Enantioselective Ag(I)-catalyzed [3+2] cycloaddition of azomethine ylides using a chiral ferrocene-based phosphine–phosphoramidite ligand having a stereogenic P-center

A series of chiral ferrocene-based phosphine–phosphoramidite ligands (PPFAPhos) have been employed in the Ag(I)-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with dimethyl maleate. The results showed that the ligand with a stereogenic P-center in the phosphino moiety displayed the best diastereo- and enantioselectivities, in which up to 99% enantiomeric excesses and 99/1 endo/exo selectivities have been achieved.

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Trimethyl (2R,3S,4R,5S)-5-(4-chlorophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18ClNO6Ee = 95%[α]D22=-33.8 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

(2R,3S,4R,5S)-5-(4-Chlorophenyl)pyrrolidine-2-carboxylic ethyl ester-3,4-dicarboxylic dimethyl esterC17H20ClNO6Ee = 90%[α]D22=-40.9 (c 1.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-phenylpyrrolidine-2,3,4-tricarboxylateC16H19NO6Ee = 84%[α]D23=-58.0 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

(2R,3S,4R,5S)-5-Phenylpyrrolidine-2-carboxylic ethyl ester-3,4-dicarboxylic dimethyl esterC17H21NO6Ee = 85%[α]D23=-48.3 (c 0.9, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(4-fluorophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18FNO6Ee = 87%[α]D23=-58.4 (c 1.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(4-bromophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18BrNO6Ee = 94%[α]D23=-47.2 (c 0.8, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(4-nitrophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18N2O8Ee = 98%[α]D23=-52.6 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(4-trifluoromethylphenyl)pyrrolidine-2,3,4-tricarboxylateC17H18F3NO6Ee = 99%[α]D23=-39.5 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(4-methylphenyl)pyrrolidine-2,3,4-tricarboxylateC17H21NO6Ee = 78%[α]D23=-45.7 (c 0.8, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(3-nitrophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18N2O8Ee = 90%[α]D23=-51.6 (c 1.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(3-trifluoromethylphenyl)pyrrolidine-2,3,4-tricarboxylateC17H18F3NO6Ee = 90%[α]D23=-47.7 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Trimethyl (2R,3S,4R,5S)-5-(1-naphthyl)pyrrolidine-2, 3,4-tricarboxylateC20H21NO6Ee = 90%[α]D23=-38.1 (c 0.9, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3S,4R,5S)

Methyl (1S,3R,3aS,6aR)-3-(4-chlorophenyl)-4,6-dioxo-5-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC20H17ClN2O4Ee = 36%[α]D20=+47.4 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (1S,3R,3aS,6aR)

(2R,4R,5S)-5-(4-Chlorophenyl)-pyrrolidine-2,4-dicarboxylic acid 4-tert-butyl ester 2-methyl esterC17H22ClNO4Ee = 24%[α]D23=-2.2 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,4R,5S)

Trimethyl (2R,3R,4R,5S)-5-(4-chlorophenyl)pyrrolidine-2,3,4-tricarboxylateC16H18ClNO6Ee = 84%[α]D22=-11.4 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (2R,3R,4R,5S)