Enantioselective synthesis of multifunctionalized 4H-pyran derivatives using bifunctional thiourea-tertiary amine catalysts

A series of novel chiral multifunctionalized 4H-pyran derivatives were easily accessed via the one-pot asymmetric Michael addition-cyclization reaction between malononitrile and β,γ-unsaturated α-keto esters catalyzed by chiral bifunctional thiourea-tertiary amine catalysts. With the optimized reaction conditions, the desired products were obtained with 50–68% yields and 72–88% ees.

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(R)-Methyl 6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylateC14H12N2O3Ee = 78%[α]D22.1=-105.6 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 6-amino-5-cyano-4-(4-fluorophenyl)-4H-pyran-2-carboxylateC14H11FN2O3Ee = 81%[α]D22.1=-68.1 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 6-amino-4-(4-chlorophenyl)-5-cyano-4H-pyran-2-carboxylateC14H11ClN2O3Ee = 82%[α]D22.1=-132.4 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 6-amino-4-(4-bromophenyl)-5-cyano-4H-pyran-2-carboxylateC14H11BrN2O3Ee = 88%[α]D22.1=-50.7 (c 1.00, CHCl3);Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-Methyl 6-amino-5-cyano-4-(2,4-dichlorophenyl)-4H-pyran-2-carboxylateC14H10Cl2N2O3Ee = 88%[α]D22.1=-189.5 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-Methyl 6-amino-5-cyano-4-(4-nitrophenyl)-4H-pyran-2-carboxylateC14H11N3O5Ee = 72%[α]D22.1=-10.3 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 6-amino-5-cyano-4-(4-ethoxyphenyl)-4H-pyran-2-carboxylateC16H16N2O4Ee = 85%[α]D22.1=-96.1 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-Methyl 6-amino-4-(2-bromophenyl)-5-cyano-4H-pyran-2-carboxylateC14H11BrN2O3Ee = 83%[α]D22.1=-173.5 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-Methyl 6-amino-5-cyano-4-(2,5-dimethoxyphenyl)-4H-pyran-2-carboxylateC16H16N2O5Ee = 80%[α]D22.1=-153.8 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Benzyl 6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylateC20H16N2O3Ee = 80%[α]D22.1=-55.6 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-4-Bromobenzyl 6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylateC20H15BrN2O3Ee = 80%[α]D22.1=-50.1 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Isopropyl 6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylateC16H16N2O3Ee = 75%[α]D22.1=-63.0 (c 1.00, CDCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Allyl 6-amino-5-cyano-4-phenyl-4H-pyran-2-carboxylateC16H14N2O3Ee = 77%[α]D22.1=-99.5 (c 1.00, CDCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)