Use of ionic liquid as solvent in the oxidation of furans with singlet oxygen

Article abstract of DOI:10.1055/s-0030-1258211

The photocatalytic oxidation of a furan to a hydroxybutenolide in good yield is the first step of a one-pot synthesis of a γ-substituted α,β-unsaturated γ-butyrolactone in the ionic liquid 1-hexyl-3-methylimidazolium chloride ([HMIM][Cl]). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258211

SHORT PAPER
3415
Use of Ionic Liquid as Solvent in the Oxidation of Furans with Singlet Oxygen
O
xidation of Furan
l
s
ioune Fall, Massène Sène, Emilia Tojo, Generosa Gómez, Yagamare Fall*
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain
Fax +34(986)812262; E-mail: yagamare@uvigo.es
Received 8 July 2010; revised 13 July 2010
glucal into a furan diol that we had previously employed
Abstract: The photocatalytic oxidation of a furan to a hydroxy-
butenolide in good yield is the first step of a one-pot synthesis of a
g-substituted a,b-unsaturated g-butyrolactone in the ionic liquid 1-
hexyl-3-methylimidazolium chloride ([HMIM][Cl]).
for the photooxidative synthesis of a chiral butenolide
with singlet dioxygen.2d
The photooxidation of furans to butenolides is a common
Key words: ionic liquids, singlet oxygen oxidation, butenolide final key step in the total syntheses of many natural prod-
ucts.8 It is typically carried out in dichloromethane at
synthesis
–78 °C in the presence of a hindered base, using Rose
Bengal as photosensitizer,9 as is illustrated in Scheme 1
for the conversion of furan 1 into hydroxybutenolide 2.
We began the work described here by extending the use of
ILs to this reaction. It is worth mentioning that very few
studies concerning the reactivity of singlet oxygen (1O2)
in ILs have been carried out.10
Continuing research on the chemical and photochemical
generation of singlet molecular oxygen (1O2), the mecha-
nisms of its interactions, and the means of exerting ste-
reocontrol thereof, feeds its increasing popularity in
chemical synthesis, especially in biomimetic strategies.1
As part of our ongoing programme on the syntheses of bi-
ologically active natural products, we have successfully
used the oxidation of furan with singlet dioxygen for the
preparation of oxacyclic,2 carbocyclic,3 azacyclic4 and
thiacyclic5 systems. In consonance with a current trend in
academic and industrial research, in recent years we have
also begun to work towards the replacement of toxic vol-
atile organic solvents with ionic liquids (ILs) in these and
other reactions. The intense interest of organic chemists in
ILs as solvents is due not only to the probable non-toxic
nature of many members of this family (though by no
means all!),6 nor solely to such general characteristics as
thermal and chemical stability, negligible vapour pres-
sure, and non-flammability (many of which properties
contribute to environmental friendliness), but also to the
wide spectrum of suitable anions and cations available,
which allows their optimisation as regards such parame-
ters as loading capacity or solubility in other solvents. In
an earlier study,7 for example, we identified 1-butyl-3-
methylimidazolium methyl sulfate ([Bmim][MSO4]) as
an excellent solvent for the catalytic transformation of D-
We chose five different ILs as potentially suitable sol-
vents. The reaction was carried out at room temperature,
and the results are summarised in Table 1. Best yields
were obtained with chloride as anion (entries 4 and 5). In
particular,
1-hexyl-3-methylimidazolium
chloride
([HMIM][Cl]) afforded a 76% yield of 2 in just two hours,
without any need for Hünig’s base.
By means of our recently published method,2d,5b hydroxy-
butenolide 2 was easily dehydroxylated (Scheme 2), af-
fording a 74% yield of g-substituted a,b-unsaturated g-
butyrolactone 3, which has been used in enantiomerically
pure form by Gao et al.11 to obtain the biologically active
compound (+)-9a-epi-stemoamide. The present route to 3
constitutes a much more environmentally friendly ap-
proach than the method used by Gao et al., which involved
the reaction of an epoxide with the dilithio derivative of
phenylselenoacetic acid, followed by an oxidation–elimi-
nation reaction of the resulting g-substituted a-phenyl-
seleno-g-butyrolactones.12
O2, hν, Rose Bengal, –79 °C, 14 h
O
OTBDPS
O
OTBDPS
O
OH
2
MeOH,
N
74%
1
H
OTBDPS
••
O
N
O
O
Scheme 1 Oxidation of furan 1 with 1O2 in dichloromethane
SYNTHESIS 2010, No. 20, pp 3415–3417
x
x.
x
x
.
2
0
1
0
Advanced online publication: 13.08.2010
DOI: 10.1055/s-0030-1258211; Art ID: Z17510SS
© Georg Thieme Verlag Stuttgart · New York

3416
A. Fall et al.
SHORT PAPER
Furan 12c and the ILs tested in the present work: 1,3-dimethylimida-
zolium methyl sulfate ([MMIM][MeSO4]),13 1-octyl-3-methylimi-
dazolium chloride ([OMIM][Cl]),14 1-hexyl-3-methylimidazolium
chloride ([HMIM][Cl]),14 1-ethyl-3-methylimidazolium tetrafluo-
roborate ([EMIM][BF4]),15 and tetramethyl guanidinium lactate
([TMG][LAC])16 were synthesised according to known procedures.
Table 1 Oxidation of Furan 1 with 1O2 in Ionic Liquidsa
IL
O2 , hν, Rose Bengal, r.t.
OTBDPS
O
1
O
OTBDPS
Hydroxybutenolide 2
O
OH
To a solution of furan 1 (112 mg, 0.31 mmol) in [HMIM][Cl] (1
mL), which was previously purged with O2, was added Rose Bengal
(6.2 mg, 0.02 equiv) and the mixture was irradiated with a 200 W
lamp, under an O2 atmosphere. The reaction was monitored by TLC
(EtOAc–n-hexane, 5:95). At the end of the reaction (2 h), H2O (10
mL) was added and the product was extracted with CH2Cl2 (3 × 25
mL). The organic phase was dried over Na2SO4, filtered and the sol-
vent was removed by rotatory evaporation to give a residue, which
was purified by chromatography on silica (EtOAc–n-hexane, 1:1) to
afford hydroxybutenolide 2.
2
Entry
Time (h)
Yield (%)
IL
1
2
3
4
5
[EMIM][BF4]
[MMIM][MeSO4]
[TMG][LAC]
[OMIM][Cl]
3
5
3
3
2
16
11
13
66
76
Yield: 92 mg (76%); colourless liquid; Rf = 0.13 (EtOAc–n-hexane,
30%).
1H NMR (400 MHz, CDCl3): d = 7.70 (m, 4 H, o-PhH), 7.43 (m,
6 H, p,m-PhH), 7.25 (d, J = 5.60 Hz, 1 H, CH-3), 6.10 (d,
J = 5.59 Hz, 1 H, CH-4), 3.74 (m, 2 H, CH2-3¢), 2.10 (m, 2 H, CH2-
1¢), 1.27 (m, 2 H, CH2-2¢), 1.07 (s, 9 H, CH3-t-Bu).
[HMIM][Cl]
a See the general experimental section for abbreviations.
We considered whether the preparation of 3 from 1 might
be made both more efficient and even more environmen-
tally friendly by being carried out in [HMIM][Cl] in one
pot. Thus, we followed the oxidation of 1 with singlet di-
oxygen as described above by reduction of the product in
situ with sodium borohydride under Luche conditions, ob-
taining a 47% yield of g-butyrolactone 3 (Scheme 3).14
13C NMR (100 MHz, CDCl3): d = 170.98 (C=O), 155.09 (CH-4),
135.61 (o-Ph), 132.75 (C-Ph), 130.01 (p-Ph), 127.8s9 (m-Ph),
122.68 (CH-3), 107.64 (C-5), 64.27 (CH2-3¢), 35.99 (CH2-1¢), 26.72
(CH3-t-Bu), 26.34 (CH2-2¢), 19.11 (C-t-Bu).
One-Pot Synthesis of g-Butyrolactone 3 in [HMIM][Cl]
To a solution of furan 1 (95 mg, 0.26 mmol) in [HMIM][Cl] (2 mL),
which was previously purged with O2, was added Rose Bengal (5.3
mg, 0.02 equiv) and the mixture was irradiated with a 200 W lamp,
under an O2 atmosphere for 2 h. The mixture was allowed to reach
r.t., then NaBH4 (39 mg, 1.04 mmol) and a catalytic amount of
CeCl3·7H2O were added at 0 °C. The mixture was stirred at 0 °C for
1 h, then acidified with concentrated HCl. After extraction with
EtOAc (3 × 25 mL), the organic phases were dried over Na2SO4 and
the solvent was removed by rotatory evaporation. The residue was
purified by chromatography on silica (EtOAc–n-hexane, 1:9) to af-
ford g-butyrolactone 3.
In conclusion, we have shown that ionic liquids can serve
as green solvents in the photocatalytic oxidation of furans
to hydroxybutenolides, and that this reaction can be ex-
tended to a one-pot preparation of g-substituted a,b-unsat-
urated g-butyrolactones. We are currently working on
enantioselective versions of this reaction featuring chiral
ionic liquids derived from the chiral pool.
Yield: 47 mg (47%); Rf = 0.43 (EtOAc–n-hexane, 30%).
Solvents were purified and dried by standard procedures before use.
1
Melting points are uncorrected. H and 13C NMR spectra were re-
1H NMR (400 MHz, CDCl3): d = 7.67 (dd, J = 0.92, 1.13 Hz, 4 H,
o-PhH), 7.44 (m, 6 H, p,m-PhH), 7.42 (d, J = 7.73 Hz, 1 H, CH-3),
6.12 (dd, J = 1.87, 1.91 Hz, 1 H, CH-4), 5.07 (m, 1 H, CH-5), 3.73
(t, J = 5.11 Hz, 2 H, CH2-3¢), 1.93 (m, 1 H, CH2-1¢), 1.75 (m, 3 H,
CH-1¢, CH2-2¢), 1.07 (s, 9 H, CH3-t-Bu).
13C NMR (100 MHz, CDCl3): d = 173.14 (C=O), 156.30 (CH-4),
135.55 (o-Ph), 133.64 (C-Ph), 129.74 (p-Ph), 127.74 (m-Ph),
corded with a Bruker ARX-400 spectrometer (1H: 400 MHz, 13C:
100.61 MHz) using TMS as internal standard (chemical shifts in d
values, J in Hz). Mass spectrometry was carried out with a Hewlett
Packard 5988A spectrometer. Flash chromatography was per-
formed on silica gel (Merck 60, 230–400 mesh); analytical TLC
was performed on plates precoated with silica gel (Merck 60 F254,
0.25 mm).
1) NaBH4, CeCl3•7H2O, MeOH
2) HCl
O
O
OTBDPS
OTBDPS
O
3
O
2
74%
OH
Scheme 2
1) O2 , hν, Rose Bengal, r.t.
2) NaBH4, CeCl3•7H2O
3) HCl
IL
O
OTBDPS
OTBDPS
O
3
O
47%
1
Scheme 3
Synthesis 2010, No. 20, 3415–3417 © Thieme Stuttgart · New York

SHORT PAPER
Oxidation of Furans
3417
121.62 (CH-3), 83.18 (C-5), 63.06 (CH2-3¢), 29.87 (CH2-1¢), 27.82
(CH3-t-Bu), 26.88 (CH2-2¢), 19.23 (C-t-Bu).
(5) (a) Boullosa, S.; Gándara, Z.; Pérez, M.; Gómez, G.; Fall, Y.
Tetrahedron Lett. 2008, 49, 4040. (b) Besada, P.; Pérez, M.;
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Chem. Rev. 1999, 99, 2071. (b) Wasserscheid, P.; Keim, W.
Angew. Chem. Int. Ed. 2000, 39, 3772. (c) Sheldon, R.
Chem. Commun. 2001, 2399. (d) Wilkes, J. S. Green Chem.
2002, 4, 73. (e) Scammells, P. J.; Scott, J. L.; Singer, R. D.
Aust. J. Chem. 2005, 58, 155. (f) Bica, K.; Gaertner, P. Eur.
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Acknowledgment
This work was financially supported by the Spanish Ministry of
Education and Science (CTQ2007-61788), the Spanish Ministry of
Foreign Affairs and Cooperation (PCI A/023040/09) and the Xunta
de Galicia (INCITE08PXIB314253PR, INCITE08ENA314019ES
and INCITE08PXIB314255PR). The work of the NMR and MS di-
visions of the research support services of the University of Vigo
(CACTI) is also gratefully acknowledged. A.F. and M.S. thank
Asiyla Gum Company SARL for research fellowships.
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(c) Montagnon, T.; Tofi, M.; Vassilikogiannakis, G. Acc.
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Synthesis 2010, No. 20, 3415–3417 © Thieme Stuttgart · New York