Highly enantioselective organocatalytic α-selenylation of aldehydes using hypervalent iodine compounds

Article abstract of DOI:10.1016/j.tetasy.2013.02.008

The highly enantioselective organocatalytic α-selenylation reaction of aldehydes using a hypervalent iodine compound as an oxidative agent from commercially available phenyl diselenide under mild oxidative conditions is described. This transformation affords α-selenyl aldehydes in good yields and with excellent enantioselectivities. By using hypervalent iodine compounds, it opens up a suitable and alternative way for the preparation of biologically active building blocks such as β-hydroxy alcohols, α-amino acids, and α-hydroxy esters.

Full text of DOI:10.1016/j.tetasy.2013.02.008

Tetrahedron: Asymmetry 24 (2013) 254–259
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Tetrahedron: Asymmetry
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Highly enantioselective organocatalytic
a-selenylation of aldehydes using
hypervalent iodine compounds
⇑
´
Martin Kamlar, Jan Vesely
Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 128 43 Praha 2, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 December 2012
Accepted 13 February 2013
The highly enantioselective organocatalytic
a-selenylation reaction of aldehydes using a hypervalent
iodine compound as an oxidative agent from commercially available phenyl diselenide under mild oxi-
dative conditions is described. This transformation affords -selenyl aldehydes in good yields and with
excellent enantioselectivities. By using hypervalent iodine compounds, it opens up a suitable and alter-
native way for the preparation of biologically active building blocks such as b-hydroxy alcohols, -amino
acids, and -hydroxy esters.
a
a
a
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
reported. In organocatalysis, successful attempts at the asymmet-
ric a-selenylation reaction of aldehydes were reported by Melchi-
The biochemical role of selenium in mammals and other ani-
mals was established in 1973, by the discovery of selenium in
the active site of the antioxidant enzyme glutathione peroxidase.1
General interest in the use of organoselenium compounds in
molecular biology intensified after the discovery that organosele-
nium compounds are much less toxic than inorganic selenium spe-
orre5 and Córdova6,7 in 2007, using secondary amine catalysis. In
both methodologies, prolinol-derived catalysts and N-(phenylsele-
no)phthalimide were employed as air-stable sources of the phenyl-
selenyl functionality. Recently, two examples of transformations
including the organocatalyzed formation of
hydes were reported on; an asymmetric three-step synthesis of
-hydroxy-(E)-b,
-unsaturated esters developed by Posner8 and
a-selenylated alde-
cies.2 There is also
a
growing interest in organoselenium
a
c
compounds in other scientific areas, such as enzymology, bioor-
ganic chemistry, and material science, which has led to an increas-
ing demand for organic structures containing selenium atoms.3 In
addition, achiral and chiral organoselenium compounds represent
important intermediates in the organic synthesis of other impor-
tant classes of organic substances. Until now, organic chemists
have employed various organoselenium compounds in many use-
ful synthetic transformations, such as cyclization and elimination
reactions, as well as sigmatropic rearrangements.4 The high syn-
an enantioselective preparation of
a
-alkyl a-vinyl amino acids re-
ported by Armstrong9 (Scheme 1).
SePh
∗
O
O
Bz
´R
NHCO2R´´
CO2Et
N
O
∗
∗
thetic utility of
a-arylselenylated carbonyl compounds, especially
a
-arylselenylated aldehydes and ketones that can be readily trans-
Ref.[8]
O
Ref.[5]
formed into valuable building blocks, has attracted the attention of
many organic chemists. A number of approaches have been suc-
∗
R´
OH
cessfully used for the preparation of enantiomerically pure a-aryl-
selenylated carbonyl compounds, but only a limited amount of
work dealing with asymmetric selenylation methodologies has
been reported to date. Due to the increasing demand for the devel-
opment of powerful and environmentally friendly methodologies,
several examples of organocatalytic transformations affording
Ref.[7]
a-Selenylated aldehydes as valuable intermediates.
Scheme 1.
Based on our recent efforts to expand upon this area of
asymmetric aminocatalysis10 and hypervalent iodine chemistry,
we herein focus on the development of alternative routes to
enantiomerically pure
a-arylselenylated compounds or including
the formation of those derivatives as key intermediates have been
enantiomerically pure
a-selenylated aldehydes using readily-
available diselenides in the presence of hypervalent iodine(III)
compounds.
⇑
Corresponding author. Tel.: +420 221 951 305; fax: +420 221 951 226.
E-mail address: jxvesely@natur.cuni.cz (J. Vesely´).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.02.008

´
255
M. Kamlar, J. Vesely / Tetrahedron: Asymmetry 24 (2013) 254–259
while the O-TMS-protected diphenylprolinol Ia catalyzed
a
-sele-
2. Results and discussion
nylation of iso-valeraldehyde 1a with good efficiency, only moder-
ate enantioselectivity was obtained (Table 1, entry 1). A significant
enhancement of the rate was observed in the presence of an acidic
additive (p-nitrobenzoic acid). Unsatisfying results were obtained
with MacMillan 2nd generation catalyst Ic and pyrrolidine-derived
In order to successfully develop an amine-promoted asymmet-
a-selenylation of aldehydes, we focused on the use of readily-
ric
available diselenides as the source of selenium reagent. Initially
we focused on the development of an oxidative system that could
serve for the mediation of arylselenium species from symmetrical
diselenides. Taking into account the presence of an easily-oxidized
aldehyde functionality present in the substrate, and that hyperva-
lent iodine(III) compounds act as mild oxidants,11 preferentially
IBA and other iodine(III) compounds were examined.
´
catalysts Id, Id, Ic. The use of Jorgensens catalyst Id led to the for-
mation of 5a in only trace amounts. When catalyst Ib was em-
ployed, the corresponding
a-selenoaldehyde 5a was obtained in
high yield with excellent enantioselectivity (Table 1, entry 2).
Encouraged by these results, we decided to optimize the reac-
tion conditions (solvent, temperature, hypervalent iodine(III) com-
pound, catalyst-loading, Table 2). A solvent screen revealed that
imidazolidinone Ib catalyzed the formation of 5a with the highest
enantioselectivity at 0 °C in toluene (Table 2, entry 2), while the
At the outset of our studies, we considered the use of iodoben-
zene diacetate 3a12 as a mild oxidant together with phenyl disele-
nide 2 and iso-valeraldehyde 1a activated with secondary amine
catalyst I successfully been used for
a
-selenylations.5,6 However,
Table 1
Screening of catalysts for the
a
-selenylation of isovaleraldehyde
I(OAc)2
Ib
1. catalyst (0.2 equiv.)
p-nitrobenzoic acid (0.2 equiv.)
2. NaBH4
*
OH
(PhSe)2
CHO
+
+
1. toluene (1 mL), 0 °C
2. MeOH (2 mL), -20 °C
SePh
1a
2
3a
5a
F3C
CF3
CF3
CH3
N
O
CH3
O
Ph
Ph
OTMS
N
N
CH3
CH3
Ph
Ph
CH3
CH3
N
H
N
H
N
H
N
H
N
H
CH3
OTMS
CF3
Ia
Ib
Ic
Id
Ie
Entry
Catalyst
Temp (°C)
Time (h)
Yield (%)
ee (%)a
1
2
3
4
5
la
Ib
Ic
Id
le
0
0
0
0
0
70
40
40
70
72
55
69
62
—
ꢀ84
98
70
n.d.
21
51
Experimental conditions: a mixture of 1a (0.25 mmol), catalyst Ib and acid (20%), 2 (0.25 mmol), and 3a (0.25 mmol) in the
toluene (1 mL) was stirred at 0 °C for the time shown in the Table. After full conversion and in situ reduction the crude product
was purified by column chromatography.
a
Determined by HPLC (AD 90:10 Hept:iPrOH, 0.5 mL).
Table 2
Screening of the solvent and catalyst loading of isovaleraldehyde
1. catalyst Ib (0.2 equiv.)
p-nitrobenzoic acid (0.2 equiv.)
I(OAc)2
2. NaBH4
SePh
OH
(PhSe)2
CHO
+
+
1. Solvent (1 mL), 0 °C
2. MeOH (2 mL), -20 °C
1a
2
3a
5a
Entry
Solvent
Temp (°C)
Time (h)
Conversion (%)
100
100
100
100
65
100
100
100
Yield (%)
eea (%)
1
2
3
4
5
6
7
8
Toluene
Toluene
CH2CI2
THF
25
0
0
0
0
0
0
0
3
40
24
72
72
40
140
45
69
65
42
50
33
62
35
61
84
98
82
77
MeCN
75
Toluene
Toluene
Toluene
98b
92c
98d
Experimental conditions: a mixture of 1a (0.25 mmol), catalyst Ib and acid (20%), 2 (0.25 mmol), and 3a (0.25 mmol) in the
selected solvent (1 mL) was stirred at 0 °C for the time shown in the Table. After full conversion and in situ reduction the crude
product was purified by column chromatography.
a
Determined by HPLC (AD 90:10 Hept:iPrOH, 0.5 mL).
10% catal. loading
5% catal. loading
PhIO used instead of PhI(OAc)2.
b
c
d

´
256
M. Kamlar, J. Vesely / Tetrahedron: Asymmetry 24 (2013) 254–259
13
use of PhI(OAc)2 in comparison with PhIO and PhI(O2CCF3)2 led
to higher yields of 5a. It should be noted that while the enantiocon-
trol of the studied reaction is highly temperature-dependent (entry
1), only a slight decrease in the enantiocontrol was observed when
5 mol % of catalyst was used (entry 7).
The reaction efficiency was strongly dependent on the catalyst-
loading, the reaction temperature (Table 2), the type of iodine com-
pound, the ratios of hypervalent iodine compound 3, phenyl disel-
tions, although significant amounts of
a,a-diselenylated aldehydes
were detected when employing a higher excess of 2 within the
a
-
selenylation reaction. Sterically demanding aldehydes, such as iso-
valeraldehyde (entry 1) and 3,3-dimethylbutyraldehyde were also
well-tolerated for the reported transformations. For example, the
reaction between phenyl diselenide, PhI(OAc)2, and 3,3-dimethyl-
butyraldehyde 1a gave the corresponding product 5b, after
in situ reduction, in 66% yield with 95% ee (entry 5). The use 3-
phenylpropionaldehyde 1f, as an example of an aromatic aldehyde,
led to the formation of the corresponding compound 5f in 67%
yield and 99% ee (entry 6). The use of aldehydes containing an ester
group was also successfully examined. In the case of an ester moi-
ety, benzyl 4-formylbutanoate 1g afforded the corresponding alco-
hol 5g in 70% yield with 99% ee (entry 7).
enide
2 and aldehyde 1, and the presence of an acid (p-
nitrobenzoic acid) for the formation of enamine intermediate.
The results in Table 3 show that PhI(OAc)2 is able to mediate the
formation of phenyl selenium from phenyl diselenide but does
not oxidize phenyl selenide to phenyl selenium. When an excess
of PhI(OAc)2 was used (entry 1), conversion to the corresponding
4a (50%) as well as the formation of another unidentified product
was observed.
The absolute configuration of
a-selenylated aldehydes 4a was
ascertained by chemical correlation. Following the procedure
developed by Córdova et al.6we prepared the highly enantiopure
compound ent-5a, with an (S)-absolute configuration,
In order to study the scope of the a-selenylation reaction, vari-
ous aldehydes including alkyl, alkenyl, aromatic, and ester moieties
were tested (Table 4). When aliphatic aldehydes, such as pentanal
and heptanal, were used, the corresponding alcohols 5c, 5d were
obtained in 67% and 66% yield, respectively, both with excellent
enantioselectivity (entries 2 and 3). The formation of diselenylated
products was not observed under the optimized reaction condi-
{½a 2D5
¼ ꢀ8:5 (c 1.1, CHCl3)}. Based on our protocol we obtained
ꢁ
highly enantiopure compound 5a, {½a D25
¼ þ9:4 (c 0.6, CHCl3)},
ꢁ
which clearly indicates that the absolute configuration of the cor-
responding aldehyde 4a is (2R). Based on the observed results
and previous reports, in Scheme 2 we propose a mechanism for
Table 3
Optimization of the reagent ratio of the
a-selenylation reaction
I(OCOR)2
Ib
SePh
CHO
catalyst (0.2 equiv.)
p-nitrobenzoic acid (0.2 equiv.)
CHO
(PhSe)2
+
+
toluene (1 mL), R.T.
1a
2
3
4a
Entry
R
Ratio 1:2:3
Time (h)
Conversion (%)a
1
2
3
4
5
CH3
CH3
CF3
CF3
CH3
1:0.5:1
1:0.5:0.5
1:0.5:1
1:0.5:0.5
1:1:1
12
16
24
24
2
100b
50c
30
50
100
a
B
c
Determined by 1H NMR.
Formation of 4a and non-identified highly unstable aldehyde product (ratio 1:1).
50% Conversion to 4a was also observed after 72 h.
Table 4
Substrate scope of the organocatalytic a-selenylation of aldehydes
I(OAc)2
Ib
1. catalyst (0.1 equiv.)
p-nitrobenzoic acid (0.1 equiv.)
SePh
2. NaBH4
(PhSe)2
R
CHO
+
+
OH
R
1. toluene (1 mL), 0 °C
2. MeOH (2 mL), -20 °C
1a-g
2
3a
5a-g
Entry
R
Temp. (°C)
Time (h)
Yield (%)
ee (%)a
1
2
3
4
5
6
7
/Pr
0
0
0
0
0
0
0
40
50
50
48
40
20
20
69
66
67
51
66
67
70
98
99
99
99
95
99
99
n-Pentyl
n-Propyl
n-Allyl
f-Butyl
Bn
CH2CO2Bn
Experimental conditions: a mixture of 1a–g (0.25 mmol), catalyst Ib and acid (20%), 2 (0.25 mmol), and 3a (0.25 mmol) in
toluene (1 mL) was stirred at 0 °C for the time shown in the Table. After full conversion and in situ reduction the crude product
was purified by column chromatography.
a
Determined by HPLC. Absolute configuration of compounds 5b–5g was assigned by analogy to absolute configuration of
5a.

´
257
M. Kamlar, J. Vesely / Tetrahedron: Asymmetry 24 (2013) 254–259
(PhSe)2
PhI(OAc)2
+
our
a-selenylation methodology, whereby the hypervalent iodine
2
3a
species 3a plays a crucial role as the phenyl selenium mediator,
which avoids oxidation of the aldehyde functionality.
PhI(OAc)+ PhSe-
Next, we decided to extend our methodology to b-keto es-
ters.14,15 The treatment of ester 7 with phenyl diselenide and
PhI(OAc)2 in the presence of cinchona alkaloid derivatives as cata-
O
Ph
lysts (10 mol %) led to the formation of the corresponding
a-sele-
PhSe+ -OAc
N
nylated product 8 (Table 5). Despite the high efficiency of the
above mentioned methodology (yields of 8 up to 93%), further opti-
mization of the reaction conditions (solvent, catalyst, temperature)
revealed limited enantiocontrol, affording only slightly enantioen-
H2O
N
R
HOAc
I
riched a-selenylated products (up to 36% ee, Table 5). Other b-keto
O
esters with more bulky alkyl groups showed similar results in
terms of efficiency and selectivity of the reaction. Nevertheless,
the aforementioned results represent the first high yielding report
in the area of selenylation reaction of b-keto esters, which are valu-
able building blocks in the synthesis of structurally diverse organic
molecules.16
O
N
R
Ph
1
O
N
N
Ph
N
H
PhSe+
R
O
II
N
3. Conclusion
O
Ph
N
PhSe
In conclusion, we have reported on a highly enantioselective
PhSe
organocatalytic
a-selenylation reaction of aldehydes using a
R
hypervalent iodine compound as an oxidative agent from commer-
cially available starting materials under mild oxidative conditions.
H2O
R
This transformation affords a-selenyl aldehydes in good yields and
4
with excellent enantioselectivities. By using hypervalent iodine
compounds, we have opened up a suitable and alternative route
for the preparation of biologically active building blocks such as
III
a-phenylselenylation of aldehydes.
Scheme 2. Proposed mechanism of the
b-hydroxy alcohols,8
a a
-amino acids,9,17 -hydroxy esters,18 and
Table 5
Screening results for the a-selenylation of ester 7
O
O
O
O
catalyst (10 %)
+
(PhSe)2
+
PhI(OAc)2
OEt
OEt
SePh
toluene (1 mL),
temperature
7
2
3a
8
Entry
Solvent
Catalyst
Time (h)
Temperature (°C)
Yield (%)
ee (%)a
1
2
3
4
5
6
7
8
9
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
I
1
1
1
1
1
16
10
2
25
25
25
25
25
0
0
25
25
93
35
42
64
58
94
94
87
85
36
ꢀ3
8
18
8
28
36
30
22
II
III
IV
V
I
I
I
I
THF
DCM
2
Experimental conditions: a mixture of 7 (0.1 mmol), catalyst (10%), 2 (0.2 mmol), and 3a (0.2 mmol) in toluene (1 mL) was
stirred at rt for the time shown in the Table. After full conversion the crude product was purified by column chromatography.
a
Determined by HPLC (IB 95:5 Hept:iPrOH, 1 ml).
X-
Cl-
N
O
N
N
R1O
HO
R2
MeO
MeO
N
N
N
(R1 = allyl, X = Br-)
IV (R1 = H, X = Cl-)
(R1 = H, R2 = Ph)
III
I
II
V (R1 = adamantoyl Cl-, R2 = anthracene)

´
M. Kamlar, J. Vesely / Tetrahedron: Asymmetry 24 (2013) 254–259
258
allylic amines.19 Mechanistic studies and further applications of
hypervalent iodine compounds are currently ongoing in our
laboratory.
In a vial equipped with a teflon-coated stirrer bar, catalyst IIa
(0.01 mmol, 5 mg, 10 mol %) was dissolved in toluene (1 mL). After
the addition of ester 7 (0.1 mmol, 16 mg, 1 equiv), the solution was
stirred for ca. 10 min at rt, then phenyl diselenide (0.2 mmol,
62 mg, 2 equiv) and iodobenzene diacetate 3a (0.2 mmol, 64 mg,
1 equiv) were added and the mixture was stirred at the same tem-
perature for an appropriate time. After completion of the reaction
(TLC monitoring), the mixture was purified by chromatography to
4. Experimental
4.1. General
give the desired a-selenylated compound 8.
Chemicals and solvents were either purchased (puriss p.A.)
from commercial suppliers or purified by standard techniques.
For thin-layer chromatography (TLC), silica gel plates Merck 60
F254 were used, and compounds were visualized by irradiation
with UV light and/or by treatment with a solution of phosphomo-
lybdic acid (25 g), Ce(SO4)2ꢂH2O (10 g), concd H2SO4 (60 mL), and
H2O (940 mL) followed by heating or by treatment with a solution
of p-anisaldehyde (23 mL), concd H2SO4 (35 mL), acetic acid
(10 mL), and ethanol (900 mL) followed by heating.
4.4. (R)-3-Methyl-2-(phenylselanyl)butan-1-ol 5a
Colorless oil, 69% yield, 98% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (90/10 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 230 nm, tmajor = 12.1 min, tminor = 13.5 min);
1H NMR (600 MHz, CDCl3): d = 7.58–7.56 m, 2H), d = 7.28–7.23
(m, 3H), d = 3.74 (dd, J = 5.46 Hz, J0 = 11.76 Hz, 1H), d = 3.66 (dd,
J = 7.26 Hz, J0 = 11.76 Hz, 1H), d = 3.16 (dt, J = 7.3 Hz, J0 = 5.5 Hz,
1H), d = 2.23 (br s, OH), d = 2.06–2.00 (m, 1H), d = 1.06 (dd,
J = 6.7 Hz, J0 = 13.86 Hz, 6H) ppm; 13C NMR (151 MHz, CDCl3):
d = 134.57 (2C), 129,11 (3C), 127.55, 63.30, 60.02, 29.94, 21.14,
Flash chromatography was performed by using silica gel Merck
60 (particle size 0.040–0.063 mm). 1H, 19F, and 13C NMR spectra
were recorded with Bruker AVANCE III 600 or Varian VNMRs 300
instruments. Chemical shifts are given in ppm relative and cou-
pling constants J are given in Hz. The spectra were recorded in
CHCl3-d1 as solvent at room temperature which served as internal
standard (d = 7.26 ppm) for 1H NMR and (d = 77.0 ppm) for 13C
NMR. Chiral HPLC was carried out using a LCP 5020 Ignos liquid
chromatography pump with LCD 5000 spectrophotometric detec-
tor with column Daicel ChiralpakÒ AD. High-resolution mass spec-
tra were recorded with a LTQ Orbitrap XL spectrometer. IR DRIFT
20.48 ppm; ½a 2D5
ꢁ
¼ þ9:4 (c 0.6, CHCl3); IR (KBr):
m = 3354, 3072,
3055, 3013, 2956, 2926, 2869, 1945, 1873, 1808, 1715, 1580,
1473, 1437, 1069, 1021, 740, 692 cmꢀ1; HRMS (TOF) m/z calcd
for [M+H]+ = 245.0439, found = 245.0448.
4.5. (R)-3,3-Dimethyl-2-(phenylselanyl)butan-1-ol 5b
spectras were recorded with Nicolet AVATAR 370 FT-IR in cmꢀ1
.
Colorless oil, 66% yield, 95% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (90/10 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 230 nm, tmajor = 5.9 min, tminor = 6.6 min); 1H
NMR (600 MHz, CDCl3): d = 7.61–7.60 (m, 2H), d = 7.27–7.25 (m,
4.2. General procedure for the organocatalytic asymmetric
selenylation of aldehydes
a-
I
secondary amine (0.2 equiv.)
p-nitrobenzoic acid
(0.2 equiv.)
I(OAc)2
NaBH4
R
R
R
CHO
(PhSe)2
O
H
+
+
O
MeOH (2 mL)
-20 °C
toluene (1 mL), 0 °C
SePh
SePh
5
1
2
3a
4
In a vial equipped with a teflon-coated stirrer bar, catalyst Ib
(0.05 mmol, 12 mg, 20 mol %) and p-NO2C6H4CO2H (0.05 mmol,
8 mg, 20 mol %) were dissolved in toluene (1 mL). After the addi-
tion of aldehyde 2 (0.25 mmol, 1.0 equiv), the solution was stirred
for ca 10 min at 0 °C, then diphenyl diselenide (0.25 mmol, 78 mg,
1 equiv) and iodobenzene diacetate 3a (0.25 mmol, 80 mg, 1 equiv)
were added and the mixture was stirred at the same temperature
for an appropriate time (40 h). After completion of the reaction, the
mixture was diluted in cooled MeOH (2 mL, ꢀ20 °C). Solid NaBH4
(excess) was then added in one portion. After completion of the
reaction the solution was poured into a cooled mixture of EtOAc/
1 M HCl (ꢀ20 °C). The water layer was extracted with EtOAc and
the combined organics were dried over MgSO4, filtered, and con-
centrated in vacuo. The residue was purified by chromatography
3H), d = 3.88 dd, J = 4,02 Hz, J0 = 11.94 Hz, 1H), d = 3.63 Hz (dd,
J = 8.7 Hz, J0 = 11.94 Hz, 1H), d = 3.13 Hz (dd, J = 4.08 Hz,
J0 = 8.76 Hz, 1H), d = 2.45 (br s, OH), d = 1.10 (s, 9H) ppm; 13C
NMR (151 MHz, CDCl3): d = 134.06 (2C), 130.60, 129.15 (2C),
127.36, 67.55, 62.11, 34.85, 28.77 ppm; ½a D25
¼ ꢀ2:7 (c 1.1, CHCl3);
ꢁ
IR (KBr):
m = 3440, 3072, 3058, 3016, 2959, 2902, 2869, 1945, 1873,
1796, 1736, 1577, 1476, 1437, 1392, 1368, 1242, 1072, 1042, 743,
689 cmꢀ1 HRMS (TOF) m/z calcd for [M+H]+ = 259.0596,
;
found = 259.0592.
4.6. (R)-2-(Phenylselanyl)pentan-1-ol 5c
Colorless oil, 67% yield, 99% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (98/2 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 230 nm, tmajor = 18.6 min, tminor = 19.8 min);
1H NMR (600 MHz, CDCl3): d = 7.57–7.56 (m, 2H), d = 7.32–7.26
(m, 3H), d = 3.62 (dd, J = 4.86 Hz, J0 = 11.64 Hz, 1H), d = 3.53 (dd,
J = 6.78 Hz, J0 = 11.64 Hz, 1H), d = 3.27–3.23 (m, 1H), d = 2.27 (br s,
OH), d = 1.66–1.47 (m, 4H), d = 0.93 (t, 4H) ppm; 13C NMR
(151 MHz, CDCl3): d = 135.38 (2C), 129.06 (2C), 127.91, 127.41,
to give the desired a-seleno alcohol derivatives 5.
4.3. General procedure for organocatalytic
keto ester 7
a-selenylation of b-
64.25, 50.27, 33.77, 20.99, 13.78 ppm; ½a D25
¼ þ19:3 (c 0.6, CHCl3);
ꢁ
O
O
O
O
IR (KBr):
m = 3363, 3072, 3058, 3013, 2959, 2926, 2866, 1948, 1876,
catalyst (10 %)
1799, 1715, 1577, 1461, 1473, 1437, 1024, 737, 692 cmꢀ1; HRMS
+
(PhSe)2
+
PhI(OAc)2
OEt
OEt
SePh
toluene (1 mL),
temperature
(TOF) m/z calcd for [M+H]+ = 245.0439, found = 245.0450.
7
2
3a
8

´
259
M. Kamlar, J. Vesely / Tetrahedron: Asymmetry 24 (2013) 254–259
4.7. (R)-2-(Phenylselanyl)heptan-1-ol 5d
1174, 1135, 1000, 743, 692 cmꢀ1; HRMS (ESI) m/z calcd for
[M+Na]+ = 373.0319, found = 373.0312.
Colorless oil, 66% yield, 99% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (95/5 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 190 nm, tmajor = 14.9 min, tminor = 16.8 min);
1H NMR (600 MHz, CDCl3): d = 7.57–7.56 (m, 2H), d = 7.34–7.26
(m, 3H), d = 3.62 (dd, J = 4.86 Hz, J0 = 11.64 Hz, 1H), d = 3.52 (dd,
J = 6.78 Hz, J0 = 11.64 Hz, 1H), d = 3.26–3.21 (m, 1H), d = 2.20 (br s,
OH), d = 1.69–1.64 (m, 1H), d = 1.61–1.55 (m, 2H), d = 1.48–1.44
(m, 1H), d = 1.33–1.26 (m, 4H), d = 0.89 (t, J = 6.9 Hz, 3H) ppm;
13C NMR (151 MHz, CDCl3): d = 135.40 (2C), 129.07 (2C), 127.93,
127.43, 64.25, 50.60, 31.62, 31.53, 27.48, 22.49, 14.01 ppm;
4.11. Ethyl 2-oxo-1-(phenylselanyl)cyclopentanecarboxylate 8
Colorless oil, 93% yield, 36% ee. The ee was determined by HPLC
analysis using Chiralpak IB column (95/5 heptane/i-PrOH, flow rate
1 mL/min; k = 190 nm, tmajor = 7.9 min, tminor = 8.5 min); 1H NMR
(600 MHz, CDCl3): d = 7.64ꢀ7.62 m, 2H), d = 7.41–7.38 (m, 1H),
d = 7.33–7.30 (m, 2H), d = 4.19 (q, J = 7.14 Hz, 2H), d = 2.55–2.50
(m, 1H), d = 2.45–2.39 (m, 1H), d = 2.33–2.27 (m, 1H), d = 2.09–
2.05 (m, 1H), d = 2.00–1.90 (m, 2H), d = 1.24 (t, J = 7.2 Hz, 3H),
ppm; 13C NMR (151 MHz, CDCl3): d = 207.57, 169.55, 137.55 (2C),
129.74, 129.00 (2C), 126.49, 62.13, 58.86, 36.91, 34.27, 19.11,
½
a 2D5
ꢁ
¼ þ15:4 (c 0.7, CHCl3); IR (KBr):
m = 3351, 3069, 3058, 3013,
2953, 2932, 2866, 2863, 1942, 1876, 1802, 1733, 1580, 1479,
1464, 1060, 1039, 1024, 1000, 743, 692 cmꢀ1; HRMS (TOF) m/z
calcd for [M+H]+ = 273.0752, found = 272.0750.
14.00 ppm; ½a 2D5
ꢁ
¼ ꢀ63:5 (c 1.2, CHCl3); IR (KBr):
m = 3075, 3055,
2977, 2935, 2899, 1751, 1730, 1715, 1577, 1476, 1257, 1230,
1141, 1018 cmꢀ1; HRMS (ESI) m/z calcd for [M+Na]+ = 335.01561,
found = 335.01561.
4.8. (R)-2-(Phenylselanyl)pent-4-en-1-ol 5e
Colorless oil, 51% yield, 99% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (95/5 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 190 nm, tmajor = 19.9 min, tminor = 21.8 min);
1H NMR (600 MHz, CDCl3): d = 7.59ꢀ7.57 m, 2H), d = 7.32–7.27
(m, 3H), d = 5.92–5.85 (m, 1H), d = 5.14–5.10 (m, 2H), d = 5.14–
5.10 (m, 2H), d = 3.66 (dd, J = 5.16 Hz, J0 = 11.64 Hz, 1H), d = 3.58
(dd, J = 6.3 Hz, J0 = 11.64 Hz, 1H), d = 3.33–3.28 (m, 1H), d = 2.46
(dt, J = 5.7 Hz, J0 = 1.26 Hz, 2H), d = 2.16 (br s, OH) ppm; 13C NMR
(151 MHz, CDCl3): d = 135.48, 135.37 (2C), 129.13 (2C), 128.03,
Acknowledgements
We gratefully acknowledge the Ministry of Education of the
Czech Republic (the Grant No. MSM0021620857) and Czech Sci-
ence Foundation (Grant No. P207/10/0428) for the financial
support.
References
127.34 117.37, 63.88, 48.65, 48.65, 36.25 ppm; ½a D25
¼ þ14:0 (c
ꢁ
1. (a) Flohe, L.; Günzler, W. A.; Schock, H. H. FEBS Lett. 1973, 32, 132; (b) Rotruck, J.
T.; Pope, A. L.; Ganther, H. E.; Swanson, A. B.; Hafeman, D. G.; Hoekstra, W. G.
Science 1973, 179, 588.
0.3, CHCl3); IR (KBr):
m = 3357, 3069, 3055, 2995, 2977, 2929,
2872, 1951, 1882, 1829, 1715, 1577, 1479, 1437, 1075, 1021,
997, 740, HRMS (TOF) m/z calcd for
689 cmꢀ1
[M+H]+ = 243.0283, found = 243.0289.
2. Klayman, D. L.; Günther, W. H. H. Organic Selenium Compounds: Their Chemistry
and Biology; John Wiley & Sons: New York, 1973.
;
3. Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. Rev. 2001, 101, 2125.
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Santi, C.; Santoro, S.; Battistelli, B. Curr. Org. Chem. 2010, 14, 2442; (c)
Freudendahl, D. M.; Shahzad, S. A.; Wirth, T. Eur. J. Org. Chem. 2009, 11, 1649–
1664; (d) Freudendahl, D. M.; Santoro, S.; Shahzad, S. A.; Santi, C.; Wirth, T.
Angew. Chem. 2009, 121, 8559–8562. Angew. Chem., Int. Ed. 2009, 48, 8409–
8411.; (e) Browne, D. M.; Wirth, T. Curr. Org. Chem. 2006, 10, 1893–1903; (f)
Wirth, T. Angew. Chem. 2000, 112, 3890–3900. Angew. Chem., Int. Ed. 2000, 39,
3740–3751.; (g) Wirth, T. Organoselenium Chemistry: Modern Developments
in Organic Synthesis. In Topics in Current Chemistry; Springer: Berlin, 2000; (h)
Wirth, T. Tetrahedron 1999, 55, 1–28; (i) Back, T. G. Organoselenium Chemistry A
Practical Approach; Oxford University Press: Oxford, 1999. etc..
5. Tiecco, M.; Carlone, A.; Sternativo, S.; Marini, F.; Bartoli, G.; Melchiorre, P.
Angew. Chem., Int. Ed. 2007, 46, 6882–6885.
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amines, see also:, Zhao, G.-L.; Rios, R.; Vesely´, J.; Eriksson, L.; Córdova, A.
Angew. Chem., Int. Ed. 2008, 47, 8468–8472.
4.9. (R)-3-Phenyl-2-(phenylselanyl)propan-1-ol 5f
Colorless oil, 67% yield, 99% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (95/5 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 230 nm, tmajor = 24.8 min, tminor = 27.1 min);
1H NMR (600 MHz, CDCl3): d = 7.51ꢀ7.49 m, 2H), d = 7.27–7.17
(m, 8H), d = 3.58 (dd, J = 4.44 Hz, 1H), d = 3.53–3.45 (m, 2H), d =
3.01–2.94 (m, 2H), d = 3.13 (br s, OH) ppm; 13C NMR (151 MHz,
CDCl3): d = 139.01, 135.26 (2C), 129.12 (2C), 129.07 (2C), 128.45
(2C), 128.00, 127.56, 126.55, 63.10, 50.55, 38.16 ppm;
½
a 2D5
ꢁ
¼ þ14:1 (c 0.7, CHCl3); IR (KBr):
m = 3380, 3102, 3058, 3028,
2998, 2932, 2869, 1951, 1879, 1805, 1736, 1601, 1580, 1476,
1455, 1431, 1066, 1021, 1000, 743, 698 cmꢀ1; HRMS (TOF) m/z
calcd for [M+H]+ = 292.0366, found = 292.0373.
8. Hess, L. C.; Posner, G. H. Org. Lett. 2010, 12, 2120–2122.
9. Armstrong, A.; Emmerson, D. P. G. Org. Lett. 2010, 13, 1040–1043.
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ˇ
Dziedzic, P.; Córdova, A.; Vesely´, J. Adv. Synth. Catal. 2011, 7, 1096–1108; (c)
ˇ
ˇ
´
Cíhalová, S.; Valero, G.; Schimer, J.; Humpl, M.; Dracínsky, M.; Moyano, A.; Rios,
4.10. (R)-Benzyl 4-hydroxy-3-(phenylselanyl)butanoate 5g
R. Tetrahedron 2011, 67, 8942–8950; (d) Kamlar, M.; Bravo, N.; Alba, A.-N. R.;
ˇ
´
Hybelbauerová, S.; Císarová, I.; Vesely, J.; Moyano, A.; Rios, R. Eur. J. Org. Chem.
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Moyano, A.; Rios, R. Tetrahedron Lett. 2009, 50, 5021–5024.
Colorless oil, 70% yield, 99% ee. The ee was determined by HPLC
analysis using Chiralpak AD-H column (95/5 heptane/i-PrOH, flow
rate 0.5 mL/min; k = 190 nm, tmajor = 30.3 min, tminor = 32.6 min);
1H NMR (600 MHz, CDCl3): d = 7.47 d, J = 7.2 Hz, 2H), d = 7.26–
7.16 (m, 8H), d = 5.05 (d, J = 3.54 Hz, 2H), d = 3.60–3.50 (m, 3H),
d = 2.73 (dd, J = 6.72 Hz, J0 = 16.26 Hz, 1H), d = 2.62 (dd,
J = 7.14 Hz, J0 = 16.26 Hz, 1H), d = 2.15 (br s, OH) ppm; 13C NMR
(151 MHz, CDCl3): d = 171.43, 135.71 (2C), 135.56, 129.21 (2C),
128.57 (2C), 128.35 (3C), 126.70, 66.72, 64.39, 43.13, 37.37 ppm;
11. Qian, W.; Jin, E.; Bao, W.; Zhang, Y. Angew. Chem., Int. Ed. 2005, 44, 952–955.
12. Hossain, Md. D.; Kitamura, T. Tetrahedron Lett. 2006, 47, 7889–7891.
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Chem. Soc. 2007, 129, 441–449.
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16. Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975, 97, 5434.
17. Burkhardt, E. R.; Rieke, R. D. J. Org. Chem. 1985, 50, 417.
18. Lerough, P.; Paulmier, C. Tetrahedron Lett. 1983, 1984, 25.
19. Shea, R. G.; Fitzner, J. N.; Fankhauser, J. E.; Spaltenstein, A.; Carpino, P. A.;
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5243.
½
a 2D5
ꢁ
¼¼ þ6:8 (c 1.2, CHCl3); IR (KBr):
m = 3443, 3058, 3028, 2947,
2878, 1954, 1885, 1727, 1577, 1476, 1458, 1434, 1299, 1213,