| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1345741 | Tetrahedron: Asymmetry | 2006 | 15 Pages |
(S)-(−)-(Benzotriazol-1-yl)- and (S)-(−)-(benzotriazol-2-yl)-alkan-2-ols 7a–9a, 7b–9b and their (R)-(+)-acetates 10a–12a and 10b–12b were prepared in high enantiomeric excess via lipase from Pseudomonas fluorescens (Amano AK) catalyzed enantioselective acetylation of racemic alcohols 4a–6a and 4b–6b with vinyl acetate in tert-butyl methyl ether or toluene at 23 °C. The enantioselectivity of this transformation was dependent on the length of the alkyl chain with E-values ranging from 30 to 57. Several benzotriazole substituted ketones 1a–3a and 1b–3b were synthesized from 1H-benzotriazole and corresponding haloketones. These compounds were stereoselectively reduced with Baker’s yeast in water or in organic solvent containing 5% v/v of water at 30 °C to give the (S)-(−)-alcohol. Better stereoselectivity was observed in the kinetic resolution of racemic alcohols 4a–6a and 4b–6b (ee = 69–92% at 44–52% conversion) compared to reduction of corresponding prochiral ketones 1a–3a and 1b–3b with Baker’s yeast (ee = 40–67% at 39–89% conversion). Enhanced enantioselectivities were observed at lower temperatures.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
(S)-(−)-(Benzotriazol-1-yl)-propan-2-olC9H11N3OEe = 98%[α]D24=-28.6 (c 1.46, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(S)-(−)-(Benzotriazol-1-yl)-butan-2-olC10H13N3OEe = 95%[α]D24=-32.1 (c 1.33, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(S)-(−)-(Benzotriazol-1-yl)-pentan-2-olC11H15N3OEe = 96%[α]D24=-24.6 (c 1.51, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(S)-(−)-(Benzotriazol-2-yl)-propan-2-olC9H11N3OEe = 95%[α]D24=-19.4 (c 1.33, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(S)-(−)-(Benzotriazol-2-yl)-butan-2-olC10H13N3OEe = 97%[α]D24=-25.1 (c 1.28, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(S)-(−)-(Benzotriazol-2-yl)-pentan-2-olC11H15N3OEe = 96%[α]D24=-33.3 (c 1.49, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)
(R)-(+)-2-Acetoxy-1-(benzotriazol-1-yl)-pentan-2-olC11H13N3O2Ee = 94%[α]D24=+29.3 (c 1.55, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
(R)-(+)-2-Acetoxy-1-(benzotriazol-1-yl)-pentan-2-olC12H15N3O2Ee = 98%[α]D24=+39.2 (c 1.49, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
(R)-(+)-2-Acetoxy-1-(benzotriazol-1-yl)-pentan-2-olC13H17N3O2Ee = 96%[α]D24=+21.9 (c 1.39, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
(R)-(+)-2-Acetoxy-1-(benzotriazol-2-yl)-propan-2-olC11H13N3O2Ee = 97%[α]D24=+18.9 (c 1.49, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
(R)-(+)-2-Acetoxy-1-(benzotriazol-2-yl)-butan-2-olC12H15N3O2Ee = 93%[α]D24=+27.1 (c 1.22, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
(R)-(+)-2-Acetoxy-1-(benzotriazol-2-yl)-pentan-2-olC13H17N3O2Ee = 98%[α]D24=+19.9 (c 1.35, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)
