7-oxabicyclo[2.2.1]heptadiene derivatives: Reactivity towards Bronsted acids

Article abstract of DOI:10.1039/a908451g

7-Oxabicyclo[2.2.1]heptadiene derivatives can be converted to phenols, fulvenes and/or the products from a retro-Diels-Alder-like reaction by treatment with Bronsted acids; the outcome of the reaction depends on the experimental conditions and the nature of the Bronsted acid used.

Full text of DOI:10.1039/a908451g

7-Oxabicyclo[2.2.1]heptadiene derivatives: reactivity towards Brønsted acids
Alain Maggiani, Arlette Tubul and Pierre Brun*
Laboratoire de Synthèse Organique Sélective, GCOPL, ESA 6114, Université de la Méditerranée, Faculté des
Sciences de Luminy, 163 Avenue de Luminy, case 901, F-13288 Marseille Cedex 9, France.
E-mail: brun@chimlum.univ-mrs.fr
Received (in Liverpool, UK) 22nd October 1999, Accepted 4th November 1999
7-Oxabicyclo[2.2.1]heptadiene derivatives can be converted
to phenols, fulvenes and/or the products from a retro-Diels–
Alder-like reaction by treatment with Brønsted acids; the
outcome of the reaction depends on the experimental
conditions and the nature of the Brønsted acid used.
described.5–8 We report here the results obtained when 1 is
reacted with Brønsted acids.
As with Lewis acids, depending on the nature of the Brønsted
acid, phenols 2 and/or hydroxyfulvenes 3 are formed. However,
another reaction was observed: a retro-Diels–Alder like reaction
(retro-DA) leading to 4 and DMAD 5 (Scheme 2).
During the course of our investigations we have synthesised a
large variety of arylphenols. These compounds are easily
obtained via Diels–Alder reaction between arylfurans and
dimethyl acetylenedicarboxylate (DMAD).1 However, in most
cases a mixture of the phenolic and the oxabicyclic derivatives
is obtained. The proportions of the two species depend on the
nature and the position of the substituent on the phenyl group.
7-Oxabicyclo[2.2.1]heptadiene derivatives are often used in
organic synthesis as synthons for natural product elaboration.2,3
We have shown previously that dimethyl 1-aryl-7-oxabicyclo-
[2.2.1]heptadiene-2,3-dicarboxylates 1 can be converted to
phenols 2 or to 6-hydroxyfulvenes 3 by reaction with Lewis
acids.4 Depending on the acid used, 2 or 3 can be formed in a
totally selective and quantitative way (Scheme 1). Never in the
past have such high yields and such a selectivity been
Our results are reported in Table 1. These results were
obtained using 1-(2-chlorophenyl)-7-oxabicyclo[2.2.1]hepta-
diene-2,3-dicarboxylate as a model compound, but similar
results were observed with 1 for R = p-nitro or p-acyl.
In the presence of gaseous HCl or with glacial AcOH (entries
4, 6–9) the retro-DA reaction is totally regioselective and is the
only process observed. In AcOH, the conversion rate increases
with the temperature. However, the retro-DA reaction is not a
purely thermal one, as exemplified by the absence of conversion
when 1 is heated at reflux in a CHCl3–CCl4 mixture (entry
10).
When mineral aqueous acids are used (HCl or H2SO4) the
results depend on the experimental conditions and particularly
on the solvent and temperature (entries 1–3, 5). In Et2O, at room
temperature, only the phenol 2 is formed. In CH2Cl2, with
H2SO4, only tars are formed starting from compound 1. With
aqueous HCl, under heating, the reaction is not selective and the
Scheme 1
Scheme 2
Table 1 Influence of the Brønsted acids nature on the behaviour of 1a
Yield (%)b
Entry
Acid
Solvent
T/°C
t/h
1
2
3
4 + 5
1
2
3
4c
5
6
7
8
9
HCl (aq.)
HCl (aq.)
HCl (aq.)
HCl (g)
H2SO4
AcOH
AcOH
AcOH
AcOH
None
CH2Cl2
CH2Cl2
Et2O
CH2Cl2
Et2O
—
—
—
—
55
reflux
25
25
25
25
60
90
reflux
reflux
24
24
24
48
24
48
48
48
48
48
44–37
8
89
6–0
72
50–63
11
9
11
100
5
100
40
25
18
95
60
75
82
10
CHCl3–CCl4
100
a
Reagents and conditions: i, aq. HCl or H2SO4, Et2O, room temp.; ii, aq. HCl, CH2Cl2, reflux; iii, anhydrous HCl, Et2O or CH2Cl2, room temp. (or
AcOH, reflux.) b The indicated yields are based on pure isolate compounds. c Ref. 9.
Chem. Commun., 1999, 2495–2496
This journal is © The Royal Society of Chemistry 1999
2495

retro-DA process is observed along with the formation of 2 and
3. The ratio of the different compounds depends on the
temperature, and the yield of the retro-DA reaction increases
with the temperature (entries 1, 2) while the yield of fulvene 3
decreases. It must be noted that the formation of the fulvene 3
and the retro-DA reaction are totally regioselective processes:
only the 6-hydroxyfulven 3 and the 2-arylfurane 4 are formed,
without any traces of another regioisomers.
With Lewis acids, 2 and 3 can be obtained selectively as
unique compounds. Similarly with gaseous HCl or AcOH, the
retro-DA-like reaction is the only one observed. Although we
have no evidence for the mechanism of that reaction, we have
observed, by thin layer chromatography, that an intermediate
compound is formed during the reaction with gaseous HCl. This
compound could not be isolated as it is rapidly converted to
arylfuran and DMAD. This suggest that the retro-DA-like
process could occur by chlorination (or acetoxylation in the case
of AcOH) of the starting compound followed by subsequent
rearrangements.
Our results show the great reactivity of 7-oxabicyclo-
[2.2.1]heptadiene derivatives towards Brønsted acids. This was
also demonstrated with Lewis acids. However, although with
Lewis acids it is possible to synthesise phenols and/or
6-hydroxyfulvenes, we have shown that with Brønsted acids it
is also possible to observe a quantitative and totally re-
gioselective retro-Diels–Alder like reaction in AcOH or with
gaseous HCl. Although, in our case, the retro-DA products are
the same as the ones used for preparing the starting compound
1, our observations may be applied to other 7-oxabicyclo-
[2.2.1]heptadiene derivatives and thus could be very useful, as
interest in retro-Diels–Alder reactions as a tool in organic
synthesis is increasing.10
Notes and references
1 A. Maggiani, A. Tubul and P. Brun, Synthesis, 1997, 631.
2 R. D. Little and G. N. Muller, J. Am. Chem. Soc., 1981, 103, 2744.
3 R. D. Little, G. L. Caroll and J. L. Petersen, J. Am. Chem. Soc., 1983,
105, 928.
4 A. Maggiani, A Tubul and P. Brun, Tetrahedron Lett., 1998, 39,
4485.
5 P. Vogel, B. Willhalm and H. Prinzbach, Helv. Chim. Acta, 1969, 52,
584.
6 D. S. Stusche and H. Prinzbach, Chem. Ber., 1973, 106, 3817.
7 A. Bruggink, H. Hogeveenh and T. B. Middlekoop, Tetrahedron Lett.,
1972, 4961.
8 R. K. Bansal, A. W. McCulloch, P. W. Rasmussen and A. G. McInnes,
Can. J. Chem., 1975, 53, 138.
9 General procedure for the retro-DA reaction induced by anhydrous
HCl: a stirred solution of the oxabicyclic derivative 1 in CH2Cl2 (0.5 ml
per 0.1 mmol of substrate) was saturated with anhydrous HCl (between
1.5 and 2 h). The solution was stirred at room temperature for 48 h. The
solution was washed with water to neutrality. The organic layer was
dried over MgSO4 and then concentrated under vacuum. The crude
product was purified by flash chromatography (eluent: hexane–Et2O).
10 R. Bloch and G. Mandville, Novel strategies for the use of retro-Diels–
Alder reactions in stereoselective synthesis, in Recent research
developments in organic chemistry, ed. S. G. Pandalai, TRN, Triva-
drum, India, 1998, vol. 2, pp. 411-452.
Communication 9/08451G
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Chem. Commun., 1999, 2495–2496