Enantioselective synthesis of heteroaromatic epoxyketones under phase-transfer catalysis using d-glucose- and d-mannose-based crown ethers

Heteroaromatic epoxyketones have been synthesized in an asymmetric Darzens condensation of 2-chloroacetylfuran or 2- and 3-chloroacetylthiophene with aromatic aldehydes and in the enantioselective epoxidation of α,β-enones with an N-methylpyrrole unit, in both cases in the presence of d-glucose- 1 or d-mannose-based 2 crown ethers as phase transfer catalysts. The use of d-glucose-based 1 lariat ether as the catalyst gave the best results. The α,β-epoxyketones with a furan or a thiophene moiety were obtained in good enantioselectivities (up to 86% ee) as well as excellent diastereoselectivities (up to 98:2), but the epoxyketones with a pyrrole-ring were formed in the Darzens condensation in low yields and enantioselectivities. The epoxyketones with an N-methylpyrrole moiety isolated from the epoxidation of the corresponding α,β-enones were obtained in significant enantioselectivities (in ee values up to 81%) in the presence of catalyst 1 under mild reaction conditions.

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(2R,3S)-2,3-Epoxy-1-(2-furyl)-3-phenylpropan-1-oneC13H10O3Ee 54% (1H NMR with Eu(hfc)3)[α]D22=-117.7 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S)

trans-(−)-2,3-Epoxy-1-(2-furyl)-3-(2-tolyl)-propan-1-oneC14H12O3Ee 57% (1H NMR with Eu(hfc)3)[α]D22=-33.1 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-furyl)-3-(2-chlorophenyl)-propan-1-oneC13H9ClO3Ee 70% (1H NMR with Eu(hfc)3)[α]D22=-14.9 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-furyl)-3-(4-chlorophenyl)-propan-1-oneC13H9ClO3Ee 62% (1H NMR with Eu(hfc)3)[α]D22=-146.5 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-furyl)-3-pyperonyl-propan-1-oneC14H10O5Ee 64% (1H NMR with Eu(hfc)3)[α]D22=-151.3 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-furyl)-3-(2-naphthyl)-propan-1-oneC17H12O3Ee 28% (1H NMR with Eu(hfc)3)[α]D22=-73.6 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-phenylpropan-1-oneC13H10O2SEe 71% (1H NMR with Eu(hfc)3)[α]D22=-169.8 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S) (assigned by comparing the specific rotation with that of the known compound)

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-(2-chlorophenyl)-propan-1-oneC13H9ClO2SEe 51% (1H NMR with Eu(hfc)3)[α]D22=-10.0 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-(3-chlorophenyl)-propan-1-oneC13H9ClO2SEe 60% (1H NMR with Eu(hfc)3)[α]D22=-142.1 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-(4-chlorophenyl)-propan-1-oneC13H9ClO2SEe 65% (1H NMR with Eu(hfc)3)[α]D22=-139 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-(4-fluorophenyl)-propan-1-oneC13H9FO2SEe 62% (1H NMR with Eu(hfc)3)[α]D22=-119.7 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(2R,3S)-2,3-Epoxy-1-(2-thienyl)-3-(2-tolyl)-propan-1-oneC14H12O2SEe 68% (1H NMR with Eu(hfc)3)[α]D22=-45.7 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S) (assigned by X-ray diffraction analysis)

trans-(+)-2,3-Epoxy-1-(2-thienyl)-3-(1-naphthyl)-propan-1-oneC17H12O2SEe 64% (1H NMR with Eu(hfc)3)[α]D22=+54 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-thienyl)-3-(2-naphthyl)-propan-1-oneC14H12O2SEe 62% (1H NMR with Eu(hfc)3)[α]D22=-163 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

(2R,3S)-2,3-Epoxy-1-(2-thienyl)-3-piperonyl-propan-1-oneC14H10O4SEe 86% (1H NMR with Eu(hfc)3)[α]D22=-131.5 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S) (assigned by X-ray diffraction analysis)

trans-(−)-2,3-Epoxy-1-(3-thienyl)-3-phenylpropan-1-oneC13H10O2SEe 52% (1H NMR with Eu(hfc)3)[α]D22=-72.2 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(3-thienyl)-3-(2-tolyl)-propan-1-oneC14H12O2SEe 52% (1H NMR with Eu(hfc)3)[α]D22=-19.3 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(3-thienyl)-3-(1-naphthyl)-propan-1-oneC17H12O2SEe 54% (1H NMR with Eu(hfc)3)[α]D22=+51.9 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-pyrrolyl)-3-phenylpropan-1-oneC13H11NO2Ee 36% (1H NMR with Eu(hfc)3)[α]D22=-77.3 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-pyrrolyl)-3-(2-tolyl)-propan-1-oneC14H13NO2Ee 20% (1H NMR with Eu(hfc)3)[α]D22=-1.2 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

(2R,3S)-2,3-Epoxy-1-(2-pyrrolyl)-3-(1-naphthyl)-propan-1-oneC18H13NO2Ee 51% (1H NMR with Eu(hfc)3)[α]D22=+24.9 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3S) (assigned by X-ray diffraction analysis)

(2R,3S)-2,3-Epoxy-1-(2-pyrrolyl)-3-(2-naphthyl)-propan-1-oneC18H13NO2Ee 18% (1H NMR with Eu(hfc)3)[α]D22=-40 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-phenylpropan-1-oneC14H13NO2Ee 79% (1H NMR with Eu(hfc)3)[α]D22=-209.5 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(2-chlorophenyl)-propan-1-oneC14H12ClNO2Ee 51% (1H NMR with Eu(hfc)3)[α]D22=-7 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(3-chlorophenyl)-propan-1-oneC14H12ClNO2Ee 79% (1H NMR with Eu(hfc)3)[α]D22=-207 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(4-chlorophenyl)-propan-1-oneC14H12ClNO2Ee 81% (1H NMR with Eu(hfc)3)[α]D22=-211.4 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(2-tolyl)-propan-1-oneC15H15NO2Ee 65% (1H NMR with Eu(hfc)3)[α]D22=-49.7 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(3-tolyl)-propan-1-oneC15H15NO2Ee 70% (1H NMR with Eu(hfc)3)[α]D22=-196.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(4-tolyl)-propan-1-oneC15H15NO2Ee 79% (1H NMR with Eu(hfc)3)[α]D22=-216.3 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(+)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(1-naphthyl)-propan-1-oneC18H15NO2Ee 70% (1H NMR with Eu(hfc)3)[α]D22=+88 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(2-N-methylpyrrolyl)-3-(2-naphthyl)-propan-1-oneC18H15NO2Ee 77% (1H NMR with Eu(hfc)3)[α]D22=-219.7 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalyst