BrN2O87% ee[α]D20=-117.3 (c 0.104, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Amino-4-(4-nitrophenyl)-5,6-diphenyl-4H-pyran-3-carbonitrileC24H19N3O382% ee[α]D20=-121.0 (c 0.062, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Amino-5,6-diphenyl-4-(thiophen-2-yl)-4H-pyran-3-carbonitrileC22H16N2OS86% ee[α]D20=-93.3 (c 0.108, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Amino-4-isopropyl-5,6-diphenyl-4H-pyran-3-carbonitrileC21H20N2O91% ee[α]D20=+69.6 (c 0.056, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-Ethyl 2-amino-4,5,6-triphenyl-4H-pyran-3-carboxylateC21H18N2O387% ee[α]D20=+22.1 (c 0.068, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Amino-6-methyl-4,5-diphenyl-4H-pyran-3-carbonitrileC20H16N2O282% ee[α]D20=-65.4 (c 0.130, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Amino-5-methyl-4,6-diphenyl-4H-pyran-3-carbonitrileC19H18N2O95% ee[α]D20=+11.6 (c 0.086, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)