Novel preparation of (−)-4-hydroxycyclohex-2-enone: reaction of 4-hydroxycyclohex-2-enone and 4-hydroxycyclopent-2-enone with some thiols

A new route to (R)-4-hydroxycyclohex-2-enone from cyclohexanedione monoketal (27% yield) commences with reaction of the ketal with nitrosobenzene catalysed by l-proline. 4-Hydroxycyclohex-2-enone and 4-hydroxycyclopent-2-enone react with thiols to afford the corresponding syn-disubstituted cycloalkanones.

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(1S,3S,4R)-4-(Benzylthio)cyclopentane-1,3-diolC12H16O2SEe >98% (HPLC)[α]D = +57.2 (c 0.66, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (1S,3S,4R)

(1R,3S,4R)-4-(Benzylthio)cyclopentane-1,3-diolC12H16O2SEe >96% (HPLC)[α]D = +97.1 (c 1.05, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (1R,3S,4R)

(R)-4-Benzylsulfanyl-cyclopent-2-enoneC12H12OSEe >99% (HPLC)[α]D = +178 (c 1.0, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: 4(R)

(S)-4-Benzylsulfanyl-cyclopent-2-enoneC12H12OSEe >99% (HPLC)[α]D = −178 (c 1.0, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: 4(S)

(3R,4S)-3-Benzylsulfanyl-4-hydroxy-cyclopentanoneC12H14O2SEe >99% (HPLC)[α]D = +60 (c 1.0, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (3R,4S)

(1S,3S,4S)-4-(Benzylthio)cyclopentane-1,3-diolC12H16O2SEe >98%(HPLC)[α]D = +40.9 (c 0.44, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (1S,3S,4S)

trans-1,4-Dioxa spiro[4.5]decane-7,8-diolC8H14O4Ee = 94% (Chiral GC)[α]D = 0 (c 0, CH2Cl2)Source of chirality: proline organocatalysisAbsolute configuration: (7S,8S)

(1R,3S,4S)-4-(Benzylthio)cyclopentane-1,3-diolC12H16O2SEe >98% (HPLC)[α]D = −39.3 (c 0.89, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (1R,3S,4S)