Synthesis of enantiomerically enriched β-hydroxy selenides by catalytic asymmetric ring opening of meso-epoxides with (phenylseleno)silanes

Article abstract of DOI:10.1016/j.tet.2008.01.126

The first example of the enantioselective ring opening of meso-epoxides by (phenylseleno)silanes using salen(Cr)complexes as catalyst is described. This desymmetrization reaction constitutes a simple and convenient approach to synthetically versatile optically active β-hydroxy selenides.

Full text of DOI:10.1016/j.tet.2008.01.126

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3337e3342
www.elsevier.com/locate/tet
Synthesis of enantiomerically enriched b-hydroxy selenides
by catalytic asymmetric ring opening of meso-epoxides
with (phenylseleno)silanes
*
*
Marcello Tiecco , Lorenzo Testaferri, Francesca Marini , Silvia Sternativo,
Francesca Del Verme, Claudio Santi, Luana Bagnoli, Andrea Temperini
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Universita` di Perugia, 06123 Perugia, Italy
Received 6 November 2007; received in revised form 16 January 2008; accepted 31 January 2008
Available online 3 February 2008
Abstract
The first example of the enantioselective ring opening of meso-epoxides by (phenylseleno)silanes using salen(Cr)complexes as catalyst is
described. This desymmetrization reaction constitutes a simple and convenient approach to synthetically versatile optically active b-hydroxy
selenides.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Desymmetrizations; Enantioselective synthesis; Organoselenium compounds; meso-Epoxides
1. Introduction
seleniumreagents,7 andtheasymmetricaldolreactionswithenan-
tiomerically pure a-seleno ketones, esters, or amides8 (reagent-
controlled asymmetric syntheses, path c and path d).
b-Hydroxy selenides are useful intermediates for a variety of
synthetic transformations. Together with classical reactions,
such as the reductive deselenenylation to alcohols1 or the
oxidation to allylic alcohols,1 simple and convenient conversions
into tetrahydrofurans,2 1,3-oxazolidinones,3 aminoalcohols,3 and
b-aryl-selenides4,5 have been recently reported in the literature. In
view of their large synthetic utilization, several approaches to
enantiomerically enriched b-hydroxy selenides with different
skeleton and stereochemical requirements have been developed.
The most common procedures (Scheme 1) are the lipase-
promoted kinetic resolutions of racemic b-hydroxy selenides
(path a),6 the regio and stereospecific ring opening of commercial
enantiopure epoxides by arylselenolates1 (substrate-controlled
asymmetric syntheses, path b), the asymmetric seleno-hydroxyl-
ation of alkenes promoted by enantiomerically pure electrophilic
O
R3SeNa
+
R2
R1
enantiopure
OH
R2
enzymatic
R2
SeR3
path b
R1
kinetic
R3SeX
+
R2=H
resolution
R1
path c
enantiopure
rac
path a
R2=H
CH3CN, H2O
OH
*
R2 (R1)
*
R1
path d
SeR3
path f
TiCl4, Et3N
O
R3SeH
chiral catalyst
+
O
R2
R1
R1
+
NaBH4
R1
H
SeR3
path e
enantiopure
R2=COR, CO2R, CONRR'
N
H
O
R1=H
R3SeX
+
* Corresponding authors. Tel.: þ39 075 585 5100; fax: þ39 075 585 5116
(M.T.); tel.: þ39 075 585 5105; fax: þ39 075 585 5116 (F.M.).
E-mail addresses: tiecco@unipg.it (M. Tiecco), marini@unipg.it (F.
Marini).
R1
R2
Scheme 1. Preparation of optically active b-hydroxy selenides.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.126

3338
M. Tiecco et al. / Tetrahedron 64 (2008) 3337e3342
Table 1
Asymmetric ring opening of stilbene oxide 1a: optimization of the reaction
conditions
Catalyst-controlled asymmetric syntheses have been
scarcely investigated. Very recently, we have prepared b-hy-
droxy selenides in excellent enantiomeric purity by the chiral
amine catalyzed a-selenenylation of aldehydes followed by
in situ reduction (path e).9 b-Hydroxy selenides with two
contiguous chiral centers have been prepared by the enantio-
selective ring opening of meso-epoxides with benzeneselenol
in the presence of the heterobimetallic salen TitaniumeGal-
lium complex (path f).10 We now report the first desymmet-
rization of meso-epoxides by (phenylseleno)silane 2a and
commercial or easily accessible salen catalysts.11 This nucle-
ophilic selenium source is more easy to handle than the eas-
ily oxidizable and malodorous benzeneselenol.
SePh
Si
O
SePh
Ph
HO
Ph
Catalyst 5 mol%
r.t. 96 h
+
Ph
Ph
1a
2a
3a
Entry Catalyst
Temperature Solvent
(additive)
Yielda (%) erb
1
Salen(Ti)(OiPr)2 RT
Salen(Zn) __ RT
Salen(Cr)SbF6 RT
Hexane
Hexane
TBME
Hexane
Toluene
TBME
Hexane
Toluene
TBME
46
69
73
69
60
60
60
67
82
64:36
2
50:50
69:31
82:18
77:23
63:37
84:16
89:11
89:11
73:27
96:4
3
4
Salen(Cr)Cl
Salen(Cr)Cl
(Salen)CrCl
Salen(Cr)BF4
Salen(Cr)BF4
Salen(Cr)BF4
Salen(Cr)BF4
Salen(Cr)BF4
Salen(Cr)BF4
Salen(Cr)BF4
RT
RT
5
6
RT
RT
7
2. Results and discussion
8
RT
RT
9
The (phenylseleno)silanes 2aec employed for the present
investigation were prepared by analogy with the procedures
described in the literature as indicated in Scheme 2.12 These
compounds can be purified by distillation or crystallization
and stored for several days without particular precautions.
10
11
12
13
a
RT
TBME (TMEDA) 99
TBME (TMEDA) 92
TBME (t-BuOH) 99
TBME (Bu4NF) 35
ꢀ10 ꢁC
ꢀ10 ꢁC
ꢀ10 ꢁC
77:23
87:13
Yields determined on isolated compounds after column chromatography.
Enantiomeric ratios determined by HPLC on a Chiralpack AD-H column.
b
R1
Cl Si R2
R1
(PhSe)2
R1
PhSe Si R2 2b R1= i-Pr; R2 = i-Pr
2c R1= Ph; R2 = t-Bu
2a R1= Me; R2 = t-Bu
NaH THF
by the comparison of the specific optical rotation with that
reported in the literature.16 Considering that 3a is formed
with complete anti diastereoselectivity it can be confidently
assumed that 3a has the absolute configuration as indicated
in Table 1.
We next examined the scope of this ring opening reaction by
carrying out the desymmetrization reactions on other meso-ep-
oxides. The epoxides 1feh are commercially available. The
aryl epoxides 1bee were prepared17 from substituted benzyl io-
dides and appropriate commercial benzaldehydes via Wittig
reactions. The crude alkenes were submitted to epoxidation
with m-CPBA without purification. cis-Epoxides, which under
the reaction conditions employed are the major or the sole reac-
tion products, were obtained in pure form after column
chromatography.
R1
PhSeNa
Scheme 2. Preparation of the (phenylseleno)silanes 2aec.
Preliminary experiments were performed, at room temper-
ature and under air atmosphere, on stilbene oxide 1a in order
to evaluate the efficiency of the selenium reagents 2aec13 and
of several (R,R)-salen(metal)complexes in different solvents
(0.5 M solutions). The best results in terms of yield and er
were obtained using the tert-butyl(dimethyl)(phenylseleno)si-
lane 2a. Under the same reaction conditions 2b gave similar
er, but considerably poorer yields, and 2c was ineffective.
The results of several selected experiments carried out with
2a are reported in Table 1. The best results in terms of yield
and enantiomeric ratio were obtained with salen(Cr)BF4 in
tert-butylmethyl ether (entry 9).
The results of the desymmetrization experiments of the
epoxides 1beh are reported in Table 2. The results obtained
on stilbene oxide 1a under optimized reaction conditions
(method A) are also reported for comparison. The absolute
configurations of compounds 3bee were assigned by analogy
with 3a, whereas those of compounds 3feh were attributed by
comparison of the HPLC retention times (Chiralcel OD-H
column) with those previously reported in the literature.10
In order to obtain good levels of enantioselectivity it was
essential to use low reaction temperatures. Notably the enan-
tioselectivity of the process depends on the structure of the
starting epoxide. In fact, higher enantiomeric ratios were ob-
tained with stilbene oxide 1a and the p-substituted aryl epox-
ides 1bed. As already observed for 1a the addition of
TMEDA (method A) significantly improved the efficiency of
the process in the cases of the aryl epoxides 1bee (entries
2e5). Cyclic or alkyl epoxides gave instead moderate to
good results when TMEDA was not added (method B).
Further optimization of the reaction was then attempted.
The effects of the temperature and the addition of 1 equiv of
tert-butanol,1 tetrabutylammonium fluoride,14 or tetramethyl-
ethylendiamine (TMEDA),15 as activating agents for the sily-
lated organoselenium reagents, have been investigated (entries
10e13). The results of these experiments indicate that the use
of a low temperature and TMEDA as additive can dramatically
improve the yield and the selectivity of the reaction (entry 11).
In this case 3a was obtained with 92% yield and 96:4 er. These
results are considerably better than those previously re-
ported.10 Further improvements were not observed by using
10% of the catalyst, more concentrated solutions (2 M), or
lower reaction temperatures.
The stereochemical attribution of compound 3a was
effected by reductive deselenenylation with tributyltin hy-
dride and AIBN in refluxing toluene. The 1,2-diphenyletha-
nol thus obtained has the R configuration as demonstrated

M. Tiecco et al. / Tetrahedron 64 (2008) 3337e3342
3339
Table 2
Asymmetric ring opening of meso-epoxides 1aeh
Entry
1
Epoxide
Product
Temperature
Yield (%)
A 92
er
O
SePh
Ph
HO
ꢀ10 ꢁC
ꢀ10 ꢁC
96:4
Ph
Ph
Ph
3a
1a
O
HO
SePh
2
A 50
85:15
F
3b
F
F
F
1b
O
HO
HO
HO
SePh
Seph
SePh
ꢀ10 ꢁC
RT
A 53
A 31a
86:14
72:28
3
4
Br
3c
Br
Br
Br
1c
ꢀ10 ꢁC
RT
RT
A 25b
A 70b
A 53a,b
84:16
O
80:20
81:19
CN
3d
CN
1d
NC
NC
O
ꢀ10 ꢁC
RT
A 50
A 94
A 34a
75:25
66:34
64:36
5
6
RT
MeO
OMe
3e
OMe MeO
1e
SePh
HO
O
ꢀ10 ꢁC
ꢀ10 ꢁC
A 52
B 71
64:36
75:25
1f
3f
O
SePh
HO
ꢀ10 ꢁC
ꢀ10 ꢁC
A 70
B 88
67:33
81:19
7
8
1g
3g
SePh
CH3
HO
O
ꢀ10 ꢁC
B 60
76:24
CH3
H3C
H3C
1h
3h
Method A: reactions carried out with salen(Cr)BF4 of 5 mol % in TBME in the presence of 1 equiv of TMEDA for 96 h.
Method B: reactions carried out with salen(Cr)Cl of 5 mol % in Et2O, without TMEDA for 96 h.
a
Reaction carried out in the absence of TMEDA following method A.
Reaction carried out in CH2Cl2 following method A.
b
3. Conclusions
4. Experimental
In conclusion we have described the first enantioselective
ring opening of meso-epoxides by (phenylseleno)silanes as
nucleophilic selenium source and commercial or readily avail-
able salen(chromium) complexes as catalysts. These reactions
constitute a simple and convenient approach to the synthetically
versatile, optically active b-hydroxy selenides. The enantiose-
lectivity of the process depends on the structure of the starting
epoxide. Good to excellent results (up to 92% yield and 96:4 er)
were obtained on stilbene epoxide and on its p-substituted
derivatives in the presence of TMEDA as additive.18 The results
described in this paper nicely complement those obtained using
benzeneselenol as the nucleophile, which were particularly
efficient in the desymmetrization of cyclic or alkyl epoxides.
4.1. General
New compounds were characterized by H, 13C NMR, and
mass spectra. 1H and 13C NMR spectra were recorded on
1
a
Bruker Avance-DRX 400 instrument (at 400 and
100.62 MHz, respectively) with CDCl3 as solvent and TMS
as internal reference. GCeMS analyses were carried out
with an HP 6890 gas chromatograph (HP-5MS capillary col-
umn 30 m, ID 0.25 mm, film 0.25 mm) equipped with an HP
5973 Mass Selective Detector; for the ions containing sele-
nium only the peaks arising from the selenium-80 isotope
are given. HPLC analyses were performed on an HP 1100
instrument equipped with a chiral column and an UV detector.

3340
M. Tiecco et al. / Tetrahedron 64 (2008) 3337e3342
Optical rotations were measured with a Jasco DIP-1000 digital
polarimeter. Elemental analyses were carried out on a Carlo
Erba 1106 Elemental Analyzer. Thin layer chromatography
(TLC) was performed on silica gel 60 F254 (Merck) on alumi-
num sheets. Column chromatography was performed using
silica gel Merck 60 (70e230 mesh). For flash chrotography
silica gel Merck 60 (230e400 mesh) was used.
4.3. Synthesis of the (phenylseleno)silanes
(Phenylseleno)silanes 2aec were prepared according to the
literature procedure.12 Spectral data of compounds 2a and 2c
are identical to those previously described. In the case of
compound 2b the by-products were removed by distillation
under vacuum and the residue was sufficiently pure to be
directly employed for the ring opening reactions. Physical
and spectral properties of compound 2b are reported below.
4.2. Synthesis of the meso-epoxides
Epoxides 1a and 1feh are commercial compounds (Aldrich).
Epoxides 1bee have been prepared from substituted benzyl
iodides and appropriate commercial benzaldehydes via a Wittig
reaction followed by oxidation with m-CPBA according to the
procedure described in the literature.17 Intermediates have
been employed without any purification. Chemical overall
yields determined after purification by column chromatography,
and physical and spectral data of compounds 1bed are reported
below. GCeMS spectra of compounds 1b and 1c are not
reported since these products suffered decomposition during
the analysis. Compound 1e has spectral properties identical to
those previously described.17
4.3.1. Triisopropyl(phenylseleno)silane 2b
1
Yield 40%, 1.4 g; yellow oil, slightly impure; H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.70e7.65 (m, 2H,
SePh), 7.30e7.14 (m, 3H, SePh), 1.36e1.28 (m, 3H, CH),
1.13 (d, 18H, J¼7.4 Hz, CH3); 13C NMR (100 MHz, CDCl3,
25 ꢁC, TMS): d¼137.1 (2C), 128.6 (2C), 126.9, 124.7, 18.6
(6C), 13.2 (3C); MS (70 eV, EI): m/z (%) 314 (56) [Mþ],
271 (100), 243 (14), 229 (53), 215 (13), 201 (40), 187 (20),
157 (30), 123 (24), 105 (34), 77 (28), 59 (31).
4.4. Catalysts
The (R,R)-salen(Cr)Cl is commercially available. The
(R,R)-salen(Ti)(OiPr)2,11f the (R,R)-salen(Zn)(II),19 the (R,R)-
4.2.1. cis-2,3-Bis(4-fluorophenyl)oxirane (1b)
salen(Cr)BF4,20 and the (R,R)-salen(Cr)SbF6 have been pre-
21
Thiscompoundwasobtainedinpure form (45% yield, 0.95 g)
after flash chromatography (light petroleum to light petroleum/
diethyl ether 96:4). Oil; Rf 0.60 (light petroleum/diethyl ether
pared according to standard procedures.
1
80:20); H NMR (400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.20e
4.5. Asymmetric ring opening of meso-epoxides: method A
and method B
7.00 (m, 4H, Ph), 7.0e6.75 (m, 4H, Ph), 4.25 (s, 2H, CHO);
13C NMR (100 MHz, CDCl3, 25 ꢁC, TMS): d¼162.1 (d, 2C,
1JCF¼244.3 Hz), 129.9 (2C), 128.4 (d, 4C, JCF¼8.0 Hz),
Method A: the meso-epoxides 1aeg (0.5 mmol) and
(R,R)-salen(Cr)BF4 (0.025 mmol) were dissolved in TBME
(0.5 M), and then 2a (0.61 mmol) and TMEDA (0.5 mmol)
were added. The resulting mixture was stirred for 96 h and
then filtered under vacuum through a plug of silica gel with
30 mL of light petroleum/diethyl ether 70:30. The filtrate
was concentrated and the crude mixture was analyzed by
NMR. The crude b-hydroxy selenides 3aeg were purified
by flash chromatography.
Method B: the meso-epoxides 1feh were treated under the
experimental conditions described for method A, but using
salen(Cr)Cl as catalyst in Et2O and in the absence of TMEDA.
Physical and spectral data of 3feh are comparable with
those reported in the literature.10 Physical and spectral data
of compounds 3aee are described below together with the
eluant employed for the purification.
3
2
114.8 (d, 4C, JCF¼21.5 Hz), 59.0 (2C). Anal. Calcd for
C14H10F2O: C, 72.41; H, 4.34. Found: C, 72.54; H, 4.19.
4.2.2. cis-2,3-Bis(4-bromophenyl)oxirane (1c)
This compound was obtained in pure form (36% yield,
0.9 g) after column chromatography (light petroleum to light
petroleum/diethyl ether 90:10). White solid; mp¼84e86 ꢁC;
Rf 0.58 (light petroleum/diethyl ether 80:20); 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.30e7.20 (m, 4H, Ph),
7.02e6.80 (m, 4H, Ph), 4.25 (s, 2H, CHO); 13C NMR
(100 MHz, CDCl3, 25 ꢁC, TMS): d¼133.0 (2C), 131.2 (4C),
128.5 (4C), 121.8 (2C), 59.2 (2C). Anal. Calcd for
C14H10Br2O: C, 47.50; H, 2.85. Found: C, 47.35; H, 2.78.
4.2.3. cis-2,3-Bis(4-cyanophenyl)oxirane (1d)
This compound was obtained in pure form (30% yield,
0.7 g) after column chromatography (light petroleum/diethyl
ether 70:30 to diethyl ether). White solid; mp¼172e174 ꢁC;
Rf 0.15 (light petroleum/diethyl ether 60:40); 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.50e7.26 (m, 4H, Ph),
7.25e7.01 (m, 4H, Ph), 4.45 (s, 2H, CHO); 13C NMR
(100 MHz, CDCl3, 25 ꢁC, TMS): d¼138.4 (2C), 131.4 (4C),
126.9 (4C), 117.8 (2C), 111.5 (2C), 58.7 (2C); MS (70 eV,
EI): m/z (%) 246 (100) [Mþ], 217 (74), 190 (35), 130 (33),
115 (63), 88 (22). Anal. Calcd for C16H10N2O: C, 78.03; H,
4.09; N, 11.38. Found: C, 77.87; H, 4.19; N, 11.50.
4.5.1. (1S,2S)-1,2-Diphenyl-2-(phenylseleno)ethanol (3a)
This compound was obtained in pure form (92% yield,
165.6 mg) after flash chromatography (light petroleum to light
petroleum/diethyl ether 90:10). Oil; Rf 0.42 (light petroleum/di-
ethyl ether 80:20); [a]2D3 þ152.9 (c 3.1, CHCl3); HPLC (Chiral-
pack AD-H (250ꢂ4.6 mm ID), eluant: hexane/iPrOH 95:5, flow
rate: 1 mL/min, UV detection at 230 nm), tR: minor enantiomer
24.3 min, major enantiomer 30.2 min. 1H NMR (400 MHz,
CDCl3, 25 ꢁC, TMS): d¼7.48e7.44 (m, 2H, SePh), 7.30e7.20
(m, 11H, Ph, SePh), 7.03e6.99 (m, 2H, SePh), 5.08 (d, 1H,

M. Tiecco et al. / Tetrahedron 64 (2008) 3337e3342
3341
J¼8.8 Hz, CHO), 4.53 (d, 1H, J¼8.8 Hz, CHSe), 3.40 (br s, 1H,
hexane/iPrOH 75:25, flow rate: 0.75 mL/min, UV detection
13
OH); C NMR (100 MHz, CDCl3, 25 ꢁC, TMS): d¼140.8,
at 230 nm), tR: minor enantiomer 17.53 min, major enantiomer
1
139.9, 135.3 (2C), 128.9 (2C), 128.7, 128.4 (2C), 128.0 (4C),
127.9, 127.7, 127.0, 126.7 (2C), 76.6, 59.9. Anal. Calcd for
C20H18OSe: C, 67.99; H, 5.14. Found: C, 68.21; H, 5.21.
25.97 min. H NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.52e7.48 (m, 2H, Ph), 7.45e7.40 (m, 2H, Ph),
7.35e7.19 (m, 7H, Ph, SePh), 7.08e6.95 (m, 2H), 5.07 (d,
1H, J¼8.3 Hz, CHO), 4.37 (d, 1H, J¼8.3 Hz, CHSe), 3.50
13
4.5.2. (1S,2S)-1,2-Bis(4-fluorophenyl)-2-(phenylseleno)-
ethanol (3b)
(br s, 1H, OH); C NMR (100 MHz, CDCl3, 25 ꢁC, TMS):
d¼145.6, 144.8, 135.9 (2C), 132.1 (4C), 129.3 (2C), 129.0
(2C), 128.9, 127.4 (2C), 127.0, 118.4 (2C), 112.0, 111.2,
75.2, 58.4. Anal. Calcd for C22H16N2OSe: C, 65.51; H, 4.00;
N, 6.95. Found: C, 65.66; H, 4.17; N, 6.83.
This compound was obtained in pure form (50% yield,
97.5 mg) after flash chromatography (light petroleum to light
petroleum/diethyl ether 80:20). Oil; Rf 0.65 (light petroleum/
diethyl ether 60:40); [a]2D3 þ110.5 (c 1.1, CHCl3); HPLC
(Chiralpack AD-H (250ꢂ4.6 mm ID), eluant: hexane/iPrOH
90:10, flow rate: 1 mL/min, UV detection at 230 nm), tR: mi-
4.5.5. (1S,2S)-1,2-Bis(3-methoxyphenyl)-2-(phenylseleno)-
ethanol (3e)
1
nor enantiomer 11.98 min, major enantiomer 13.29 min. H
This compound was obtained in pure form (50% yield,
103.5 mg) after flash chromatography (light petroleum to light
petroleum/diethyl ether 70:30). Oil; Rf 0.44 (light petroleum/
diethyl ether 60:40); [a]2D3 þ52.13 (c 1.1, CHCl3); HPLC
(Chiralpack AD-H (250ꢂ4.6 mm ID), eluent: hexane/iPrOH
90:10, flow rate: 1 mL/min, UV detection at 230 nm), tR: ma-
NMR (400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.35e7.25 (m,
2H, SePh), 7.25e7.0 (m, 5H, Ph, SePh), 6.90e6.70 (m, 6H,
Ph), 4.92 (d, 1H, J¼8.6 Hz, CHO), 4.30 (d, 1H, J¼8.6 Hz,
CHSe), 3.1 (br s, 1H, OH); 13C NMR (100 MHz, CDCl3,
1
25 ꢁC, TMS): d¼162.2 (d, JCF¼244.8 Hz), 161.6 (d,
4
1JCF¼245.0 Hz), 136.2 (d, JCF¼3 Hz), 135.5 (2C), 135.3 (d,
1
jor enantiomer 34.86 min, minor enantiomer 37.60 min. H
3
4JCF¼3 Hz), 129.9 (d, 2C, JCF¼8.0 Hz), 129.0 (2C), 128.3
NMR (400 MHz, CDCl3, 25 ꢁC, TMS): d¼7.45e7.35 (m,
2H, SePh), 7.35e6.95 (m, 5H, Ph, SePh), 6.75e6.45 (m,
6H, Ph), 4.96 (dd, 1H, J¼2.5, 8.6 Hz, CHO), 4.38 (d, 1H,
J¼8.6 Hz, CHSe), 3.64 (s, 3H, OMe), 3.60 (s, 3H, OMe),
2.66 (d, 1H, J¼2.5 Hz, OH); 13C NMR (100 MHz, CDCl3,
25 ꢁC, TMS): d¼159.3, 159.2, 142.4, 141.4, 135.3 (2C),
129.1, 129.0, 128.9 (2C), 128.7, 128.0, 120.9, 119.2, 113.9,
113.5, 112.8, 112.1, 76.3, 59.7, 55.1 (2C); MS (70 eV, EI):
m/z (%) 278 (58), 240 (24), 227 (23), 207 (42), 195 (38),
165 (19), 149 (13), 135 (92), 121 (100) 107 (23), 91 (18),
77 (25). Anal. Calcd for C22H22O3Se: C, 63.92; H, 5.36.
Found: C, 63.79; H, 5.18.
3
(d, 2C, JCF¼8.0 Hz), 128.2, 128.1, 115.0 (d, 4C,
2JCF¼21.3 Hz), 75.9, 58.7; MS (70 eV, EI): m/z (%) 390
(<1), 266 (47), 233 (18), 216 (40), 201 (19), 185 (44), 158
(27), 137 (13), 123 (79) 109 (100), 95 (33), 77 (21), 51
(12). Anal. Calcd for C20H16F2OSe: C, 61.70; H, 4.14. Found:
C, 61.61; H, 4.28.
4.5.3. (1S,2S)-1,2-Bis(4-bromophenyl)-2-(phenylseleno)-
ethanol (3c)
This compound was obtained in pure form (53% yield,
135.7 mg) after flash chromatography (light petroleum to light
petroleum/diethyl ether 90:10). Oil; Rf 0.44 (light petroleum/
diethyl ether 80:20); [a]D23 þ42.0 (c 1.1, CHCl3); HPLC (Chir-
alpack AD-H column (250ꢂ4.6 mm ID), eluant: hexane/
iPrOH 90:10, flow rate: 0.75 mL/min, UV detection at
230 nm), tR: minor enantiomer 21.41 min, major enantiomer
Acknowledgements
Financial support from MIUR, National Projects
PRIN2003, PRIN2005 and FIRB2001, and Consorzio CINM-
PIS is gratefully acknowledged.
1
23.76 min. H NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.35e7.20 (m, 9H, Ph, SePh), 7.07e7.01 (m, 2H, Ph),
6.85e6.80 (m, 2H), 4.95 (d, 1H, J¼8.7 Hz, CHO), 4.36 (d,
1H, J¼8.7 Hz, CHSe), 3.30 (br s, 1H, OH); 13C NMR
(100 MHz, CDCl3, 25 ꢁC, TMS): d¼139.7, 138.6, 135.5
(2C), 131.2 (4C), 130.0 (2C), 129.0 (2C), 128.4 (2C), 128.3,
127.9, 121.7, 120.9, 75.5, 58.4; MS (70 eV, EI): m/z (%) 355
(24) [MþꢀPhBr], 326 (86), 281 (36), 247 (40), 207 (69),
185 (100), 169 (59), 155 (41), 139 (16) 118 (18), 91 (25),
77 (39), 63 (16). Anal. Calcd for C20H16Br2OSe: C, 47.00;
H, 3.16. Found: C, 47.12; H, 3.27.
References and notes
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This compound was obtained in pure form (25% yield,
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CH2Cl2/MeOH 98:2). White solid; mp¼113e117 ꢁC; Rf 0.49
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3342
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