Bisoxazoline ligands with an axial-unfixed biaryl backbone: the effects of the biaryl backbone and the substituent at oxazoline ring on Cu-catalyzed asymmetric cyclopropanation

The synthesis of novel C2-symmetric bisoxazoline ligands with an axial-unfixed biaryl backbone and different substituents at the oxazoline ring is reported. The diastereomer equilibrium of these ligands in solution and their complexation behavior with the copper(I) ion were studied. Their application in Cu-catalyzed cyclopropanation of styrene, with diazoacetate, was carried out and the effects of the biaryl backbone and the substituent on the oxazoline ring in the catalysis were examined. The best result was obtained with the ligand having a 1,1′-binaphthyl backbone and a t-butyl group on the oxazoline ring, which afforded 89% de and 96% de for the trans- and cis-products of the above asymmetric cyclopropanation reaction, respectively.

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3,3′-Bis[(4′S)-tert-Butyloxazolin-2′-yl]-2,2′-binaphthylC34H36N2O2[α]D9=-78.5 (c 0.5, CHCl3)Source of chirality: (S)-(+)-leucinolAbsolute configuration: (S)

5,5′-Dichloro-2,2′-bis[(4′S)-tert-butyloxazolin-2′-yl]-1,1′-biphenylC26H30Cl2N2O2[α]D13=-96.6 (c 0.5, CHCl3)Source of chirality: (S)-(+)-leucinolAbsolute configuration: (S)

5,5′-Diphenyl-2,2′-bis[(4′S)-isopropyloxazolin-2′-yl]-1,1′-biphenylC36H36N2O2[α]D13=-59.0 (c 0.5, CHCl3)Source of chirality: (S)-(+)-valinolAbsolute configuration: (S)

2,2′-Bis[(4′R)-(hydroxymethyl)oxazolin-2′-yl]-1,1′-biphenylC20H20N2O4[α]D9=+53.4 (c 0.51, CHCl3)Source of chirality: l-serine methyl esterAbsolute configuration: (R)

2,2′-Bis[(4′R)-(methoxymethyl)oxazolin-2′-yl]-1,1′-biphenylC22H24N2O4[α]D9=+150.5 (c 0.49, CHCl3)Source of chirality: l-serine methyl esterAbsolute configuration: (R)

2,2′-Bis[(4′R)-(ethoxymethyl)oxazolin-2′-yl]-1,1′-biphenylC24H28N2O4[α]D9=+116.4 (c 0.51, CHCl3)Source of chirality: l-serine methyl esterAbsolute configuration: (R)

2,2′-Bis[(4′S)-(dimethylhydroxymethyl)oxazolin-2′-yl]-1,1′-biphenylC24H28N2O4[α]D27=+71.2 (c 0.70, CHCl3)Source of chirality: l-serine methyl esterAbsolute configuration: (S)

2,2′-Bis[(4′S)-(dimethylmethoxymethyl)oxazolin-2′-yl]-1,1′-biphenylC26H32N2O4[α]D10=+11.9 (c 0.50, CHCl3)Source of chirality: l-serine methyl esterAbsolute configuration: (S)