J.-J. Filippi et al. / Tetrahedron Letters 44 (2003) 6647–6650
6649
(
0.99 g, 5 mmol), HMDO (1.35 g, 1.67 equiv.) and
to reaction allowed us to check the entire consumption
of the initial lactones, which were poorly converted into
the expected compounds. Thus, preliminary studies
were performed to assess the reactivity of these sub-
strates to our system. d- and o-lactones (17a and 18a,
respectively) were submitted to reaction with conven-
tional heating, including an internal standardization.
The course of the reaction was monitored for 1 h, and
this allowed us to check that the reaction provided
similar results to those already observed for the
microwave procedure. Moreover, d- and o-thionolac-
tones were irradiated in the presence of HMDO, and
their stability was checked under these conditions.
P4S10 (0.56 g, 0.25 equiv.) was irradiated in solventless
conditions to provide similar amounts of b and d (entry
2
) as observed for LR (entry 1).
Using HMDO in a system where P4S10 is replaced by
Lawesson’s reagent allowed us to improve the selectiv-
ity of our procedure for the formation of the expected
thionolactones b. Although an excellent selectivity is
observed, the conversion has not reached more than
8
4% (entry 3). At least 0.75 equiv. of LR/HMDO were
required to reach a satisfying conversion (entry 4). As
8
–10
described in previous reports,
variable amounts of a
bis(trimethylsilyl)anisylthiophosphonate are present in
reaction mixtures. Moreover, irradiating LR and
HMDO allowed us to check that this product is not
observed when the reaction is carried out in the absence
of carbonyl compound.
In conclusion, we have developed a new and useful
procedure which seems to be very effective for the
synthesis of g-thionolactones, and can be easily scaled
up to larger quantities. The reactivity of the d- and
o-lactones to our procedure is still under investigation,
and work is currently in progress to adjust an efficient
synthetic procedure for further extension to a wider
variety of lactones.
At the end of the reaction, the internal temperature
reached 120°C. In order to check the microwave effect
on the system, the reaction was performed (lactone 5
mmol, LR 0.75 equiv., HMDO 0.75 equiv.) with con-
ventional heating at 120°C for 5 min, after which the
reaction reached 27% conversion only. In addition, 3 h
of reaction were required to reach a similar conversion
to that obtained by microwave procedure, with a very
good selectivity.
References
1
. Scheibye, S.; Kristensen, J.; Lawesson, S. O. Tetrahedron
979, 20, 1339–1343.
. Cava, M. P.; Levinson, M. I. Tetrahedron 1985, 41,
061–5087.
1
2
5
Lawesson’s reagent has been described as undergoing a
1
1,12
3. Olsson, R.; Hansen, C.; Andersson, C. M. Tetrahedron
Lett. 2000, 41, 7947–7950.
monomer-dimer equilibrium in solution,
while the
13
monomer is known to be the reactive species. In
addition, thionation reactions have been rationalized in
terms of nucleophilic attack of carbonyl oxygen upon
the electrophilic phosphorus of the monomer species. It
has been proposed that microwaves accelerate polar
transition state reactions, thus our procedure was
favourably performed under microwave irradiation.
4. Heravi, M. M.; Rajabzadeh, G.; Rahimidazeh, M.;
Bakavoli, M.; Ghassemzadeh, M. Synth. Commun. 2001,
15, 2231–2234.
5
6
. Varma, R. S.; Kumar, D. Org. Lett. 1999, 1, 697–700.
. Filippi, J. J.; Fernandez, X.; Lizzani-Cuvelier, L.;
Loiseau, A. M. Tetrahedron Lett. 2002, 43, 6267–6270.
. Curphey, T. J. Tetrahedron Lett. 2002, 43, 371–373.
. Curphey, T. J. J. Org. Chem. 2002, 67, 6461–6473.
. Curphey, T. J. Tetrahedron Lett. 2000, 41, 9963–9966.
1
4
7
8
9
Thus, the g-alkyl-g-lactones were readily converted into
their thiono-analogues (entries 4–12) and the expected
compounds were isolated in an 80–96% range. Addi-
tionally, a multigram synthesis (25 mmol) of g-
thionodecalactone was run, and the expected
thionolactone 11b was isolated with an 88% yield (entry
1
1
0. Sauer, R. O. J. Am. Chem. Soc. 1944, 22, 1707–1710.
1. Meisel, M. In Multiple Bond and Low Coordination in
Phosphorus Chemistry; Regitz, M.; Scherer, O. J., Eds.;
Thieme: Stuttgart, 1990; Chapter 6, 434.
12. Paulussen, H.; Haitjema, H.; Van Asselt, R.; Mylle, P.;
Adriaensens, P.; Gelan, J.; Vanderzande, D. Polymer
11). This procedure was successfully extended to syn-
thesize thiono-analogues of whisky lactone and cis-jas-
mone lactone which are representative flavouring
lactones. As a result, thionowhisky lactone and cis-jas-
mone thionolactone were, respectively, obtained with
2
000, 41, 3121–3127.
3. Rauchfuss, T. B.; Zank, G. A. Tetrahedron Lett. 1986,
7, 3445–3448.
1
2
1
1
4. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199–9223.
5. Procedure A: A mixture of lactone (5 mmol), Lawesson’s
reagent (1.52 g, 3.75 mmol) and hexamethyldisiloxane
7
3% (entry 13) and 65% yields (entry 14). On the other
hand, g-phenyl-g-butyrolactone strongly tended to pro-
duce a higher amount of dithio-analogue (entry 15) due
to its ring oxygen atom in benzylic position. Thus,
g-phenyl-dithiobutyrolactone 16d was readily synthe-
sized using 1 molar equiv. of LR only, affording the
expected dithiolactone with 94% yield.
(
0.61 g, 3.75 mmol) was placed in a Schlenk-type glass
tube fitted with a carefully tightened rubber septum under
nitrogen atmosphere, and was exposed to microwave
irradiation at maximal wattage (850 W), and stirred with
a vortex between irradiations of 30’’ duration each, after
which the internal temperature reached 120±5°C. After
cooling to room temperature, the reaction mixture was
dissolved in dichloromethane and adsorbed on silica gel.
Thionolactones were purified by column chromatography
using a mixture of hexane/Et O (9/1) or pentane/Et O
d-Lactones (entries 17) and o-lactones (entry 18), which
usually require higher reaction temperatures than g-lac-
tones, were submitted to the procedure applied for the
g-lactones, but provided moderate selectivities and low
yields. The internal standardization which is used prior
2
2
(9/1) for the most volatile lactones (entries 5 and 6).
Filippi, Jean-Jacques
