Unexpected formation of 3,3a,4,7a-tetrahydrobenzofuran-2,5-dione as well as arene carboxylic acids upon formal double exo nucleophilic addition of R1R2C-COO- to anisolechromium tricarbonyl complexes

Article abstract of DOI:10.1039/a808072k

Bis(trimethylsily)ketene acetals of the general structure 2 (R¹ = H,Me,R² = Me,Et,Pr(i),CMe = CH₂) react at -78°C in the presence of Bu(t)OK with a series of arenechromium tricarbonyl complexes 3 to give as expected, after oxidation with I₂ followed by silica gel chromatography, arylcarboxylic acids 7. In the case of anisolechromium tricarbonyl 8, besides the m-methoxyarylcarboxylic acids, tetrahydrobenzofuran-2,5-diones 11, are formed as the result of a double nucleophilic addition.

Full text of DOI:10.1039/a808072k

Unexpected formation of 3,3a,4,7a-tetrahydrobenzofuran-2,5-diones as well as
arene carboxylic acids upon formal double exo nucleophilic addition of
1
2 2
2
R R C COO to anisolechromium tricarbonyl complexes
a
a
a
b
b
Moncef Bellassoued,* Evelyne Chelain, J e´ r oˆ me Collot, Henri Rudler* and Jacqueline Vaissermann
a
Laboratoire de Synth e` se Organom e´ tallique associ e´ au CNRS, Universit e´ de Gergy-Pontoise, 5 Mail Gay Lussac,
Neuville-sur-Oise, 95031 Cergy-Pontoise Cedex, France
Laboratoire de Synth e` se Organique et Organom e´ tallique, UMR 7611 and Laboratoire de Chimie des M e´ taux de
Transition, URA 419, Universit e´ Pierre et Marie Curie T 44-45, 4 place Jussieu, 75252 Paris Cedex 5, France.
E-mail: rudler@ccr.jussieu.fr
b
Received (in Liverpool, UK) 16th November 1998, Accepted 30th November 1998
Bis(trimethylsily)ketene acetals of the general structure 2
O
R
Me
1
2
i
(
2
R = H, Me, R = Me, Et, Pr , CMe = CH ) react at 278 °C
t
Me
Me
OSiMe3
OEt
t
R
OEt
in the presence of Bu OK with a series of arenechromium
) Bu OK, –78 °C
1
Me
+
tricarbonyl complexes 3 to give as expected, after oxidation
2
3
) I2, –78 °C
) H2O
2
with I followed by silica gel chromatography, arylcarboxylic
acids 7. In the case of anisolechromium tricarbonyl 8, besides
the m-methoxyarylcarboxylic acids, tetrahydrobenzofuran-
Cr(CO)3
1
3
4
2
,5-diones 11, are formed as the result of a double
nucleophilic addition.
Ph
+
3
Complexation of an arene group to Cr(CO)
3
allows, via an
OSiMe3
O
addition–oxidation sequence, the introduction of various sub-
stituents on the arene nucleus and, as a result, the construction
O
O
5
R = H
6
1
of complex molecules. Although a large array of substituted
Scheme 1
2
aryls bearing various functional groups (CN, CO R, etc.) have
been prepared since the pioneering work of Semmelhack and
Card,2,3 a method to directly introduce a carboxylic acid has still
reaction conditions, this complex gave with 2 (R
1
= H, R =
2
i
been lacking.
Pr ) a mixture of two compounds which could be separated by
silica gel chromatography. The physical data of the less polar
product corresponded to those of the expected arylcarboxylic
During our investigations directed towards the synthesis of
pyrrole-containing aryl acids from arenechromium tricarbonyl
4
acid 9c (41%).
7
The 13C NMR spectrum of the more polar
complexes, we were faced with this problem. Here we describe
a successful approach based on the interaction of arenechro-
mium tricarbonyl complexes with potassium enolates originat-
compound (23%), obtained as white crystals, mp 72 °C, showed
signals at d 195.50, 142.73 and 131.49, typical for a cyclohex-
enone, and also signals at d 175.92 and 72.27, which agree with
ing from bis(trimethylsilyl)ketene acetals5,6 which leads to not
1
only arylcarboxylic acids, but also to the unexpected formation
of g-functionalized cyclohexenones from anisole.
The following set of transformations allowed the reactivity of
such potassium enolates towards arenechromium tricarbonyl to
be assessed.
the presence of a g-lactone. The H NMR spectrum is also in
accord with the presence of these two functional groups, with
signals at d 6.76 (dd) and 6.19 (d) for the protons of the double
bond, and at d 5.15 (dm) for a proton geminated to oxygen.
Taken together, these data are fully consistent with
Thus, a solution of complex 3 (R = OPh, 1.53 g, 5 mmol)
and of the ketene acetal 1 (1.36 g, 7.5 mmol) in THF (10 ml)
11c,
3-isopropyl-3,3a,4,7a-tetrahydrobenzofuran-2,5-dione
7
(Scheme 2). 11a and 11b (together with the known acids) were
t
was treated at 278 °C with a slight excess of Bu OK (1 M) in
THF (8 ml) in the presence of HMPA (6 ml). After 1.5 h at this
Table 1
2
temperature, a solution of I (6.20 g, 5 equiv.) in THF (15 ml)
R
cooled to 278 °C was slowly added. The solution was then
O
R1
R1
OSiMe3
OSiMe3
progressively warmed to room temperature overnight. Treat-
t
1
) Bu OK, –78 °C
R
OH
ment with Et
extraction with Et
left an oil which was chromatographed on silica gel. Elution
with mixtures of light petroleum–Et O gave the aryl ester 4
0.72 g, 52%) (Scheme 1). Under the same conditions, the silyl
2
O and aqueous sodium bisulfite, followed by
+
R2
O and evaporation of the solvents in vacuo,
R2
2) I , –78 °C
) H2O
2
2
3
Cr(CO)3
2
7
2
3
7
(
enol ether of butyrolactone 5 led to a-phenylbutyrolactone 6
Yield
of 7 (%)
(
30%).7
Entry
2/equiv.
R1
R2
R
The bis(trimethylsilyl) acetals 2 behaved similarly. For
example, a solution of complex 3 (R = OPh, 0.6 g, 2 mmol) and
1
2
3
4
5
6
7
8
9
2
2
2
1.5
2
1.5
2
2
H
H
H
H
H
H
Me
Me
H
Me
Me
Et
H
OPh
H
OPh
H
OPh
H
68
79
66
61
94
85
63
77
23
1
2
acetal 2 (R = H, R = Me, 0.9 g, 4 mmol) in THF (10 ml) was
t
treated at 278 °C with a THF solution of Bu OK (5 ml) in the
presence of HMPA (3 ml), then with I
2
(2.1 g) in THF (10 ml)
Et
i
Pr
to give, after workup and silica gel chromatography as above,
i
7
Pr
fenoprofen 7 (0.38 g, 79%). This transformation is of a general
Me
Me
CMeNCH
scope giving the known acids in fairly good yields (Table 1).
Surprisingly, in the case of complex 8, derived from anisole,
the course of the reaction was different. Under exactly the same
OPh
H
1
2
Chem. Commun., 1999, 187–188
187

R1 R2
R1
O
OMe
H
R2
MeO
O
O
R1
OSiMe3
OSiMe3
1
) I2
–
O
+
OSiMe3
2) H2O
R2
H
Cr(CO)3
Cr(CO)3
10
11
2
8
t
Scheme 3
1
2
3
) Bu OK, –78 °C
) I2, –78 °C
) H2O
tion of a trans-fused system to a cis-fused one could occur
during the purification step (Scheme 3).
O
R1
R1
H
R2
To summarise, arylcarboxylic acids can be obtained in one
step from readily available bis(trimethylsilyl)ketene acetals and
arenechromium tricarbonyl complexes together with products
resulting from an intramolecular trapping reaction. Work is in
progress to establish the mechanism of the latter transformation,
to find the conditions that would make the bicyclic lactones the
exclusive products of the reaction, and to attempt their
enantioselective synthesis since in the case of 11b,c three
contiguous chiral centers are formed with high diastereo-
selectivity.
MeO
OH
O
R2
+
O
O
H
11
9
a R1 = R2 = Me
40%
37%
41%
6%
17%
23%
1
2
b R = H R = Et
1
2
i
c R = H R = Pr
Scheme 2
obtained under the same conditions. A final confirmation of the
structure came from a radiocrystallographic study on 11a,
shown in the CAMERON projection in Fig. 1.8
Notes and References
1
M. F. Semmelhack, Comprehensive Organic Synthesis, ed. B. M. Trost
and I. Fleming, Pergamon, Oxford, 1991, vol. 4, p. 517; E. P. K u¨ ndig,
Pure Appl. Chem., 1985, 57, 1855.
2
M. F. Semmelhack and H. T. Hall, J. Am. Chem. Soc., 1974, 96,
7
091.
3
4
R. J. Card and W. S. Trayhanovsky, Tetrahedron Lett., 1973, 3823.
A. Parlier, M. Rudler, H. Rudler, R. Goumont, J. C. Daran and J.
Vaissermann, Organometallics, 1994, 13, 4708.
5
6
7
C. Ainsworth and Y. N. Kuo, J. Organomet. Chem., 1973, 46, 73.
M. Bellassoued and M. Gaudemar, Tetrahedron Lett., 1990, 31, 209.
Selected data for 4: d
m, 5H), 6.85–6.95 (m, 1H), 4.13 (q, J 8, 2H), 1.55 (s, 6H), 1.17 (t, J 8,
H). d (50 MHz, CDCl ) 176.42, 157.12, 147.08, 129.7, 129.55,
23.21, 120.64, 118.7, 111.7, 60.90, 46.50, 26.51, 14.08. MS (EI) m/z
H 3
(200 MHz, CDCl ) 7.32–7.27 (m, 3H), 7.05–7.01
(
3
1
2
2
d
3
1
C
3
+
84 (M ). For 6: d
H), 3.60 (dd, J 9.5, 1H), 2.77–2.61 (m, 1H), 2.51–2.35 (m, 1H).
(50 MHz, CDCl ) 177.6, 136.76, 128.62, 128.0, 127.7, 66.64, 45.57,
1.64. MS (EI) m/z 212 (M ). For 7 (R = OPh): d
1.0 (br s, 1H), 7.38–6.87 (m, 9H), 3.49 (t, J 6, 1H), 2.10 (m, 1H), 1.77
m, 1H), 0.92 (t, J 7.2, 3H). d (50 MHz, CDCl ) 180.43, 157.50, 157.07,
H
(200 MHz, CDCl) 7.40–7.25 (m, 5H), 4.50–4.25 (m,
C
3
+
H
3
(200 MHz, CDCl )
Fig. 1 X-Ray structure of 11a. Important bond distances (Å): C(5)–O(3),
(
C
3
1
.209(2); C(6)–C(7), 1.313(3); C(7a)–O(1), 1.457(2); O(1)–C(2), 1.351(2):
1
5
d
5
1
1
49.43, 129.87, 123.44, 123.87.44, 123.0, 119.01, 118.82, 117.70,
3.30, 26.40, 12.20. MS (EI) m/z 256 (M ). For 11a: mp 69 °C;
C(2)–O(2), 1.193(2).
+
H
(200 MHz, CDCl
.10 (dd, J 3.4, 0.8, 1H), 2.81 (dd, J 13.8 and 6.4, 1H), 2.51 (ddd, J 13.8,
0.6 and 6.4), 1.25 (s, 3H), 1.09 (s, 3H). d (50 MHz, CDCl ) 196.17,
80.24, 141.61, 132.12, 70.97, 43.32, 35.25, 24.71, 20.05.
3
) 6.84 (dd, J 10.2, 3.4, 1H), 6.14 (d, J 10.2, 1H),
As expected for anisole,9,10 addition of the enolate to the
arenechromium system took place at the meta position to give
1
C
3
0, but it was followed by the concomitant formation of a
cyclohexenone (originating from the dienol ether) and of a
lactone (originating from the trimethylsilyl carboxylate group).
Although the formation of 3-substituted cyclohexenones via
8 Crystal data for 11a: colorless plates monoclinic space group P2 /n, a
= 11.369(3), b = 6.145(3), c = 13.537(4) Å, b = 105.53(2)°, Z = 4,
R = 0.0476, R * = 0.0564, GOF = 1.11. Collected reflections 2505,
w
1
independent reflections, 2186 (q = 1–28°, Mo-Ka radiation, Rint
=
nucleophilic addition to anisolechromium tricarbonyl com-
plexes is a known and important process,1
1–13
0.0079). The obtained structure model was first refined anisotropically
for all non-hydrogen atoms and isotropically for the hydrogen atoms
using 1549 reflections. CCDC 182/1116.
the formation of
fused systems containing a 4-substituted cyclohexenone such as
1 has to the best of our knowledge not been observed up to
now.
The mechanism of this transformation, which corresponds to
1
9
M. F. Semmelhack, J. J. Harrison and Y. Thebtaranonth, J. Org. Chem.,
1
979, 44, 3275.
1
0 J. C. Boutonnet, F. Rose-Munch and E. Rose, Tetrahedron Lett., 1985,
26, 3989.
11 M. F. Semmelhack and A. Yamashita, J. Am. Chem. Soc., 1980, 102,
a formal (3 + 2) cycloaddition, is still a matter of speculation.
Nevertheless, the presence of the methoxy group is fundamental
since no lactones were detected in its absence (vide supra): its
role is probably to activate the g-position or to stabilize a crucial
intermediate for the ring-closing step. Moreover, two observa-
tions could militate in favour of two successive exo addition
reactions, the second one taking place after the oxidation step,
5924.
1
2 H. G. Schmalz and K. Schellhaas, Angew. Chem., Int. Ed. Engl., 1997,
5, 2146.
3
1
1
3 A. J. Pearson and A. V. Gontcharov, J. Org. Chem., 1998, 63, 152.
4 M. F. Semmelhack, H. T. Hall, M. Yoshifuji, G. Clark, T. Bargar and K.
Hirotsu, J. Am. Chem. Soc., 1979, 101, 3535.
probably on an iodinated ring. First, 11 could not be detected
1
5 E. P. K u¨ ndig and D. P. Simmons, J. Chem. Soc., Chem. Commun., 1983,
before the iodine treatment of the intermediate 10,1
4,15
second,
1
320.
the cis junction of the two rings could indicate that the
carboxylato group enters also in an exo way although isomeriza-
Communication 8/08072K
188
Chem. Commun., 1999, 187–188