Lipase kinetic enantiomeric resolution of 1-heteroarylethanols

The use of lipases offers a simple and straightforward method toward various chiral secondary alcohols. Here we examined the lipase resolution of 1-heteroarylethanols. Racemic substrates were subjected to a two step resolution strategy. The difference between the substituent sizes around the chiral fragment allowed the successful isolation of the (S)-alcohols with assistance of the Burkholderia cepacia lipase (ee ⩾ 96%). The (R)-isomers were obtained after hydrolysis of the enantioenriched O-acetylated alcohols either with Candida antarctica lipase B or with potassium carbonate. The performance of the latter step was found to be substrate dependent.

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(1S)-1-(2-Methyl-1,3-thiazol-4-yl)ethanolC6H9NOSee = 98%[α]D20 = −52.3 (c 1.4, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)

(1S)-1-(1,3-Thiazol-5-yl)ethanolC5H7NOSee = 99%[α]D20 = −13.1 (c 1.3, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)

(1S)-1-(5-Methyl-1,3,4-oxadiazol-2-yl)ethanolC5H8N2O2ee = 96%[α]D20 = −17.9 (c 1.0, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)

(1S)-1-(1-Methyl-1H-pyrazol-4-yl)ethanolC6H10N2Oee = 98%[α]D20 = −7.7 (c 1.3, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)

(1S)-1-(1-Phenyl-1H-pyrazol-4-yl)ethanolC11H12N2Oee = 96%[α]D20 = −14.6 (c 1.1, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)

(1S)-1-(1-Benzyl-1H-pyrazol-4-yl)ethanolC12H14N2Oee = 97%[α]D20 = −4.2 (c 1.6, EtOH)Source of chirality: Burkholderia cepacia lipase resolutionAbsolute configuration: (1S)