Active metallic indium-mediated ring-opening of epoxides with diphenyl diselenides: A novel one-pot synthesis of β-hydroxy selenides in aqueous media

Article abstract of DOI:10.3184/030823407X218011

An efficient and simple one-pot procedure for the synthesis of β-hydroxy selenides in aqueous media through highly regioselective ring-opening of epoxides with diphenyl diselenide in the presence of active metallic indium is described.

Full text of DOI:10.3184/030823407X218011

JOURNAL OF CHEMICAL RESEARCH 2007
JUNE, 325–327
RESEARCH PAPER 325
Active metallic indium-mediated ring-opening of epoxides with diphenyl
diselenides: a novel one-pot synthesis of b-hydroxy selenides in aqueous
media
Xian Chena, Huayue Wua*, Weike Sua,b*, Rong Xua, Miaochang Liua and Jinchang Dinga,c
aCollege of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, P.R. China
bCollege of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical Engineering,
Hangzhou 310014, P.R. China
cWenzhou Vocational and Technical College, Wenzhou 325035, P.R. China
An efficient and simple one-pot procedure for the synthesis of b-hydroxy selenides in aqueous media through
highly regioselective ring-opening of epoxides with diphenyl diselenide in the presence of active metallic indium is
described.
Keywords: β-hydroxy selenides, diphenyl diselenide, epoxides, active metallic indium
β-Hydroxy selenides are highly valuable intermediates in
organic synthesis.1 They can be transformed into allylic
alcohols, olefins, halohydrins, vinyl selenides, epoxides and
heterocyclic compounds.2 Consequently, several methods
have been developed for the synthesis of β-hydroxy selenides.3
The most common method is the ring-opening of epoxides with
phenyl selenide anion generated from diphenylselenide with
tributyphosphine in alkaline medium,4 sodium borohydride,2a
Sm–TMSCl,5 indium(I) iodide6 or zinc.7 Although ring-
opening of epoxides involving some of the above-mentioned
methods have their own advantages, each suffers from one or
more drawbacks such as unsatisfactory regioselectivity,4 long
reaction periods2a,7 and excessive reagents.4-7 Furthermore,
most of above mentioned procedures are carried out in
anhydrous organic solvents. Thus, the development of new
reagents, capable of promoting the ring opening reaction
under mild conditions (including aqueous or neutral media) is
highly desirable.
Recently, indium metal and selected indium(III) compounds
have emerged as an attractive and promising tool in organic
synthesis. This is largely due to their high reactivity in
promoting various reactions, low toxiꢀty and high stability
toward water and air compared with other metals.8 Aiming
at the development of green and more effiꢀent organic
methodologies, recently we have been focusing our research
on the application of active metallic indium in organic
synthesis.9 As a continuation of our research in this area, we
report here an effiꢀent and convenient one-pot synthesis of
CH3CN-H2O
r. t.
Sm
InCl3 4H2O
In*
+
+
SePh
OH
O
In*
+
PhSe-SePh
OH
SePh
reflux
R1
R1
R1
1
2
3
Scheme 1
β-hydroxy selenides (2 and/or 3, Scheme 1) through a regio-
and steroselective ring opening of epoxides with diphenyl
diselenide mediated by active metallic indium generated
in situ from Sm/InCl3•4H2O under neutral conditions in
aqueous media.
Initially, as an optimisation process, the reaction of
epichlorohydrin 1a with PhSeSePh under various conditions
was investigated. The results are summarised in Table 1.
As shown in Table 1, these preliminary results lead to the
following conclusions: First of all, in the presence of the in
situ formed active indium, epichlorohydrin reacts smoothly
with PhSeSePh and affords the corresponding β-hydroxy
selenide with excellent regioselectivity and in good yield.
Of the two possible products, 2a and 3a, only 3a was obtained.
Secondly, among the solvents studied, CH3CN/H2O was
found to be most suitable for this reaction from the point view
of yields (entries 1–4). Thirdly, long reaction times (>0.5 h)
do not necessarily result in higher yields (entries 1, 6).
Table 1 Reaction of epichlorohydrin with PhSeSePh under various conditions
OH
SePh
In*
O
PhSe-SePh
+
+
OH
Cl
SePh
Cl
Cl
reflux
1a
Solvent b
3a
2a
Entrya
Temperature
Time/h
Yield/%c,d
1
2
3
4
5
6
7
CH3CN/H2O (9/1)
THF/H2O (9/1)
C2H5OH/H2O (9/1)
CH2Cl2/H2O(9/1)
CH3CN/H2O(9/1)
CH3CN/H2O(9/1)
CH3CN/H2O(3/1)
reflux
reflux
reflux
reflux
r.t.
reflux
reflux
0.5
0.5
0.5
0.5
2
86
75
80
81
70
87
79
2
0.5
aAmount of reagents: Epicholorohydrin (2 mmol) and PhSeSePh (1 mmol).
bv/v ratio.
cRatio of 3a/2a > 99/1.
dIsolated yields based on PhSeSePh.
* Correspondent. E-mail: hywu3@163.com
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326 JOURNAL OF CHEMICAL RESEARCH 2007
This is probably due to the gradual loss of activity of the
indium reagent over longer periods of time. Lastly, while
increasing the amount of water causes a decrease in the yield
(entries 1, 7), it should be highlighted that this reaction still
gives a fairly good yield even with as much as 33% water in
the solvent system (entry 7). After exploring a wide array of
conditions, we arrived at a best result that the reaction should
be carried out under refluxing for 0.5 h in CH3CN/H2O (9/1).
The mild reaction conditions, excellent regioselectivity
and good yields encouraged us to examine the scope and
generality of the present method. Thus, several structurally
diverse epoxides were studied and the results are listed in
Table 2.
The results in Table 2 reveal that various epoxides react
readily with diphenyldiselenide under the present reaction
conditions to give the desired products with impressive yields.
Interestingly, no evidence was found for the formation of the
corresponding diols in aqueous media. In the case of alkyl-
substituted unsymmetrical epoxides, the reaction proceeds
with a remarkable regio-selectivity to give only 3 of the two
possible regio-isomers (2 and 3, Scheme 1) as a result of the
exclusive attack of the selenide anions on the less hindered
carbon of the epoxide (entries 1–4). On the contrary, with
aryl-substituted epoxides (entries 5 and 6), the attack occurs
preferentialy at the benzylic carbon atom, the more hindered
carbon of the epoxide, to give another regioisomer, 2e or
2f as main products respectively. However, for 3-OR-1,2-
epoxypropane, R groups affect the regioselectivity remarkably
(entries 7–9). Interestingly, ring-opening of 1,2-epoxy-3-
naphthaleneoxy-propane gave only one isomer 3h, which
shows excellent regioselectivity (entry 9).
Furthermore, some insight into the stereoselectivity of the
present method was obtained from reactions carried out on
two cyclic epoxides (entries 10 and 11), which exclusively
give the corresponding anti-β-hydroxy selenides in 73% and
69% yields respectively. No trace of the syn-adducts was
detected by 1H NMR spectroscopy.4
To extend the scope of the ring-opening reaction, (S)-
epichlorohydrin[12] was studied under similar conditions
(Scheme 2). The reaction was found to be highly regioselective
and stereospeꢀfic, which demonstrated that original chirality
in the epoxides was retained. The corresponding products were
obtained in good yield (85%) and high ee (98%). Enantiopure
β-hydroxy selenides are important intermediates in organic
synthesis.13
OH
*
In*
O
PhSe-SePh
+
Cl
SePh
Cl
reflux
*
(R) 98% ee
(S)
20
[α]D +39.8
Scheme 2
In conclusion, a faꢀle and effiꢀent one-pot procedure
for the preparation of β-hydroxy selenides is described.
Compared with previously reported methods for the ring-
opening of epoxides, this method has several advantages,
such as good regioselectivity, short reaction times, relatively
environmentally friendly processes and neutral reaction
conditions. Studies to extend the application of active metallic
indium in green organic synthesis are currently underway in
our laboratory.
Experimental
Diphenyl diselenide (m.p 59–61°C; Lit. 60–62°C) was prepared
through a known procedure.14 Melting points were uncorrected.
IR spectra were recorded on a Bruker-EQUINOX55 spectrometer.
1H NMR and 13C NMR spectra were obtained on a Bruker AC 300
instrument using CDCl3 as solvent and TMS as internal reference.
Mass spectra were measured with Thermo Finnigan LCQ-Advantage.
Elemental analyses were carried out using a Carlo-Erba EA1112
instrument. Chiral LC’s were obtained on a chiracel OJ-H column
with a mobile phase of iso-PrOH/hexane (1/99) at a flow rate of
0.8 ml/min and UV detection at 254 nm.
General procedure for preparation of β-hydroxy selenides
To a flask containing InCl3•4H2O (1 mmol), samarium powder
(1 mmol) and CH3CN (9 ml) was slowly added 1 ml H2O.
Upon adding of H2O, vigorous reaction took place to give a light
black speꢀes (active metallic indium) in several minutes. Then
PhSeSePh (1 mmol) was added and the mixture was refluxed for
10 min to give an almost colourless solution. To this solution was
then added the epoxide substrate (2 mmol) and it was stirred for a
certain period of time as indicated in Tables 1 and 2. Upon completion
(monitored by TLC), the solution was aꢀdified with 10% HCl until
the pH value was about 5. The aqueous solution was extracted with
Et2O (2 × 15 ml) and the combined organic phases were dried over
anhydrous Na2SO4. After evaporation of the solvent under reduced
pressure, the resulting crude product was purified by silica gel column
chromatography eluting with petroleum ether and ethyl acetate (9:1)
to give the corresponding β-hydroxy selenides. The physical and
spectroscopic data of all compounds are as follows.
1-chloro-3-(phenylselanyl)propan-2-ol (3a)5: 1H NMR: δ 2.73
(d, J = 5.1 Hz, 1H), 3.05 (dd, J = 12.9, 7.1 Hz, 1H), 3.14 (dd, J = 12.9,
Table 2 Reaction of epoxides with PhSeSePh mediated by active indium
Entrya
R1
Productsb
Regioselectivity/b/ac
Yield/%d
1
2
3
4
5
6
7
8
ClCH2
3a5
3b10
99/1
99/1
86
85
81
80
82
80
82
83
CH3
CH3(CH2)4CH2
CH2 =CH(CH2)5CH2
Ph
4-Cl(C6H4)
PhCH2OCH2
4-Cl(C6H4)OCH2
3c10
99/1
3d
99/1
3e/2e4
3f/2f6
3g/2g2h
3h/2h11
24/76
32/68
31/69
75/25
OCH2
9
3i
99/1
–
86
73
10
O
O
2j4
11
2k4
–
69
aReaction conditions: CH3CN/H2O (9/1, v/v), reflux, 0.5 h.
bAll products are known compounds except for 3d and 3i.
cThe ratio of two regio-isomers was determined by 1H NMR.
dIsolated yields.
PAPER: 07/4526

JOURNAL OF CHEMICAL RESEARCH 2007 327
5.5 Hz, 1H), 3.66 (m, 2H), 3.92 (m, 1H), 7.26–7.30 (m, 3H), 7.52–
Anti-2-(phenylselanyl)cyclohexanol (2j)4: 1H NMR: δ 1.21–1.38
(m, 4H), 1.61–1.75 (m, 2H), 2.15 (m, 2H), 2.88 (ddd, J = 12.0, 10.0,
4.0 Hz, 1H), 2.93 (s, 1H), 3.32 (dt, J = 9.9, 4.1 Hz, 1H), 7.25–7.36
(m, 3H), 7.57–7.61 (m, 2H). IR ν(cm-1): 3444 (OH).
7.56 (m, 2H). IR ν (cm-1): 3438 (OH).
20
(R)-(+)-1-chloro-3-(phenylselanyl)propan-2-ol: [α]D
+ 39.8
(c 1.01, CHCl3). HPLC analysis using a Chiracel OJ-H column [iso-
PrOH/hexane: 1/99; flow rate: 0.8 ml/min; detector: 254 nm] showed
it to 98% ee. Retention time: 15.04 min (major), 16.47 min (minor).
1-(phenylselanyl)propan-2-ol (3b)10: 1H NMR: δ 1.27 (d, J = 6.2 Hz,
3H), 2.59 (br s, 1H), 2.88 (dd, J = 12.7, 7.7 Hz, 1H), 3.09 (dd,
J = 12.7, 4.0 Hz, 1H), 3.86 (m, 1H), 7.24–7.27 (m, 3H), 7.50–7.54
(m, 2H). IR ν (cm-1): 3466 (OH).
Anti-2-(phenylselanyl)cyclooctanol (2k)4: 1H NMR: δ 1.25–2.31
(m, 12H), 2.62 (br s, 1H), 3.31 (ddd, J = 12.0, 10.0, 4.0 Hz), 3.69
(dt, J = 10.1, 2.9 Hz, 1H), 7.25-7.32 (m, 3H), 7.58–7.61 (m, 2H).
IR ν (cm-1): 3444 (OH).
We are grateful to the National Natural Sꢀence Foundation
of China (No. 20476098 and 20504023) and Natural Sꢀence
Foundation of Zhengjiang Province (No. Y405015 and
Y405113) for finanꢀal support.
1-(phenylselanyl)octan-2-ol (3c)10: 1H NMR: δ 0.84 (t, J = 6.3 Hz,
3H), 1.25–1.54 (m, 10H), 2.41 (d, J = 3.8 Hz, 1H), 2.88 (dd, J = 12.7,
5.7 Hz, 1H), 3.14 (dd, J = 12.7, 3.4 Hz, 1H), 3.64 (m, 1H), 7.24–7.27
(m, 2H), 7.50–7.53 (m, 3H). IR ν (cm-1): 3434 (OH).
1-(phenylselanyl)dec-9-en-2-ol (3d): 1H NMR: δ 1.25–1.55 (m,
10H), 2.02 (q, J = 6.7 Hz, 2H), 2.35 (d, J = 3.57 Hz, 1H), 2.87 (dd,
J = 12.7, 8.6 Hz, 1H), 3.15 (dd, J = 12.7, 3.4 Hz, 1H), 3.66 (m, 1H),
4.96 (m, 2H), 5.80 (m, 1H), 7.25–7.27 (m, 3H), 7.51–7.55 (m, 2H).
13C NMR: δ 25.7, 28.8, 28.9, 29.4, 33.7, 36.6, 37.3, 69.8, 114.2,
127.3, 129.2, 129.4, 133.0, 139.1. MS(EI): 312 (M+), 310, 172, 170,
158, 141, 123, 95, 81, 79, 81,67, 55. IR ν (cm-1): 3422 (OH). Anal.
Calcd for C16H24OSe: C, 61.73; H, 7.77. Found: C, 61.6; H, 7.7.
1-phenyl-2-(phenylselanyl)ethanol (3e)4: 1H NMR: δ 2.33 (br s,
1H), 4.02–4.07 (m, 2H), 4.99 (dd, J = 7.1, 5.9 Hz, 1H), 7.25–7.50
(m, 10H).
Received 12 March 2007; accepted 15 May 2007
Paper 07/4526 doi: 10.3184/030823407X218011
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PAPER: 07/4526