Asymmetric phase transfer Darzens reactions catalyzed by d-glucose- and d-mannose-based chiral crown ethers

Liquid–liquid phase asymmetric Darzens condensations were carried out in the presence of d-glucose- and d-mannose-based crown ethers 1 and 2 as the catalyst. The use of d-glucose-based lariat ether 1 as the catalyst gave the best results. The reaction of 4-phenyl-α-chloroacetophenone, 2-chloro-1-tetralone, and 2-chloro-1-indanone with various aromatic aldehydes afforded the corresponding aromatic α,β-epoxyketones in moderate to high enantiomeric excess (ee up to 96%) under mild reaction conditions. The substituents of the benzaldehyde used as the reactants had a significant impact on the chemical yields and enantiomeric excess. The absolute configuration of some epoxyketone products was determined by single-crystal X-ray analysis.

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trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-phenylpropan-1-oneC21H16O2Ee 96% (1H NMR with Eu(hfc)3)[α]D22=-173 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-(2R,3S)-2,3-Epoxy-1-(biphen-4-yl)-3-(2-chlorophenyl)propan-1-oneC21H15ClO2Ee 84% (1H NMR with Eu(hfc)3)[α]D22=-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-(biphen-4-yl)-3-(3-chlorophenyl)propan-1-oneC21H15ClO2Ee 60% (1H NMR with Eu(hfc)3)[α]D22=-110 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(4-chlorophenyl)propan-1-oneC21H15ClO2Ee 64% (1H NMR with Eu(hfc)3)[α]D22=-108 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalyst

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(4-fluorophenyl)propan-1-oneC21H15FO2Ee 55% (1H NMR with Eu(hfc)3)[α]D22=-81 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(2-nitrophenyl)propan-1-oneC21H15NO4Ee 40% (1H NMR with Eu(hfc)3)[α]D22=-63 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(3-nitrophenyl)propan-1-oneC21H15NO4Ee 45% (1H NMR with Eu(hfc)3)[α]D22=-63 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(4-nitrophenyl)propan-1-oneC21H15NO4Ee 51% (1H NMR with Eu(hfc)3)[α]D22=-119 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(2-methylphenyl)propan-1-oneC22H18O2Ee 60% (1H NMR with Eu(hfc)3)[α]D22=-32 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(3-methylphenyl)propan-1-oneC22H18O2Ee 64% (1H NMR with Eu(hfc)3)[α]D22=-122 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(4-methylphenyl)propan-1-oneC22H18O2Ee 70% (1H NMR with Eu(hfc)3)[α]D22=-130 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(+)-2,3-Epoxy-1-(biphen-4-yl)-3-(naphth-1-yl)propan-1-oneC25H18O2Ee 66% (1H NMR with Eu(hfc)3)[α]D22=+75 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1-(biphen-4-yl)-3-(naphth-2-yl)propan-1-oneC25H18O2Ee 74% (1H NMR with Eu(hfc)3)[α]D22=-129 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-2,3-Epoxy-1,3-di(biphen-4-yl)-4-chlorobutan-1-oneC28H21ClO2Ee 10% (1H NMR with Eu(hfc)3)[α]D22=-35 (c 1, CH2Cl2)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

(−)-(2R,3′S)-3′-Phenyl-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H14O2Ee 74% (1H NMR with Eu(hfc)3)[α]D22=-144 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3′S)

trans-(−)-3′-(2-Chlorophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13ClO2Ee 36% (1H NMR with Eu(hfc)3)[α]D22=-15 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Chlorophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13ClO2Ee 44% (1H NMR with Eu(hfc)3)[α]D22=-122 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

(−)-(2R,3′S)-3′-(4-Chlorophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13ClO2Ee 59% (1H NMR with Eu(hfc)3)[α]D22=-137 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (2R,3′S) (assigned by X-ray diffraction analysis)

trans-(−)-3′-(2-Nitrophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13NO4Ee 54% (1H NMR with Eu(hfc)3)[α]D22=-83 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Nitrophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13NO4Ee 43% (1H NMR with Eu(hfc)3)[α]D22=-83 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(4-Nitrophenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC17H13NO4Ee 75% (1H NMR with Eu(hfc)3)[α]D22=-145 (c 0.5, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(2-Methylphenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC18H16O2Ee 40% (1H NMR with Eu(hfc)3)[α]D22=-32 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Methylphenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC18H16O2Ee 65% (1H NMR with Eu(hfc)3)[α]D22=-142 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(4-Methylphenyl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC18H16O2Ee 55% (1H NMR with Eu(hfc)3)[α]D22=-133 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(+)-3′-(Naphth-1-yl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC21H16O2Ee 32% (1H NMR with Eu(hfc)3)[α]D22=+36 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

(−)-(2R3′S)-3′-(Naphth-2-yl)-3,4-dihydro-1H-spiro(naphthalene-2,2′-oxiran)-1-oneC21H16O2Ee 59% (1H NMR with Eu(hfc)3)[α]D22=-225 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: 2R,3′S (assigned by X-ray diffraction analysis)

trans-(−)-3′-Phenylspiro(inden-2,2′-oxiran)-1(3H)-oneC16H12O2Ee 65% (1H NMR with Eu(hfc)3)[α]D22=-246 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(2-Chlorophenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC16H11ClO2Ee 85% (1H NMR with Eu(hfc)3)[α]D22=-31 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Chlorophenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC16H11ClO2Ee 59% (1H NMR with Eu(hfc)3)[α]D22=-229 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(4-Chlorophenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC16H11ClO2Ee 37% (1H NMR with Eu(hfc)3)[α]D22=-140 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(2-Nitrophenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC16H11NO4Ee 20% (1H NMR with Eu(hfc)3)[α]D22=-69 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Nitrophenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC16H11NO4Ee 62% (1H NMR with Eu(hfc)3)[α]D22=-152 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(2-Methylphenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC17H14O2Ee 49% (1H NMR with Eu(hfc)3)[α]D22=-104 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(3-Methylphenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC17H14O2Ee 63% (1H NMR with Eu(hfc)3)[α]D22=-233 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(4-Methylphenyl)spiro(inden-2,2′-oxiran)-1(3H)-oneC17H14O2Ee 58% (1H NMR with Eu(hfc)3)[α]D22=-240 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(Naphth-1-yl)spiro(inden-2,2′-oxiran)-1(3H)-oneC20H14O2Ee 47% (1H NMR with Eu(hfc)3)[α]D22=-29 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown

trans-(−)-3′-(Naphth-2-yl)spiro(inden-2,2′-oxiran)-1(3H)-oneC20H14O2Ee 15% (1H NMR with Eu(hfc)3)[α]D22=-72 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: unknown