Enantiomerically enriched cryptone by lipase catalysed kinetic resolution

Thiophenol was added to racemic cryptone (4-isopropyl-2-cyclohexene-1-one) and the resulting 1,4-addition products, cis- and trans-4-isopropyl-3-(phenylsulfanyl)cyclohexanone were separated and the latter reduced to rac-1,3-cis-1,4-trans-4-isopropyl-3-(phenylsulfanyl)cyclohexanol, which was subjected to lipase catalysed resolution by acylation catalysed by CAL-B (Candida antarctica lipase B). The alcohol enantiomers obtained were oxidised. The remaining alcohol was separated from the produced acetate, which was hydrolysed to the alcohol. The initial products, probably sulfoxidoketones spontaneously decomposed to furnish enantiomerically enriched (R)- and (S)-cryptone with up to 76% and 98% ee, respectively.

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(1R,3R,4S)-4-Isopropyl-3-(phenylsulfanyl)cyclohexanolC15H22OS[α]D20=-118 (c 1.94, EtOH)Source of chirality: Lipase catalysed resolutionAbsolute configuration (1R,3R,4S)

Acetic acid (1R,3R,4S)-4-isopropyl-3-(phenylsulfanyl)cyclohexyl esterC17H24O2S[α]D20=-29.7 (c 2.19, EtOH)Source of chirality: Lipase catalysed resolutionAbsolute configuration (1R,3R,4S)

(4S)-4-Isopropyl-2-cyclohexene-1-oneC9H14O[α]D20=+89.9 (c 2.27, EtOH)Source of chirality: Lipase catalysed resolutionAbsolute configuration (4S)