Enantiomeric purity enrichment of (R)-tetrahydrothiophene-3-ol sulfonyl derivatives by crystallization

(R)-Tetrahydrothiophene-3-ol sulfonyl derivatives 3–19 were prepared by introduction of various sulfonyl groups at the hydroxyl group of (R)-tetrahydrothiophene-3-ol 1 with low enantiomeric purity (68–74% ee). Crystallization was applied to improve their enantiomeric purity. Improvement in enantiomeric purity depended on the introduced sulfonyl group. The enantiomeric purity of enantiomeric sulfonyl derivatives was improved to more than 90% ee by simple crystallization without using seed crystals. These products from crystallization provided not only higher %ee crystals but also a higher %ee mother liquor. The enantiomeric purity of diastereomeric sulfonyl derivatives was improved remarkably, and the product of the derivative 18 provided the mother liquor with 100% de. Crystallization of these sulfonyl derivatives showed a novel and interesting feature that mother liquors with high enantiomeric purity were obtained in many cases.

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(R)-Tetrahydrothiophene-3-olC4H8OS98.7% ee by HPLC[α]D20 = +30.3 (c 0.57, MeOH)Absolute configuration: (R)

(R)-3-[(4-Chlorobenzenesulfonyl)oxy]tetrahydrothiopheneC10H11ClO3S260.3% ee by HPLC[α]D20 = +10.0 (c 0.49, MeOH)Absolute configuration: (R)

(R)-3-[(2-Naphthalenesulfonyl)oxy]tetrahydrothiopheneC14H14O3S294.2% ee by HPLC[α]D20 = +13.5 (c 0.50, MeOH)Absolute configuration: (R)

(R)-3-[(p-Toluenesulfonyl)oxy]tetrahydrothiopheneC11H14O3S268.5.2% ee by HPLC[α]D20 = +13.7 (c 0.52, MeOH)Absolute configuration: (R)

(R)-3-[(4-Acetamidebenzenesulfonyl)oxy]tetrahydrothiopheneC12H15NO4S268.5% ee by HPLC[α]D20 = +13.7 (c 0.52, MeOH)Absolute configuration: (R)

(R)-3-[(5-(Dimethylamino)naphthalene-1-sulfonyl)oxy]tetrahydrothiopheneC16H19NO3S284.9% ee by HPLC[α]D20 = +19.9 (c 0.50, MeOH)Absolute configuration: (R)

(R)-3-[(Benzylsulfonyl)oxy]tetrahydrothiopheneC11H14O3S281.3% ee by HPLC[α]D20 = +11.1 (c 0.52, MeOH)Absolute configuration: (R)

(R)-3-[(3,4-Dimethoxybenzenesulfonyl)oxy]tetrahydrothiopheneC12H16O5S268.6% ee by HPLC[α]D20 = +10.6 (c 0.52, MeOH)Absolute configuration: (R)

(R)-3-[((+)-10-Camphorsulfonyl)oxy]tetrahydrothiopheneC14H22O4S2100% de by HPLC[α]D20 = +45.8 (c 0.50, MeOH)Absolute configuration: (R)

(R)-3-[(4-Methoxybenzenesulfonyl)oxy]tetrahydrothiopheneC11H14O4S274.3% ee by HPLC[α]D20 = +12.1 (c 0.51, MeOH)Absolute configuration: (R)

(R)-3-[(1-Naphthalenesulfonyl)oxy]tetrahydrothiopheneC14H14O3S273.7% ee by HPLC[α]D20 = +19.3 (c 0.50, MeOH)Absolute configuration: (R)

(R)-3-[((−)-10-Camphorsulfonyl)oxy]tetrahydrothiopheneC14H22O4S294.6% de by HPLC[α]D20 = −15.7 (c 0.50, MeOH)Absolute configuration: (R)