Synthesis of Enantiopure β-Azidoalcohols and β-Hydroxynitriles
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= +19.63 [c = 1.03, CHCl3; Ͼ99%ee (R)]. For characterisation see
the Supporting Information.
(R)-1-Azido-2-octanol (4d): 30 mg (57%) of a yellowish oil. [α]2D0
=
–5.5 [c = 1, CHCl3; (R)], ref.[6a] [α]2D0 = –1.0 (c = 2.0, CH2Cl2;
30%ee). For characterisation see the Supporting Information.
General Procedure for the 50 mg Scale Three-Step Cascade Em-
ploying ADH-A, HheC and NaCN: Lyophilised cells of E. coli Tu-
nerTM (DE3)/pET22b-ADH-A (100 mg) were rehydrated in Tris-
SO4 buffer (5 mL, 200 m, pH 7.5, 160 m NaN3) for 1 h at 30 °C
and 120 rpm. 2-Propanol (50 µL, 0.65 mmol) and the substrate (1a:
40 µL, 0.27 mmol; 1c: 54 mg, 0.35 mmol) were added, and the mix-
ture was incubated for 4 h at 30 °C and 120 rpm. HheC preparation
(500 µL, 20 U) and NaCN (40 mg, 0.82 mmol) were added and in-
cubation continued for 44 h. The mixture was extracted with
EtOAc (2ϫ10 mL), dried with Na2SO4 and evaporated under re-
duced pressure to give the crude product. Flash chromatography
(silica; petroleum ether/EtOAc, 5:1) furnished the pure hydroxyni-
trile.
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(S)-3-Hydroxy-4-phenoxybutanenitrile (5a): 18 mg (38%) of a yel-
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(S)-3-Hydroxy-3-phenylpropanenitrile (5c): 29 mg (53%) of a yel-
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Supporting Information (see footnote on the first page of this arti-
cle): Synthetic procedures and NMR spectroscopic data for all in-
vestigated compounds; conditions for GC, HPLC and GC–MS
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1
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Acknowledgments
Financial support by the University of Graz and Fonds zur
Förderung Wissenschaftlicher Forschung (FWF) (project number
P18537-B03) is gratefully acknowledged. Halohydrin dehalo-
genases were kindly provided by Julich Chiral Solutions, a Codexis
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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