Chiral phosphoric acid catalyzed 1,3-dipolar cycloadditions of aldehydes, diethyl α-aminomalonate, and nitroalkenes

A one-pot three component 1,3-dipolar cycloaddition reaction of an aldehyde, α-aminomalonate, and nitroalkene has been developed through binaphthol derived chiral phosphoric acids. This reaction represents one of the most enantioselective catalytic approaches to access structurally diverse pyrrolidine derivatives.

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Diethyl (3R,4R,5R)-4-nitro-5-(4-nitrophenyl)-3-phenylpyrrolidine-2,2-dicarboxylateC22H23N3O880% yield, 73% ee[α]D20 = +29.3 (c 0.43, CH2Cl2)

3-(4-Bromophenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC22H22BrN3O884% yield, 77% ee[α]D20 = +55.4 (c 0.39, CH2Cl2)

Diethyl 4-nitro-3-(3-nitrophenyl)-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC22H22N4O1090% yield, 65% ee[α]D20 = +47.1 (c 0.87, CH2Cl2)

Diethyl 3-(4-chlorophenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC22H22ClN3O885% yield, 70% ee[α]D20 = +27.8 (c 0.78, CH2Cl2)

Diethyl 3-(4-cyanophenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC23H22N4O881% yield, 74% ee[α]D20 = +61.4 (c 0.7, CH2Cl2)

Diethyl 3-(4-methoxyphenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC23H25N3O971% yield, 70% ee[α]D20 = +46.4 (c 0.7, CH2Cl2)

Diethyl 3-(3-bromophenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC22H22BrN3O874% yield, 56% ee[α]D20 = +24.5 (c 0.4, CH2Cl2)

Diethyl 3-(3-chlorophenyl)-4-nitro-5-(4-nitrophenyl)pyrrolidine-2,2-dicarboxylateC22H22ClN3O871% yield, 57% ee[α]D20 = +25.9 (c 0.66, CH2Cl2)

Diethyl 5-(4-bromophenyl)-4-nitro-3-phenylpyrrolidine-2,2-dicarboxylateC22H23BrN2O692% yield, 62% ee[α]D20 = +24.1 (c 0.86, CH2Cl2)

Diethyl 3,5-bis(4-bromophenyl)-4-nitropyrrolidine-2,2-dicarboxylateC22H22Br2N2O688% yield, 70% ee[α]D20 = +43.4 (c 1.0, CH2Cl2)

Diethyl 5-(4-chlorophenyl)-4-nitro-3-phenylpyrrolidine-2,2-dicarboxylateC22H23ClN2O690% yield, 53% ee[α]D20 = +19.3 (c 0.76, CH2Cl2)

Diethyl 3-(4-bromophenyl)-5-(4-cyanophenyl)-4-nitropyrrolidine-2,2-dicarboxylateC23H22BrN3O686% yield, 84% ee[α]D20 = +59.3 (c 0.82, CH2Cl2)

Diethyl 5-(4-cyanophenyl)-4-nitro-3-phenylpyrrolidine-2,2-dicarboxylateC23H23N3O676% yield, 74% ee[α]D20 = +28.6 (c 0.67, CH2Cl2)

Diethyl-4-nitro-3,5-diphenylpyrrolidine-2,2-dicarboxylateC22H24N2O642% yield, 23% ee[α]D20 = +26.6 (c 0.43, CH2Cl2)