Asymmetric oxidation of sulfenates to sulfinates as a new route to optically active ortho-phosphorylated phenyl sulfoxides

An asymmetric synthesis of benzenesulfinates bearing a phosphonate group at the ortho-position, based on the diastereoselective oxidation of the corresponding sulfenates, has been developed. For this purpose, a number of sulfenates were prepared in high yields by TFFA-promoted condensation of different chiral alcohols with a suitable sulfenyl chloride precursor. Diastereomeric excesses were determined by 31P NMR spectroscopic data with the configuration of the newly created stereogenic centre being assigned through correlation and chemical studies. A practical synthesis of both enantiomers of diisopropyl (2-methylsulfinyl)phenylphosphonate 6 in enantiomeric excess close to 85% is also presented.

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(−)-Menthyl 2-(diisopropylphosphoryl)benzenesulfenateC22H37O4PS[α]D = −105 (c 1.0, CHCl3)Source of chirality: commercial (−)-mentholAbsolute configuration: (1R,2S,5R)Ee = 100%

(−)-8-Phenylmenthyl 2-(diisopropylphosphoryl)benzenesulfenateC28H41O4PS[α]D = +40.0 (c 0.5, CHCl3)Source of chirality: commercial (−)-8-phenyl mentholAbsolute configuration: (1R,2S,5R)Ee = 100%

(−)-trans-2-Phenyl-1-cyclohexyl 2-(diisopropylphosphoryl)benzenesulfenateC24H34O4PS[α]D = −149.5 (c 1.0, CHCl3)Source of chirality: commercial (−)-trans-2-phenyl-cyclohexanolAbsolute configuration: (1R,2S)Ee = 100%

(−)-Bornyl 2-(diisopropylphosphoryl)benzenesulfenateC22H36O4PS[α]D = −38.5 (c 0.74, CHCl3)Source of chirality: commercial (−)-borneolEe = 100%

(+)-(Diacetone-d-glucosyl) 2-(diisopropylphosphoryl)benzenesulfenateC24H37O10PS[α]D = −139.1 (c 1.0, CHCl3)Source of chirality: commercial (+)-diacetone-d-glucoseEe = 100%

(+)-(2,4,6-Triisopropylphenyl)-2-ethyl 2-(diisopropylphosphoryl)benzenesulfenateC29H46O4PS[α]D = +54.7 (c 0.85, CHCl3)Source of chirality: (R)-1-[(2,4,6-triisopropylphenyl)]ethan-2-olAbsolute configuration: (R)Ee = 100%

(1R,2S,5R)-Menthyl (R)-2-(diisopropylphosphoryl)benzenesulfinateC22H37O5PS[α]D = +10.0 (c 1.0, CHCl3)Source of chirality: commercial (−)-menthol and asymmetric oxidationAbsolute configuration: major RS + minor SSDe = 76%

(1R,2S,5R)-8-Phenylmenthyl (R)-2-(diisopropylphosphoryl)benzenesulfinateC28H41O5PS[α]D = −15.2 (c 0.7, CHCl3)Source of chirality: commercial (−)-8-phenyl menthol and asymmetric oxidationAbsolute configuration: major RS + minor SSDe = 65%

(1R,2S)-trans-2-Phenyl-1-cyclohexyl (S)-2-(diisopropylphosphoryl)benzenesulfinateC24H34O5PS[α]D = −56.9 (c 2.9, CHCl3)Source of chirality: commercial (1R,2S)-trans-2-phenylcyclohexanol and asymmetric oxidationAbsolute configuration: major SS + minor RSDe = 74%

(S)-Bornyl (S)-2-(diisopropylphosphoryl)benzenesulfinateC22H36O5PS[α]D = +3.0 (c 0.75, CHCl3)Source of chirality: commercial (S)-borneol and asymmetric oxidationAbsolute configuration: major SS + minor RSDe = 25%

(Diacetone-d-glucosyl) (R)-2-(diisopropylphosphoryl)benzenesulfinateC24H37O11PS[α]D = +13.6 (c 1.88, CHCl3)Source of chirality: commercial diacetone-d-glucose and asymmetric oxidationAbsolute configuration: major RS + minorSSDe = 55%

(R)-(2,4,6-Triisopropylphenyl)-2-ethyl (R)-2-(diisopropylphosphoryl)benzenesulfinateC29H46O5PS[α]D = +47.0 (c 1.35, CHCl3)Source of chirality: (R)-1-[(2,4,6-triisopropylphenyl)]ethan-2-ol and asymmetric oxidation with (−)-8,8-dichloro-camphorsulfonyloxaziridineAbsolute configuration: major RS + minor SSDe = 86%

(−)-Diisopropyl (2-methylsulfinyl)phenylphosphonateC13H21O4PS[α]D = −145.2 (c 1.3, CHCl3)Source of chirality: chiral sulfinateAbsolute configuration: SSEe = 86%