Tellurium and iodine promoted cyclofunctionalization of alkenyl substituted β-keto esters

Article abstract of DOI:10.1055/s-1999-2679

This work describes the use of aryltellurium trichloride and iodine as suitable cyclization reagents for alkenyl substituted β-keto esters. The reaction takes place via the enolic form of the dicarbonyl compounds, giving the corresponding five-membered cy

Full text of DOI:10.1055/s-1999-2679

LETTER
567
Tellurium and Iodine Promoted Cyclofunctionalization of Alkenyl Substituted
b-Keto Esters
H. M. C. Ferraz*, M. K. Sano, A. C. Scalfo
Instituto de Química, Universidade de São Paulo, C.P. 26077, 05599-070-São Paulo-SP, Brazil
Fax 55-11-815-5579; E-mail: hmferraz@quim.iq.usp.br
Received 7 March 1999
As an extension of our previous works,8,9,15 and in analogy
Abstract: This work describes the use of aryltellurium trichloride
to those cited above, we investigated the behaviour of a
and iodine as suitable cyclization reagents for alkenyl substituted β-
series of α- and γ-alkenyl-β-keto esters toward aryltelluri-
keto esters. The reaction takes place via the enolic form of the dicar-
um trichloride. For comparison purposes, the same sub-
strates were also submitted to treatment with iodine. The
paper by Stefani et al.16 prompts us to disclose our first re-
sults on the cyclization of four of these β-keto esters,
namely 2-5, which are closely related to those studied by
them. The results are summarized in Scheme 1.
bonyl compounds, giving the corresponding five-membered cyclic
ethers in good yields.
Key words: cyclization, carbonyl compounds, tellurium and iodine
compounds
The development of new methods for preparing tetrahy-
drofuran derivatives continues to be an active research ar-
ea, since they are useful intermediates in the synthesis of
many natural products.1 In particular, the tetrahydrofuran
moiety of general pattern 1, containing an exocyclic dou-
ble bond, has been applied in many studies toward the
synthesis of Nonactic Acid,2-5 the monomeric structure of
an important class of antibiotics called Nonactins.6
The tellurocyclofunctionalization of unsaturated sub-
strates has been the subject of continuous studies in our
laboratories. Starting from γ,δ-unsaturated carboxylic ac-
ids, it is possible to obtain tellurolactones in good to ex-
cellent yields,7 while alkenols lead to the corresponding
cyclic telluroethers, also in good yields.8-10
Ley et al.11 have already shown that alkenyl-substituted-
β-dicarbonyl compounds can be cyclized using selenium
electrophiles, and that one can selectively achieve the
product of an O-cyclization (kinetic control) or that of a
C-cyclization (thermodynamic control), depending upon
the reaction conditions. Antoniolleti et al.,12,13 as well as
Iqbal and Pandey,14 have reported a similar iodo-O-cy-
clization of a series of alkenyl-substituted β-keto esters
and ketones, all of them bearing the alkenyl chain at the
α-position. An analogous iodine-promoted cyclization of
β-enamino esters and ketones, which led to synthetically
valuable precursors for the pyrrole nucleous, has already
been described by us.15 Nevertheless, the tellurocyclo-
functionalization of alkenyl β-keto esters appears to be
unprecedented.
Scheme 1
Ar = p-methoxyphenyl
To the best of our knowledge, the above results constitute
the first examples of the synthesis of 2,5-disubstituted tet-
rahydrofurans bearing exocyclic double bonds, either by
iodo- or by tellurocyclization. Unfortunately, the β-keto
ester 5 fails in reacting with p-methoxyphenyltellurium
Synlett 1999, No. 5, 567–568 ISSN 0936-5214 © Thieme Stuttgart · New York

568
H. M. C. Ferraz et al.
LETTER
Experimental
trichloride, and only the iodocyclic derivative 9 was ob-
tained. It must be mentioned that a product similar to 8b,
bearing a phenyl instead of the methyl group, has already
been described by Antonioletti.13
The β-keto esters 2-5 were prepared by previously described
methods.20,21 All the products were characterized by IR, H NMR
1
and 13C NMR spectra.
General procedure for iodocyclization: A mixture of I2 (1.5
mmol), anhydrous Na2CO3 (1.5 mmol) and β-keto ester (1 mmol) in
dry CH2Cl2 (20 ml) was stirred at room temperature till the starting
material disappeared (GC). Then AcOEt was added and the organic
phase was washed with sodium thiosulfate solution (0.1 N), brine,
dried over anhydrous MgSO4 and the solvent was evaporated.
General procedure for tellurocyclization: A mixture of β-keto es-
ter (2 mmol) and p-methoxyphenyltellurium trichloride (2.2 mmol)
in 30 ml of recently distilled chloroform was heated under reflux for
the time indicated in Scheme 1. The solvent was evaporated and the
residue filtered through silica gel using chloroform as eluent.
The E double bond geometry for products 6a, 6b, 7a, 7b
and 9 was assigned on the basis of the chemical shifts of
the C3-ring methylene protons, in the 300 MHz 1H NMR
spectrum, as well as by comparison with the seleno ana-
logues.17 The bicyclic products 8a, 8b and 9 exhibit cis
fused rings, assigned by analogy with other examples8,18
and by the coupling constants between H-C4 and H-C9,
which indicate an axial-equatorial relationship (8a:3.49-
3.61d(m, H-C4); 5.33d(t, J = 9.6Hz, H-C9); 4.06-4.31d(m,
H-C8); 8b:3.19d(br q, J = 7.7Hz, H-C4); 4.73d(dd, J = 7.7
and 4.9Hz, H-C9); 4.55-4.59d(m, H-C8); 9:2.60-2.70d(m,
H-C4); 4.59d(t, J = 4.9Hz, H-C9); 4.47((q J = 4.9Hz, H-
C8)). The assigned configurations are a direct conse-
quence of the well-known mechanism of the electrophile-
promoted cyclization, which proceeds via a trans-diaxial
addition to the double bond.19
Acknowledgement
We are indebted to FAPESP, CNPq and CAPES for financial sup-
port of this work.
References and Notes
The previously mentioned structural moiety 1 is repre-
sented in our series of examples by the cyclic esters 6a,
6b, 7a and 7b. In order to explore the synthetic potential
of these derivatives, compound 6a was treated with
NaBH4, giving the telluride 10, which was in turn reduced
with Bu3SnH to afford the α-methyl derivative 11 in ex-
cellent yield. On the other hand, dehydroiodination of 6b
with DBU provided the formation of the α-methylene
derivative 12, also in good yield (Scheme 2).
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Chem. Soc. Perkin Trans. I 1986, 303.
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Scheme 2
In conclusion, we believe the methodology here described
should be useful for constructing synthetically valuable
cyclic ethers. The extension of these studies to other sub-
strates is under way in our laboratory.
Article Identifier:
1437-2096,E;1999,0,05,0567,0568,ftx,en;S05098ST.pdf
Synlett 1999, No. 5, 567–568 ISSN 0936-5214 © Thieme Stuttgart · New York