Asymmetric synthesis of chiral bisoxazolines and their use as ligands in metal catalysis

Novel C2- and C1-symmetric chiral bisoxazolines with a cyclic backbone have been synthesized in an asymmetric manner starting from meso anhydrides. All synthetic steps are easy to perform and lead to the desired products in good overall yields. Preliminary investigations revealed the applicability of these new compounds as ligands in transfer hydrogenations and various metal-catalyzed enantioselective C–C-bond forming reactions such as cyclopropanations and Diels–Alder reactions.

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(1R,2R)-2-Methoxycarbonylcyclopentane-1-carboxylic acidC8H12O4Ee = 96%[α]D25=-83.6(c3.60,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

(1R,2R)-2-Cyclopentane-1,2-dicarboxylic acidC7H10O4Ee = 96%[α]D25=-75.7(c0.65,acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

(1S,2S)-2-[2′-Hydroxy-1′-(S)-tert-butylethylcarbamoyl]-cyclopentane-1-carboxylic acid methyl esterC14H25NO4De >99% (NMR), Ee >99%[α]D25=+36.1(c1.00,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,1′S)

(1R,2R)2-[2′-Hydroxy-1′-(S)-tert-butylethylcarbamoyl]-cyclopentane-1-carboxylic acid methyl esterC14H25NO4De >99% (NMR), Ee >99%[α]D25=-68.2(c1.00,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′S)

(1R,2R)-2-[2′-Hydroxy-1′-(R)-phenylethylcarbamoyl]-cyclopentane-1-carboxylic acid methyl esterC16H21NO4De >99% (NMR), Ee >99%[α]D25=-84.0(c1.10,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′R)

(1S,2S)-2-[2′-Hydroxy-1′-(S)-tert-butylethylcarbamoyl]-cyclopentane-1-carboxylic acidC13H23NO4De >99% (NMR), Ee >99%[α]D25=+46.5(c1.03,acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,1′S)

(1R,2R)-2-[2′-Hydroxy-1′-(S)-tert-butylethylcarbamoyl]-cyclopentane-1-carboxylic acidC13H23NO4De >99% (NMR), Ee >99%[α]D25=-55.9(c0.56,acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′S)

(1R,2R)-2-[2′-Hydroxy-1′-(R)-phenylethylcarbamoyl]-cyclopentane-1-carboxylic acidC15H19NO4De >99% (NMR), Ee >99%[α]D25=-96.9(c1.00,acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′R)

(1R,2R)-Cyclopentane-1,2-dicarboxylic acid bis-[(2′-hydroxy-1′-(R)-phenylethyl)-amide]C23H28N2O4De >99% (NMR), Ee >99%[α]D25=-162.5(c1.00,DMSO)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′R)

(1R,2R)-Cyclopentane-1,2-dicarboxylic acid bis-[(2′-hydroxy-1′-(S)-phenylethyl)-amide]C23H28N2O4De >99% (NMR), Ee >99%[α]D25=+31.5(c1.10,MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,1′S)

(1R,2R)-Cyclopentane-1,2-dicarboxylic acid bis-[(2′-hydroxy-1′-(S)-tert-butylethyl)-amide]C19H36N2O4De >99% (NMR), Ee >99%[α]D25=-42.7(c1.10,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,1′S)

(1S,2S)-Cyclopentane-1,2-dicarboxylic acid bis-[(2′-hydroxy-1′-(S)-tert-butylethyl)-amide]C19H36N2O4De >99% (NMR), Ee >99%[α]D25=+76.6(c0.50,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2S,1′S)

(1S,2S-Cyclopentane-1,2-dicarboxylic acid 1-[(2′-hydroxy-1′-(S)-tert-butylethyl)-amide]-2-[2″-hydroxy-1″-(S)-phenylethyl)-amide]C21H32N2O4De >99% (NMR), Ee >99%[α]D25=+117.2(c1.00,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2S,1′S,1′S)

(1S,2S-Cyclopentane-1,2-dicarboxylic acid 1-[(2′-hydroxy-1′)-(S)-tert-butylethyl)-amide]-2-[(2″-hydroxy-1″-(R)-phenylethyl)-amide]C21H32N2O4De >99% (NMR), Ee >99%[α]D25=+4.2(c1.15,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2S,1′S,1″R)

(1R,2R)-Cyclopentane-1,2-dicarboxylic acid 1-[(2′-hydroxy-1′-(S)-tert-butylethyl)-amide]-2-[2″-hydroxy-1″-(R)-phenylethyl)-amide]C21H32N2O4De >99% (NMR), Ee >99%[α]D25=-135.5(c0.40,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,1′S,1″R)

(1R,2R)-Cyclopentane-1,2-dicarboxylic acid 1-[(2′-hydroxy-1′-(S)-tert-butylethyl)-amide]-2-[(2″-hydroxy-1″-(S)-phenylethyl)-amide]C21H32N2O4De >99% (NMR), Ee >99%[α]D25=+6.0(c1.00,MeOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,1″S,1″S)

(1R,2R)-Bis-[4′-(R)-phenyloxazolin-2′-yl]-cyclopentaneC23H24N2O2De >99% (NMR), Ee >99%[α]D25=-20.8(c0.65,CHCl3)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,4′R)

(1R,2R)-Bis-[4′-(R)-phenyloxazolin-2′-yl]-cyclopentaneC23H24N2O2De >99% (NMR), Ee >99%[α]D25=-189.6(c3.00,CHCl3)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,4′R)

(1R,2R)-Bis-[4′-(S)-tert-butyloxazolin-2′-yl]-cyclopentaneC19H32N2O2De >99% (NMR), Ee >99%[α]D25=-186.9(c1.08,CHCl3)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2R,4′S)

(1S,2S)-Bis-[4′-(S)-tert-butyloxazolin-2′-yl]-cyclopentaneC19H32N2O2De >99% (NMR), Ee >99%[α]D25=+2.5(c0.69,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4′S)

(1S,2S)-[4′-(S)-tert-Butyloxazolin-2′-yl]-[4″-(S)-phenyloxazolin-2″-yl]-cyclopentaneC21H28N2O2De >99% (NMR), Ee >99%[α]D25=+9.6(c1.56,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4′S,4″S)

(1S,2S)-[4′-(S)-tert-Butyloxazolin-2′-yl]-[4″-(R)-phenyloxazolin-2″-yl]-cyclopentaneC21H28N2O2De >99% (NMR), Ee >99%[α]D25=+110.2(c1.00,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4′S,4″R)

(1R,2R)-[4′-(S)-tert-Butyloxazolin-2′-yl]-[4″-(R)-phenyloxazolin-2″-yl]-cyclopentaneC21H28N2O2De >99% (NMR), Ee >99%[α]D25=-96.9(c2.00,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,4′S,4″R)

(1S,2S)-[4′-(S)-tert-Butyloxazolin-2′-yl]-[4″-(S)-phenyloxazolin-2″-yl]-cyclopentaneC21H28N2O2De >99% (NMR), Ee >99%[α]D25=-197.3(c1.02,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,4′S,4″S)