Enantioselective Michael addition of malonates to aromatic nitroalkenes catalyzed by monosaccharide-based chiral crown ethers

The asymmetric Michael addition of diethyl malonate and α-substituted diethyl malonates to aromatic nitroalkenes was carried out under mild reaction conditions in a solid–liquid phase transfer reaction in the presence of α-d-glucopyranoside- and α-d-mannopyranoside-based crown ethers as the catalysts. The use of d-glucose-based lariat ether 1 gave the best results. The substituents of the β-nitrostyrene and the diethyl malonate had a significant impact on the chemical yields and enantioselectivity. The addition of diethyl-2-acetamidomalonate to aromatic nitroalkenes afforded the corresponding Michael adducts in moderate to high enantiomeric excess (ee up to 99%). The reaction of diethyl-2-methylmalonate with 2-nitro-β-nitrostyrene gave the adduct with 93% enantiomeric excess in the presence of crown catalyst 1.

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(−)-Diethyl-2-acetamido-2-(2-nitro-1-phenylethyl)malonateC17H22N2O7Ee 99% (chiral HPLC)[α]D22=-42.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: (S)

(−)-Diethyl-2-acetamido-2-(1-(2-chlorophenyl)-2-nitroethyl)malonateC27H21ClN2O7Ee 67% (chiral HPLC)[α]D22=-11.3 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(3-chlorophenyl)-2-nitroethyl)malonateC27H21ClN2O7Ee 72% (chiral HPLC)[α]D22=-14 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(4-chlorophenyl)-2-nitroethyl)malonateC27H21ClN2O7Ee 99% (chiral HPLC)[α]D22=-36 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(2-nitro-1-(4-nitrophenyl)ethyl)malonateC17H21N3O9Ee 97% (chiral HPLC)[α]D22=-22 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(3-methoxyphenyl)-2-nitroethyl)malonateC18H24N2O8Ee 34% (chiral HPLC)[α]D22=-14.2 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(4-methoxyphenyl)-2-nitroethyl)malonateC18H24N2O8Ee 60% (chiral HPLC)[α]D22=-10.6 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-benzo[d][1,3]dioxol-5-yl)-2-nitroethyl)malonateC18H22N2O9Ee 72% (chiral HPLC)[α]D22=-33 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(naphthalen-2-yl)-2-nitroethyl)malonateC21H24N2O7Ee 45% (chiral HPLC)[α]D22=-47.7 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(2-nitro-1-(thiophen-2-yl)ethyl)malonateC15H20N2O7SEe 11% (chiral HPLC)[α]D22=-13.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-acetamido-2-(1-(furan-2-yl)-2-nitroethyl)malonateC15H20N2O8Ee 13% (chiral HPLC)[α]D22=-19.9 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-(2-nitro-1-phenylethyl)malonateC15H19NO6Ee 20% (chiral HPLC)[α]D22=-3 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-methyl-2-(2-nitro-1-phenylethyl)malonateC16H21NO6Ee 42% (chiral HPLC)[α]D22=-25.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-butyl-2-(2-nitro-1-phenylethyl)malonateC19H27NO6Ee 22% (chiral HPLC)[α]D22=-23.9 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-(Diethyl-2-acetoxy-2-(2-nitro-1-phenylethyl)malonateC17H21NO8Ee 29% (chiral HPLC)[α]D22=-13.1 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-(1-(2-methoxyphenyl)-2-nitroethyl)-2-methylmalonateC17H23NO7Ee 70% (chiral HPLC)[α]D22=-20.4 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-(1-(3-methoxyphenyl)-2-nitroethyl)-2-methylmalonateC17H23NO7Ee 48% (chiral HPLC)[α]D22=-30.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-(1-(4-methoxyphenyl)-2-nitroethyl)-2-methylmalonateC17H23NO7Ee 15% (chiral HPLC)[α]D22=-21.6 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(+)-Diethyl-2-methyl-2-(2-nitro-1-(2-nitrophenyl)ethyl)malonateC16H20N2O8Ee 93% (chiral HPLC)[α]D22=+17.5 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-methyl-2-(2-nitro-1-(3-nitrophenyl)ethyl)malonateC16H20N2O8Ee 52% (chiral HPLC)[α]D22=-20 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined

(−)-Diethyl-2-methyl-2-(2-nitro-1-(4-nitrophenyl)ethyl)malonateC16H20N2O8Ee 8% (chiral HPLC)[α]D22=-17.6 (c 1, CHCl3)Source of chirality: asymmetric synthesis by chiral catalystAbsolute configuration: not determined