Asymmetric epoxidation of substituted chalcones and chalcone analogues catalyzed by α-d-glucose- and α-d-mannose-based crown ethers

The chiral monoaza-15-crown-5 lariat ethers annellated to methyl-4,6-O-benzylidene-α-d-glucopyranoside-1 or mannopyranoside 2 have been applied as phase-transfer catalysts in the epoxidation of substituted chalcones and chalcone analogues with tert-butylhydroperoxide resulting in significant asymmetric induction. It was found that the position of the substituents in the aromatic ring of the chalcone had an influence both on the chemical yields and enantiomeric excesses. The lowest enantioselectivities (62–83% ee) were found in the case of ortho-substituted model compounds. The highest ee values (ee of 83–97%) were obtained in the case of para-substituted models. From among the chalcone analogues, the maximum ee (90–92%) was detected for the model compound having α-tert-butyl- and β-aryl groups. Using glucose-based crown ether 1, formation of the (−)-enantiomer was preferred, while applying mannose-based 2 as the catalyst, the (+)-enantiomer was in excess.

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(2R,3S)-2,3-Epoxy-3-(2,4-dichlorophenyl)-1-phenylpropan-1-oneC15H10Cl2O2Ee 99% (1H NMR with Eu(hfc)3)[α]D22=-47.1 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S)

(+)-2,3-Epoxy-3-(2,6-dichlorophenyl)-1-phenylpropan-1-oneC15H10Cl2O2Ee 70% (1H NMR with Eu(hfc)3)[α]D22=+48.3 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(−)-2,3-Epoxy-3-(2-chloro-6-flourophenyl)-1-phenylpropan-1-oneC15H10ClFO2Ee 24% (1H NMR with Eu(hfc)3)[α]D22=-20.0 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(−)-4,4-Dimethyl-1,2-epoxy-1-(napht-1-yl)pentan-3-oneC17H18O2Ee 85% (1H NMR with Eu(hfc)3)[α]D22=-47.8 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(−)-4,4-Dimethyl-1,2-epoxy-1-(napht-2-yl)pentan-3-oneC17H18O2Ee 92% (1H NMR with Eu(hfc)3)[α]D22=-253.2 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(2R,3S)-2,3-Epoxy-1-(2-nitrophenyl)-3-phenylpropan-1-oneC15H11NO4Ee 80% (1H NMR with Eu(hfc)3)[α]D22=-258.0 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S)

(2R,3S)-2,3-Epoxy-1-(3-nitrophenyl)-3-phenylpropan-1-oneC15H11NO4Ee 99% (1H NMR with Eu(hfc)3)[α]D22=-146.6(c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S)