A convenient approach to renewable hydroperoxides

Article abstract of DOI:10.1016/S0040-4039(01)00794-8

2-(1-Hydroperoxyalkyl)-furans and 6-hydroperoxy-2H-pyran-3(6H)-ones are alternatively accessible by acid-catalyzed oxidation of 2-furyl alcohols with hydrogen peroxide under appropriate conditions. Representative compounds of both classes of hydroperoxides have been used, as easily renewable oxygen donors, in asymmetric sulfoxidation reactions.

Full text of DOI:10.1016/S0040-4039(01)00794-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4577–4579
A convenient approach to renewable hydroperoxides
Antonio Massa,a Laura Palombib and Arrigo Scettria,*
aDipartimento di Chimica, Universita` di Salerno 84081 Baronissi, Salerno, Italy
bDipartimento di Chimica, Ingegneria Chimica e Materiali, Universita` di L’Aquila, 67010 Coppito, L’Aquila, Italy
Received 5 March 2001; revised 4 May 2001; accepted 11 May 2001
Abstract—2-(1-Hydroperoxyalkyl)-furans and 6-hydroperoxy-2H-pyran-3(6H)-ones are alternatively accessible by acid-catalyzed
oxidation of 2-furyl alcohols with hydrogen peroxide under appropriate conditions. Representative compounds of both classes of
hydroperoxides have been used, as easily renewable oxygen donors, in asymmetric sulfoxidation reactions. © 2001 Published by
Elsevier Science Ltd.
Cheap, safe, environmentally acceptable, energy- and
resource-saving processes represent some of the main
features of advanced chemical methodologies; besides,
the availability of highly efficient and selective proce-
dures is particularly important from the preparative
point of view, since it may often allow the direct use of
either crude intermediates or reagents, avoiding tedious
and expensive purification processes.
corresponding furylhydroperoxides 2: the reaction takes
places at room temperature by treatment of 1 with 30%
hydrogen peroxide (2 equiv.) in 1,2 dimethoxyethane
(DME) solution in the presence of catalytic amounts
(0.12 equiv.) of p-toluenesulfonic acid (PTSA) (Scheme
1).
Compounds 2 have shown satisfactory stability under
both the reaction conditions and in the course of isola-
tion and purification procedures so that they can be
obtained in good yields as pure products by silica gel
column chromatography (Table 1).
In connection with our previous research concerning
the employment of new oxygen donors in highly enan-
tioselective epoxidation1 and sulfoxidation2,3 reactions,
achieving an efficient approach to easily renewable
hydroperoxides, to be used in stereoselective oxidative
processes, seemed to be an important preparative
target.
It is noteworthy that no decomposition of 2 could be
observed after 1 month at −4°C.
One of the typical procedures for the synthesis of
hydroperoxides, involving treatment of alcohols with
hydrogen peroxide in an acidic medium,4,5 suffers from
some disadvantages: the reaction, usually performed on
tertiary or benzylic alcohols, often requires low values
of conversion in order to reduce significant decomposi-
tion of the hydroperoxides, promoted by temperature
and/or acidic catalyst. Moreover, because of the rela-
tive stability of the final products, isolation and purifi-
cation may represent further difficult aspects of this
approach.
Scheme 1.
Table 1. Conversion of furylalcohols 1 into furylhydroper-
oxides 2
Product
R
Reaction time (h)
Yield (%)
2a
2b
2c
2d
H
n-Hexyl
14
7
8
65
75
71
65
Me n-Hexyl
Me n-Pentyl
Me n-Octyl
We wish to report a very simple and cheap procedure
for the conversion of 2-furylcarbinols of type 1 into the
7
All the yields refer to isolated chromatographically pure compounds
whose structures were confirmed by spectroscopic data (IR, 1H
NMR and 13C NMR).
Keywords: sulfoxides; asymmetric reaction; oxidation.
* Corresponding author. E-mail: scettri@unisa.it
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00794-8

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A. Massa et al. / Tetrahedron Letters 42 (2001) 4577–4579
Scheme 2.
More interestingly, in the presence of greater amounts
of 30% hydrogen peroxide (5 equiv.) and PTSA (0.40
equiv.), intermediates of type 2 have been shown to
suffer further oxidation to give 6-hydroperoxy-2H-
pyran-3(6H)-one derivatives 3 in very high yields (usu-
ally >85%), as supported by 1H NMR analysis (400
MHz) on crude 3 (Scheme 2).
In conclusion, two different families of easily renewable
hydroperoxides are accessible by a very simple and
benign procedure and their potential synthetic value is
confirmed by preliminary use in asymmetric sulfoxida-
tion reactions.
Typical experimental procedure for the synthesis of
hydroperoxides 2 (or 3):
Compound 1 (or 4) (2.0 mmol) is dissolved in 21 ml of
DME (or 11 ml) and treated with 2 equiv. of 30%
hydrogen peroxide (or 5 equiv.) in the presence of 0.12
equiv. of PTSA (or 0.40 equiv.) at room temperature as
indicated in Table 1 (or Table 2). The reaction is
The structures of hydroperoxides 3 were confirmed by
comparison of the spectroscopic data of compounds 4,
quantitatively obtained by in situ reduction with
dimethylsulfide, with those of authentic samples pre-
pared according to a literature procedure6 (Scheme 3).
It is noteworthy that this one-pot, cheap and safe
sequence allows an efficient approach to products of
type 4, which are well-known both as bio-active
compounds7 and key-intermediates in the synthesis of
more complex molecules.8–11
Table 2. Conversion of furyl alcohols 1 into hydroperox-
ides 3
Product
R1
R2
Reaction time
(h)
Yield (%)
In every case compounds 3 can again be obtained in
very high yield (>90%) by submitting 4 to the usual
treatment with hydrogen peroxide. Compounds 2a and
3e have been chosen as representative hydroperoxides
for asymmetric sulfoxidation according to Modena’s
procedure12 and very promising results have been
obtained by using 2a (Scheme 4, Table 3) both in terms
of efficiency and enantioselectivity.
3b
3c
3d
3e
3f
H
H
H
n-Hexyl
Cyclohexyl
i-Propyl
18
23
16
7
75 (90/10)
77 (93/7)
84 (92/8)
77
Me Me
Et n-Hexyl
5
65 (50/50)
All the yields refer to isolated chromatographically pure compounds
whose structures were confirmed by spectroscopic data (IR, 1H
NMR and 13C NMR). Values in parentheses refer to diastereoiso-
meric ratios calculated by careful integration of the signals relative to
olefinic protons in the 1H NMR spectra (400 MHz) performed on
crude 3.
In all the reported experiments chiral sulfoxides were
isolated as R predominant enantiomers pointing out the
same sense of selectivity as Modena’s12 and Kagan’s13
procedures.
Table 3. Asymmetric sulfoxidation with hydroperoxides 2a
and 3e
It is noteworthy that in all the experiments the corre-
sponding reduction products 1a or 4e could be recov-
ered and recycled as indicated in Scheme 3.
Entry
Hydroperoxide
R
Yield (%)a
e.e. (%)b
a
b
c
2a
2a
3e
3e
Me
Cl
Me
Cl
61
82
77
80
98
93
68
64
d
a All the yields refer to isolated chromatographically pure compounds
(R configuration) whose structures were confirmed by spectroscopic
data (IR, 1H NMR and 13C NMR).
b E.e. values were determined by HPLC analysis using Chiralcel OB
column at u=254 nm.
Scheme 3.
Scheme 4.
.

A. Massa et al. / Tetrahedron Letters 42 (2001) 4577–4579
4579
monitored by TLC and, after the disappearance of 1,
hedron: Asymmetry 1998, 9, 1817.
4. Davies, A. G.; Feld, R. J. Chem. Soc. 1956, 665.
5. Kochi, J. K. J. Am. Chem. Soc. 1962, 84, 1193.
the mixture is diluted with Et2O (70 ml). The organic
phase is washed with brine and dried over magnesium
sulfate. After the removal of the solvent the resulting
crude product 2 (or 4) is purified by silica gel column
chromatography by elution with light petroleum/diethyl
ether mixtures.
6. Ho, T. L.; Sapp, S. G. Synth. Commun. 1983, 13, 207.
7. Laliberte`, R.; Medawar, G.; Lefebre, Y. J. Med. Chem.
1973, 16, 1084.
8. Georgiadis, M. P. J. Med. Chem. 1976, 19, 34.
9. Georgiadis, M. P.; Apostolopoulos, C. D.; Haroutou-
nian, S. A. J. Heterocyclic Chem. 1991, 28, 599.
10. Azimoto, H.; Asano, S.; Uemura, D. Tetrahedron Lett.
1997, 38, 7761.
References
1. Lattanzi, A.; Bonadies, F.; Scettri, A. Tetrahedron:
Asymmetry 1997, 8, 2141.
2. Lattanzi, A.; Bonadies, F.; Senatore, A.; Soriente, A.;
Scettri, A. Tetrahedron: Asymmetry 1997, 8, 2473.
3. Palombi, L.; Bonadies, F.; Pazienza, A.; Scettri, A. Tetra-
11. Matsumura, Y.; Shirai, K.; Maki, T.; Itakura, Y.;
Kodera, Y. Tetrahedron Lett. 1998, 39, 2339.
12. Di Furia, F.; Modena, G.; Seraglia, R. Synthesis 1984,
325.
13. Kagan, H. B.; Rebiere, F. Synlett 1990, 643.
.