Gold-catalyzed regioselective hydration of homopropargyl alcohols followed by diastereoselective reduction: An easy access to cis 2,5-disubstituted tetrahydrofurans

Article abstract of DOI:10.2174/157017809790442989

A gold (III)-catalyzed hydration of homopropargyl alcohols led to the corresponding γ-hydroxy ketones, which were directly reduced by Ph ₃SiH in the presence of a Lewis acid, to afford the expected 2,5-disubstituted tetrahydrofurans as a diaste

Full text of DOI:10.2174/157017809790442989

630
Letters in Organic Chemistry, 2009, 6, 630-636
Gold-Catalyzed Regioselective Hydration of Homopropargyl Alcohols
Followed by Diastereoselective Reduction: An Easy Access to cis 2,5-
Disubstituted Tetrahydrofurans
Thi Xuan Mai Nguyen, Blandine Séon-Méniel, Jean-Christophe Jullian and Bruno Figadère*
Laboratoire de Pharmacognosie, associé au CNRS (BioCIS), Université de Paris-Sud, Faculté de Pharmacie, rue J.-B.
Clément, F-92296 Châtenay-Malabry, France
Received April 28, 2009: Revised October 20, 2009: Accepted October 20, 2009
Abstract: A gold (III)-catalyzed hydration of homopropargyl alcohols led to the corresponding ꢀ-hydroxy ketones, which
were directly reduced by Ph3SiH in the presence of a Lewis acid, to afford the expected 2,5-disubstituted tetrahydrofurans
as a diastereomeric mixture. NMR analysis of the compounds so obtained allowed us to confirm that the cis isomers were
the major isomers that can be used for the preparation of new products.
Keywords: Regioselective hydration, diastereoselective reduction, natural products, cascade reactions.
INTRODUCTION
in the presence of PdCl2(CH3CN)2 to afford the expected
ꢀ-hydroxy ketones [10]. We thus decided to hydrate under
palladium catalysis alcohol 3a (obtained by Yamaguchi
coupling reaction [11] between racemic allyl gycidol 1a and
hexyne 2a) and to directly reduce the ꢀ-hydroxy ketone
intermediate, which is in equilibrium with the cyclic
hemiketal, with Et3SiH-BF3.OEt2[12] (Scheme 1).
Unexpectedly the corresponding 2,5-disubstituted THF 4a
was obtained as a 60:40 cis/trans diastereomeric mixture in
low yield and as the free alcohol since the allyl protecting
group was also removed. We thus decided to study the Au
(III) catalyzed hydration of alcohol 3a [13], followed by the
direct reduction of the ꢀ-hydroxyketone intermediate
(Scheme 2).
2,5-Disubstituted tetrahydrofurans are found in many
natural products, as well as in pharmacologically active
products [1]. Access to this class of compounds has been
reviewed [2] and recently we have published the
diastereoselective preparation of trans 2,5-disubstituted
tetrahydrofurans based on a highly diastereoselective C-
glycosylation of lactol acetates with titanium enolates of
achiral N-acetyl oxazolidin-2-thiones [3].
Gold catalysts are nowadays used as powerful Lewis
acids for the activation of carbon-carbon triple bonds toward
various nucleophiles [4]. Indeed, H2O/alcohols [5], alkynes
[6], azides [7], carbonyl groups [8], have been successfully
used. Gold catalysts present several advantages when
compared to other noble metals (Pd, Pt, Ir, etc…): i) gold is
more abundant that other noble metals, ii) metallic gold is
biocompatible, iii) Au (III) has been reported to be possess
antiproliferative properties against human tumor cell lines
[9].
When compound 3a was treated by 5 mol% of
NaAuCl4.2H2O in a mixture of CH2Cl2/H2O (9:1) at room
temperature for 30 min, starting material 3a was consumed
and a complex mixture of the ꢀ-hydroxy ketone and the cis
and trans cyclic hemiketal intermediates was obtained. The
solvent was then evaporated under vacuum, then CH2Cl2 was
added, and the temperature brought to –78°C. BF3.OEt2 (1
equiv) was then added followed by either Et3SiH or Ph3SiH
This publication reports on highly regioselective Au (III)
catalyzed hydration of homopropargyl alcohols, easily
accessible from the coupling reaction of epoxides and
alkynes, followed by the Ph3SiH diastereoselective reduction
of the ꢀ-hydroxy ketones so obtained, to afford the major cis
2,5-disubstituted tetrahydrofurans. These results show
furthermore, that Au (III) can also be used in the reductive
step, acting as a very efficient Lewis acid.
(2.5 equiv) [14]. After
3 hours, the expected 2,5-
disubstituted THF 4a was obtained in good isolated yields
(75 and 83%, respectively) and with d.r. = 55:45 and 70:30,
respectively. Unfortunately, isomers could not be easily
separated by flash chromatography on silica gel, however
GC/MS allowed us to determine the diastereomeric ratios.
The major isomer was determined to be the cis isomer based
on NMR studies and on mechanistic considerations (see
below). It is important to note that the allyl-protecting group
was stable under these reaction conditions, whereas it was
removed when palladium (II) was used as a catalyst.
Furthermore, Ph3SiH reduction was more diastereoselective
than Et3SiH reduction (70:30 vs 55:45). Generalization of
this method was then studied. Thus alcohols 3b-f (obtained
in 43-82 % yield by Yamaguchi coupling reactions between
the required racemic glycidol derivatives and the desired
alkynes, see Experimental Part) were treated under the
RESULTS AND DISCUSSION
Recently we have shown that highly functionalized
homopropargyl alcohols could be regioselectively hydrated
*Address correspondence to the author at the Laboratoire de
Pharmacognosie, associé au CNRS (BioCIS), Université de Paris-Sud,
Faculté de Pharmacie, rue J.-B. Clément, F-92296 Châtenay-Malabry,
France; Tel: +33 (0)1 46 83 55 92; Fax: +33 (0)1 46 83 53 99;
E-mail: bruno.figadere@ u-psud.fr
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

An Easy Access to cis 2,5-Disubstituted Tetrahydrofurans
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
631
O
BuLi, BF3.OEt2
HO
+
O
1a
2a
3a
O
1) PdCl2(CH3CN)2,
CH2Cl2/H2O (9:1)
HO
O
OH
O
O
O
2) Et3SiH, BF3.OEt2
O
HO
4a : 13%, d.r. = 60:40
Scheme 1. Pallado-catalyzed approach.
R
R
OH
HO
O
R
HO
NaAuCl4.2H2O
CH2Cl2/H2O (9:1), r.t.
PO
O
3a-f
OP
OP
Et3SiH, BF3.OEt2
CH2Cl2, -78°C
or
O
Ph3SiH, BF3.OEt2
CH2Cl2, -78°C
R
+
PO
H
O
H
H
H
2a-d
1a-c
O
R
R
PO
+
PO
major cis 4a-f
minor trans 4a-f
Scheme 2. Gold-catalyzed approach.
reaction conditions designed above (5 mol% NaAuCl4.2H2O,
CH2Cl2/H2O (9:1), r.t., 30 min) followed by Ph3SiH-
BF3.OEt2 reduction. The results are summarized in Table 1
(see Scheme 2 and Table 1).
silica gel. NOESY spectra of both isomers were slightly
different, such as in the major cis isomer 4d a noe was
observed between the carbinol protons at ꢀ 4.90 and 4.34
ppm, whereas in the minor trans 4d no noe was observed
between the two corresponding protons at ꢀ 5.01 and 4.45
ppm (Fig. 1).
It is interesting to note that the expected THF 4a-e are
obtained in moderate to excellent yields (39-98 %), and with
a moderate to good diastereoselectivity. However 3f could
not be hydrated under these reaction conditions even when
temperature and solvent were changed (reflux and either
MeOH, EtOH, CH3CN). In the case of compound 4e, it is
important to note that the THP protecting group was also
removed under these reaction conditions (probably due to the
slightly acidic conditions of NaAuCl4 in the presence of
water5a). Nevertheless, it is noteworthy that allyl ethers,
pivalate and p-toluylsulfonate groups were stable under these
conditions.
Based on these findings, and on the mechanism of the
reaction (see below), we then assumed that all major isomers
4a-e were the cis THFs.
Then we decided to study the one-pot reaction conditions
for this new preparation of cis 2,5-disubstituted THF
(Scheme 3). Alcohol 3a was poured into CH2Cl2 and 5 mol%
of NaAuCl4.2H2O was added followed by H2O (1 equiv).
After 1h, Ph3SiH (2.5 equiv) was added at room temperature
and the reaction was stopped when no modification was
observed by TLC (3 h). After purification, compound 4a was
thus obtained in 53 % yield and with a d.r. = 75:25. It is
interesting to note that the diastereoselectivity is slightly
In the case of compound 4d, we were satisfied to separate
the major and minor isomers by flash chromatography on

632 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Nguyen et al.
Table 1. NaAuCl4.2H2O Catalyzed Hydration, Followed by Ph3SiH-BF3.OEt2 Reduction of 3a-f
P of Alcohols 3
R of Alcohols 3
THF Products 4
Yield (%)a
d.r.b
CH2=CHCH2
pCH3C6H4SO2
tBuCO
n-Bu
n-Bu
4a
4b
4c
4d
4e
4f
83
62
56
39
98c
0
70:30
73:27
80:20
70:30
80:20
-
n-Bu
tBuCO
mClC6H4
THPO(CH2)14
Si(CH3) 3
CH2=CHCH2
CH2=CHCH2
aisolated yields after 2 steps for the mixture of cis and trans 4a-f; bdetermined by GC/MS; cwith removal of the THP protecting group.
no n.o.e
n.o.e
Cl
Cl
H
O
O
H
H
H
H
H
O
O
O
O
ꢀ = 5.01 ppm
ꢀ = 4.45 ppm
ꢀ= 4.90 ppm
ꢀ = 4.34 ppm
major cis 4d
minor trans 4d
Fig. (1). Noe observed for compound 4d.
H
H
O
Bu
Bu
Bu
O
O
HO
NaAuCl4.2H2O (5%)
H2O (1 equiv), CH2Cl2, r.t.
major cis 4a
+
then Ph3SiH,
3a
H
H
O
O
53 %
d.r. = 75:25
minor trans 4a
Scheme 3. One pot gold-catalyzed hydration followed by reduction of compound 3ª.
better than when Ph3SiH-BF3.OEt2 was used (see Table 1,
entry 1).
was added at room temperature to afford, after 3h of stirring
and work-up and purification, the diastereomeric mixture of
cis and trans THF 4g (d.r. = 85:15) in 60 % yield. Removal
of the allyl protecting group was then efficiently performed
by treatment of this unseparable mixture of diastereomers 4g
by Et3SiH in the presence of 5 mol% PdCl2(CH3CN)2 in
CH2Cl2 to give the free primary alcohols. Then treatment of
the latter as described in ref [1c] would lead to the target
bioactive compound 6.
From a mechanistic point of view, Au (III) catalyst may
activate the triple bond that will lead to a dihydofuran gold
species, through a 5-endo dig cyclization, and then to the
cyclic hemiketal by hydrolysis. The corresponding
hemiketal, by Au (III) Lewis acid activation will then lead to
the cyclic oxonium species that will be reduced by the bulky
Ph3SiH reagent on the less sterically demanding face
(pathway “a”) (Fig. 2). It is noteworthy that diastereomeric
ratios observed in these reactions are typically what is
expected for nucleophilic additions on 3,4-nonsubstituted
cyclic oxoniums [15].
CONCLUSION
In conclusion, this study shows that the very simple Au
(III) catalyst, NaAuCl4.2H2O, can be advantageously used as
a soft Lewis acid for two domino transformations, namely
the regioselective hydration of non-terminal homopropargyl
alcohols and the diastereoselective reduction of cyclic
hemiketals to afford in good yield and high
diastereoselectivity the corresponding cis 2,5-disubstituted
THF. Furthermore, we showed that in the palladium
Then platelet aggregation factor from Uriach Pharma 6
was formally synthesized through this procedure as depicted
in Scheme 4 [16]. Butyllithium was added to heptadecyne 2e
at low temperature in THF followed by racemic allyl
glycidol 1a in the presence of BF3.OEt2 to give the
homopropargyl alcohol 3g in 70 % yield. Then alcohol 3g
was treated by 5 mol% of NaAuCl4.2H2O and H2O (1 equiv)
in CH2Cl2 at room temperature. After 1h, Ph3SiH (2.5 equiv)

An Easy Access to cis 2,5-Disubstituted Tetrahydrofurans
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
633
H
O
H2O
+
R
PO
R
-
Cl
Cl
Au
AuCl3
Cl
-
H
OH
H
O
R
O
+
PO
AuCl3
AuCl3
OP
a
H
R
O
+
R
Ph3SiH
HO
OP
b
OP
H
H
H
H
O
O
R
R
+
OP
OP
major cis
minor trans
Fig. (2). Proposed mechanism.
BuLi, BF3.OEt2
THF, -78°C
HO
12
O
+
O
70%
12
3g
1a
2e
O
NaAuCl4.2H2O (5%)
H2O (1 equiv), CH2Cl2, r.t.
60 %
d.r. = 85:15
then Ph3SiH,
H
H
H
H
O
O
C15H31
C15H31
+
O
O
major cis 4g
minor trans 4g
Et3SiH,PdCl2(CH3CN)2 cat.
then reference 1c
Et
O
H
H
O
N
+
C15H31
Cl-,
N
O
Ac
6
Scheme 4. Formal synthesis of compound 6.
catalyzed removal reaction of allyl protecting group, Bu3SnH
[17] can be efficiently replaced by the less toxic Et3SiH
reagent.
Flash chromatography was performed with silica gel 60
(9385 Merck), silica gel S (31607 Riedel-de-Haën), and
silica gel 60H (7736 Merck). TLC was performed on plates
coated with silica gel 60F254 (554 Merck). Plates were
visualised by spraying with Dragendorff’s reagent or with
50% H2SO4 and then heating.
MATERIALS AND METHODS
Solvents were purified according to the procedures des-
cribed. 1H- and 13C-NMR spectra were recorded at 200 MHz
or 400 MHz, and 50 or 100 MHz, respectively. Chemical
shifts (ꢀ) were expressed in ppm with the protonated solvent
as reference. Patterns were described according to Hoye et
al. [18], and coupling constants (J) were given in hertz (Hz).
1-Allyloxynon-4-yn-2-ol (3a)
To a solution of alkyne 2a-e (15 mmol, 1.5 equiv) in
anhydrous THF (30 mL) was added at -78°C butyllithium
(16 mmol, 1.6 equiv). After 1 h, protected glycidol 1a-c (10

634 Letters in Organic Chemistry, 2009, Vol. 6, No. 8
Nguyen et al.
mmol, 1 equiv) in THF (5 mL) was added followed by
BF3.THF (15 mmol, 1.5 equiv). After 2 h of stirring, a
NaHCO3 saturated aqueous solution (5 mL) was added, and
extracted three times with ethyl acetate (3 x 30 mL). The
combined organic layers were dried over MgSO4 then
filtered and concentrated in vacuo. The products were then
purified by flash chromatography with a mixture of
dichloromethane and ethyl acetate (95: 5) to give clear
yellow oil. Yield: 72% (1.42 g). 1H NMR (400 MHz): ꢀ 0.90
(t, J= 7.2 Hz, 3H), 1.39 (m, 2H), 1.46 (m, 2H), 2.15 (m, 2H),
2.41 (m, 2H), 3.44 (dd, J= 9.6, 6.8 Hz, 1H), 3.56 (dd, J= 9.6,
4.0 Hz, 1H), 3.89 (m, 1H), 4.03 (d, J= 5.6 Hz, 2H), 5.20 (d,
J= 10.4 Hz, 1H), 5.28 (dd, J= 17.2, 1.6 Hz, 1H), 5.91 (tdd,
J= 5.6, 10.4, 17.2 Hz, 1H). 13C NMR (75 MHz): ꢀ 13.4, 18.2,
21.7, 23.7, 30.8, 69.0, 72.1, 72.9, 75.4, 82.5, 116.9, 134.4. IR
(cm-1): ꢁ 3440, 2930, 2865, 2035, 2020, 1740, 1430, 1240,
1090. ESI-MS m/z : 219 (M+Na).
1-Allyloxy-5-trimethylsilanylpent-4-yn-2-ol (3f)
Yield: 63%. 1H NMR (300 MHz): ꢀ 0.14 (s, 9H), 2.39 (d,
J= 4.8 Hz, 1H), 2.45 (dd, J= 6.0, 2.7 Hz, 2H), 3.44 (dd, J=
9.6, 6.6 Hz, 1H), 3.55 (dd, J= 9.6, 3.9 Hz, 1H), 3.91 (m, 1H),
4.02 (dt, J= 1.2, 5.4 Hz, 2H), 5.20 (dq, J= 10.5, 1.2 Hz, 1H),
5.30 (dq, J= 17.4, 1.2 Hz, 1H), 5.9 (tdd, J= 5.4, 10.5, 17.4
Hz, 1H). 13C NMR (75 MHz): ꢀ 0.02, 25.0, 68.8, 72.3, 72.7,
87.3, 102.5, 117.3, 134.4. IR (cm-1): ꢁ 2180, 1250, 1095,
940. ESI-MS m/z : 213 (M+H).
1-Allyloxyicos-4-yn-2-ol (3g)
1
Yield: 70%. H NMR (300 MHz): ꢀ 0.88 (t, J= 5.4 Hz,
3H), 1.25 (brs, 26H), 1.47 (m, 2H), 2.15 (t, J= 6.3 Hz, 2H),
2.41 (m, 2H), 3.44 (ddd, J= 6.9, 9.6, 0.9 Hz, 1H), 3.56 (ddd,
J= 9.6, 3.9, 0.9 Hz, 1H), 3.89 (m, 1H), 4.03 (dd, J= 5.6, 1.2
Hz, 1H), 5.19 (dd, J= 10.2, 1.2 Hz, 1H), 5.28 (dt, J= 17.4,
1.2 Hz, 1H), 5.90 (tdd, J= 5.6, 10.2, 17.4 Hz, 1H). 13C NMR
(75 MHz): ꢀ 14.1, 18.7, 22.7, 23.9, 28.9, 29.0, 29.2, 29.3,
29.6, 29.7, 31.9, 69.1, 72.3, 73.0, 75.4, 83.0, 117.2, 134.5. IR
(cm-1): ꢁ 2920, 2855, 2355, 1465, 1090, 925. ESI-MS m/z :
351 (M+H).
2-hydroxylnon-4-yn-1-yl p-toluylsulfonate (3b)
1
Yield: 60%. H NMR (300 MHz): ꢀ 0.89 (t, J= 6.9 Hz,
3H), 1.39 (m, 4H), 1.97 (brs, OH), 2.10 (m, 1H), 2.40 (m,
2H), 2.44 (s, 3H), 3.94 (qd, J= 6.3, 4.2 Hz, 1H), 4.02 (dd, J=
10.2, 6.3 Hz, 1H), 4.13 (dd, J= 10.2, 4.2 Hz, 1H), 7.35 (d, J=
8.4 Hz, 2H), 7.80 (d, J= 8.4 Hz, 2H). 13C NMR (50 MHz): ꢀ
13.5, 18.3, 21.6, 21.9, 23.6, 30.8, 68.0, 72.1, 73.8, 84.0,
128.0, 129.9, 132.9, 145.0. IR (cm-1): ꢁ 3440, 2935, 1600,
1455, 1360, 1190, 1175, 1095. ESI-MS m/z : 311 (M+H).
2-Allyloxymethyl-5-butyltetrahydrofuran (4a)
To a solution of homopropargyl alcohol 3a-f (0.25 mmol,
1 equiv) in a 9:1 mixture of CH2Cl2/H2O (2 mL),
NaAuCl4.2H2O (0.05 equiv) was added at r.t.. After 30 min
of stirring, the reaction mixture was extracted with EtOAc (3
x 2 mL). The combined organic layers were dried over
MgSO4, filtered and concentrated under vacuum. The crude
products were dissolved in CH2Cl2 (5 mL) and BF3.OEt2 (1
equiv) was added at –78°C followed by either Et3SiH or
Ph3SiH (2.5 equiv). After 3 to 5 h of stirring (see in Table 1)
a NaHCO3 saturated aqueous solution (5 mL) was added,
and extracted three times with ethyl acetate (3 x 5 mL). The
combined organic layers were dried over MgSO4, filtered
and concentrated under vacuum. The purification by flash
chromatography on silica gel of the expected products
(CH2Cl2/cyclohexane 9:1) led to 4a-e (for yields and d.r., see
2-hydroxylnon-4-yn-1-yl 2,2-dimethylpropanoate (3c)
1
Yield: 82%. H NMR (400 MHz, CDCl3): ꢀ 0.89 (t, J=
7.6 Hz, 3H), 1.21 (s, 9H), 1.37 (m, 2H), 1.46 (m, 2H), 2.15
(t, J= 6.8 Hz, 2H), 2.42 (m, 2H), 3.94 (quint, J= 6.0 Hz, 1H),
4.14 (m, 2H). 13C NMR (100 MHz, CDCl3): ꢀ 13.5, 18.4,
21.9, 24.2, 27.1, 30.9, 38.8, 67.0, 68.6, 74.6, 83.6, 178.6. IR
(liquid phase in CH2Cl2, cm-1): ꢁ 2960, 1730, 1282, 1155,
916, 733. ESI-MS m/z : 263 (M+Na).
1
1-(3-chlorophenyl)-4-hydroxypent-4-yn-1-yl 2,2-dimethyl-
propanoate (3d)
in the text). H NMR (400 MHz) cis and trans mixture : ꢀ
0.89 (t, J= 6.8 Hz, 3H), 1.32 (m, 4H), 1.45 (m, 2H), 1.62 (m,
2H), 1.93 (m, 0.70x2H), 2.01 (m, 0.30x2H), 3.44 (m, 2H),
3.83 (m, 0.70x1H), 3.94 (m, 0.30x1H), 4.04 (m, 0.70x1H and
2H), 4.16 (m, 0.30x1H), 5.15 (dd, J= 1.2, 10.4 Hz, 1H), 5.27
(dd, J= 1.2, 17.2 Hz, 1H), 5.91 (tdd, J= 5.6, 10.4, 17.2 Hz,
1H). 13C NMR (75 MHz): ꢀ 14.0, 22.8, 28.2, 28.3, 28.4,
28.7, 30.8, 31.7, 35.5, 35.6, 72.4, 73.1, 73.2, 77.3, 77.8, 79.5,
80.1, 116.8, 134.9. IR (cm-1): ꢁ 2925, 2860, 1465, 1380,
1085. ESI-MS m/z : 221 (M+Na).
1
Yield: 43%. H NMR (400MHz, CDCl3): ꢀ 1.23 (s, 9H),
2.45 (brs, OH), 2.68 (d, J= 6.0 Hz, 2H), 4.09 (quint, J= 4.8
Hz, 1H), 4.20 (dd, J= 6.0, 11.2 Hz, 1H), 4.27 (dd, J= 4.0,
11.2 Hz, 1H), 7.24 (m, 3H), 7.39 (brs, 1H). 13C NMR (100
MHz, CDCl3): ꢀ 24.7, 27.2, 38.9, 67.1, 68.6, 81.8, 86.2,
124.8, 128.3, 129.5, 129.8, 131.6, 134.1, 178.7. IR (liquid
phase in CH2Cl2, cm-1): ꢁ 3470, 2970, 1730, 1590, 1560,
1475, 1400, 1285, 1155, 1095, 1035, 785. ESI-MS m/z; 295
(M+H), 297(M+H).
1-Allyloxy-14-tetrahydropyranyloxynonadec-4-yn-2-ol (3e)
2,5-epoxynonan -1-yl p-toluylsulfonate (4b)
Yield: 56%. 1H NMR (300 MHz, CDCl3): ꢀ 1.25 (s,
20H), 1.54 (m, 9H), 1.65-1.80 (m, 2H), 2.14 (tt, J= 6.9, 2.7
Hz, 2H), 2.41 (m, 2H), 3.36 (dt, J= 9.6, 6.6 Hz, 1H), 3.44
(dd, J= 9.6, 6.6 Hz, 1H), 3.50 (m, 1H), 3.57 (dd, J= 9.6 , 3.9
Hz, 1H), 3.72 (dt, J= 9.6, 6.6 Hz, 1H), 3.88 (m, 2H), 4.03
(dt, J= 5.4, 1.2 Hz, 2H), 4.57 (t, J= 2.7 Hz, 1H), 5.20 (dd, J=
1.2, 10.5 Hz, 1H), 5.30 (dd, J= 1.2, 17.1 Hz, 1H), 5.91 m,
1H). IR (liquid phase in CH2Cl2, cm-1): ꢁ 2925, 2855, 1465,
1120, 1075, 1025, 920. ESI-MS m/z : 459 (M+Na).
1H NMR (400 MHz) cis and trans mixture : ꢀ 0.87 (t, J=
6.8 Hz, 3H), 1.28 (m, 4H), 1.46 (m, 3H), 1.68 (m, 1H), 1.91
(m, 2H), 2.44 (s, 3H), 3.81 (m, 1H), 3.98 (m, 2H), 4.06 (m,
0.73x1H), 4.16 (m, 0.27x1H), 7.33 (d, J= 8.0 Hz, 2H), 7.80
(d, J= 8.0 Hz, 2H). 13C NMR (100 MHz): ꢀ 14.0, 21.6, 22.7,
27.9, 28.2, 28.3, 30.8, 35.2, 35.4, 71.8, 75.4, 75.7, 79.9, 80.6,
128.0, 129.8, 133.0, 144.7. IR (cm-1): ꢁ 2925, 2860, 1460,
1365, 1190, 1175, 1095, 965.

An Easy Access to cis 2,5-Disubstituted Tetrahydrofurans
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
635
1
2,5-epoxynonan-1-yl 2,2-dimethylpropanoate (4c)
(85:15) in 60 % yield : H NMR (400 MHz) cis and trans
mixture : ꢀ 0.89 (t, J= 6.4 Hz, 3H), 1.25 (m, 13H), 1.42 (m,
3H), 1.64 (m, 2H), 1.93 (m, 0.85x2H), 2.01 (m, 0.15x2H),
3.43 (m, 2H), 3.82 (m, 0.85x1H), 3.94 (m, 0.15x1H), 4.03
(m, 0.80x1H and 2H), 4.14 (m, 0.15x1H), 5.16 (d, J= 10.4
Hz, 1H), 5.27 (dd, J= 0.8, 17.6 Hz, 1H), 5.91 (tdd, J= 5.6,
10.4, 17.6 Hz, 1H). 13C NMR (100 MHz): ꢀ 14.1, 14.2, 22.7,
26.1, 26.2, 28.2, 28.7, 29.3, 29.6, 29.7, 29.8, 30.8, 31.7, 31.9,
35.8, 35.9, 72.4, 73.1, 73.2, 77.8, 79.5, 80.1, 116.8, 134.9. IR
(cm-1): ꢁ 2925, 2860, 1465, 1380, 1085. ESI-MS m/z : 375
(M+Na).
1H NMR (400 MHz) cis and trans mixture : ꢀ 0.88 (t, J=
6.8 Hz, 3H), 1.20 (s, 9H), 1.31 (m, 4H), 1.55-1.70 (m, 4H),
1.93 (m, 2H), 3.84 (q, J= 6.0 Hz, 0.80x1H), 3.93 (q, J= 6.0
Hz, 0.20x1H ), 4.05 (m, 0.80x1H and 2H), 4.20 (m,
0.20x1H). 13C NMR (100 MHz): ꢀ 14.0, 22.8, 27.2, 27.9,
28.3, 30.9, 35.6, 38.8, 66.4, 75.9, 76.3, 79.6, 80.2, 178.5. IR
(cm-1): ꢁ 2960, 1730, 1480, 1395, 1285, 1155, 1100, 1035.
ESI-MS m/z : 265 (M+Na).
5-(mchlorophenyl)-2,5-epoxypentan-1-yl 2,2-dimethyl-pro-
panoate cis 4d
ACKNOWLEDGEMENTS
1H (400MHz, CDCl3) ꢀ 1.23 (s, 9H), 1.85 (m, 2H), 2.12
(m, 1H), 2.31 (m, 1H), 4.22 (m, 2H), 4.32 (m, 1H), 4.90 (t,
J= 7.6 Hz, 1H), 7.23 (m, 3H), 7.37 (brs, 1H); 13C (100 MHz,
CDCl3) ꢀ 178.5, 145.0, 134.3, 129.5, 127.4, 125.7, 123.8,
80.7, 77.3, 66.1, 38.8, 34.6, 28.0, 27.2; ESI-MS m/z; 319
(M+Na), 321 (M+Na); IR cm-1: ꢁ 1725, 1480, 1280, 1150,
1080, 1035, 880; ESI-HRMS Calcd for [M+Na]+
C16H21O3ClNa: 319.1077 and 321.1047 Found: 319.1071
and 321.1062.
We thank the CNRS for financial support, and R. Koudih
for preliminary experiments.
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