Novel catalytic tandem isomerisation/cyclisation reaction of α-methallyloxy carboxylic acids

Article abstract of DOI:10.1002/ejoc.200600300

A new tandem isomerisation/cyclisation of α-methallyloxy carboxylic acids leading to substituted 1,3-dioxolan-4-ones in 60-70 % yields was catalysed by Cu(OTf)₂ or Al(OTf)₃. Extension to the synthesis of oxathiolanones and oxathianon

Full text of DOI:10.1002/ejoc.200600300

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600300
Novel Catalytic Tandem Isomerisation/Cyclisation Reaction of α-Methallyloxy
Carboxylic Acids
Xavier Chaminade,[a] Lydie Coulombel,[a] Sandra Olivero,[a] and Elisabet Dunach*[a]
Keywords: Isomerisation / Cyclisation / Dioxolanone / Lewis acid
A new tandem isomerisation/cyclisation of α-methallyloxy
carboxylic acids leading to substituted 1,3-dioxolan-4-ones
in 60–70% yields was catalysed by Cu(OTf)2 or Al(OTf)3. Ex-
tension to the synthesis of oxathiolanones and oxathianones
is also described.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Transition metal catalysed cycloisomerisation of unsatu-
Preliminary cyclisation studies were carried out with
rated hydrocarbons is an attractive and atom-economical model substrate 1a (R1 = Ph, R2 = Me, Table 1). Its intra-
route for the preparation of carbo- and heterocycles.[1] This molecular cyclisation was examined with several Lewis
reaction has been successfully applied to the cyclisation of acids derived from triflates, such as Co(OTf)2, Cu(OTf)2,
enyne and diyne derivatives.[2] The catalytic cycloisomeri-
sation of olefinic alcohols has recently been reported by the
Table 1. Cycloisomerisation of α-methallyloxy carboxylic acids 1a–
use of transition-metal complexes[3–7] and constitutes a
1f (R2 = Me) using copper(II) triflate (5 mol-%) as the catalyst in
refluxing 1,2-dichloroethane.
novel and alternative method for the construction of oxy-
genated heterocycles. The novel use of tin(IV) triflate as a
Lewis super-acid for cycloisomerisation of non-activated
olefinic alcohols,[8] prompted us to examine other Lewis
acid catalysed cyclisation processes under aprotic condi-
tions.
Here we present a new reaction based on the Lewis acid
catalysed tandem isomerisation/cyclisation of α-allyloxy
carboxylic acids of type 1, in order to obtain the corre-
sponding six- and/or seven-membered ring oxygenated het-
erocycles 2 and 3, respectively, according to Scheme 1.
Scheme 1. Expected reactivity of α-methallyloxy carboxylic acids
in the presence of a Lewis acid catalyst.
Some dioxanone 2 and dioxepanone 3 derived heterocy-
cles have been isolated from natural sources[9] and present
biological activities. These heterocycles may also have some
potential interest in flavour and fragrance chemistry.[10]
[a] Laboratoire de Chimie des Molécules Bioactives et des Arômes,
CNRS, UMR 6001, Université de Nice-Sophia Antipolis,
Parc Valrose, 06108 Nice cedex 2, France
E-mail: dunach@unice.fr
[a] See ref.[15]
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Catalytic Tandem Isomerisation/Cyclisation Reaction of α-Methallyloxy Carboxylic Acids SHORT COMMUNICATION
Zn(OTf)2, Al(OTf)3 and Sc(OTf)3. The most efficient and
In order to extend the scope of this tandem isomeris-
selective catalytic systems were copper(II) and alumini- ation/cyclisaton process to the synthesis of other 1,3-di-
um(III) triflates, used in a 5 mol-% ratio with respect to 1a oxolan-4-ones, the influence of other R1 substituents in
in refluxing 1,2-dichloroethane. Cu(OTf)2 presented a substrates 1, with R2 = Me, was first examined. The results
higher catalytic activity and the complete conversion of 1a obtained for the Cu(OTf)2-catalysed cycloisomerisation are
was attained after 0.5 h. In contrast, the reaction of 1a with presented in Table 1.
Al(OTf)3 was completed after 2.5 h. The cyclisation of 1a
All the substrates 1a–1f led to quantitative cyclisation
with Cu(OTf)2 could also be run in refluxing nitromethane, yields and the corresponding dioxolanones 4a–4f were ob-
but no conversion was observed in refluxing dichlorometh- tained as the major products in 62–70% yields. Whatever
ane after 24 h.
the nature of the R1 substituent, the isomerisation/cyclis-
With copper(II) triflate, the reaction of 1a afforded a ation process occurred selectively. The cis isomer of dioxol-
quantitative cyclisation, with a mixture of two compounds. anones 4 was always favoured. The cis/trans assignments
The expected dioxanone 2a (R1 = Ph, R2 = Me), formed as were determined by NOESY-NMR experiments on isolated
the minor product in 28% yield, and the unexpected dioxol- compounds.
anone 4a, obtained in 68% yield and a cis/trans ratio of
Cycloisomerisations with Al(OTf)3 occurred at a lower
58:42 (Scheme 2). The rearrangement leading to 4a was also rate than with Cu(OTf)2. For 1a, dioxolanone 4a was ob-
observed with other triflate-based catalytic systems and no tained in 70% yield and a cis/trans ratio of 61:39. The
conditions were found leading to dioxepanone 3a.
cyclisation of 1e occurred in 1.5 h [to be compared to 0.5 h
The formation of the five-membered heterocycle 4 can with Cu(OTf)2 under the same conditions], affording 77%
be explained by a first CuII-catalysed isomerisation of the of 4e (cis/trans =75:25). It was also checked in reactions
double bond to form the enol ether intermediate 5 before with 1b, 1c and 1e that there was no additional isomeris-
the cyclisation/hydrocarboxylation occurs (Scheme 2). The ation from 2 to 4 after 24 h.
double-bond isomerisation of allylic ethers to the corre-
We further extended the cyclisation process to other sub-
sponding enol ethers has already been described with other strates using differently substituted olefins. In the reaction
transition metal complexes.[11,12] However, to the best of with the non-substituted allyl ether derivative 1g (R1 = Ph,
our knowledge, no example of a tandem isomerisation/ R2 = H), no conversion took place in refluxing 1,2-dichloro-
cyclisation process has yet been reported.
ethane after 24 h with either copper or aluminium triflates.
The CuII triflate catalyses the double-bond isomerisation In the case of prenyl, crotyl or cinnamyl ether derivatives
of 1 to 5, the double bond in 5 being more stable due to its of mandelic acid (1h, 1i, 1j, respectively, Scheme 3), with
higher substitution and to the conjugation with the α-oxy- both catalysts the starting compound was consumed but no
gen atom. Moreover, the CuII Lewis acid coordinates to the cyclisation occurred. The main reaction product was man-
carboxylate group of 1 (and 5) and enhances the acidity of delic acid, obtained almost quantitatively and issued from
the carboxylic acid, allowing its addition to the double the cleavage of the carbon–oxygen bond of the allylic moi-
bond of intermediate 5. The cylisation of the carboxylate ety of substrates 1i–1j.
group of 5 by a hydrocarboxylation of the double bond can
then occur both on the most substituted olefinic carbon
atom to form the 1,3-dioxanone 2 or on the carbon atom α
to the oxygen atom to form the corresponding 1,3-dioxol-
anone 4. Whereas the formation of 2 can be explained by
the stabilisation of the tertiary carbocation intermediate,
Scheme 3. Catalytic C–O cleavage of allyloxy carboxylic acids 1h
(R3 = R4 = Me), 1i (R3 = Me, R4 = H) and 1j (R3 = Ph, R4 = H).
the formation of 4 is favoured by the stabilisation of the
carbocation intermediate by the α-oxygen atom.
The catalytic and selective cleavage of the allyl–oxygen
The nature of the catalyst, and in particular that of the bond of allyl ethers 1h–1j using metal triflates constitutes
triflate anion was essential for the success of the reaction. an alternative method of deprotection of these deriva-
No cyclisation occurred in the presence of CuCl2 or AlCl3. tives.[11,13,14]
The particular Lewis acidity of CuII triflate enhanced the
Our experiments pointed out an important difference in
double-bond isomerisation as well as its regioselective hy- reactivity between the behaviour of the methallyl group and
drocarboxylation. that of other differently substituted or non-substituted al-
Scheme 2. Copper(II) triflate catalysed cycloaddition reaction of 1a–1f involving double-bond isomerisation.
Eur. J. Org. Chem. 2006, 3554–3557
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X. Chaminade, L. Coulombel, S. Olivero, E. Dunach
SHORT COMMUNICATION
Scheme 4. Aluminium(III)-catalysed tandem isomerisation/cyclisation of thioallyl derivative 1k.
lylic ether double bonds. The results seem to indicate that function and the methallyl ester 1m of -lactic acid
the isomerisation of the double bond constitutes a key step (Scheme 6). In this case, we expected the addition of the O–
for the success of the tandem isomerisation/cyclisation reac- H group of the alcohol across the double bond to form a
tion leading to dioxolanones. In the case of the methallyl six-membered heterocycle. With Al(OTf)3, 1m led exclu-
group, the isomerisation of 1a–1f to an enol ether 5 sively to the five-membered ring compound 4m in a 38%
(Scheme 2) is being highly favoured, affording a trisubsti- yield by isomerisation of the double bond of the allylic ester
tuted double bond α to the oxygen atom. In the case of the to a vinyl carboxylate intermediate 5m and selective intra-
prenyl (1h), crotyl (1i) or cinnamyl (1j) derivatives, the molecular addition. The formation of 4m indicated that
double-bond isomerisation is less favoured and the cleavage with the Lewis acid, the alcohol function was also able to
of the C–O bond is then facilitated by the Lewis acid add to the double bond in the absence of a protic catalyst.
through the formation of a more stable allylic cation inter-
mediate (Scheme 3).
The use of copper(II) triflate instead of aluminium(III)
triflate led to similar results. The cyclisation of 1m with Cu-
(OTf)2 occurred in 2 h and formed 4m in 39% yield with a
cis/trans ratio of 73:27.
The present work constitutes the first example of a tan-
dem isomerisation/cyclisation process and constitutes also
the first example of direct and catalytic preparation of diox-
olanones and their sulfur analogues. It is also a novel exam-
ple of catalytic “super” Lewis acid reactivity.
In conclusion, copper(II) and aluminium(III) triflates
were shown to be efficient catalysts for the isomerisation/
cyclisation of α-methallyloxy carboxylic acids. The tandem
reaction was carried out efficiently and allowed the forma-
tion of 2,5-disubstituted 1,3-dioxolan-4-ones in yields of
60–70%. The same isomerisation/cyclisation reaction was
extended to α-thiomethallyloxy carboxylic acids for the syn-
thesis of oxathiolanones and oxathianones. The tandem
process also occurred with α-hydroxy methallyl esters.
Other allylic ethers underwent allylic deprotection. The sim-
plicity of the catalytic system, the use of commercially avail-
able CuII or AlIII triflates without the need of ligand and
the relative mild reaction conditions are to be emphasised.
We also examined the reactivity of two analogous thi-
omethallyl derivatives 1k and 1l. With these substrates, the
best cyclisation results were obtained using Al(OTf)3 as the
catalyst. The cycloisomerisation of thiolactic acid derivative
1k (Scheme 4) occurred with a 65% conversion in refluxing
nitromethane after 0.5 h. As with the analogous ether deriv-
ative 1c, the methallyl sulfide 1k underwent a tandem iso-
merisation/cyclisation process, affording 2-isopropyl-4-
methyl-1-oxa-3-thiolan-5-one (4k) in 62% yield.
The Al(OTf)3-catalysed reaction of thiobenzoic acid de-
rivative 1l afforded exclusively the six-membered ring 4l in
83% isolated yield (Scheme 5). The formation of benzooxa-
thianone 4l can also be explained by a tandem isomeri-
sation/cyclisation process.
Scheme 5. Isomerisation/cyclisation reaction of thiobenzoic acid
derivative 1l catalysed by Al(OTf)3.
Acknowledgments
An additional example of isomerisation/cyclisation was
further examined by considering the reverse intramolecular
Acknowledgments is made to the French Ministry of Education
reaction: the possibility of cyclisation between an α-hydroxy for doctoral scholarships to X. C. and L. C.
Scheme 6. Tandem isomerisation/cyclisation of the methallyl ester of -lactic acid catalysed by Al(OTf)3.
3556 Eur. J. Org. Chem. 2006, 3554–3557
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Catalytic Tandem Isomerisation/Cyclisation Reaction of α-Methallyloxy Carboxylic Acids SHORT COMMUNICATION
[14] H. Tsukamoto, Y. Kondo, Synlett 2003, 7, 1061–1063.
[15] General procedure for catalytic tandem isomerisation/cycli-
sation of 1a–f: Substrate 1 (1 mmol) was added to a refluxing
dry 1,2-dichloroethane solution (15 mL) of copper(II) or alu-
minium(III) triflate (5 mol-%, 0.05 mmol) under an inert gas
and the reaction was monitored by GC analysis of aliquots.
After complete conversion, the reaction mixture was treated
with saturated NaHCO3 solution and extracted with 3×30 mL
of Et2O. The organic layer was dried with MgSO4 and the sol-
vent evaporated under vacuum. The cis/trans ratio of com-
pounds 4 was determined by 1H NMR and GC. The dioxol-
anones were purified and separated by column chromatog-
raphy on silica gel using hexane/diethyl ether mixtures as the
eluents. The products were analysed by 1H and 13C NMR spec-
troscopy and mass spectrometry. Compounds 4a,[16] 4b[17] and
4c[18] are known.
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