Enzymatic preparation of (1S,2R)- and (1R,2S)-stereoisomers of 2-halocycloalkanols

The stereoisomers of cis-2-halocycloalkanols were resolved by a kinetically controlled transesterification with vinyl acetate in the presence of lipases in organic media. High enantioselectivities (ee >98%) and good isolated yields were obtained for all substrates using the appropriate lipase. Burkholderia cepacia lipase was the most efficient enzyme for the resolution of these substrates. The enantiomeric purities of the compounds were defined by derivatization with Mosher’s acid and the absolute configurations were determined by chemical correlation.

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(1S,2R)-(−)-2-BromocyclopentanolC5H9BrOde ∼99% (NMR), ee 99%[α]D20=-31.4 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1S,2R)

(1R,2S)-(+)-2-BromocyclopentanolC7H11BrO2de ∼99% (NMR), ee 98%[α]D20=+51.0 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1R,2S)

(1S,2R)-(−)-2-IodocyclopentanolC5H9IOde ∼100% (NMR), ee 98%[α]D20=-31.5 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1S,2R)

(1R,2S)-(+)-2-IodoocyclopentanolC7H11IO2de ∼99% (NMR), ee 98%[α]D20=+62.6 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1R,2S)

(1R,2S)-(+)-2-ChloroocyclohexanolC6H11ClOde ∼98% (NMR), ee 96%[α]D20=+30.0 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1R,2S)

(1S,2R)-(+)-2-ChloroocyclohexanolC8H13ClO2de ∼98% (NMR), ee 96%[α]D20=+50.0 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1S,2R)

(1S,2R)-(−)-2-IodocyclopentanolC6H11BrOde 99% (NMR), ee >99%[α]D20=-31.7 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1S,2R)

(1R,2S)-(+)-2-IodocyclopentanolC8H13BrO2de 99% (NMR), ee 98%[α]D20=+61 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1R,2S)

(1S,2R)-(−)-2-IodocyclopentanolC6H11IOde ∼100% (NMR), ee 98%[α]D20=-31.4 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1S,2R)

(1R,2S)-(+)-2-IodocyclopentanolC8H13IO2de ∼100% (NMR), ee 98%[α]D20=+62.5 (c 1, CHCl3).Source of chirality: enzymatic resolutionBurkholderia cepacia lipaseAbsolute configuration: (1R,2S)