J. Pietruszka, R. C. Simon, F. Kruska, M. Braun
FULL PAPER
[9]
C. Paizs, P. Täthinen, M. Tosa, C. Majdik, F. D. Irimie, L. T.
Kanerva, Tetrahedron 2004, 60, 10533–10540.
and cooled to –78 °C. A solution of nBuLi in hexane (1.6 ,
4.2 mL, 6.7 mmol) was added by syringe. The mixture was then
allowed to reach –20 °C, and the stirred solution in the first flask
was then added through a cannula. The mixture was allowed to
warm to room temperature overnight and was then heated gently
at reflux for 1 h. After the system had cooled to room temperature,
water (5 mL) and HCl (2 , 5 mL) were added. The aqueous layer
was separated and extracted three times with three portions of Et2O
(50 mL). The combined organic layers were washed with saturated
aqueous NaHCO3 and dried with Na2SO4. The solvent was re-
moved in a rotary evaporator and the residue was subjected to col-
umn chromatography on silica gel with chloroform to give (R)-8
(231 mg, 0.61 mmol, 21%) as a yellowish oil. Rf = 0.29 (chloro-
form). [α]2D0 = +20.0 (c = 1.08, CHCl3); HPLC: column = Chirapak
AS, average: 0.46 cm, length: 25 cm, flow = 1.0 mLmin–1, λ =
225 nm, solvent ratio = 99:1 (n-heptane/2-propanol), tR[(S)-8] =
14.8 min and tR[(R)-8] = 18.3 min. 1H NMR (500 MHz, CDCl3): δ
= 2.36–2.52 (m, 2 H, CH2), 2.91–3.14 (m, 2 H, CH2), 3.76 (s, 3 H,
OMe), 3.95 (s, 3 H, OMe), 5.10 (dd, J1 = 5.93, J2 = 8.41 Hz, 1 H,
[10]
Preliminary communication: a) S. Daum, F. Erdmann, G. Fi-
scher, B. Féaux de Lacroix, A. Hessamiam-Alinejad, S.
Houben, W. Frank, M. Braun, Angew. Chem. Int. Ed. 2006, 45,
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2240.
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Applied enzymes and suppliers: a) Fluka: Candida antarctica
lipase B (CAL-B), Pseudomonas cepacia (Amano Lipase PS),
pig liver lipase (PPL); b) Boehringer Mannheim (now Roche
diagnostics): Pseudomonas cepacia (Chirazyme L1), porcine
pancreas lipase (PPL, Chirazyme L7), Thermomyces lanuginose
lipase (Chirazyme L8), Alacaligenes sp. lipase (Chira-
zyme L10), lipase from thermophilic microorganism (Chira-
zyme L12), pig pancreas esterase (PLE, Chirazyme E1), pig
pancreas esterase (PLE, esterase E2), esterase from thermo-
philic microorganism (E3), esterase E4; c) Juelich Chiral solu-
tions (now Codexis): Esterase R0, pig liver esterase (PLE),
Streptomyces diastatochromogenes (esterase SD), Bacillus subti-
lis esterase (BS), Bacillus subtilis esterase (BS1), Bacillus subtilis
esterase (BS3), Bacillus subtilis esterase (BS4), lipase OI; d)
Sangyo (Japan): Pseudomonas cepacia lipase (Lipase SL), Ach-
romobacter sp. lipase (Lipase AL), Rhizopus sp. lipase (Li-
pase UL), Candida cylindracea lipase (MY). For complete re-
sults of the screening see the Supporting Information.
a) K. Faber, in: Biotransformations in Organic Chemistry,
Springer, Heidelberg, 5th ed., 2004, pp. 63–97; b) U. T.
Bornscheuer, R. J. Kazlauskas, in: Hydrolases in Organic Syn-
thesis, Wiley-VCH, Weinheim, 2nd ed., 2006, pp. 27–28.
[11]
[12]
[13]
[14]
[15]
[16]
[17]
3
4
CO-CH), 6.88 (dd, J3Ј,4Ј = 8.96, J3Ј,F = 4.54 Hz, 1 H, 3Ј-H), 6.97
3
3
4
(ddd, J4Ј,3Ј = 8.71, J4Ј,F = 8.04, J4Ј,6Ј = 3.16 Hz, 1 H, 4Ј-H), 7.02
3
4
3
(dd, J6Ј,F = 9.10, J6Ј,4Ј = 3.12 Hz, 1 H, 6Ј-H), 7.05 (d, J5,6
8.63 Hz, 1 H, 5-H), 7.66 (dd, J6,5 = 8.63, J6,2 = 2.37 Hz, 1 H, 6-
H), 7.72 (d, J2,6 = 2.31 Hz, 1 H, 2-H), 7.06–7.28 (m, 4 H, arom-
=
3
4
4
CH, indanyl) ppm. 13C NMR (125 MHz, CDCl3): δ = 29.3 (C-2,
indanyl), 31.9 (C-3, indanyl), 55.7 (OMe), 56.2 (OMe), 57.0
(COCH), 111.3, 124.6, 125.1, 126.1, 127.1, 128.6, 131.4, 133.9,
142.1, 144.7, 157.4 (arom.-CH, without fluoro coupling), 112.7,
114.7, 117.5, 130.4, 131.0, 153.0, 157.5 (arom.-CH, with fluoro cou-
pling), 203.7 (CO) ppm. 19F NMR (470 MHz, CDCl3): δ = –124.3
3
3
4
(ddd, JF,6Ј = 8.55, JF,4Ј = 8.47, JF,3Ј = 4.62 Hz, 1 F) ppm. GC-
MS (EI, 70 eV): m/z (%) = 376 (6) [M]+, 259 (100) [C15H12O3F]+.
Supporting Information (see also the footnote on the first page of
this article): A complete list of enzymes screened for the kinetic
enzymatic resolution.
[18]
Acknowledgments
We gratefully acknowledge the Deutsche Forschungsgemeinschaft
(DFG) and Ministry of Innovation, Science, Research and Tech-
nology of the German federal state of North Rhine-Westphalia for
the generous support of our projects. Donations from BASF AG,
Boehringer Mannheim GmbH (now Roche diagnostics), Chemetall
GmbH, Cognis GmbH, Julich Chiral Solutions GmbH (now Co-
dexis), and Wacker AG were greatly appreciated.
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[22] Note: ln(eeS/eeS0) = 2·krac·t.
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Received: September 8, 2009
Published Online: October 23, 2009
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Eur. J. Org. Chem. 2009, 6217–6224