Cycloisomerization of olefinic carboxylic acids catalyzed by trifluoromethanesulfonic acid

Article abstract of DOI:10.1081/SCC-200046534

The trifluoromethanesulfonic acid-catalyzed cyclization of various differently substituted unsaturated carboxylic acids affords selectively substituted lactones in good yields. The reactions use 0.5 to 5% molar ratio of catalyst and can be run without solvent.

Full text of DOI:10.1081/SCC-200046534

w
Synthetic Communications , 35: 153–160, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200046534
Cycloisomerization of Olefinic Carboxylic
Acids Catalyzed by
Trifluoromethanesulfonic Acid
Lydie Coulombel
Laboratoire Ar oˆ mes, Synth e` ses et Interactions, UMR CNRS 6001
Universit e´ de Nice-Sophia Antipolis, Parc Valrose, Nice cedex 2, France
Elisabet Du n˜ ach
Laboratoire de Chimie Bio-Organique, UMR CNRS 6001 Universit e´ de
Nice-Sophia Antipolis, Parc Valrose, Nice cedex 2, France and
Laboratoire Ar oˆ mes, Synth e` ses et Interactions, UMR CNRS 6001
Universit e´ de Nice-Sophia Antipolis, Parc Valrose, Nice cedex 2, France
Abstract: The trifluoromethanesulfonic acid-catalyzed cyclization of various differ-
ently substituted unsaturated carboxylic acids affords selectively substituted lactones
in good yields. The reactions use 0.5 to 5% molar ratio of catalyst and can be run
without solvent.
Keywords: Lactones, cyclization, trifluoromethanesulfonic acid, unsaturated car-
boxylic acids
Lactones constitute a class of interesting compounds of wide occurrence in
natural products.
[1–3]
They are also found in the aromas of more than 120
[4]
foodstuffs and are often used as flavors and food additives. Intramolecular
cyclization of unsaturated carboxylic acids is one of the most straightforward
routes to the synthesis of lactones and leads directly to the desired products.
Received in Poland September 19, 2004
Address correspondence to Elisabet Du n˜ ach, Laboratoire de Chimie Bio-
Organique, UMR CNRS 6001 Universit e´ de Nice-Sophia Antipolis, Parc Valrose
0
6108 Nice cedex 2, France. E-mail: dunach@unice.fr

154
L. Coulombel and E. Du n˜ ach
Table 1. Influence of the solvent in the acid-catalyzed cyclization of 1f to 2f with
mol% of triflic acid
5
Temperature
(8C)
Time
(h)
Conversion
(%)
Yield of 2f
a
(%)
Solvent
CH Cl
ClCH CH Cl
2
2
40
84
7
48
86
48
86
4
2
2
CH
Toluene
3
NO
2
101
111
1.5
7
100
80
100
80
a
Yield of 2f obtained by GC, calculated on converted 1f. Lactone 2f was obtained as
an approximative 60 : 40 mixture of isomers.
Usually, this cyclization is promoted by an electrophilic reagent such as
iodine, phenylselenium chloride, mercuric, or palladium salts.
[5–12]
Never-
theless, a second step is necessary to remove the reagent. Acid-catalyzed
cyclization of unsaturated acids is a well-known reaction but occurs mostly
[
13–16]
with over-stoichiometric quantities of acid.
We report herein that a variety of substituted g- and d-lactones can be
easily prepared from differently substituted unsaturated carboxylic acids in
excellent yields using triflic acid as the catalyst, in 0.5 to 5% molar ratio. It
is worth noting that, to our knowledge, triflic acid has not yet been reported
in the acid-catalyzed cycloisomerization to lactones.
We first examined the influence of the solvent for this reaction as well as
that of the reaction temperature, with a terminal g,d-unsaturated acid,
2
-methyl-4-pentenoic acid 1f, used as model-compound (Table 1).
Table 2. Influence of the nature of the catalyst in the acid-
catalyzed cyclization of 1f in refluxing nitromethane
Catalyst
5 mol%)
Time
(h)
Conversion
(%)
Yield of 2f
a
(%)
(
H
H
2
3
SO
PO
4
24
24
24
1.5
10
–
10
–
4
p-TsOH.H O
2
20
100
20
100
TfOH
a
Yield of 2f obtained by GC, calculated on converted 1f. Lactone 2f
was obtained as an approximate 60 : 40 mixture of isomers.

Cycloisomerization of Olefinic Carboxylic Acids
155
d
g
g
d
b
g
g
b

156
L. Coulombel and E. Du n˜ ach
d
g
g
b

Cycloisomerization of Olefinic Carboxylic Acids
157

158
L. Coulombel and E. Du n˜ ach
As shown in Table 1, the most efficient cyclization of 1f to lactone 2f
resulted in refluxing nitromethane, in which the lactone was formed quantitat-
ively. All the cyclizations of 1f effected with TfOH resulted in very clean and
efficient reactions, and only the 5-membered-ring lactone was formed as an
approximate 60/40 mixture of cis/trans isomers.
In order to compare the cyclization efficiency of 1f with different classic
protic acids as the catalysts, sulphuric acid, p-toluenesulfonic acid, and phos-
phoric acid were tested. Table 2 presents the different results in the presence of
5
mol% of acid in refluxing nitromethane. Whereas 1f was completely
converted into 2f after 1.5 h with triflic acid as the catalyst, only 20% of 2f
were converted after 24 h with p-toluenesulfonic acid and 10% with sulfuric
acid. These examples illustrate the much higher efficiency of TfOH as the
catalyst in the cycloisomerization reaction.
We then extended the TfOH-catalysed cyclisation procedure to other
differently substituted and non-activated b,g- or g,d-unsaturated acids in
refluxing CH Cl or CH NO , and Table 3 summarises the results obtained.
2
2
3
2
The influence of the substitution on the double bond and of the length of
the chain was first examined in entries 1–5. When the carboxylic acid has a
terminal disubstituted double bond such as in 5-methylhex-4-enoic acid 1a
(
entry 1), the reaction can also be carried out in refluxing dichloromethane
in the presence of catalytic amount of triflic acid to give exclusively the
-membered ring lactone 2a in quantitative yield. This high selectivity can
6
be explained by the stability of the carbocation intermediate. In the same
way, the cyclization of 4-methyl-4-pentenoic acid 1b with a disubstituted
double bond afforded only the 5-membered ring lactone 2b quantitatively
(entry 2).
No reaction occurred in refluxing dichloromethane when the double bond
was terminal (as in 1e or 1f) or 1,2-disubstituted (as in 1c or 1d). In these
cases, the cyclization was efficient in refluxing nitromethane (entries 3 to
7
). For the carboxylic acids with an internal disubstituted double bond such
as in 1c or 1d, two almost equally stable carbocation intermediates can be
formed and consequently two different lactones. The cyclization of 1c was
regiospecific and led only to the formation of the g-lactone 2c; the four-
membered ring compound could not be detected (entry 3). However, the car-
boxylic acid 1d possessing a g,d-unsaturated double bond gave a mixture of
0
the corresponding five- and six-membered ring lactones 2d and 2d in a 72/
2
8 ratio (entry 4).
The cyclization of the carboxylic acids bearing a terminal double bond
such as in 1e, 1f, or 1g was regiospecific and led to the corresponding
g-lactones in quantitative GC yields (entries 5–7). The isolated yields were
lower because of the volatility of some of the products. However, no polymer-
ization occurred when the cyclization of 1e was carried out in the presence
of undecane as the internal standard; a quantitative yield of 2e was
obtained. In the case of 3,5-disubstituted lactones 2f and 2g, a mixture of

Cycloisomerization of Olefinic Carboxylic Acids
159
two diastereoisomers was obtained; a 60/40 ratio of cis and trans isomers was
determined by NOESY experiments. We further examined the cyclization of
unsaturated dicarboxylic acid 1h which could either afford the 5- or the
7
-membered ring lactones. As shown in Table 3 (entry 8), the only product
formed was the 5-membered ring lactone 2h which was isolated after esteri-
fication in the presence of potassium carbonate and methyl iodide in DMF
to give the corresponding lactone methyl ester.
It is important to note that the TfOH-catalyzed cyclization could be
performed in the absence of solvent. Thus, carboxylic acid 1f (entry 6)
could be completely and quantitatively converted into g-lactone 2f in the
presence of only 0.5% molar ratio of triflic acid at 1008C, in a reaction
without solvent.
In conclusion, we describe here a novel, powerful, and efficient catalytic
cycloisomerization of nonactivated unsaturated carboxylic acids to lactones in
quantitative yields. The reaction combines both the atom-economy concept
and the possibility to work in the absence of solvent with low catalyst
ratios, which are important issues in green chemistry.
REFERENCES
1
. Drioli, S.; Felluga, F.; Forzato, C.; Nitti, P.; Pitacco, G.; Valentin, E. Synthesis of
(
þ) and (2)-Phaseolinic acid by combination of enzymatic hydrolysis and
chemical transformations with revision of the absolute configuration of the
natural product. J. Org. Chem. 1998, 63 (7), 2385–2388.
. Rossi, R.; Bellina, F.; Mannina, L. A novel protocol for the stereoselctive synthesis
2
3
4
5
of variously substituted (Z)-5-Ylidene-5H-furan-2-ones. Tetrahedron Lett. 1998,
39 (19), 3017–3020.
. Pour, M.; Spulak, M.; Balsanek, V.; Kunes, J.; Buchta, V.; Waisser, K. 3-Phenyl-5-
methyl-2H,5H-furan-2-ones: tuning antifungal activity by varying substituents on
the phenyl ring. Bioorg. Med. Chem. Lett. 2000, 10 (16), 1893–1895.
. Dufoss e´ , L.; Latrasse, A.; Spinnler, H-E. Importance of lactones in food flavors:
Structure, distribution, sensory properties and biosynthesis. Sciences des
Aliments 1994, 14 (1), 17–50.
. Ohfune, Y.; Kurokawa, N. Efficient syntheses of naturally occurring 3,4-dihydrox-
yprolines: electrophile-mediated lactonization of 2-amino-3-hydroxy-4-pentenoic
acid derivatives. Tetrahedron Lett. 1985, 26 (43), 5307–5308.
6
7
8
9
. Larock, R. C.; Hightower, T. R. Synthesis of unsaturated lactones via palladium-
catalyzed cyclization of alkenoic acids. J. Org. Chem. 1993, 58 (20), 5298–5300.
. Kang, S. H.; Lee, J. H.; Lee, S. B. An improved reductive demercuration of orga-
nomercurials using triethylborane. Tetrahedron Lett. 1998, 39 (1/2), 59–62.
. Jonasson, C.; Horvath, A.; Baeckvall, J. E. Intramolecular Palladium(II)-Catalyzed
1
,2-Addition to Allenes. J. Am. Chem. Soc. 2000, 122 (40), 9600–9609.
. Chavan, S. P.; Sharma, A. K. Iodolactonization and iodoetherification of b,
g-unsaturated and alcohols using FeCl3 and NaI. Tetrahedron Lett. 2001, 42,
4923–4924.

160
L. Coulombel and E. Du n˜ ach
10. Tiecco, M.; Testaferri, L.; Temperini, A.; Bagnoli, L.; Marini, F.; Santi, C.
Oxidation of diphenyl diselenide with 2,3-dichloro-5,6-dicyanobenzoquinone
(DDQ). A new method for the electrophilic phenylselenenylation of alkenes
under mild conditions. Synlett 2001, 11, 1767–1771.
1. Gruttadauria, M.; Aprile, C.; Noto, R. Stereocontrolled approach to d- and
1
2
g-lactones and 1,3-diols. The role of X ion in the selenolactonization. Tetra-
hedron Lett. 2002, 43 (9), 1669–1672.
1
2. Curini, M.; Epifano, F.; Marcotullio, M. C.; Montanari, F. Oxonew-KI induced
lactonization and etherification of unsaturated acids and alcohols: A formal
synthesis of Mintlactone. Synlett 2004, 2, 368–370.
13. Ansell, M. F.; Palmer, M. H. The cyclization of olefinic acids to ketones and
lactones. Quart. Rev.(London) 1964, 18 (2), 211–225.
1
4. Tiecco, M.; Testaferri, L.; Tingoli, M. Acetoxy lactonization of alkenyl acetic
acids promoted by ammonium persulfate and trifluoromethanesulfonic acid in
acetic acid. Tetrahedron 1993, 49 (24), 5351–5358.
1
1
5. Mali, R. S.; Babu, K. N. Efficient synthesis of a-benzylidene-g-methyl-g-butyro-
lactones. Helv. Chim. Acta 2002, 85 (10), 3525–3531.
6. Miura, Ka.; Hayashida, J.; Takahashi, T.; Nishikori, H.; Hosomi, A. Acid-
catalyzed intramolecular addition of a carboxy group to vinylsilanes.
J. Organomet. Chem. 2003, 686 (1–2), 242–250.