Efficient organocatalytic asymmetric synthesis of 2-amino-4H-chromene-3-carbonitrile derivatives

The organocatalytic enantioselective tandem Michael addition–cyclization of malononitrile to nitroalkenes for the direct synthesis of chiral 2-amino-4H-chromene-3-carbonitrile derivatives was investigated. Good yields and enantioselectivities (up to 91% ee) were achieved. This organocatalytic asymmetric tandem Michael addition–cyclization provides an efficient route toward the synthesis of optically active functionalized chromenes.

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(R)-2-Amino-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H9N3O3ee = 91%[α]D25=-20.8 (c 1.76, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-6-chloro-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H8ClN3O3ee = 78%[α]D25=-49.1 (c 1.96, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-6-bromo-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H8 BrN3O3ee = 66%[α]D25=-6.6 (c 3.47, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-6-nitro-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H8N4O5ee = 56%[α]D25=+74.3 (c 2.08, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-8-methoxy-4-(nitromethyl)-4H-chromene-3-carbonitrileC12H11N3O4ee = 40%[α]D25=-9.4 (c 2.80, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-8-ethoxy-4-(nitromethyl)-4H-chromene-3-carbonitrileC13H13N3O4ee = 55%[α]D25=-14.6 (c 3.02, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-6,8-dichloro-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H7Cl2N3O3ee = 13%[α]D25=-4.9 (c 1.63, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Amino-6,8-dibromo-4-(nitromethyl)-4H-chromene-3-carbonitrileC11H7Br2N3O3ee = 71%[α]D25=-6.9 (c 3.50, ethyl acetate)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)