Enantiomerically pure organoseleno-1-arylethanols by enzymatic resolution with Candida antarctica lipase: Novozym 435

Article abstract of DOI:10.1016/j.tetasy.2007.04.019

Racemic organoseleno-1-arylethanols were prepared by ortho-lithiation of arylethanols, followed by sequential reaction with elemental selenium and alkyl halides and by reaction of either aryldiazonium chlorides with diphenyldiselenide or with lithium and

Full text of DOI:10.1016/j.tetasy.2007.04.019

Tetrahedron: Asymmetry 18 (2007) 1048–1053
Enantiomerically pure organoseleno-1-arylethanols by enzymatic
resolution with Candida antarctica lipase: Novozym 435
a
a
a
a
´
Alvaro T. Omori, Leonardo F. Assis, Leandro H. Andrade, Joao V. Comasseto
˜
a,b,
*
´
and Andre L. M. Porto
aInstituto de Quı´mica, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes, 748, CEP 05508-900 Sa˜o Paulo, SP, Brazil
bInstituto de Quı´mica de Sa˜o Carlos, Universidade de Sa˜o Paulo, Av. Trabalhador Sa˜o-carlense, 400, CEP 13566-590 Sa˜o Carlos-SP, Brazil
Received 14 February 2007; accepted 20 April 2007
Available online 1 June 2007
Abstract—Racemic organoseleno-1-arylethanols were prepared by ortho-lithiation of arylethanols, followed by sequential reaction with
elemental selenium and alkyl halides and by reaction of either aryldiazonium chlorides with diphenyldiselenide or with lithium and mag-
nesium alkylselenolates. Enantiomerically enriched organoseleno-1-arylethanols were obtained by kinetic resolution of the racemic mix-
tures by esterification catalyzed by Candida antarctica lipase (Novozym 435). In some cases, enantiomeric excesses of up to 99% were
obtained both for alcohols and acetates.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Chiral alcohols are important intermediates in the synthesis
of many pharmaceuticals and fine chemicals.1 The biocata-
lyzed reduction of ketones2 and the enzymatic kinetic reso-
lution of racemic alcohols3 are presently among the most
employed methods for obtaining access to enantiomerically
enriched alcohols. Both methods have been used by us in
recent studies,4 specially to obtain chiral compounds con-
taining chalcogen atoms.4a,b,f–j Organochalcogen com-
pounds are used in synthetic organic chemistry5 and for
pharmaceutical and toxicological studies.6 In view of the
importance of chirality in both fields,7 it is of interest to de-
velop synthetic routes to enantiomerically enriched organo-
chalcogen compounds. Herein, we report the preparation
and the enzymatic kinetic resolution of ortho-, meta-, and
para-organoseleno-1-arylethanols. Two routes were em-
ployed to prepare the racemic compounds, the ortho-lithia-
tion of arylethanols followed by reaction with elemental
selenium and then with an alkyl halide and by reaction of
meta- and para-acetophenyl diazonium chlorides with
diphenyldiselenide, or with lithium methylselenolate and
bromomagnesium ethylselenolate, followed by reduction
of the selenoacetophenones with sodium borohydride.
2.1. Synthesis of organoseleno-1-arylethanols
2.1.1. Synthesis by the ortho-metallation method. Selenides
3a and 3b were prepared by a one-pot sequence from race-
mic 1-phenylethanol 1a. Alcohol 1a was treated with
2 equiv of n-BuLi/TMEDA in dry pentane. The dilithiated
intermediate 2a was converted into compound 3a by reac-
tion with elemental selenium, followed by the addition of
ethylbromide. In a similar way, the dilithiated intermediate
2b was also converted to selenide 3b by the addition of
methyl iodide (Scheme 1).
2.1.2. Synthesis by the aryldiazonium method. Recently we
have synthesized organoselenoacetophenones for biocata-
lytic studies.4a,b These ketones were prepared from bromo-
acetophenones by a laborious multistep sequence. The
global yields of the organoselenoacetophenones were poor
(13–43%).4a,b Herein, organoselenoacetophenones were
prepared in a straightforward manner starting from com-
mercially available meta- and para-aminoacetophenones 4
(Scheme 2).
The reaction was performed in an aqueous medium at 0 ꢁC
and in the presence of air. An open flask was used as
the reaction vessel. The reaction consisted of the addition
of an aqueous solution of aryldiazonium chloride 5 to a
*
Corresponding author. Tel.: +55 16 3373 8103; fax: +55 16 3373 9952;
e-mail: almporto@iqsc.usp.br
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.04.019

´
A. T. Omori et al. / Tetrahedron: Asymmetry 18 (2007) 1048–1053
1049
OH
OH
OLi
Li
1) Se0
2) R2X
n-BuLi (2 eq.)
TMEDA
pentane
R
R
SeR2
R
reflux, 12 h
1
3
2
R2X = CH3CH2I
or CH3I
1a R = H
(RS)-3a
1b R = CH3
(R =H; R2 = C2H5, 58 %)
(RS)-3b
2a R = H
2b R = CH3
(R = CH3; R2 = CH3, 44 %)
Scheme 1. Organoseleno-1-arylethanols by the ortho-metallation method.
O
O
1) NaHCO3
1) HCl / H2O
2) NaNO2
2) (PhSe)2 or RSeM
H2N
N2+Cl-
R = CH3; CH2CH3
M = Li, MgBr
4a meta-NH2
4b para-NH2
5a meta-N2+Cl-
5b para-N2+Cl-
OH
O
O
NaBH4
MeOH
+
R1Se
R1Se
Se)2
8a R1Se = p-SeMe (95 %)
8b R1Se = p-SeEt (90 %)
8c R1Se = m-SePh (88 %)
8d R1Se = p-SePh (90 %)
6a R1Se = p-SeMe (60 %)
6b R1Se = p-SeEt (33 %)
6c R1Se = m-SePh (71 %)
6d R1Se = p-SePh (69 %)
7
Scheme 2. Organoseleno-1-arylethanols by the diazonium chloride method.
solution of either diphenyldiselenide, MeSeLi or EtSeMgBr
in THF. In all cases, the desired selenoacetophenones 6
were formed as the main product while diarylselenide 7
was formed as a by-product. It was observed that when
the reaction mixture was stirred for several hours, the aryl-
or alkylselenoacetophenones 6a–6d initially formed were
completely converted to the respective diarylselenoace-
tophenones 7. The diazonium chloride method, in compar-
ison to the previously reported one,4a,b required neither dry
conditions nor protection–deprotection steps. Further-
more, the organoselenoacetophenones were obtained in
better global yields (33–71%). The organoseleno-1-phenyl-
ethanols 8a–8d were then prepared by reduction of the
aryl- and alkylselenoacetophenones 6 with NaBH4 in meth-
anol (Scheme 2).
>99%) and in good isolated yields (Table 1, entries 1, 2,
6). When hexane was used as the solvent, selenide 3b did
not react. The reaction was then performed at higher tem-
perature (40 ꢁC), with no success. By changing from hexane
to the more polar t-butylmethylether, the kinetic resolution
of 3b occurred with good conversion and enantioselectivity
(ee >99%, Table 1, entry 2). On the other hand, compounds
3a and 8b showed a different behavior. The (S)-alcohols
were obtained in >99% ee, but acetates 9a and 10b were
obtained with modest enantioselectivity (Table 1, entries
3 and 5).
2.3. Determination of the enantiomeric excesses and absolute
configuration
The enantiomeric excesses of alcohols 3a, 3b and 8a, 8b
were calculated from the chiral GC chromatograms. The
chromatographic separation for alcohols 8c, 8d was very
poor. In view of this fact, compounds 8c and 8d were trans-
formed into 1-phenylethanol 1a by removing the organo-
selenium group with n-butyllithium in THF (Scheme 3).
Acetates 9a, 9b, and 10a–10d were previously hydrolyzed
and subsequently reacted with n-BuLi to afford 1a (Scheme
4). It was supposed that the lithium–selenium exchange
reaction and the acetate hydrolysis did not affect the
2.2. Enzymatic resolution
The enzymatic resolution of the organoseleno compounds
3a–3b and 8a–8d was performed in 24 h. As can be ob-
served in Table 1, the resolution was very efficient with
compounds 3b, 8a, and 8d, which contain the organoseleno
group at the ortho- and para-positions. Alcohols (S)-8a,
(S)-3b, and (S)-8d and acetates (R)-10a, (R)-9b, and (R)-
10d were obtained with high enantiomeric excesses (ee

´
A. T. Omori et al. / Tetrahedron: Asymmetry 18 (2007) 1048–1053
1050
Table 1. Enzymatic resolution of organoseleno alcohols 3a, 3b, 8a–8d and phenylethanol 1a catalyzed by lipase from Candida antarctica (Novozym 435)
Entry
(R,S)-Alcohols
cb (%)
ee Alcohols (%)
Yielda (%)
ee Acetates (%)
Yielda (%)
Ef
1
2
3
4
5
6
7
8a
3b
3a
8b
8c
8d
1a
50
50
57
52
50
40
50
(S)-8a (99)
(S)e-3b (99)
(S)-3a (99)
(S)-8b (99)
(S)c-8c (90)
(S)c-8d (99)
(S)-1a (99)
40
43
36
41
40
43
43
(R)d-10a (99)
(R)d-9b (99)
(R)d-9a (76)
(R)d-10b (90)
(R)d-10c (90)
(R)d-10d (99)
(R)-11 (99)
41
45
43
41
43
40
45
>200
>200
37
99
58
>200
>200
The reaction was carried out at 32 ꢁC using (R,S)-alcohols 1a, 3 and 8, vinyl acetate, hexane, and Novozym 435.
a Isolated yield.
b c: Conversion calculated from the enantiomeric excesses of the substrate (eeS) and the product (eeP), c = (eeS)/(eeP + eeS).11
c ee of 1-phenylethanol after reaction with n-BuLi (Scheme 4).
d ee of 1-phenylethanol after hydrolysis followed by reaction with n-BuLi (Scheme 4).
e tert-Butylmethylether was used as the solvent instead of hexane.
f E: enantiomeric ratio.
OAc
OH
OH
lipase (Novozym 435)
+
SeR1
R
SeR1
R
SeR1
R
Hexane or
tert-butylmethylether
OAc
(R,S)-3a
(R,S)-3b
(R,S)-8a
(R,S)-8b
(R,S)-8c
(R,S)-8d
(R,S)-1a
(S)-3a
(S)-3b
(S)-8a
(S)-8b
(S)-8c
(S)-8d
(S)-1a
R1Se = o-SeEt
R1Se = o-SeMe
R1Se = p-SeMe
R1Se = p-SeEt
R1Se = m-SePh
R1Se = p-SePh
1-phenylethanol
(>99 % ee)
(>99 % ee)
(>99 % ee)
(>99 % ee)
(90 % ee)
(76 % ee)
(>99 % ee)
(>99 % ee)
(90 % ee)
(90 % ee)
(>99 % ee)
(>99 % ee)
(R)-9a
R = H
(R)-9b
(R)-10a
(R)-10b
(R)-10c
(R)-10d
(R)-11
R = CH3
R = H
R = H
R = H
R = H
R = H
(>99 % ee)
(>99 % ee)
Scheme 3. Lipase-catalyzed acetylation of organoseleno-1-arylethanols 1a, 3a, 3b, and 8a–8d.
OH
OH
1) n-BuLi / THF , 0 °C
R1Se
2) H2O
(S)-phenylethanol 1a
OH
OAc
OH
K2CO3
MeOH / H2O
1) n-BuLi / THF , 0 °C
2) H2O
R1Se
R1Se
(R)-phenylethanol 1a
Scheme 4. Chemical transformations performed to transform organoseleno-1-arylethanols into (R)- and (S)-1-phenylethanol.
stereogenic center of 8c, 8d, 9a, 9b, and 10a–10d. To sup-
port this assumption, alcohol (S)-3a (ee >99%) was trans-
formed into (S)-1a by reaction with n-butyllithium and an
identical enantiomeric excess (ee >99%) was observed for
the deselenated product. The absolute configurations of
alcohols 8a, 8c, and 8d were determined by comparison with
the optical rotation described in the literature.4a The abso-
lute configurations of alcohols 3a, 3b, and 8b, and acetates
9a, 9b, and 10a–10d were attributed by chromatographic
comparison with authentic samples of (R) and (S)-1a after
removing the organoselenium group as shown in Scheme 4.
The results obtained showed that the stereochemical pref-
erence of CALB for the organoselenoarylethanols was in
accordance with the Kazlauskas rule.8
3. Conclusion
The ortho-metallation and the aryldiazonium chloride
methods are convenient routes to organoselenoaryletha-
nols. These compounds are efficiently resolved by the lipase
from Candida antarctica (Novozym 435). The absolute

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A. T. Omori et al. / Tetrahedron: Asymmetry 18 (2007) 1048–1053
1051
stereochemistry of the resolved alcohols and acetates is in
accordance with the Kazlauskas rule.
and the residue was purified by silica gel column chroma-
tography eluting with a mixture of hexane and ethyl acetate
(9:1).
4. Experimental
4.1. General
Compound 3b was prepared in a similar way, using ethyl
iodide instead of methyl iodide in the alkylation step.
1-(2-(Ethylselanyl)-4-methylphenyl)ethanol 3b. Yield: 2.0 g
1
All solvents and chemicals used were previously purified
according to the usual methods.9 Column chromatography
was carried out with Merck silica gel (230–400 Mesh). Thin
layer chromatography (TLC) was performed on silica gel
(44%). Yellow oil. H NMR (300 MHz) d: 7.20 (m, 3H),
5.21 (q, J = 6.4 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 2.00
(s, 1H), 1.48 (d, J = 6.4 Hz, 3H). 13C NMR (75 MHz) d:
142.8, 137.8, 131.0, 129.9, 127.6, 125.2, 68.7, 24.0, 21.0,
7.6. IR (film) cmꢀ1: 3377, 2971, 2925, 2868, 1480, 1448,
1424, 901, 822. MS: m/z (relative intensity): 230 (M+,
12), 212 (9), 194 (7), 182 (6), 119 (65), 105 (15), 91 (100),
89 (26), 77 (19), 65 (37), 50 (22), 43 (98). Calculated for
C10H14OSe: C, 52.41; H, 6.16. Found: C, 52.70; H, 6.28.
1
F-254 on aluminum. H and 13C NMR spectra were re-
corded on either a Varian DPX-300 (1H: 300 MHz; 13C:
75 MHz) or a Bruker DRX-500 (1H: 500 MHz; 13C:
125 MHz) spectrometer using as internal standard tetra-
methylsilane and the central peak of CDCl3 at 77 ppm.
Chemical shifts (d) are given in ppm, coupling constants
(J) in Hz and multiplicities are indicated by s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet) and br
(broad). Near infrared spectra were recorded on a Bomem
1-(2-(Ethylselanyl)phenyl)ethanol 3a. Yield: 2.7 g (58%).
Yellow oil. 1H NMR (300 MHz) d: 7.53–7.44 (m, 2H),
7.29–7.14 (m, 2H), 5.28 (q, J = 6.3 Hz, 1H), 2.90 (q,
J = 7.2 Hz, 2H), 2.45 (br, 1H), 1.46 (d, J = 6.3 Hz, 3H),
1.41 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz) d: 146.9,
132.6, 128.7, 127.8, 127.3, 125.5, 69.1, 24.2, 21.2, 15.2. IR
(film) cmꢀ1: 3374, 2972, 2925, 2867, 1445, 1373, 1336,
1232, 1197, 1128, 1085, 1052, 1006, 898, 754, 666. MS:
m/z (relative intensity) 232 (M++2, 5), 230 (M+, 27), 228
(M+ꢀ2, 14), 201 (28), 199 (17), 197 (9), 183 (34), 181
(17), 105 (46), 91 (21), 78 (29), 77 (35), 65 (7), 43 (100). Cal-
culated for C10H14OSe: C, 52.41; H, 6.16. Found: C, 52.49;
H, 5.98.
MB-100 spectrophotometer. Peaks are reported in cmꢀ1
.
Low resolution mass spectrometers were obtained in a Shi-
madzu GCMS-17A/QP5050A instrument equipped with
capillary column HP-1 (J&W Scientific 25 m · 0.32 mm ·
1.05 lm). Elemental analyses were performed at the Micro-
analytical Laboratory of the Chemistry Institute—Univer-
sity of Sao Paulo. The IUPAC names were obtained using
˜
the software ChemDraw Ultraꢂ, version 8.0. Conversions
and enantiomeric excesses of the enzyme-catalyzed reac-
tions were determined using a Shimadzu GC-17A gas chro-
matograph equipped with a chiral capillary column
Chirasil-Dex CB b-cyclodextrin (25 m · 0.25 mm)—
Varian. The carrier gas was hydrogen with a pressure of
100 kPa. Optical rotations were measured in a Jasco
DIP-378 polarimeter and the reported data refer to the
Na-line value using a 1 dm cuvette. Novozym 435 (immo-
bilized lipase from Candida antarctica) was obtained as a
4.2.2. Preparation of organoselenoacetophenones from aryl-
diazonium chlorides. The appropriate aminoacetophe-
none (3.5 mmol), hydrochloric acid (0.8 mL) and water
(0.8 mL) were mixed in a 10 mL round bottomed flask.
The solution was cooled to 0 ꢁC and an aqueous solution
of sodium nitrite (256 mg, 3.7 mmol in 1 mL of H2O) was
added dropwise with vigorous stirring. The mixture was
stirred for 5 min and an aqueous solution of sodium bicar-
bonate added slowly until pH 7. The solution was then
transferred with a Pasteur pipette to another 10 mL round
bottomed flask containing a solution of diphenyldiselenide
or alkylselenolate (1 mmol) in THF (3 mL). The biphasic
solution was continuously stirred at room temperature un-
til the gas evolution had ceased. The mixture was then di-
luted with brine (20 mL) and extracted with ethyl acetate
(2 · 30 mL) and dried over MgSO4. The solvent was evap-
orated and the residue purified by silica gel column chro-
matography eluting with a mixture of hexane and ethyl
acetate. The organoselenoacetophenones were employed
in the reduction step without further purification.
´
gift from Novo Nordisk (Parana-Brazil). Orbital shakers,
Tecnal TE-421 or Superohm G-25, were employed for
the biocatalyzed transformations.
4.2. Synthesis of the substrates
4.2.1. Preparation of the organoseleno-1-arylethanols by
ortho-metallation. The procedure was adapted from the
Wirth method.10 To a two-necked round-bottomed flask
equipped with a reflux condenser and a septum under N2
were added (R,S)-1-phenylethanol 1a (2.44 g, 20 mmol),
N,N,N,N-tetramethylethylenediamine (4.64 g, 40 mmol)
and dry pentane (50 mL). The solution was cooled to
0 ꢁC and n-butyllithium from a 2.0 M solution in hexane
(20.5 mL, 41 mmol) was added dropwise. The bright yellow
solution was refluxed for 12 h. The solution was again
cooled to 0 ꢁC and dry THF (20 mL) was added, followed
by selenium (1.58 g, 20 mmol). After stirring for 3 h at
room temperature, methyl iodide (2.18 g, 20 mmol) was
added and the solution was stirred for an additional
30 min. A 1 M HCl solution (100 ml) was then added and
the resulting solution was extracted three times with ethyl
ether (3 · 40 mL). The combined organic phases were
dried over MgSO4. The solvents were removed in vacuum
4.2.2.1. General procedure for the reduction reaction of
the organoselenoacetophenones 6a–d. Organoseleno phen-
ylethanols 8a–8d were prepared by reduction of the corre-
sponding organoselenoacetophenones 6a–6d with NaBH4
as previously described.4a
The spectral data of the compounds 8a, 8c, and 8d are in
agreement with those reported in the literature.4a

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A. T. Omori et al. / Tetrahedron: Asymmetry 18 (2007) 1048–1053
1052
1-(4-(Methylselanyl)phenyl)ethanol 8a. Yield: 0.194 g (90%).
1-(3-(Phenylselanyl)phenyl)ethanol 8c. Yield: 0.253 g (91%).
1-(4-(Phenylselanyl)phenyl)ethanol 8d. Yield: 0.244 g (88%).
(RS)-1-(4-(Ethylselanyl)phenyl)ethanol
30 min hold, retention time [(R)-8b = 13 min, (S)-8b =
14 min].
8b:
150 ꢁC,
(RS)-1-(3-(Phenylselanyl)phenyl)ethanol 8c: 150 ꢁC, 2 ꢁC/
min up to 180 ꢁC, retention time [(R)-8c = 32.1 min,
(S)-8c = 32.8 min].
1-(4-(Ethylselanyl)phenyl)ethanol 8b. Yield: 196 g (85%).
Oil. 1H NMR (500 MHz) d: 7.44 (d, J = 8.4 Hz, 2H),
7.23 (d, J = 8.1 Hz, 2H), 4.81 (q, J = 6.3 Hz, 1H), 2.89
(q, J = 7.8 Hz, 2H), 2.39 (br, 1H), 1.44 (d, J = 6.6 Hz,
3H), 1.42 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz) d:
144.6, 132.6, 129.0, 126.1, 69.9, 25.1, 21.4, 15.5. IR (film)
cmꢀ1: 3362, 2973, 2924, 2867, 1491, 1448, 1422, 1231,
1087, 1072, 898, 589, 543. MS: m/z (relative intensity):
232 (M++2, 8), 230 (M+, 44), 228 (M+ꢀ2, 22), 215 (56),
213 (30), 187 (10), 157 (25), 107 (11), 91 (13), 78 (68), 43
(100). Calculated for C10H14OSe: C, 52.41; H, 6.16. Found:
C, 52.32; H, 6.25.
(RS)-1-(4-(Phenylselanyl)phenyl)ethanol 8d: 150 ꢁC, 2 ꢁC/
min up to 180 ꢁC, retention time [(R)-8d = 34.2 min, (S)-
8d = 34.8 min].
(RS)-1-Phenylethanol 1a: 110 ꢁC, 1 ꢁC/min up to 118 ꢁC,
50 ꢁC/min up to 180 ꢁC retention time for 7 [(R)-1a =
6.9 min; (S)-1a = 7.6 min].
4.4. Assignment of the absolute configuration
The absolute configurations of compounds 8a, 8c, and 8d
were determined by comparison of the sign of the measured
specific rotation with those of the literature.4a The absolute
configurations of alcohols 3a, 3b, and 8b were assigned by
chromatographic comparison with standard samples of
(R)- and (S)-1a after removal of the organoselenium group
of 3a, 3b, and 8b with n-butyllithium in THF (Section 2.3).
Acetates 9a, 9b, and 10a–10d were converted into 1a by
hydrolysis with aqueous K2CO3 followed by reaction with
n-butyllithium in THF, and the absolute configuration and
enantiomeric excesses of the obtained samples were
assigned by chromatographic comparison with authentic
samples of (R)- and (S)-1a (Table 1).
4.3. Enzymatic resolutions
To a 50 mL Erlenmeyer flask containing 10 mL of hexane,
1 mL of vinyl acetate and 200 mg of Novozym 435 was
added the appropriate alcohol [3b, 8a–8d (150 mg) and 3a
(230 mg)]. The reaction mixture was stirred on a rotary
shaker (32 ꢁC, 160 rpm) for 24 h. After this time, the mix-
ture was filtered and the solvent evaporated. The residue
was purified by silica gel column chromatography using
hexane/ethyl acetate as eluent. The yields and ee are shown
in Table 1.
25
4.3.1. Evaluation of the enzymatic resolution of organo-
seleno-1-arylethanols by GC analysis. The reaction progress
was monitored by collecting 0.1 mL samples at 24 h. These
samples were analyzed by GCMS (1 lL) in a HP-1 column.
After isolation and purification, the products of the biocata-
lyzed reactions were analyzed by GC/FID in a chiral capil-
lary column. Organoseleno alcohols 8a, 8b and 3a, 3b were
chromatographically compared with the racemic mixtures.
The enantiomers of alcohols 8c and 8d and acetates 9a, 9b,
and 10a–10d could not be resolved by chiral capillary col-
umn chromatography (Chirasil-Dex CB—Varian). The
enantiomeric excesses of these compounds were determined
by chromatographic comparison with an authentic sample
of (R,S)-1a after their transformation into 1a by reaction
with n-butyllithium in THF at 0 ꢁC (Section 2.3, Scheme 4).
(ꢀ)-(S)-1-(4-(Methylselanyl)phenyl)ethanol 8a: ½aꢁD
¼
¼
ꢀ44:4 (c 1.4, CHCl3), ee 99%.
25
(+)-(R)-1-(4-(Methylselanyl)phenyl)ethyl acetate 10a: ½aꢁD
þ127:3 (c 1.4, CHCl3), ee 99%.
(ꢀ)-(S)-1-(2-(Ethylselanyl)-4-methylphenyl)ethanol
3b:
25
½aꢁD ¼ ꢀ50:7 (c 1.24, CHCl3), ee 99%.
(+)-(R)-1-(2-(Ethylselanyl)-4-methylphenyl)ethyl acetate 9b:
25
½aꢁD ¼ þ40:8 (c 1.57, CHCl3), ee 99%.
25
(ꢀ)-(S)-1-(2-(Ethylselanyl)phenyl)ethanol 3a: ½aꢁD ¼ ꢀ54:2
(c 1.4, CHCl3), ee 99%.
25
(+)-(R)-1-(2-(Ethylselanyl)phenyl)ethyl acetate 9a: ½aꢁD
¼
General GC conditions: Injector: 220 ꢁC; detector: 220 ꢁC;
pressure: 100 kPa.
þ31:3 (c 1.4, CHCl3), ee 76%.
25
(ꢀ)-(S)-1-(4-(Ethylselanyl)phenyl)ethanol 8b: ½aꢁD ¼ ꢀ55:4
(RS)-1-(4-(Methylselanyl)phenyl)ethanol 8a: 150ꢁC, 30 min
hold, retention time [(R)-8a = 17 min, (S)-8a = 18 min].
(c 1.3, CHCl3), ee 99%.
25
(+)-(R)-1-(4-(Ethylselanyl)phenyl)ethyl acetate 10b: ½aꢁD
¼
¼
¼
(RS)-1-(2-(Ethylselanyl)-4-methylphenyl)ethanol
3b:
þ88:4 (c 1.3, CHCl3), ee 90%.
150 ꢁC (30 min hold) ꢀ10 ꢁC min ꢀ180 ꢁC (5 min), reten-
25
tion time [(R)-3b = 15.5 min, (S)-3b = 19.5 min].
(ꢀ)-(S)-1-(3-(Phenylselanyl)phenyl)ethanol 8c: ½aꢁD
ꢀ30:0 (c 1.2, CHCl3), ee 90%.
(RS)-1-(2-(Ethylselanyl)phenyl)ethanol 3a: 80 ꢁC, 1 ꢁC/min
up to 180 ꢁC, retention time [(R)-3a = 66 min, (S)-3a =
68 min].
25
(+)-(R)-1-(3-(Phenylselanyl)phenyl)ethyl acetate 10c: ½aꢁD
þ43:3 (c 1.2, CHCl3), ee 90%.

´
A. T. Omori et al. / Tetrahedron: Asymmetry 18 (2007) 1048–1053
1053
25
4. (a) Andrade, L. H.; Omori, A. T.; Porto, A. L. M.;
Comasseto, J. V. J. Mol. Catal. B: Enzymatic 2004, 29, 47–
54; (b) Comasseto, J. V.; Omori, A. T.; Porto, A. L. M.;
Andrade, L. H. Tetrahedron Lett. 2004, 45, 473–476; (c)
Comasseto, J. V.; Omori, A. T.; Andrade, L. H.; Porto, A. L.
M. Tetrahedron: Asymmetry 2003, 14, 711–715; (d) Raminelli,
C.; Comasseto, J. V.; Andrade, L. H.; Porto, A. L. M.
Tetrahedron: Asymmetry 2004, 15, 3117–3122; (e) Comasseto,
J. V.; Andrade, L. H.; Omori, A. T.; Assis, L. F.; Porto, A. L.
M. J. Mol. Catal. B: Enzymatic 2004, 29, 55–61; (f) Costa, C.
E.; Clososki, G. C.; Barchesi, H. B.; Zanotto, S. P.;
Nascimento, M. G.; Comasseto, J. V. Tetrahedron: Asymme-
try 2004, 15, 3945–3954; (g) Comasseto, J. V.; Assis, L. F.;
Andrade, L. H.; Schoenlein-Crusisus, I. H.; Porto, A. L. M.
J. Mol. Catal. B: Enzymatic 2006, 39, 24–30; (h) Vieira, T. O.;
Ferraz, H. M. C.; Andrade, L. H.; Porto, A. L. M.
Tetrahedron: Asymmetry 2006, 17, 1990–1994; (i) Dos
Santos, A. A.; Da Costa, C. E.; Princival, J. L.; Comasseto,
J. V. Tetrahedron: Asymmetry 2006, 17, 2252–2259; (j)
Bassora, B. K.; Da Costa, C. E.; Gariani, R. A.; Comasseto,
J. V.; Dos Santos, A. A. Tetrahedron Lett. 2007, 48, 1485–
1487.
(ꢀ)-(S)-1-(4-(Phenylselanyl)phenyl)ethanol 8d: ½aꢁD
¼
¼
ꢀ28:3 (c 1.1, CHCl3), ee 99%.
25
(+)-(R)-1-(4-(Phenylselanyl)phenyl)ethyl acetate 10d: ½aꢁD
þ84:4 (c 1.1, CHCl3), ee 99%.
25
(ꢀ)-(S)-1-Phenylethanol (S)-1a: ½aꢁD ¼ ꢀ51 (c 2.1, CHCl3),
ee 99%.
25
(+)-(R)-1-Phenylethyl acetate (R)-11: ½aꢁD ¼ þ45:3 (c 2.0
CHCl3), ee 99%.
Acknowledgements
The authors would like to thank Novozymes (Curitiba-
Parana-Brazil) for CALB gift. L. F. Assis and A. T. Omori
thank FAPESP for fellowships. L. H. Andrade, A. L. M.
Porto, and J. V. Comasseto thank FAPESP and CNPq
for support.
´
5. (a) Organoselenium Chemistry; Back, T., Ed.; Oxford Uni-
versity Press, 1999; (b) Petragnani, N.; Stefani, H. A.
Tellurium in Organic Synthesis, 2nd updated and enlarged
ed.; Elsevier—Academic Press, 2007; (c) Comasseto, J. V.;
Clososki, G. C.; Cunha, R. L. O. R. In Tellurium in:
Comprehensive Organometallic Chemistry (COMC-3); Min-
gos, D. M. P., Crabtree, R. H., Eds.; Elsevier: Amsterdam,
2007; Vol. 9, pp 587–648.
References
1. (a) Schulze, B.; Wubbolts, M. G.. Curr. Opin. Biotechnol.
1999, 10, 609–615; (b) Patel, N. Curr. Opin. Drug Discov.
Devel. 2003, 6, 902–920; (c) Patel, P. N. Curr. Opin. Drug
Discov. Devel. 2006, 9, 741–764; (d) Patel, R. N. Enzyme
Microb. Technol. 2002, 31, 804–826; (e) Schoemaker, H. E.;
Mink, D.; Wubbolts, M. G. Science 2003, 299, 1694–1697.
2. (a) Groger, H.; Chamouleau, F.; Orologas, N.; Rollmann, C.;
Drauz, K.; Hummel, W.; Weckbecker, A.; May, O. Angew.
Chem., Int. Ed. 2006, 45, 5677–5681; (b) Rodrigues, J. A. R.;
6. Zeni, G.; Ludtke, D. S.; Panatieri, R. B.; Braga, A. L. Chem.
¨
Rev. 2006, 106, 1032–1076.
7. Thayer, A. M. Chem. Eng. News 2006, 84, 15.
8. Kazlauskas, R. J.; Weissfloch, A. N. E.; Rappaport, A. T.;
Cuccia, L. A. J. Org. Chem. 1991, 56, 2656–2665.
9. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification
of Laboratory Chemicals, 2nd ed.; Pergamon Press: London,
1980.
10. Wirth, T.; Kulicke, K. J.; Fragale, G. J. Org. Chem. 1996, 61,
2686–2689.
11. Faber, K. Biotransformation in Organic Chemistry, 4th ed.;
Springer: Berlin, 2000.
Moran, P. J. S.; Conceic¸ao, G. J. A.; Fardelone, L. C. Food
˜
Technol. Biotechnol. 2004, 42, 295–303; (c) Nakamura, K.;
Yamanaka, R.; Matsuda, T.; Harada, T. Tetrahedron:
Asymmetry 2003, 14, 2659–2681.
3. For examples see: (a) Gotor-Fernandez, V.; Brieva, R.;
Gotor, V. J. Mol. Catal. B: Enzymatic 2006, 40, 111–120; (b)
Ghanem, A.; Aboul-Enein, H. Y. Chirality 2005, 17, 1–15.