Halogenative kinetic resolution of β-aryloxy cyclic alcohols: chiral BINAP-mediated SN2 displacement of hydroxy groups by chlorides with inversion of stereochemistry

A series of optically active cyclic trans-β-aryloxy alcohols have been obtained by non-enzymatic kinetic resolution of the corresponding racemic aryloxy cyclic alcohols using commercially available (S)-BINAP and NCS by SN2 halogenation of a hydroxy group. The product, cis-β-aryloxy chlorides, was also obtained in optically active form with inversion of the stereochemistry.

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trans-(1R,2R)-2-(4-Bromophenoxy)cyclohexanolC12H15BrO2Ee = 26%[α]D25=-7.4 (c 1.0, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1R,2R)

cis-(1S,2R)-1-Bromo-4-(2-chlorocyclohexyloxy)benzeneC12H14BrClOEe = 46%[α]D25=-9.8 (c 1.0, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1S,2R)

trans-(1R,2R)-2-(4-Methoxyphenoxy)cyclohexanolC13H18O3Ee = 48%[α]D25=-28.4 (c 1.0, MeOH)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1R,2R)

cis-(1S,2R)-1-(2-Chlorocyclohexyloxy)-4-methoxybenzeneC13H17ClO2Ee = 53%[α]D25=-11.5 (c 1.0, MeOH)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1S,2R)

trans-(1R,2R)-2-(4-tert-Butylphenoxy)cyclohexanolC16H24O2Ee = 34%[α]D25=-13.4 (c 1.0, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1R,2R)

cis-(1S,2R)-1-tert-Butyl-4-(2-chlorocyclohexyloxy)benzeneC16H23ClOEe = 50%[α]D25=-27.7 (c 1.2, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1S,2R)

trans-(1R,2R)-2-(m-Tolyloxy)cyclohexanolC13H18O2Ee = 19%[α]D25=-10.4 (c 1.0, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1R,2R)

cis-(1S,2R)-1-(2-Chlorocyclohexyloxy)-3-methylbenzeneC13H17ClOEe = 62%[α]D25=-7.4 (c 0.5, acetone)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1S,2R)

trans-(1R,2R)-2-(3-Methoxyphenoxy)cyclohexanolC13H18O3Ee = 17%[α]D25=-11.6 (c 1.2, MeOH)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1R,2R)

cis-(1S,2R)-1-(2-Chlorocyclohexyloxy)-3-methoxybenzeneC13H17ClO2Ee = 70%[α]D25=-12.8 (c 1.0, MeOH)Source of chirality: halogenative kinetic resolutionAbsolute configuration: (1S,2R)