Lipase-catalyzed resolution of β-hydroxy selenides

Article abstract of DOI:10.1016/j.tetasy.2006.10.010

Eleven β-hydroxy selenides were kinetically resolved using an immobilized lipase (Amano PS-C II) in toluene in the presence of vinyl acetate at 30 °C. This approach provided, in several cases, both enantiomers in high enantiomeric excess. The role of the size of substituents and the behaviour of cyclic β-hydroxy selenides is also discussed. Enantiopure β-hydroxy selenides are useful building blocks. As an application of this chemistry, enantiopure (1S,2R)-indene oxide was obtained in one step from the proper enantiopure β-hydroxy selenide.

Full text of DOI:10.1016/j.tetasy.2006.10.010

Tetrahedron: Asymmetry 17 (2006) 2713–2721
Lipase-catalyzed resolution of b-hydroxy selenides
Michelangelo Gruttadauria,* Paolo Lo Meo, Serena Riela,
Francesca D’Anna and Renato Noto
`
`
Dipartimento di Chimica Organica ‘E. Paterno’, Universita di Palermo, Viale delle Scienze, Parco d’Orleans,
Pad. 17, I-90128 Palermo, Italy
Received 20 September 2006; accepted 6 October 2006
Abstract—Eleven b-hydroxy selenides were kinetically resolved using an immobilized lipase (Amano PS-C II) in toluene in the presence
of vinyl acetate at 30 °C. This approach provided, in several cases, both enantiomers in high enantiomeric excess. The role of the size of
substituents and the behaviour of cyclic b-hydroxy selenides is also discussed. Enantiopure b-hydroxy selenides are useful building
blocks. As an application of this chemistry, enantiopure (1S,2R)-indene oxide was obtained in one step from the proper enantiopure
b-hydroxy selenide.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
OH
R1
One of the most important strategies for the preparation of
non-racemic materials is the synthesis using the ‘natural
chiral pool’ as the main source of chirality.1 However, both
bioconversion,2 and asymmetric catalysis3 have emerged as
powerful methodologies to access new chiral synthons out
of the ‘chiral pool’. In the last few years, we have been
interested in the stereoselective synthesis using organosele-
nium compounds,4–7 biocatalysis8 or organocatalysis.9
Organoselenium chemistry is a powerful tool in organic
synthesis.10,11 In this context, b-hydroxy-selenides are use-
ful starting materials for several syntheses (Scheme 1).
They can be reduced to alcohols (route a),12 transformed
to allylic alcohols by oxidative elimination (route b),11 to
epoxides (route c),4,11 to allyl substituted alcohols (route
d),13 or substituted 1,3-oxazolidin-2-ones (route e).14 The
latter compounds are important molecules, which display
good antibacterial properties15,16 and are used in the phar-
maceutical chemistry.17,18 1,3-Oxazolidin-2-ones, known as
Evans’ chiral auxiliaries,19 have been used in a wide range
of asymmetric reactions, such as aldol condensations, alkyl-
ations and Diels–Alder reactions. Moreover, such com-
pounds, can also be employed for the synthesis of substi-
tuted 1,2-amino alcohols.14 Hydroxy selenides containing
an hydroxyl group in a suitable position were successfully
R2
b
OH
OH
O
SePh
R2
R1
R1
c
R1
a
R2
R2
e
d
O
OH
OH
O
NH2
R2
R1
R1
NR
R1
R2
R2
OH
SePh
O
SePh
n-1
R1
SePh
f
R1
HO
R1
+
O
n
n-2
Scheme 1. Transformations of b-hydroxy selenides.
used in the synthesis of substituted tetrahydrofurans
and tetrahydropyrans both in the exo and endo modes
(route f).20–22
*
Corresponding author. Tel.: +39 091 596919; fax: +39 091 596825;
e-mail: mgrutt@unipa.it
0957-4166/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2006.10.010

2714
M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
Chiral, non-racemic b-hydroxy selenides are usually ob-
tained using the following approaches. The natural chiral
pool as source of chirality is employed in the reactions car-
ried out using camphor diselenide as a source of electro-
philic selenium reagents. Good yields and moderate to
good facial selectivities were obtained in the asymmetric
selenohydroxylation of alkenes with camphorselenenyl
sulfate.23
OH
OH
OH
SePh
SePh
SePh
S
( )-1a
( )-1b
( )-anti-1c
OH
OH
OH
Enantiomerically enriched b-hydroxy selenides can be ob-
tained by regiospecific ring opening of the corresponding
chiral, non-racemic epoxides using sodium phenyl seleno-
late in ethanol.14 High selectivities were observed in sele-
SePh
SePh
SePh
nohydroxylation with
a chiral, non-racemic sulfur-
containing diselenide24 or with nitrogen containing chiral
diselenides, especially for styrene substrates.25 Enantio-
merically enriched b-hydroxy selenides were also obtained
after the kinetic resolution of allylic alcohols promoted
by a chiral electrophilic selenium reagent.26,27 Finally, the
enantioselective ring-opening reaction of meso-epoxides
with aryl selenols to give b-hydroxy selenides, using a
chiral Ti–Ga–Salen heterometallic catalyst, has been
performed.28
( )-anti-1d
( )-anti-1e
( )-anti-1f
OH
SePh
OH
OH
SePh
SePh
( )-anti-1g
( )-1h
( )-1i
Very few examples have been reported for the synthesis of
chiral, non-racemic b-hydroxy selenides by enzymatic
kinetic resolution. Synthetically useful chiral synthons
(R)- and (S)-2-cyclohexen-1-ols and (R)- and (S)-2-cyclo-
hepten-1-ols were prepared via enantioselective transesteri-
fication of racemic trans-2-(phenylseleno)cyclohexanol29
and trans-2-(phenylseleno)cycloheptanol30 with vinyl ace-
tate or butyrate using lipase, followed by selenoxide elimi-
nation and hydrolysis. More recently, investigations on the
enzymatic resolution of several racemic b-hydroxy sele-
nides using immobilized Candida antarctica lipase type B
(Novozym 435) have been reported.31
OH
OH
SePh
Cl
SePh
( )-1j
( )-1k
Scheme 2. b-Hydroxy selenides studied in this work.
O
R1
R2
Considering the synthetic usefulness of b-hydroxy selenides
and in connection with our synthetic investigations with
organoselenium compounds, we have started a study on
enzymatic resolution of such compounds.
PhSe or
PhSeOH/β-CD
OH
PhSeCl
H2O
R1
SePh
2. Results and discussion
R1
R2
R2
In order to study how the different nature of substituents
may affect the enzymatic resolution, we prepared several
model b-hydroxy selenides, both open-chain and annelated
(see Schemes 2 and 3).
R1MgBr
O
2.1. Synthesis of compounds 1a–k
SePh
Scheme 3. Synthetic routes to b-hydroxy selenides.
Compounds 1a, 1c, 1d and 1f were prepared by a hydroxy-
selenenylation reaction of the corresponding alkenes with
PhSeCl in acetonitrile/water.32 Compounds 1b, 1h and 1i
were prepared by the reaction of phenylselenenylacet-
aldehyde with the appropriate Grignard reagent.33
Compounds 1g and 1j were prepared by epoxide ring
opening with PhSeSePh and NaBH4.34 Compound 1k
was prepared by epoxide ring opening with PhSeOH in
the presence of b-cyclodextrin.35 Compound 1e was
prepared in situ from trans-2-bromo-1-indanol.36 Racemic
1,2-epoxy-1,2,3,4-tetrahydronaphthalene used for the syn-
thesis of compound 1g was prepared by epoxidation of the
corresponding alkene.37 The racemic 1,2-epoxy-5-hexene
used for the synthesis of compound 1j was commercially
available.

M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
2715
2.2. Enzymatic resolution
(entry 8). Compound ( )-1e bearing the OH and PhSe
groups on exchanged positions also gave excellent results
(entry 9). The reaction was faster compared to compound
( )-1d.
We started our investigations on the enzymatic resolution
using compound ( )-1a. We used PS-C II Amano lipase
and vinyl acetate in toluene. The first reaction was carried
out using a 0.44 M solution of substrate, a 0.4 mmol/50 mg
substrate/enzyme ratio and 3 equiv of vinyl acetate at
30 °C. After 48 h, the reaction did not take place (Table
1, entry 1). The reaction was repeated using a larger
amount of enzyme (100 mg) and 5 equiv of vinyl acetate.
After 48 h, we observed a low conversion (17%, entry 2).
Compound ( )-1f showed a behaviour similar to com-
pound ( )-1a. No reaction was observed (entry 10). The
reaction was repeated using a larger amount of lipase
and vinyl acetate at 60 °C (entries 11 and 12); a slow con-
version was observed. After 73 h, the conversion was 19%
with an ee value of 96%. However, a higher conversion
gave a lower ee value (conv. 31%, ee 76%). Conversely,
compound 1g gave excellent resolution (E = 500).
1
The conversion was determined from the H NMR of the
crude reaction mixture. Column chromatography was used
to separate the acetate from the alcohol. The acetate
showed a poor ee value (62%). Using the same amounts,
we carried out the reaction at a higher temperature
(60 °C). After 24 h, the conversion was high (47%) but, as
expected, poor ee values were observed for both the alcohol
and the acetate (entry 3). We also used different enzymes.
No enantioselectivity was observed with immobilized C.
antarctica lipase (Novozym 435), whereas poor ee values
were observed with Candida Rugosa lipase (CRL). In both
cases, low conversions were obtained (entries 4 and 5).
We then investigated compounds ( )-1h–j having a vinyl,
allyl and homoallyl substituent (entries 14–20). Compound
( )-1h gave ester 2h in good ee (93%) after a 25% conver-
sion. The reaction was complete after 2.5 h giving the alco-
hol and ester in an 80% ee value. Resolution of compound
( )-1i gave, after 4 h the alcohol and ester in a 49/51 ratio
and with high ee values (99% and 94%, respectively). Com-
pound ( )-1j gave almost complete conversion after 25 h
giving ester 2j in 89% ee. Finally, a high enantiomeric ratio
was obtained in the resolution of compound ( )-1k.
Compound ( )-1b was more reactive. Indeed, when carry-
ing out the reaction at 30 °C, compound ( )-1b gave a 50%
conversion after 48 h. However, in this case the ee value
was low (entry 6).
The enantiomeric excesses were determined by HPLC using
a Chiracel OD-H chiral column and n-hexane/i-propanol
as eluent (see Experimental).
Excellent resolution was found for compound ( )-1c. After
1 h the conversion was 50% with ee values >99% (entry 7).
Furthermore compound ( )-1d gave excellent resolution.
After 48 h, the conversion was 50% with ee values >99%
2.3. Configuration determination
Configurations were determined in selected cases (1a–b,d,f)
by the comparison with known products with or without
Table 1. Enantioselective lipase-catalyzed kinetic resolutions of compounds ( )-1a-ka
Entry
Compd
t (h)
c (%)
ee 1 (%)
ee 2 (%)
Conf. 1
(R)
Conf. 2
(S)
Eb
1
2c
3c,d
4c,e
5c,f
6
7
8
9
10
11c,d
12c,d
13
14
15
16
17
18
19
20
(
)-1a
48
48
24
60
24
48
1
48
1.7
120
73
161
30
1
17
47
15
<5
50
50
50
50
0
19
31
45
25
50
51
24
49
22
47
n.d.
14
44
0
n.d.
58
>99
>99
>99
—
22
34
82
31
80
>99
30
85
27
84
n.d.
62
46
0
72
—
5
4
—
—
(
(
(
(
(
)-1b
)-1c
)-1d
)-1e
)-1f
58
(S)
(R)
7
>99
>99
>99
—
96
76
>99
93
80
94
95
(S,S)
(S,S)
(S,S)
(R,R)
(R,R)
(R,R)
>200
>200
>200
—
(S,S)
(R,R)
61
10
(
(
)-1g
)-1h
(S,S)
(S)
(R,R)
(R)
>200
37
0.33
2.5
4
4
25
22
(
(
)-1i
)-1j
(S)
(S)
(R)
(R)
146
52
89
96
95
47
64
(
)-1k
0.5
2.5
(S)
(R)
104
a Conditions: 1 (0.4 mmol), lipase (50 mg), vinyl acetate (3 equiv), toluene (0.9 mL), 30 °C.
b E = ln [1 ꢀ c(1 + ee(2))]/ln [1 ꢀ c(1 ꢀ ee(2))], where c = ee(1)/[ee(1) + ee(2)].
c Lipase (100 mg), vinyl acetate (5 equiv).
d Temperature 60 °C.
e Novozym 435.
f CRL.

2716
M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
removal of the SePh group. Such investigations showed
that resolutions gave (S)-alcohols 1 and (R)-esters 2, except
for 1a. Thus for compounds 1c, 1e, 1g–k it was assumed
that the CHRSePh group was the large substituent.
OH
OH
OAc
SePh
SePh
SePh
+
( )-anti-1f
(S,S)-1f
(R,R)-2f
The configuration of enantiomerically enriched alcohol 1a
was determined by the comparison of the specific optical
rotation of (S)-1-phenyl-2-(phenylseleno)ethanol ([a] =
+14.4)14a with the enantiomerically enriched alcohol ob-
tained by us. This comparison proved that the enzyme
showed an enantiopreference for the (S)-alcohol, giving
enantiomerically enriched (R)-alcohol 1a and (S)-ester 2a
(Scheme 4).
Scheme 7. Lipase-catalyzed resolution of ( )-1f.
OH
SePh
R1
large
R2
(S)-1
+
OH
SePh
R1
OH
OH
OAc
R2
OAc
medium
SePh
SePh
SePh
SePh
( )-1
R1
+
R2
( )-1a
Scheme 4. Lipase-catalyzed resolution of ( )-1a.
(R)-1a
(S)-2a
(R)-2
Scheme 8. Kazlauskas’s rule.
For enantiomerically enriched 1b (Scheme 5), we tried a
correlation with enantiopure 1-thiophen-2-yl-ethanol how-
ever, the reductive elimination of the SePh group with
Bu3SnH and AIBN did not afford the expected product.
However, it has been reported that 2-ethylthio-1-thio-
phen-2-yl-ethanol was resolved with Humicola lanuginosa,
a lipase, which follows the Kazlauskas’s rule, to give
(S)-alcohol and (R)-ester.38 Moreover, compounds (R)-1a
and (S)-1b showed an opposite Cotton effect.
Only in the case of alcohol ( )-1a did the resolution give an
opposite enantiopreference. At lower temperatures the
bulky substituents of compound ( )-1a cause severe steric
repulsions. Indeed, on increasing the temperature, the
protein can fluctuate to relieve steric repulsion.
The CH2SePh group should be bulkier than the Ph group,
as can be seen by the comparison of the relevant MR values
(37.93 and 25.36, respectively).39 However, in the case of
compound ( )-1a the CH2SePh group was preferentially
fitted as a medium group, probably because of the free
rotation of the CH2 group. By changing the phenyl with
thiophen-2-yl, the enantiopreference was reversed. The res-
olution of 2-ethylthio-1-thiophen-2-yl-ethanol showed that
the CH2SCH2CH3 group acted as a large substituent
whereas the thiophen-2-yl acted as a medium one.38 We
believe that, in our case, the CH2SePh group was the
preferred large substituent. The steric requirement of the
thiophen-2-yl group is slightly smaller than that of a phenyl
ring (MR values 24.04 and 25.36, respectively).39 This may
explain the different behaviour between ( )-1a and ( )-1b
(Fig. 1).
OH
OAc
OH
SePh
SePh
SePh
+
S
S
S
( )-1b
(S)-1b
(R)-2b
Scheme 5. Lipase-catalyzed resolution of ( )-1b.
The configuration of enantiomerically pure alcohol
(S,S)-1d (Scheme 6) was proved by comparison of specific
rotation of 1-indanol, obtained after reductive elimination
of (S,S)-1d with Bu3SnH and AIBN.
OH
OH
OAc
SePh
SePh
medium
large
SePh
large
H
H
+
medium
O
O
H
H
H
H
S Se
Se
( )-anti-1d
(S,S)-1d
(R,R)-2d
Scheme 6. Lipase-catalyzed resolution of ( )-1d.
Figure 1. Size of substituents in compounds ( )-1a and ( )-1b.
Following the same procedure we proved that in the case of
compound ( )-1f, the lipase showed the same enantio-
preference. Indeed, we obtained (S,S)-alcohol 1f and
(R,R)-ester 2f (Scheme 7).
The annelation in compound ( )-1d gave a more rigid
molecule. In this case, the absence of rotation, makes the
CHSePh group bulkier than the fused phenyl ring.
These substrates follow the Kazlauskas’s rule,2c in which
the CH2SePh or CHSePh was the larger substituent
(Scheme 8).
Recently, a new transition-state model for the lipase-cata-
lyzed kinetic resolutions of secondary alcohols has been
proposed.40 In this model the C–O bond of the substrate

M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
2717
takes a gauche conformation with respect to the breaking
C–O bond, due to stereoelectronic effects, and the H atom
attached to the asymmetric C atom of the substrate is syn-
oriented towards the carbonyl O atom of the acetyl group.
In this model the faster-reacting enantiomer can direct the
larger substituent towards the external solvent (Fig. 2).
same reason, ( )-1e reacted faster as compared to ( )-
1d. A similar behaviour has been observed with com-
pound ( )-1g. Indeed, for the same reason it reacted at
30 °C while no reaction was observed for ( )-1f at the
same temperature. Moreover, the resolution of ( )-1g
was slower than ( )-1e, as expected. It should also be
noted that compounds ( )-1c and ( )-1e showed very
similar behaviour indicating that the fused phenyl ring
plays a minor role.
solvent
L
O
Among compounds ( )-1h–j, the higher E value has been
obtained with allyl substituted hydroxy selenide 1i. Also
the homoallyl group fits quite well in the stereoselectivity
pocket, while lower E values have been obtained with the
smaller vinyl group. It is interesting to note that compound
( )-1k, which possesses a substituent similar in size to the
vinyl group (MR vinyl: 10.99; MR CH2Cl 10.49) showed a
similar reactivity, but better resolution (E 1h 22; E 1k: 104).
H
H
O
O
H
Ser
M
N
N
selectivity
pocket
Figure 2. Ema’s model.
On the grounds of the PCL structure,41,42 this model and
simple computer molecular models, it could be seen that
1d fits very well into the enzyme pocket giving excellent
enantiopreference.
As a demonstration of the utility of enantiopure b-hydroxy
selenides, compound (S,S)-1d was transformed into enan-
tiopure (1S,2R)-indene oxide 3 (Scheme 9). This product
can be obtained by oxidation with oxone.43 We obtained
the indene oxide after the reaction with Me3OBF4 followed
by treatment with NaOH (75%).4
Also in the case of compound ( )-1f, the annelation makes
the CHSePh group bulkier than the fused phenyl ring giv-
ing good enantiopreference but, at low conversion. Indeed,
compound ( )-1f showed an intermediate behaviour be-
tween ( )-1a and ( )-1d both in terms of reactivity and
enantiopreference. Because of the annelation with the more
flexible cyclohexane ring in compound ( )-1f, the phenyl
ring can be considered a bulkier substituent than the phen-
yl ring of compound ( )-1d. As a consequence it does
not fit well (Fig. 3). In fact, no reaction was observed at
30 °C, whereas at 60 °C the reaction was slow. Following
Ema’s model, the large substituent is directed towards the
external solvent pool, whereas in the case of ( )-1d the
almost planar medium substituent fits perfectly in the
selectivity pocket. In the case of ( )-1f the medium
substituent does not fit.
OH
O
SePh
(S,S)-1d
(1S,2R)-3
Scheme 9. Synthesis of enantiopure indene oxide.
Enantiopure (1S,2R)-indene oxide can be transformed into
cis-1-amino-2-indanol,44 which has been used as a chiral
auxiliary for asymmetriÒc synthesis45–48 and is an important
component of Crixivan ,49 a potent inhibitor of the prote-
ase of human immunodeficiency virus (HIV).50,51
3. Conclusion
In conclusion we have shown that racemic b-hydroxy sele-
nides can be successfully resolved by lipase-catalyzed acet-
ylation using PS-C II lipase in the presence of vinyl acetate
with ee values up to >99%. These results allow us to broad-
en the poor set of examples reported in the literature.
Moreover, this study pointed out that bulky substituents,
such as phenyl and CH2SePh, have a detrimental effect
both on the reactivity and enantiopreference. However,
when the annelation reduces the steric hindrance of the
phenyl group, it leads to higher enantiopreference. More-
over, regioisomeric annelated compound having a greater
difference in sizes for substituents at the carbinol atom
showed high enantiopreference. Good enantiopreferences
were also observed in acyclic b-hydroxy selenides having
a vinyl, allyl, homoallyl and chloromethyl group. Finally,
even if the ee values were low, the opposite enantioprefer-
ence shown by phenyl and thiophen-2-yl substituted com-
pounds should be noted. This methodology offers an
interesting method for the synthesis of enantiopure b-
hydroxy selenides that are useful building blocks.
Figure 3.
In compound ( )-1e, the large substituent is the PhSe
group whereas the methylene group is the medium one.
The great difference in size for both groups may explain
the high enantioselectivity observed. Moreover, for the

2718
M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
4. Experimental
1 mL/min). 1H NMR (250 MHz): d 2.00 (s, 3H), 3.32
(dd, J = 12.7 and 6.1 Hz, 1H), 3.46 (dd, J = 12.7 and
7.9 Hz, 1H), 6.24 (dd, J = 7.9 and 6.1 Hz, 1H), 6.98 (dd,
J = 5.3 and 3.5 Hz, 1H), 7.08 (d, J = 3.5 Hz, 1H), 7.25–
7.30 (m, 4H), 7.53–7.57 (m, 2H); 13C NMR (62.5 MHz):
d 20.9, 33.2, 70.6, 125.6, 126.2, 126.6, 127.3, 129.1, 129.5,
133.1, 142.0, 169.8. IR (liquid film) 1740, 1577, 1535,
1477, 1437, 1229 cmꢀ1. Anal. Calcd for C14H14O2SSe: C,
51.69; H, 4.34. Found: C, 51.40; H, 4.25.
4.1. General
NMR spectra were recorded on a Bruker AC-E series
250 MHz spectrometer using CDCl3 as solvent. FT-IR
spectra were registered with a Shimadzu FTIR 8300 infra-
red spectrophotometer. Carbon and nitrogen content were
determined by combustion analysis in a Fisons EA 1108
elemental analyzer. Optical rotations were measured in
chloroform on a Jasco P1010 polarimeter. Chiral HPLC
was performed using a Shimadzu LC-10AD pump with a
SPD-M10A UV detector and Daicel column (OD-H).
28
4.2.5. (S,S)-2-(Phenylseleno)-cyclopentanol 1c. ½aꢁD
¼
þ19:7 (c 0.81, CHCl3); >99% ee. HPLC: (S,S)-1c
7.40 min, (R,R)-1c 5.80 min (n-hexane/i-PrOH 90/10;
1 mL/min). 1H NMR (250 MHz): d 1.52–1.81 (m, 4H),
1.96–2.10 (m, 1H), 2.18–2.30 (m, 1H), 2.80 (s, 1H, OH),
3.39–3.46 (m, 1H), 4.12–4.17 (m, 1H), 7.17–7.34 (m, 3H),
7.52–7.58 (m, 2H); 13C NMR (62.5 MHz): d 21.9, 31.0,
32.7, 49.4, 78.5, 127.1, 128.9, 129.4, 133.8. IR (liquid film)
3332, 1577, 1477, 1437 cmꢀ1. Anal. Calcd for C11H14OSe:
C, 54.78; H, 5.85. Found: C, 54.60; H, 5.66.
4.2. Enzymatic resolution procedure
To a solution of alcohol ( )-1 (0.4 mmol) in toluene
(0.9 mL) at 30 °C, vinyl acetate (1.2 mmol) and PS-C II
lipase (50 mg) were added. The reaction was monitored
by HPLC, then taken up with diethyl ether, filtered and
the solvent removed under reduced pressure. The residue
was checked by NMR then purified by silica gel chroma-
tography using light petroleum/ethyl acetate as eluent.
4.2.6. (R,R)-2-(Phenylseleno)-cyclopentyl acetate 2c.
28
½aꢁD ¼ ꢀ2:2 (c 1.02, CHCl3); >99% ee. HPLC: (R,R)-2c
5.45 min, (S,S)-2c 5.35 min (n-hexane/i-PrOH 98/2; 1 mL/
26
1
4.2.1. (R)-1-Phenyl-2-(phenylseleno)ethanol 1a. ½aꢁD
¼
min). H NMR (250 MHz): d 1.65–1.80 (m, 4H), 1.94 (s,
ꢀ8:6 (c 0.90, CHCl3); 44% ee. HPLC: (R)-1a 12.22 min,
3H), 2.14–2.25 (m, 2H), 3.58–3.65 (m, 1H), 5.10–5.16 (m,
1H), 7.25–7.29 (m, 3H), 7.55–7.59 (m, 2H); 13C NMR
(62.5 MHz): d 21.1, 22.5, 30.9, 31.1, 45.8, 81.4, 127.5,
129.0, 129.2, 134.2, 170.2. IR (liquid film) 1738, 1577,
1477, 1437, 1371, 1238 cmꢀ1. Anal. Calcd for C13H16O2Se:
C, 55.13; H, 5.69. Found: C, 55.32; H, 5.87.
1
(S)-1a 11.56 min (n-hexane/i-PrOH 90/10; 1 mL/min). H
NMR (250 MHz): d 3.21 (dd, J = 12.6 and 8.9 Hz, 1H),
3.32 (dd, J = 12.6 and 4.1 Hz, 1H), 3.40 (s, 1H, OH),
4.82 (dd, J = 8.9 and 4.1 Hz, 1 H), 7.31–7.39 (m, 8H),
7.57–7.61 (m, 2H); 13C NMR (62.5 MHz): d 38.2, 72.6,
126.1, 127.3, 128.0, 128.6, 129.4, 129.8, 133.1, 142.9. IR
(liquid film) 3418, 1577, 1493, 1477, 1437 cmꢀ1. Anal.
Calcd for C14H14OSe: C, 60.66; H, 5.09. Found: C,
60.49; H, 5.01.
4.2.7.
(S,S)-2,3-Dihydro-2-(phenylseleno)-1H-inden-1-ol
26
1d. ½aꢁD ¼ þ3:7 (c 0.83); >99% ee. HPLC: (S,S)-1d
15.48 min, (R,R)-1d 9.04 min (n-hexane/i-PrOH 90/10;
1
1 mL/min). Mp 101 °C. H NMR (250 MHz): d 2.26 (s,
4.2.2. (S)-1-Phenyl-2-(phenylseleno)ethyl acetate 2a.
1H, OH), 2.96 (dd, J = 16.3 and 7.6 Hz, 1H), 3.46 (dd,
J = 16.3 and 7.7 Hz, 1H), 3.78 (ddd, J = 7.7, 7.6 and
5.8 Hz, 1H), 5.19 (d, J = 5.8 Hz, 1H), 7.18–7.40 (m, 7H),
7.63–7.67 (m, 2H); 13C NMR (62.5 MHz): d 37.7, 49.3,
81.5, 124.2, 124.5, 127.2, 127.7, 128.6, 129.2, 134.7, 141.0,
143.1. IR (nujol) 3248, 1336, 1068 cmꢀ1. Anal. Calcd for
C15H14OSe: C, 62.29; H, 4.88. Found: C, 62.40; H, 4.80.
26
½aꢁD ¼ þ13:2 (c 1.38, CHCl3); 46% ee. HPLC: (S)-2a
6.09 min, (R)-2a 6.60 min (n-hexane/i-PrOH 90/10; 1 mL/
min). 1H NMR (250 MHz): d 2.00 (s, 3H), 3.21 (dd,
J = 12.8 and 6.0 Hz, 1H), 3.36 (dd, J = 12.8 and 7.9 Hz,
1H), 5.93 (dd, J = 7.9 and 6.0 Hz, 1H), 7.22–7.32 (m,
8H), 7.47–7.51 (m, 2H); 13C NMR (62.5 MHz): d 21.0,
33.4, 75.2, 126.6, 127.2, 128.4, 128.5, 129.1, 129.9, 133.1,
139.5, 169.5. IR (liquid film) 1740, 1577, 1493, 1477,
1454, 1437, 1234 cmꢀ1. Anal. Calcd for C16H16O2Se: C,
60.19; H, 5.05. Found: C, 60.30; H, 5.17.
4.2.8.
(R,R)-2,3-Dihydro-2-(phenylseleno)-1H-inden-1-yl
25
acetate 2d. ½aꢁD ¼ ꢀ83:6 (c 1.95, CHCl3); >99% ee deter-
mined as alcohol. 1H NMR (250 MHz): d 1.94 (s, 3H), 2.92
(dd, J = 16.6 and 5.4 Hz, 1H), 3.50 (dd, J = 16.6 and
7.5 Hz, 1H), 3.78 (ddd, J = 7.5, 5.4 and 4.2 Hz, 1H), 6.24
(d, J = 4.2 Hz, 1H), 7.14–7.31 (m, 7H), 7.54–7.58 (m,
2H). 13C NMR (62.5 MHz): d 20.9, 37.8, 44.8, 82.7,
124.6, 125.5, 127.1, 127.8, 128.3, 129.0, 129.1, 134.9,
139.9, 142.2. IR (liquid film) 1732, 1608, 1577, 1437,
1232 cmꢀ1. Anal. Calcd for C17H16O2Se: C, 61.64; H,
4.87. Found: C, 61.74; H, 4.99.
4.2.3.
(S)-2-(Phenylseleno)-1-thiophen-2-yl-ethanol
1b.
25
½aꢁD ¼ þ4:1 (c 0.73, CHCl3); 58% ee. HPLC: (S)-1b
52.85 min, (R)-1b 57.95 min (n-hexane/i-PrOH 98/2;
1 mL/min). 1H NMR (250 MHz): d 3.22 (s, 1H, OH),
3.28–3.45 (m, 2H), 5.05 (dd, J = 8.2 and 4.6 Hz, 1H),
6.96–6.99 (m, 2H); 7.24–7.33 (m, 4H), 7.53–7.59 (m, 2H);
13C NMR (62.5 MHz): d 38.1, 68.8, 124.1, 124.9, 126.8,
127.5, 129.3, 133.2, 146.6. IR (liquid film) 3408, 1577,
1493, 1477, 1437 cmꢀ1. Anal. Calcd for C12H12OSSe: C,
50.88; H, 4.27. Found: C, 50.69; H, 4.21.
4.2.9. (S,S)-2,3-Dihydro-1-(phenylseleno)-1H-inden-2-ol 1e.
26
½aꢁD ¼ ꢀ58:1 (c 1.01, CHCl3); >99% ee determined as ester.
1
Mp 62 °C. H NMR (250 MHz): d 2.73 (d, J = 16.6 Hz,
4.2.4. (R)-2-(Phenylseleno)-1-thiophen-2-yl-ethyl acetate
1H), 3.22 (dd, J = 16.6 and 5.3 Hz, 1H), 3.40 (s, 1H,
OH), 4.50 (d, J = 5.3 Hz, 1H), 4.63 (s, 1H), 7.25–7.40 (m,
7H), 7.56–7.58 (m, 2H); 13C NMR (62.5 MHz): d 39.6,
26
2b. ½aꢁD ¼ ꢀ20:4 (c 0.93, CHCl3); 58% ee. HPLC: (R)-
2b 6.50 min, (S)-2b 6.30 min (n-hexane/i-PrOH 90/10;

M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
2719
53.4, 78.2, 124.9, 125.4, 126.7, 127.3, 127.6, 128.7, 129.2,
133.8, 140.4, 140.6. IR (film) 3346, 1577, 1477 cmꢀ1. Anal.
Calcd for C15H14OSe: C, 62.29; H, 4.88. Found: C, 62.44;
H, 4.79.
(ddd, J = 16.9, 6.1 and 2.5 Hz, 1H), 2.97 (ddd, J = 16.9,
12.0 and 6.0 Hz, 1H), 4.70 (s, 1H), 5.31–5.35 (m, 1H),
7.07–7.20 (m, 3H), 7.30–7.42 (m, 4H), 7.61.7.65 (m 2H);
13C NMR (62.5 MHz): d 21.2, 22.5, 24.0, 44.7, 72.5,
126.1, 127.0, 128.0, 128.8, 129.2, 129.8, 131.2, 133.4,
134.4, 136.0, 170.5. IR (liquid film) 1732, 1577, 1493,
1477, 1454, 1437, 1373, 1234 cmꢀ1. Anal. Calcd for
C18H18O2Se: C, 62.61; H, 5.25. Found: C, 62.75; H, 5.31.
4.2.10. (R,R)-2,3-Dihydro-1-(phenylseleno)-1H-inden-2-yl
27
acetate 2e. ½aꢁD ¼ þ25:6 (c 1.19, CHCl3); >99% ee.
HPLC: (R,R)-2e 6.90 min, (S,S)-2e 7.30 min (n-hexane/i-
1
PrOH 98/2; 1 mL/min). Mp 58 °C. H NMR (250 MHz):
26
d 1.97 (s, 3H), 2.85 (d, J = 17.3 Hz, 1H), 3.28 (dd,
J = 17.3 and 5.7 Hz, 1H), 4.78 (d, J = 1.4 Hz, 1H), 5.54
(ddd, J = 17.3, 5.7 and 1.4 Hz, 1H), 7.19–7.36 (m, 7H),
7.51–7.55 (m, 2H); 13C NMR (62.5 MHz): d 21.1, 37.7,
50.6, 81.1, 124.6, 125.3, 127.1, 128.0, 128.1, 128.4, 128.9,
135.1, 140.6, 140.8, 170.4. IR (film) 1738, 1577, 1475,
1371, 1238 cmꢀ1. Anal. Calcd for C17H16O2Se: C, 61.64;
H, 4.87. Found: C, 61.79; H, 5.01.
4.2.15. (S)-1-(Phenylseleno)-but-3-en-2-ol (1h). ½aꢁD ¼
þ40:4 (c 0.51, CHCl3); 80% ee determined as ester. 1H
NMR (250 MHz): d 2.55 (s, 1H, OH), 3.00 (dd, J = 12.6
and 8.0 Hz, 1H), 3.14 (dd, J = 12.6 and 4.5 Hz, 1H),
4.19–4.27 (m, 1H), 5.16 (ddd, J = 10.4, 1.5 and 1.5 Hz,
1H), 5.30 (ddd, J = 17.0, 1.5 and 1.5 Hz, 1H), 5.88 (ddd,
J = 17.0, 10.4 and 5.7 Hz, 1H), 7.24–7.30 (m, 3H), 7.53–
7.57 (m, 2H); 13C NMR (62.5 MHz): d 35.6, 70.8, 115.6,
126.9, 128.9, 129.3, 132.6, 138.7. IR (liquid film) 3387,
1577, 1477, 1437 cmꢀ1. Anal. Calcd for C10H12OSe: C,
52.87; H, 5.32. Found: C, 53.00; H, 5.37.
4.2.11. (S,S)-1,2,3,4-Tetrahydro-2-(phenylseleno)naphthal-
28
en-1-ol 1f. ½aꢁD ¼ ꢀ9:7 (c 1.27, CHCl3); 34% ee deter-
mined as ester. 1H NMR (250 MHz): d 1.97 (dddd,
J = 20.2, 13.6, 8.1 and 6.7 Hz, 1H), 2.37–2.49 (m, 1H),
2.77 (s, 1H, OH), 2.83–2.94 (m, 2H), 3.49 (ddd, J = 10.3,
7.8 and 3.3 Hz, 1H), 4.71 (d, J = 7.8 Hz, 1H), 7.06–7.10
(m, 1H), 7.20–7.35 (m, 5H), 7.50–7.55 (m, 1H), 7.61–7.66
(m, 2H); 13C NMR (62.5 MHz): d 27.6, 28.7, 48.7, 71.7,
126.4, 127.2, 127.6, 128.1, 128.2, 128.6, 129.2, 135.5,
135.6, 136.9. IR (liquid film) 3385, 1577, 1477,
1437 cmꢀ1. Anal. Calcd for C16H16OSe: C, 63.37; H,
5.32. Found: C, 63.50; H, 5.37.
4.2.16. (R)-1-(Phenylseleno)-but-3-en-2-yl acetate 2h.
26
½aꢁD ¼ ꢀ5:4 (c 0.99, CHCl3); 80% ee. HPLC: (R)-2h
5.20 min, (S)-2h 4.69 min (n-hexane/i-PrOH 90/10; 1 mL/
1
min). H NMR (250 MHz): d 2.00 (s, 3H), 3.04–3.20 (m,
2H), 5.24 (d, J = 10.7 Hz, 1H), 5.31 (d, J = 16.8 Hz, 1H),
5.40–5.48 (m, 1H), 5.86 (ddd, J = 16.8, 10.7 and 6.0 Hz,
1H), 7.24–7.29 (m, 3H), 7.51–7.57 (m, 2H); 13C NMR
(62.5 MHz): d 20.9, 31.4, 73.8, 117.9, 127.2, 129.1, 129.8,
133.0, 135.2, 169.9. IR (liquid film) 1736, 1577, 1477,
1437, 1236 cmꢀ1. Anal. Calcd for C12H14O2Se: C, 53.54;
H, 5.24. Found: C, 53.62; H, 5.14.
4.2.12. (R,R)-1,2,3,4-Tetrahydro-2-(phenylseleno)naphthal-
26
en-1-yl acetate 2f. ½aꢁD ¼ ꢀ51:2 (c 0.26, CHCl3); 96%
26
ee. HPLC: (R,R)-2f 7.70 min, (S,S)-2f 9.90 min (n-hex-
ane/i-PrOH 98/2; 1 mL/min). 1H NMR (250 MHz): d
2.01–2.10 (m, 1H, overlapped with 2.04 s, 3H), 2.40–2.52
(m, 1H), 2.86–3.05 (m, 2H), 3.77 (ddd, J = 8.4, 5.1 and
3.2 Hz, 1H), 6.13 (d, J = 5.1 Hz, 1H), 7.14–7.34 (m, 7H),
7.62–7.66 (m, 2H); 13C NMR (62.5 MHz): d 21.2, 25.5,
26.9, 43.2, 73.1, 126.4, 127.7, 128.3, 128.4, 128.9, 129.1,
129.8, 133.0, 134.6, 136.6, 170.5. IR (liquid film) 1732,
1577, 1477, 1369, 1232 cmꢀ1. Anal. Calcd for C18H18O2Se:
C, 62.61; H, 5.25. Found: C, 62.79; H, 5.14.
4.2.17. (S)-1-(Phenylseleno)-pent-4-en-2-ol 1i. ½aꢁD ¼
þ30:65 (c 0.65, CHCl3); >99% ee. HPLC: (S)-1i
19.25 min, (R)-1i 18.40 min (n-hexane/i-PrOH 98/2;
1 mL/min). 1H NMR (250 MHz): d 2.30–2.41 (m, 2H),
2.82 (s, 1H, OH), 2.94 (dd, J = 12.7 and 7.9 Hz, 1H),
3.11 (dd, J = 12.7 and 4.3 Hz, 1H), 3.75–3.85 (m, 1H),
5.07–5.15 (m, 2H), 5.72–5.87 (m, 1H), 7.22–7.26 (m, 3H),
7.51–7.55 (m, 2H); 13C NMR (62.5 MHz): d 35.6, 40.6,
69.2, 117.8, 126.9, 128.9, 129.3, 132.6, 133.9. IR (liquid
film) 3423, 1577, 1477, 1437 cmꢀ1. Anal. Calcd for
C11H14OSe: C, 54.78; H, 5.85. Found: C, 54.90; H, 5.92.
4.2.13. (S,S)-1,2,3,4-Tetrahydro-1-(phenylseleno)naphthal-
22
en-2-ol 1g. ½aꢁD ¼ ꢀ20:9 (c 0.37, CHCl3); 82% ee. HPLC:
4.2.18. (R)-1-(Phenylseleno)-pent-4-en-2-yl acetate 2i.
26
(S,S)-1g 28.1 min, (R,R)-1g 48.4 min (n-hexane/i-PrOH 98/
½aꢁD ¼ ꢀ16:2 (c 0.87, CHCl3); 94% ee. HPLC: (R)-2i
1
2; 1 mL/min). H NMR (250 MHz): d 1.18–1.94 (m, 1H),
4.90 min, (S)-2i 4.62 min (n-hexane/i-PrOH 90/10; 1 mL/
1
2.35 (s, 1H, OH), 2.38–2.51 (m, 1H), 2.76 (ddd, J = 17.2,
5.8 and 5.8 Hz, 1H), 2.95 (ddd, J = 17.2, 9.2 and 5.8 Hz,
1H), 4.12–4.18 (m, 1H), 4.50 (d, J = 4.7 Hz, 1H), 7.08–
7.33 (m, 7H), 7.53–7.58 (m, 2H); 13C NMR (62.5 MHz):
d 24.7, 26.1, 50.5, 69.8, 126.1, 126.9, 127.9, 128.7, 129.1,
129.4, 131.4, 133.8, 134.5, 136.2. IR (liquid film) 3385,
1577, 1493, 1475, 1452, 1437 cmꢀ1. Anal. Calcd for
C16H16OSe: C, 63.37; H, 5.32. Found: C, 63.30; H, 5.29.
min). H NMR (250 MHz): d 1.94 (s, 3H), 2.22–2.54 (m,
2H), 3.07–3.10 (m, 2H), 5.07–5.12 (m, 2H), 5.65–5.80 (m,
1H), 7.24–7.28 (m, 3H), 7.53–7.57 (m, 2H); 13C NMR
(62.5 MHz): d 20.9, 30.9, 38.1, 72.5, 118.4, 127.1, 129.1,
129.9, 132.9, 170.3. IR (liquid film) 1740, 1577, 1477,
1493, 1436, 1371, 1234 cmꢀ1. Anal. Calcd for C13H16O2Se:
C, 55.13; H, 5.69. Found: C, 55.24; H, 5.84.
24
4.2.19.
(S)-1-(Phenylseleno)-hex-5-en-2-ol
1j. ½aꢁD ¼
4.2.14. (R,R)-1,2,3,4-Tetrahydro-1-(phenylseleno)naphthal-
þ36:3 (c 0.83, CHCl3); 85% ee. HPLC: (S)-1j 14.41 min,
(R)-1j 15.67 min (n-hexane/i-PrOH 98/2; 1 mL/min). 1H
NMR (250 MHz): d 1.59–1.69 (m, 2H), 2.08–2.25 (m,
2H), 2.93 (dd, J = 12.4 and 7.9 Hz, 1H), 3.10 (dd,
J = 12.4 and 4.5 Hz, 1H), 3.13 (s, 1H, OH), 3.70–3.80 (m,
21
en-2-yl acetate 2g. ½aꢁD ¼ ꢀ66:4 (c 0.33, CHCl3); >99%
ee. HPLC: (R,R)-2g 12.70 min, (S,S)-2g 13.53 min (n-hex-
1
ane/i-PrOH 99.5/0.5; 1 mL/min). H NMR (250 MHz): d
1.95 (s, 3H), 1.95–2.08 (m, 1H), 2.46–2.60 (m, 1H), 2.76

2720
M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
Res. 2000, 33, 421–431; (e) Regan, A. C. J. Chem. Soc.,
Perkin Trans. 1 1998, 1151–1166.
4. Riela, S.; Aprile, C.; Gruttadauria, M.; Lo Meo, P.; Noto, R.
Molecules 2005, 10, 383–393.
5. Gruttadauria, M.; Aprile, C.; Lo Meo, P.; Riela, S.; Noto, R.
Heterocycles 2004, 63, 681–690.
6. Aprile, C.; Gruttadauria, M.; Amato, M. E.; D’Anna, F.; Lo
Meo, P.; Riela, S.; Noto, R. Tetrahedron 2003, 59, 2241–2251.
7. Gruttadauria, M.; Aprile, C.; Noto, R. Tetrahedron Lett.
2002, 43, 1669–1672, and references cited therein.
8. Gruttadauria, M.; Lo Meo, P.; Noto, R. Tetrahedron Lett.
2004, 45, 83–85.
2H), 4.94–5.07 (m, 2H), 5.72–5.87 (m, 1H), 7.21–7.27 (m,
3H), 7.51–7.55 (m, 2H); 13C NMR (62.5 MHz): d 29.6,
35.3, 36.2, 69.2, 114.5, 126.6, 128.7, 129.4, 132.3, 137.7.
IR (liquid film) 3414, 1639, 1577, 1477, 1437 cmꢀ1. Anal.
Calcd for C12H16OSe: C, 56.47; H, 6.32. Found: C,
56.38, H, 6.25.
4.2.20. (R)-1-(Phenylseleno)-hex-5-en-2-yl acetate 2j.
25
½aꢁD ¼ þ3:2 (c 0.49, CHCl3); 95% ee. HPLC: (R)-2j
5.66 min, (S)-2j 4.80 min (n-hexane/i-PrOH 98/2; 1 mL/
1
min). H NMR (250 MHz): d 1.76–1.84 (m, 2H), 1.95 (s,
9. Gruttadauria, M.; Riela, S.; Aprile, C.; Lo Meo, P.; D’Anna,
F.; Noto, R. Adv. Synth. Catal. 2006, 348, 82–92.
10. Wirth, T. Organoselenium Chemistry, Modern Developments
in Organic Chemistry. Top. Curr. Chem.; Springer: Berlin,
2000 Vol. 208.
3H), 2.03–2.13 (m, 2H), 3.09 (d, J = 6.0 Hz, 2H), 4.95–
5.08 (m, 2H), 5.70–5.84 (m, 1H), 7.25–7.30 (m, 3H),
7.52–7.57 (m, 2H); 13C NMR (62.5 MHz): d 21.0, 29.5,
31.5, 32.9, 72.9, 115.2, 127.1, 129.1, 129.9, 132.9, 137.4,
170.5. IR (liquid film) 1740, 1641, 1577, 1477, 1437, 1371,
1238 cmꢀ1. Anal. Calcd for C14H18O2Se: C, 56.57; H,
6.10. Found: C, 56.74; H, 6.22.
11. Back, T. G. Organoselenium Chemistry; Oxford University
Press: Oxford, UK, 1999.
12. Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. Tetrahedron: Asymmetry 1998, 9, 919–922.
13. Tiecco, M.; Testaferri, M.; Bagnoli, L.; Terlizzi, R.; Tempe-
rini, A.; Marini, F.; Santi, C.; Scarponi, C. Tetrahedron:
Asymmetry 2004, 15, 1949–1955.
14. (a) Tiecco, M.; Testaferri, L.; Temperini, A.; Bagnoli, L.;
Marini, F.; Santi, C. Chem. Eur. J. 2004, 10, 1752–1764; (b)
Wirth, T.; Fragale, G.; Spichty, M. J. Am. Chem. Soc. 1998,
120, 3376–3381.
15. Gregory, W. A.; Tritelli, D. R.; Wang, C. L.; Wuonola, M.
A.; McRipley, R. J.; Eustice, D. C.; Eberly, V. S.; Bartholo-
mew, P. T.; Slee, A. M.; Forbes, M. J. Med. Chem. 1989, 32,
1673–1681.
4.2.21.
(S)-1-Chloro-3-(phenylseleno)-propan-2-ol
1k.
23
½aꢁD ¼ þ19:25 (c 0.32, CHCl3); 84% ee determined as ester.
1H NMR (250 MHz): d 2.66 (br s, 1H, OH), 3.07 (dd,
J = 12.8 and 7.1 Hz, 1H), 3.16 (dd, J = 13.2 and 5.6 Hz,
1H), 3.68 (d, J = 4.9 Hz, 2H), 3.90–4.00 (m, 1H), 7.26–
7.32 (m, 3H), 7.52–7.59 (m, 2H); 13C NMR (62.5 MHz):
d 32.3, 48.3, 70.0, 127.5, 128.8, 129.3, 133.0. IR (liquid film)
3400, 1577, 1477, 1437 cmꢀ1. Anal. Calcd for C9H11ClOSe:
C, 43.31; H, 4.44. Found: C, 43.44; H, 4.52.
16. Barbachyn, M. R.; Ford, C. W. Angew. Chem., Int. Ed. 2003,
42, 2010–2023.
17. Grabley, S.; Kluge, H.; Hoppe, H. U. Angew. Chem., Int. Ed.
Engl. 1987, 26, 690–693.
18. Mori, K.; Seki, M. Eur. J. Org. Chem. 1999, 2965–2967.
19. Evans, D. A.; Bartroli, J.; Shih, T. J. Am. Chem. Soc. 1981,
103, 2127–2129.
20. Gruttadauria, M.; Aprile, C.; D’Anna, F.; Lo Meo, P.; Riela,
S.; Noto, R. Tetrahedron 2001, 57, 6815–6822.
21. Gruttadauria, M.; Lo Meo, P.; Noto, R. Tetrahedron 2001,
57, 1819–1826.
4.2.22. (R)-1-Chloro-3-(phenylseleno)-propan-2-yl acetate
23
2k. ½aꢁD ¼ ꢀ8:8 (c 0.30, CHCl3); 95% ee. HPLC: (R)-2k
6.27 min, (S)-2k 5.70 min (n-hexane/i-PrOH 90/10; 1 mL/
min). 1H NMR (250 MHz): d 1.92 (s, 3H), 3.10 (d,
J = 6.3 Hz, 2H), 3.70 (J = 4.8 Hz, 1H), 5.08 (dddd,
J = 6.3, 6.3, 4.8 and 4.8 Hz, 1H), 7.18–7.24 (m, 3H), 7.49–
7.52 (m, 2H); 13C NMR (62.5 MHz): d 20.8, 28.1, 44.9,
72.2, 127.5, 129.0, 129.3, 133.1, 170.1. IR (liquid film)
1738, 1578, 1478, 1438, 1372 cmꢀ1. Anal. Calcd for
C11H13ClO2Se: C, 45.30; H, 4.49. Found: C, 45.434; H, 4.52.
22. Gruttadauria, M.; Aprile, C.; Riela, S.; Noto, R. Tetrahedron
Lett. 2001, 42, 2213–2215.
23. Tiecco, M.; Testaferri, L.; Santi, C.; Marini, F.; Bagnoli, L.;
Temperini, A.; Tomassini, C. Eur. J. Org. Chem. 1998, 2275–
2277.
24. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini,
F.; Bagnoli, L.; Temperini, A. Chem. Eur. J. 2002, 8, 1118–
1124.
25. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini,
F.; Bagnoli, L.; Temperini, A. Tetrahedron: Asymmetry 2000,
11, 4645–4650.
Acknowledgements
Financial support from the University of Palermo (funds
for selected research topics) and Italian MIUR within the
National Research Project ‘Non-aromatic heterocycles in
stereocontrolled processes’ is gratefully acknowledged.
References
26. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Bonini,
R.; Marini, F.; Bagnoli, L.; Temperini, A. Org. Lett. 2004, 6,
4751–4753.
27. Santi, C.; Tiecco, M.; Testaferri, L.; Tomassini, C.; Marini,
F.; Bagnoli, L.; Temperini, A. Phosphorus, Sulfur Silicon
Relat. Elem. 2005, 180, 1071–1075.
28. Yang, M.; Zhu, C.; Yuan, F.; Huang, Y.; Pan, Y. Org. Lett.
2005, 7, 1927–1930.
29. Izumi, T.; Nakamura, T.; Eda, Y. J. Chem. Tech. Biotechnol.
1993, 57, 175–180.
1. Blaser, H. U. Chem. Rev. 1992, 92, 935–952.
2. Selected examples: (a) Santaniello, E.; Ferraboschi, P.;
Grisenti, P.; Manzocchi, A. Chem. Rev. 1992, 92, 1071–
1140; (b) Ferrero, M.; Gotor, V. Chem. Rev. 2000, 100, 4319–
4347; (c) Bornscheuer, U. T.; Kazlauskas, R. J. In Hydrolases
in Organic Synthesis; Wiley-VCH, Ed.; Wiley: Weinheim,
1999; (d) Pamies, O.; Backvall, J.-E. Chem. Rev. 2003, 103,
3247–3262.
3. Selected examples: (a) Dieguez, M.; Pamies, O.; Claver, C.
Chem. Rev. 2004, 104, 3189–3216; (b) Chen, Y.; Yekta, S.;
Ydin, A. K. Chem. Rev. 2003, 103, 3155–3212; (c) Tian, S.-K.;
Chen, Y.; Hang, J.; Tang, L.; McDaid, P.; Deng, L. Acc.
Chem. Res. 2004, 37, 621–631; (d) Jacobsen, E. N. Acc. Chem.
30. Izumi, T.; Eda, Y. J. Chem. Tech. Biotechnol. 1995, 62, 25–29.
31. Costa, C. E.; Clososki, G. C.; Barchesi, H. B.; Zanotto, S. P.;
Nascimento, M. G.; Comasseto, J. V. Tetrahedron: Asym-
metry 2004, 15, 3945–3954.

M. Gruttadauria et al. / Tetrahedron: Asymmetry 17 (2006) 2713–2721
2721
32. For general procedure see Ref. 6.
33. For general procedure see: Baudat, R.; Petrzilka, M. Helv.
Chim. Acta 1979, 62, 1406–1410.
34. For general procedure see: Gruttadauria, M.; Lo Meo, P.;
Noto, R. Tetrahedron 1999, 55, 4769–4782.
35. Sridhar, R.; Srinivas, B.; Surendra, K.; Srilakshmi Krishna-
veni, N.; Rama Rao, K. Tetrahedron Lett. 2005, 46, 8837–
8839.
43. Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. J. Org. Chem. 1995, 60, 8412–8413.
44. Senanayake, C. H.; Roberts, F. E.; DiMichele, L. M.; Ryan,
K. M.; Liu, J.; Fredenburgh, L. E.; Foster, B. S.; Douglas, A.
W.; Larsen, R. D.; Verhoeven, T. R.; Reider, P. J. Tetra-
hedron Lett. 1995, 36, 3993–3996.
45. Gallou, I.; Senanayake, C. H. Chem. Rev. 2006, 206, 2843–
2874.
36. Sugimoto, I.; Shuto, S.; Matsuda, A. J. Org. Chem. 1999, 64,
7153–7157.
46. Palmer, M.; Walsgrove, T.; Wills, M. J. Org. Chem. 1997, 62,
5226–5228.
37. Lane, B. S.; Vogt, M.; DeRose, V. J.; Burgess, K. J. Am.
Chem. Soc. 2002, 124, 11946–11954.
38. Chimni, S. S.; Singh, S. S.; Kumar, S.; Mahajan, S.
Tetrahedron: Asymmetry 2002, 13, 511–517.
39. Hansch, C.; Leo, A. J. Substituent Constants for Correla-
tion Analysis in Chemistry and Biology; Wiley: New York,
1979.
40. 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.
41. Kim, K. K.; Song, H. K.; Shin, D. H.; Hwang, K. Y.; Suh, S.
W. Structure 1997, 5, 173–185.
47. Faller, J. W.; Lavoie, A. R. Org. Lett. 2001, 3, 3703–3706.
48. Di Simone, B.; Savoia, D.; Tagliavini, E.; Umani-Ronchi, A.
Tetrahedron: Asymmetry 1995, 6, 301–306.
49. Ghosh, A. K.; Kincaid, J. F.; Haske, M. G. Synthesis 1997,
541–544.
50. Vacca, J. P.; Dorsey, B. D.; Schleif, W. A.; Levin, R. B.;
McDaniel, S. L.; Darke, P. L.; Zugay, J.; Quintero, J. C.;
Blahy, O. M.; Roth, E.; Sardana, V. V.; Schlabach, A. J.;
Graham, P. I.; Condra, J. H.; Gotlib, L.; Holloway, M. K.;
Lin, J.; Chen, I.-W.; Vastag, K.; Ostovic, D.; Anderson, P. S.;
Emini, E. A.; Huff, J. R. Proc. Natl. Acad. Sci. U.S.A. 1994,
91, 4096–4100.
42. Schrag, J. D.; Li, Y.; Cygler, M.; Lang, D.; Burgdorf,
T.; Hecht, H.-J.; Schmid, R.; Schomburg, D.; Rydel, T. J.;
Oliver, J. D.; Strickland, L. C.; Dunaway, C. M.;
Larson, S. B.; Day, J.; McPherson, A. Structure 1997, 5,
187–202.
51. Dorsey, B. D.; Levin, R. B.; McDaniel, S. L.; Vacca, J. P.;
Gaure, J. P.; Darke, P. L.; Zugay, J.; Emini, E. A.; Schleif, W.
A.; Quintero, J. C.; Lin, J.; Chen, I.-W.; Holloway, M. K.;
Fitzgerald, P. M. D.; Axel, M. G.; Ostovic, D.; Anderson, P.
S.; Huff, J. R. J. Med. Chem. 1994, 37, 3443–3451.