928
L. C. Rocha et al. / Tetrahedron: Asymmetry 21 (2010) 926–929
detector temperature: 200 °C; oven (initial temperature): 120 °C;
oven (final temperature): 165 °C; heating rate: 2 °C minꢁ1, and
time analysis: 32.5 min. The enantiomeric excesses (ee) of iodoph-
enylethanols 1–3 and iodophenyl acetates 4–6 were determined by
gas chromatography analyses with chiral stationary phase employ-
ing the retention times obtained for both enantiomers (R/S) of the
compounds 1 to 6 which were the following: compound 1: R =
16.0 min and S = 19.0 min; compound 2: R = 16.5 min and S =
16.5 min; compound 3: S = 19.8 min and R = 20.5 min; compound
4: R = 10.5 min and S = 10.5 min; compound 5: S = 11.2 min and
R = 11.6 min, and compound 6: R = 16.5 min and S = 17.5 min. Re-
agents and solvents were used as obtained commercially and when
necessary were purified and/or dried using procedures described in
the literature.11 Column chromatography separations were carried
out using Silica Gel 60 (400–230 mesh) and hexane/ethyl acetate
mixtures as eluent. ( )-Iodophenylethanols 1–3 were obtained by
reduction of their corresponding iodoacetophenones using NaBH4
in ethanol.12 ( )-Iodophenyl acetates 4–6 were obtained by acety-
lation of their corresponding ( )-iodophenylethanols 1–3 using
acetic anhydride in pyridine.13
(S)-(ꢁ)-1-(4-Iodophenyl)ethanol
3:
experimental
data:
½
a 2D5
ꢂ
¼ ꢁ38:5 (c 6.90, CHCl3; 98% ee); literature: ½a D25
ꢂ
¼ ꢁ32:7 (c
5.99, CHCl3; 96% ee).13 The spectroscopic data are in agreement
with those reported in the literature.14
(R)-(+)-1-(2-Iodophenyl)ethyl acetate 4: experimental data:
½
a 2D5
ꢂ
¼ þ7:9 (c 0.12, CHCl3; 98% ee); literature: ½a D25
¼ ꢁ6:8 (c
ꢂ
0.785, CHCl3; 69% ee).13 The spectroscopic data are in agreement
with those reported in the literature.13
(R)-(+)-1-(3-Iodophenyl)ethyl acetate 5: experimental data:
½
a 2D5
ꢂ
¼ þ6:9 (c 0.18, CHCl3; 98% ee). 1H NMR (200 MHz, CDCl3), d
(ppm): 7.58–7.69 (m, 2H), 7.27–7.32 (m, 1H), 7.07 (t, J = 7.7 Hz,
1H), 5.78 (q, J = 6.7 Hz, 1H), 2.07 (s, 3H), 1.49 (d, J = 6.7 Hz, 3H);
13C NMR (50 MHz, CDCl3), d (ppm): 170.0, 144.0, 136.8, 135.0,
130.0, 125.3, 94.4, 71.3, 22.2, 21.2; IR (film)
m
(cmꢁ1): 3059 (H-
Ar), 1727 (C@O), 1238 (C–O); HRMS (ESI) m/z; calcd for
C
10H11IO2 [M+Na]+: 289.9804, found: 289.9797.
(R)-(+)-1-(4-Iodophenyl)ethyl acetate 6: experimental data:
½
a 2D5
ꢂ
¼ þ71:1 (c 3.80, CHCl3; 98% ee). The spectroscopic data are
in agreement with those reported in the literature.15
(S)-(ꢁ)-1-(Biphenyl-3-yl)ethanol 8: experimental data: ½a D25
¼
ꢂ
ꢁ13:0 (c 1.00, CHCl3; 98% ee). 1H NMR (200 MHz, CDCl3), d
(ppm): 7.60 (m, 1H), 7.51 (m, 2H), 7.49 (m, 1H), 7.46 (m, 2H),
7.44 (m, 1H), 7.37 (m, 1H), 7.32 (m, 1H); 13C NMR (50 MHz, CDCl3),
d (ppm): 146.4, 141.5, 141.1, 129.6, 129.0, 128.8, 127.4, 127.2,
4.2. General procedures
4.2.1. Kinetic resolution of ( )-iodophenylethanols 1–3 by
immobilized CALB lipase
128.4, 124.4, 70.6, 25.3. IR (film)
m
(cmꢁ1): 3373 (OH), 1076 (C–
To a 50-mL Erlenmeyer flask were added HPLC grade hexane
(10 mL), vinyl acetate (1 mL), immobilized CALB lipase (100 mg),
and the appropriate alcohol 1–3 (0.8 mmol, 200 mg). The Erlen-
meyer flask was sealed using a rubber stopper, and the reaction
mixture was stirred in an orbital shaker at 32 °C and 130 rpm.
The reaction progress was monitored by collecting samples
(0.1 mL) according to the time indicated in Table 1, which were
analyzed by gas chromatography with chiral stationary phase.
After the reaction was complete, the immobilized lipase was fil-
tered off. The filtrate was evaporated under reduced pressure.
The residue was purified by column chromatography on silica gel
using 8:2 hexane/ethyl acetate as eluent, yielding the enantiomeri-
cally enriched alcohols 1–3 and acetates 4–6.
O). HRMS (ESI) m/z; calcd for C14H14O [M+Na]+: 221.0942, found:
221.0935.
(S)-(ꢁ)-1-(Biphenyl-4-yl)ethanol
9:
experimental
data:
½
a 2D5
ꢂ
¼ ꢁ13:2 (c 1.00, CHCl3; 98% ee); literature: ½a D25
ꢂ
¼ ꢁ29:5 (c
1.0, CHCl3, 77% ee).16 The spectroscopic data are in agreement with
those reported in the literature.17
Acknowledgments
A.L.M.P. gratefully acknowledges CNPq and FAPESP for their
financial support. L.C.R. thanks CAPES and I.G.R. thanks CNPq for
scholarships. The authors also wish to thank Novo Nordisk
(Curitiba-Paraná, Brazil) for donation of the immobilized CALB en-
zyme (Novozym 435Ò).
4.2.2. Preparation of chiral biphenyl compounds 8–9 by the
Suzuki cross-coupling reaction
References
To a vial (20 mL) were added the appropriate (S)-alcohol 1–3
(0.3 mmol, 74 mg), phenylboronic acid (0.3 mmol, 37 mg), K2CO3
(0.6 mmol, 83 mg), Pd(PPh3)4 (0.015 mmol, 17 mg), distilled water
(1 mL), and toluene (4 mL). The vial was sealed using a cap, and the
reaction mixture was stirred for 24 h at 80 °C. Afterwards, brine
(20 mL) was added to the mixture, which was extracted with ethyl
acetate (3 ꢀ 20 mL). The organic phase was dried over MgSO4.
After filtration, the solvent was evaporated under reduced pres-
sure. The residue was purified by column chromatography on silica
gel using 7:3 hexane/ethyl acetate as eluent yielding the desired
products 8–9.
1. (a) Patel, R. N. Coord. Chem. Rev. 2008, 252, 659–701; (b) Murakami, H. Top.
Curr. Chem. 2007, 269, 273–299; (c) Patel, R. N. Curr. Opin. Drug Disc. Dev. 2006,
9, 741–764; (d) Patel, R. N. Curr. Org. Chem. 2006, 10, 1289–1321; (e) Nunez, M.
C.; Garcia-Rubino, M. E.; Conejo-Garcia, A.; Cruz-Lopez, O.; Kimatrai, M.; Gallo,
M. A.; Espinosa, A.; Campos, J. M. Curr. Med. Chem. 2009, 16, 2064–2074; (f)
Miller, C. P.; Ullrich, J. W. Chirality 2008, 20, 762–770.
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2009, 21, 449–467; (b) Ema, T.; Yamaguchi, K.; Wakasa, Y.; Yabe, A.; Okada, R.;
Fukumoto, M.; Yano, F.; Korenaga, T.; Utaka, M.; Sakai, T. J. Mol. Catal. B Enzym.
2003, 22, 181–192; (c) Kim, M. J.; Ahn, Y.; Park, J. Curr. Opin. Biotechnol. 2002,
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Naoshima, Y. J. Mol. Catal. B Enzym. 1998, 4, 53–60.
3. Malhotra, Sanjay V. Ed. Methodologies in asymmetric catalysis, American
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Technol. Biotechnol. 2004, 42, 295–303; (b) Goldberg, K.; Schroer, K.; Lutz, S.;
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K.; Lutz, S.; Liese, A. App. Microbiol. Biotechnol. 2007, 76, 249–255; (d)
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Asymmetry 2009, 20, 513–557.
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Quim. Nova 2008, 31, 813–817.
4.2.3. Assignment of the absolute configuration and
characterization data for compounds 1–9
(S)-(ꢁ)-1-(2-Iodophenyl)ethanol
1:
experimental
data:
¼ ꢁ41:3 (c
½
a 2D5
ꢂ
¼ ꢁ13:8 (c 0.07, CHCl3; 24% ee); literature: ½a D25
ꢂ
0.20, CHCl3; 97% ee).12 The spectroscopic data are in agreement
with those reported in the literature.12
(S)-(ꢁ)-1-(3-Iodophenyl)ethanol
2:
experimental
data:
½
a 2D5
ꢂ
¼ ꢁ20:7 (c 0.10, CHCl3; 98% ee). 1H NMR (200 MHz, CDCl3),
d (ppm): 7.67 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 4.84 (q,
J = 6.4 Hz, 1H), 1.70 (s, 1H), 1.45 (d, J = 6.4 Hz, 3H); 13C NMR
(50 MHz, CDCl3), d (ppm): 148.1, 136.4, 134.5, 130.2, 124.6, 94.4,
7. (a) Chenevert, R.; Pelchat, N.; Morin, P. Tetrahedron: Asymmetry 2009, 20, 1191–
1196; (b) Chenevert, R.; Pelchat, N.; Jacques, F. Curr. Org. Chem. 2006, 10, 1067–
1094.
69.5, 25.1; IR (film)
m
(cmꢁ1): 3348 (OH), 1086 (C–O); HRMS (ESI)
m/z; calcd for C8H9IO [M+Na]+: 247.9698, found: 247.9675.