Enzymatic desymmetrization of 3-arylglutaric acid anhydrides

Optically active (R)- and (S)-3-arylglutaric acid monoesters 3 were synthesized in quantitative yields and good stereoselectivities by lipase-catalyzed desymmetrization of the corresponding 3-arylglutaric anhydrides 2 with alcohols. It was observed that the stereochemical outcome of the reaction was influenced by the substituents present on the aromatic ring. The influence of the enzyme, alcohol, and solvent was systematically examined. Absolute configurations of the monoesters 3 were assigned by chemical correlation to corresponding lactones 4.

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(3S)-3-Phenylglutaric acid monomethyl esterC12H14O4[α]D20=-3.6 (c 1.10, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-Phenylglutaric acid monoethyl esterC13H16O4Ee = 78%[α]D20=-4.0 (c 1.10, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-Phenylglutaric acid monobutyl esterC15H20O4[α]D20=-2.1 (c 1.50, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-Phenylglutaric acid monobenzyl esterC18H18O4[α]D20=+0.6 (c 0.90, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-Phenylglutaric acid monoallyl esterC14H16O4[α]D20=-4.9 (c 0.88, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Chlorophenyl)-glutaric acid monomethyl esterC12H13ClO4[α]D20=-9.6 (c 0.88, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Chlorophenyl)-glutaric acid monoethyl esterC13H15ClO4Ee 68%[α]D20=-3.8 (c 0.90, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Chlorophenyl)-glutaric acid monobutyl esterC15H19ClO4[α]D20=-2.2 (c 0.90, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Chlorophenyl)-glutaric acid monobenzyl esterC18H17ClO4[α]D20=+0.4 (c 0.90, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Chlorophenyl)-glutaric acid monoallyl esterC14H15ClO4[α]D20=-6.3 (c 0.40, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Methoxyphenyl)-glutaric acid monomethyl esterC13H16O5[α]D20=+7.6 (c 0.60, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Methoxyphenyl)-glutaric acid monoethyl esterC14H18O5Ee = 68%[α]D20=+8.3 (c 0.95, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Methoxyphenyl)-glutaric acid monobutyl esterC16H22O5[α]D20=+2.3 (c 0.50, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Methoxyphenyl)-glutaric acid monobenzyl esterC19H20O5[α]D20=-0.4 (c 0.50, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Methoxyphenyl)-glutaric acid monoallyl esterC15H18O5[α]D20=+7.3 (c 0.65, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(3,4-Dichlorophenyl)-glutaric acid monomethyl esterC12H12Cl2O4[α]D20=+5.0 (c 1.00, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(3,4-Dichlorophenyl)-glutaric acid monoethyl esterC13H14Cl2O4Ee 60%[α]D20=+3.8 (c 1.00, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(3,4-Dichlorophenyl)-glutaric acid monobutyl esterC15H18Cl2O4[α]D20=+1.3 (c 0.50, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(3,4-Dichlorophenyl)-glutaric acid monobenzyl esterC18H16Cl2O4[α]D20=-1.5 (c 1.00, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(3,4-Dichlorophenyl)-glutaric acid monoallyl esterC14H14Cl2O4[α]D20=+1.7 (c 1.00, EtOH)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Fluorophenyl)-glutaric acid monomethyl esterC12H13FO4[α]D20=-4.3 (c 1.00, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Fluorophenyl)-glutaric acid monoethyl esterC13H15FO4[α]D20=-4.7 (c 1.00, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Fluorophenyl)-glutaric acid monobutyl esterC15H19FO4[α]D20=-2.2 (c 0.50, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Fluorophenyl)-glutaric acid monobenzyl esterC18H17FO4[α]D20=-1.7 (c 0.80, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(3S)-3-(4-Fluorophenyl)-glutaric acid monoallyl esterC14H15FO4[α]D20=-2.5 (c 0.90, CHCl3)Chirality source: enzymatic catalysisAbsolute configuration: (3S)

(4R)-4-(4-Fluorophenyl)-tetrahydro-2H-pyran-2-oneC11H11FO2[α]D20=-3.2 (c 1.90, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4R)

(4S)-4-(4-Fluorophenyl)-tetrahydro-2H-pyran-2-oneC11H11FO2[α]D20=+3.3 (c 1.25, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4S)

(4R)-4-Phenyltetrahydro-2H-pyran-2-oneC11H12O2[α]D20=-5.7 (c 2.10, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4R)

(4R)-4-(4-Chlorophenyl)-tetrahydro-2H-pyran-2-oneC11H11ClO2[α]D20=-8.7 (c 1.38, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4R)

(4R)-4-(4-Methoxyphenyl)-tetrahydro-2H-pyran-2-oneC12H14O3[α]D20=-7.7 (c 3.20, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4R)

(4R)-4-(3,4-Dichlorophenyl)-tetrahydro-2H-pyran-2-oneC11H10Cl2O2[α]D20=-8.1 (c 1.60, CHCl3)Chirality source: asymmetric synthesisAbsolute configuration: (4R)