Woollins reagent: A chemoselective reducing agent for 1,4-enediones and 1,4-ynediones to saturated 1,4-diones

Article abstract of DOI:10.1055/s-0032-1317343

Woollins reagent was found to act as a highly chemoselective reagent for the reduction of a wide range of 1,4-enediones and 1,4-ynediones in methanol to afford the corresponding saturated 1,4-diketones in good yields under mild reaction conditions.

Full text of DOI:10.1055/s-0032-1317343

LETTER
▌2615
letter
Woollins Reagent: A Chemoselective Reducing Agent for 1,4-Enediones and
1,4-Ynediones to Saturated 1,4-Diones
Reducing Agent for 1,4-Enediones to Saturated 1,4-Diones
Madhumita Mandal, Sourav Chatterjee, Parasuraman Jaisankar*
Department of Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Calcutta 700032, India
Fax +91(33)24735197; E-mail: jaisankar@iicb.res.in
Received: 12.07.2012; Accepted after revision: 10.09.2012
are finding it very convenient to use deep-red crystals of
Abstract: Woollins reagent was found to act as a highly chemo-
WR for selenation reactions in preference to other seleni-
selective reagent for the reduction of a wide range of 1,4-enediones
um-containing reagents, as it can be easily prepared, safe-
and 1,4-ynediones in methanol to afford the corresponding saturat-
ed 1,4-diketones in good yields under mild reaction conditions.
ly handled in air, and has a less unpleasant odor.21 WR has
been used for the synthesis of symmetrical E-olefins,22
Key words: Woollins reagent, chemoselective reduction, 1,4-ene-
diones, 1,4-ynediones, 1,4-diketones
selenoketenyl complexes,23 and novel phosphorous–
selenium heterocycles.24 In our endeavor to obtain seleno-
phenes in one of our ongoing projects on bioactive mole-
cules, we observed for the first time that the reaction of
trans-1,2-dibenzoylethylene (1a) with WR in methanol
gave the unexpected and chemoselective C–C double-
bond-reduced product 1,2-dibenzoylethane (2a) in good
yield along with the corresponding cyclized product 2,5-
diphenylfuran (3a) in minor quantity. Interestingly, treat-
ment of 1,2-dibenzoylacetylene (4a) with WR in metha-
nol also afforded the same products 2a and 3a in nearly
1,4-Diketones are important and valuable precursors for
the synthesis of heterocyclic compounds like furan, pyr-
role, and their derivatives. Literature study revealed that
1,4-diketone derivatives have good uterotrophic activity
related to estradiol.1 A variety of synthetic methodologies
have been developed for the preparation of 1,4-diketones,
but most of them require lengthy procedures, special re-
agents, and expensive transition-metal complexes.2–4
same yield. Then we have extended this relatively simple
methodology to reduce other analogues of trans-1,2-di-
A number of synthetic methodologies and reagents have
been developed to bring about chemoselective reduction
aroylethylenes 1b–e and 1,2-diaroylacetylenes 4b–e to
of C–C double bonds in α,β-unsaturated carbonyl
yield the corresponding 1,2-diaroylethanes 2b–e (Scheme
compounds5,6 by using metal catalysts, such as osmium,7
1 and Scheme 2). The results are listed in Table 1 and Ta-
iridium,8 ruthenium,9 rhodium,10 platinum,11 palladium,12
ble 2. WR works equally well with cis-1,2-
nickel,13 and cobalt.14 The chemoselective reduction of C–
C double bonds in cis- and trans-1,2-diaroylethylenes and
of triple bonds in 1,2-diaroylacetylenes are relatively little
explored, except by Doi et al.15 who used [RuHCl(CO)
(PPh3)3] as an effective catalyst for the selective reduction
of 2-ene-1,4-diones to 1,4-diketones in benzene using iso-
propanol as the hydrogen donor. Herein, we report the
highly chemoselective reduction of the double bond in
1,2-diaroylethylenes 1a–e, 1,2-benzoylacetylethylene
(5a), and 1,2-diacetylethylene (5b), and of the triple bond
in 1,2-diaroylacetylenes 4a–e to the corresponding 1,2-
dibenzoylethanes 2a–e, 1,2-benzoylacetylethane (6a) and
1,2-diacetylethane (6b) by the most familiar selenium-
containing reagent ‘Woollins reagent’ under mild reaction
conditions.
dibenzoylethylene25 as that of its trans isomer 1a to fur-
nish 2a and 3a in 67% and 16% yields, respectively.
Table 1 Reduction of trans-1,2-Diaroyl Ethylenes to 1,2-Diaroyl
Ethanes by WR
Entry
R1
R2
Time (h) Yield (%)a
1
2
3
4
5
H
H
H
H
H
Cl
1.5
1
2a 6727
2b 6430
2c 6031
2d 6832
2e 60
3a 1533
3b 1633
3c 1533
3d 1733
3e 16
Me
Cl
1
Br
Me
2
1
a Isolated yield.
2,4-Diphenyl-1,3-diselenadiphosphetane-2,4-diselenide
(PhPSe2)2, also known as Woollins reagent (WR),16 is a
selenium analogue of another well-known sulfur-contain-
ing reagent named Lawesson’s reagent, (4-MeOPhPS2)2.
Similarly, the unsymmetrical alkenone (E)-1-phenylpent-
2-ene-1,4-dione (5a)26 underwent reduction to yield 1-
After Woollins et al. reported the first time about this re- phenylpentane-1,4-dione (6a)27 in 42% yield along with
agent, a number of advanced synthetic routes have been 2-methyl-5-phenylfuran (7a) in 18% yield (Scheme 3).
reported so far for the preparation of WR.17–20 Researchers
Reduction of trans-hex-3-ene-2,5-dione (5b)28 where two
carbonyl groups are flanked by methyl groups under the
same reaction conditions yielded hexane-2,5-dione (6b)29
(Scheme 3, Table 3) along with 2,5-dimethylfuran (7b) in
46% and 17% yields, respectively. On the other hand,
SYNLETT 2012, 23, 2615–2618
Advanced online publication: 12.10.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317343; Art ID: ST-2012-B0585-L
© Georg Thieme Verlag Stuttgart · New York

2616
M. Mandal et al.
LETTER
R1
R2
R1
R2
O
O
R2
R1
R2
WR
O
+
MeOH, r.t.
R1
O
O
R1
R1
R2
R2
1a–e
2a–e
3a–e
Scheme 1 Reduction of trans-1,2-diaroylethylenes to 1,2-diaroylethanes by WR
R1
R2
O
O
O
R2
R2
R1
WR
+
MeOH, r.t.
O
O
R1
R1
R2
R1
R2
R2
R1
4a–e
2a–e
3a–e
Scheme 2 Reduction of 1,2-diaroylacetylenes to 1,2-diaroylethanes by WR
simple olefins/acetylenes (e.g., 3-nitrostyrene, 3-bromo-
Table 4 Effect of Solvent in the Reduction of trans-1,2-Dibenzoyl-
ethylene (1a) by WR
propyne, and heptyne) and α,β-unsaturated esters (e.g.,
ethyl cinnamate, ethyl propionate) did not undergo reduc-
tion under the present reaction conditions.
Solvent
Time (h)
Yield (%)a
MeOH
1.5
3
67
Table 2 Reduction of 1,2-Diaroyl Acetylenes to 1,2-Diaroylethanes
by WR
i-PrOH
40
Entry
R1
R2
Time (h) Yield (%)a
i-PrOH–H2O (7:3)
2
15
2a 6127
2b 6530
2c 6031
2d 6232
2e 60
3a 1633
3b 1533
3c 1833
3d 1633
3e 16
THF
5
n.r.
n.r.
n.r.
n.r.
1
2
3
4
5
H
H
H
H
H
Cl
1
DMF
5
Me
Cl
1
CH2Cl2
5
1.5
2
CHCl3
5
Br
Me
a Isolated yield; n.r. = no reaction.
1
a Isolated yield.
It is well known that WR is in equilibrium with a disele-
naphosphorane (PhPSe2, A), which is the true reactive
species in solution.36 This undergoes reaction with trans-
1,2-dibenzoylethylene (1a) and methanol giving the
phenylphosphonodiselenoate complex B. Upon attack by
another molecule of methanol at phosphorus, the complex
B undergoes cleavage to yield the reduced product 1,2-
dibenzoylethane (2a, Scheme 4).
O
O
WR
R4
R4
+
R3
R4
R3
R3
MeOH, r.t.
O
O
O
6a,b
7a,b
5a,b
Scheme 3 Reduction of arylalkyl and dialkyl enediones by WR
Table 3 Reduction of Arylalkyl and Dialkyl Enediones by WR
In order to support the proposed mechanism (Scheme 4),
wherein we have shown that the source of the protons is
from methanol, 1,2-dibenzoylacetylene (3a) was treated
with WR by using CD3OD as solvent. Both 1H NMR and
MS analyses of the resultant product confirmed the incor-
poration of deuterium into 2a (Figure 1).
Entry
R3
R4
Time (h) Yield (%)a
1
2
Ph
Me
Me
1.5
1.5
6a 4227
6b 4629
7a 1834
7b 1735
Me
a Isolated yield.
O
D
D
Ph
Ph
D
D
O
The role of methanol and other protic solvents in the pres-
ent methodology has been investigated. It is found that
methanol appears to be the solvent of choice (Table 4).15
Figure 1 Deuterated product of 2a
Synlett 2012, 23, 2615–2618
© Georg Thieme Verlag Stuttgart · New York

LETTER
Reducing Agent for 1,4-Enediones to Saturated 1,4-Diones
2617
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Acknowledgment
The authors thank Dr. Basudeb Achari, Emeritus Scientist, CSIR-
IICB for his valuable suggestions during writing of this manuscript.
Authors M.M. and S.C. thankfully acknowledge CSIR, New Delhi,
India and UGC, New Delhi, India respectively for the award of Re-
search Fellowships. This project was financially supported by the
Network project (ORIGIN) of CSIR, New Delhi, India.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
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ungIifoop
r
t
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2615–2618

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M. Mandal et al.
LETTER
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Synlett 2012, 23, 2615–2618
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