250 rpm for 6 h. Then, the reaction was stopped by extraction
with ethyl acetate (5 ¥ 5 mL) and the organic layer was dried
over Na2SO4. Afterwards, the organic solvents and remaining
ketone 4a were removed under reduced pressure and the crude
residue was purified using flash chromatography (hexane–CH2Cl2
1 : 1) obtaining enantiopure (R)-1a (10.1 mg, 81% yield), (S)-
2a (11.7 mg, 86% yield), and (R)-3a (7.0 mg, 75% yield). The
chemical purity of reaction products was determined by both GC
and NMR.
Notes and references
1 M. Breuer, K. Ditrich, T. Habicher, B. Hauer, R. Stu¨rmer and T.
Zelinski, Angew. Chem., Int. Ed., 2004, 43, 788.
2 Some recent examples: (a) J. Piera and J.-E. Ba¨ckvall, Angew. Chem.,
Int. Ed., 2008, 47, 3506; (b) X. Wu and J. Xiao, Chem. Commun., 2007,
2449; (c) T. Ikariya and A. J. Blacker, Acc. Chem. Res., 2007, 40, 1300;
(d) M. T. Reetz and X. Li, J. Am. Chem. Soc., 2006, 128, 1044; (e) G.-J.
ten Brink, I. W. C. E. Arends and R. A. Sheldon, Chem. Rev., 2004,
104, 4105.
3 For some reviews, see: (a) M. C. Carren˜o, G. Herna´ndez-Torres,
M. Ribagorda and A. Urbano, Chem. Commun., 2009, 6129; (b) H.
Pellissier, Tetrahedron, 2006, 62, 5559; (c) R. Bentley, Chem. Soc. Rev.,
2005, 34, 609.
General procedure for the oxidation of thioanisole (6) and
( )-2-octanol (3a) catalysed by BVMOs and ADHs
4 (a) J. Legros, J. R. Dehli and C. Bolm, Adv. Synth. Catal., 2005, 347, 19;
(b) I. Ferna´ndez and N. Khiar, Chem. Rev., 2003, 103, 3651; (c) H. L.
Holland, Nat. Prod. Rep., 2001, 18, 171.
Sulfide 6 (14.5 mM) was added to Tris-HCl buffer (50 mM, pH 7.5,
0.5 mL) containing 1% v/v DMSO. Then, NADPH (0.2 mM), the
corresponding ADH (2 U), HAPMO (2 U), and racemic alcohol
3a (30 mM) were added. When LBADH was used, magnesium
chloride (1 mM, final concentration) was added to the reaction
medium. The mixture was shaken at 30 ◦C and 250 rpm for
24 h. Then, the reactions were stopped by extraction with ethyl
acetate (2 ¥ 0.5 mL) and the organic layer was dried over Na2SO4.
Conversions and enantiomeric excesses of final compounds were
determined by GC and HPLC analysis.
5 Modern Biooxidation. Enzymes, Reactions and Applications, ed.
R. D. Schmid and V. B. Urlacher, Wiley-VCH, Weinheim,
2007.
6 (a) Recent literature: S. Buchholz and H. Gro¨ger, in Biocatalysis in the
Pharmaceutical and Biotechnology Industry, ed. R. N. Patel, CRC Press,
Boca Raton, 2007, p. 757; (b) S. M. A. de Wildeman, T. Sonke, H. E.
Schoemaker and O. May, Acc. Chem. Res., 2007, 40, 1260; (c) J. C.
Moore, D. J. Pollard, B. Kosjek and P. N. Devine, Acc. Chem. Res.,
2007, 40, 1412; (d) K. Goldberg, K. Schroer, S. Lu¨tz and A. Liese,
Appl. Microbiol. Biotechnol., 2007, 76, 237; (e) W. Kroutil, H. Mang,
K. Edegger and K. Faber, Curr. Opin. Chem. Biol., 2004, 8, 120.
7 (a) M. M. Kayser, Tetrahedron, 2009, 65, 947; (b) D. E. Torres Pazmin˜o
and M. W. Fraaije, in Future Directions in Biocatalysis, ed. T. Matsuda,
Elsevier, Dordrecht, 2007, p 107; (c) M. W. Fraaije and D. B. Janssen,
in Modern Biooxidation, ed. R. D. Schmid and V. B. Urlacher, Wiley-
VCH, Weinheim, 2007, p 77; (d) M. D. Mihovilovic, Curr. Org. Chem.,
2006, 10, 1265; (e) N. M. Kamerbeek, D. B. Janssen, J. H. Van Berkel
and M. W. Fraaije, Adv. Synth. Catal., 2003, 345, 667.
HAPMO-catalysed sulfoxidation of thioanisole (6) coupled with
the kinetic resolution of ( )-2-octanol (3a) catalysed by LBADH
8 Employing metal catalysts: (a) F. Hollmann, K. Hofstetter and A.
Schmid, Trends Biotechnol., 2006, 24, 163; (b) G. de Gonzalo, G.
Ottolina, G. Carrea and M. W. Fraaije, Chem. Commun., 2005, 3724;
(c) F. Hollmann, P.-C. Lin, B. Witholt and A. Schmid, J. Am. Chem.
Soc., 2003, 125, 8209.
Sulfide 6 (20 mg, 23 mM) was added into a preparation of cell-free
extract (in Tris-HCl buffer 50 mM pH 7.5) from recombinant
E. coli TOP10 overexpressing HAPMO (7 mL, with a total
protein concentration of approx. 10 mg mL-1, containing 1% v/v
DMSO). Then, NADPH (0.2 mM), MgCl2 (1 mM), LBADH
(20 U) and racemic 2-octanol 3a (54 mL, 47 mM) were added.
The mixture was shaken at 20 ◦C and 250 rpm for 24 h.
Then, the reaction was stopped by extraction with diethyl ether
(5 ¥ 5 mL) and the organic layer was dried over Na2SO4.
Afterwards, the organic solvents were carefully removed under
reduced pressure at low temperature and the crude residue was
purified using flash chromatography (hexane–CH2Cl2 mixtures of
increasing polarities) obtaining enantiopure (S)-7 (18.5 mg, 84%
isolated yield) and (S)-3a (20 mL, 74% isolated yield). Chemical
purity of the reaction products was determined by both GC and
NMR.
9 Recent examples employing an excess of an alcohol/ketone as hydrogen
donor/acceptor: (a) M. Kurina-Sanz, F. R. Bisogno, I. Lavandera,
A. A. Orden and V. Gotor, Adv. Synth. Catal., 2009, 351, 1842; (b) M.J.
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Synth. Catal., 2008, 350, 2322; (c) I. Lavandera, A. Kern, V. Resch,
B. Ferreira-Silva, A. Glieder, W. M. F. Fabian, S. de Wildeman and
W. Kroutil, Org. Lett., 2008, 10, 2155; (d) S. Dreyer and U. Kragl,
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Kroutil, Org. Lett., 2007, 9, 2163; (g) M. M. Musa, K. I. Ziegelmann-
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72, 30.
10 (a) E. Siu, K. Won and C. B. Park, Biotechnol. Prog., 2007, 23, 293;
(b) R. Ruinatscha, V. Ho¨llrigl, K. Otto and A. Schmid, Adv. Synth.
Catal., 2006, 348, 2015; (c) F. Hollmann, K. Hofstetter, T. Habicher, B.
Hauer and A. Schmid, J. Am. Chem. Soc., 2005, 127, 6540.
11 Recent examples: (a) H. Gro¨ger, C. Rollmann, F. Chamouleau, I.
Sebastien, O. May, W. Wienand and K. Drauz, Adv. Synth. Catal., 2007,
349, 709; (b) H. Gro¨ger, F. Chamouleau, N. Orologas, C. Rollmann,
K. Drauz, W. Hummel, A. Weckbecker and O. May, Angew. Chem.,
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Acknowledgements
A.R.-M. (FPU program) thanks the Spanish Ministerio de Ciencia
e Innovacio´n (MICINN) for her predoctoral fellowship which
is financed by the European Social Fund. F.R.B. is supported
by the Programme Alban, the European Union Program of
High Level Scholarships for Latin America (scholarship No.
E07D402519AR). C.R. thanks the Principado de Asturias for
her predoctoral fellowship. G.d.G. (Juan de la Cierva Program)
thanks MICINN for personal funding. I.L. thanks the Principado
de Asturias for personal funding (Clar´ın Program). Financial
support from MICINN (Project CTQ2007-61126) is gratefully
acknowledged. M.W.F. and D.E.T.P. receive support from the EU-
FP7 “Oxygreen” project.
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1436 | Org. Biomol. Chem., 2010, 8, 1431–1437
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