(E)-5-(Tributylstannylmethylidene)-5H-furan-2-ones: Versatile synthons for the stereospecific elaboration of γ-alkylidenebutenolide skeletons

Article abstract of DOI:10.1021/ol9900764

Formula presented Stereoselective construction of (E)-γ-tributylstannylmethylidene butenolides 1 was achieved through the palladium-catalyzed tandem cross-coupling/cyclization reactions of tributylstannyl 3-iodopropenoate derivatives with tributyltinacetylene. lododestannylation of 1 occurs with inversion of the configuration of the exocyclic double bond while the observed selectivity in the Stille reaction was found to be dependent on the nature of the aryl halide.

Full text of DOI:10.1021/ol9900764

ORGANIC
LETTERS
1
999
Vol. 1, No. 5
01-703
(
5
E)-5-(Tributylstannylmethylidene)-
H-furan-2-ones: Versatile Synthons for
7
the Stereospecific Elaboration of
γ-Alkylidenebutenolide Skeletons
†
†
†
S e´ verine Rousset, Mohamed Abarbri, J e´ r oˆ me Thibonnet,
,
†,§
,‡
Alain Duch eˆ ne,* and Jean-Luc Parrain*
Laboratoire de Physicochimie des Interfaces et des Milieux R e´ actionnels, Facult e´ des
Sciences de Tours, Parc de Grandmont, 37200 Tours, France, and Laboratoire de
Synth e` se Organique associ e´ au CNRS (ESA 6009), Facult e´ des Sciences de Saint
J e´ r oˆ me, AVenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
jl.parrain@lso.u-3mrs.fr
Received May 6, 1999
ABSTRACT
Stereoselective construction of (E)-γ-tributylstannylmethylidene butenolides 1 was achieved through the palladium-catalyzed tandem cross-
coupling/cyclization reactions of tributylstannyl 3-iodopropenoate derivatives with tributyltinacetylene. Iododestannylation of 1 occurs with
inversion of the configuration of the exocyclic double bond while the observed selectivity in the Stille reaction was found to be dependent on
the nature of the aryl halide.
5
Due to their large abundance and their biological interest
and potential medicinal value, butenolides have been exten-
sively studied. Over the past decade, an increasing amount
coupling of aldehydes or ketones with oxyfurans, alkeny-
6
7
lation of γ-lactones via their enolates or phosphorus ylides,
and olefination of maleic anhydrides with organometallic
reagents or phosphoranes were described as efficient
methods but with a major drawback in the nonselective
1
8
9
of attention has been focused on the synthesis of stereo-
2
defined γ-alkylidene butenolides which have been isolated
3
from natural sources. For example, freelingyne displays
4
(5) (a) Kraus, G. A.; Sugimoto, H. J. Chem. Soc., Chem. Commun. 1978,
antibiotic activity and rubrolides, which are marine tunicate
3
(
0. (b) D’Auria, M.; Piancatelli, G.; Scettri, A. Tetrahedron 1980, 36, 3071.
c) Asaoka, M.; Yanagida, N.; Ishibashi, K.; Takei, H. Tetrahedron Lett.
1981, 22, 4269. (d) Xu, D.; Sharpless, K. B. Tetrahedron Lett. 1994, 35,
metabolites, exhibit potent antibiotic activities in vitro.
Principally, the γ-alkylidene butenolide moiety has been
obtained by four major methods. Lewis acid catalyzed
4
685.
(
6) (a) Ford, J. A.; Wilson, C. V.; Young, W. R. J. Org. Chem. 1967,
3
2, 173. (b) Sone, M.; Tominaga, Y.; Natsuki, R.; Matsuda, Y.; Kobayashi,
†
Facult e´ des Sciences de Tours.
Facult e´ des Sciences de Saint J e´ r oˆ me.
e-mail: duchene@delphi.phys.univ-tours.fr.
G. Chem. Pharm. Bull. 1974, 22, 617. (c) Knight, D. W.; Pattenden, G. J.
Chem. Soc., Perkin Trans. 1 1975, 641.
(7) (a) Corrie, J. E. T. Tetrahedron Lett. 1971, 4873. (b) Howe, R. K. J.
Org. Chem. 1973, 38, 4164. (c) Shing, T. K. M.; Tsui, H. C.; Zhou, Z. H.
J. Org. Chem. 1995, 60, 3121.
‡
§
(
1) For reviews on butenolides, see: Rao, Y. S. Chem. ReV. 1976, 76,
25. (b) Rao, Y. S. Chem. ReV. 1964, 64, 353. (c) Knight, D. W. Contemp.
Org. Synth. 1994, 1, 287.
2) For an excellent review, see: Negishi, E.; Kotora, M. Tetrahedron
997, 53, 6707.
3) (a) Liu, F.; Negishi, E. J. Org. Chem. 1997, 62, 8591. (b) Von der
Ohe, F.; Br u¨ ckner, R. Tetrahedron Lett. 1998, 39, 1909.
4) (a) Miao, S.; Andersen, R. J. J. Org. Chem. 1991, 56, 6275. (b)
6
(8) Lardelli, G.; Dijkstra, G.; Harkes, P. D.; Boldingh, J. Recl. TraV.
(
Chim. Pays-Bas 1966, 85, 43.
1
(9) (a) Ingham, C. F.; Massy-Westrop, R. H.; Reynolds, G. D.; Thorpe,
W. D. Aust. J. Chem. 1975, 28, 2499. (b) Begley, M. J.; Gedge, D. R.;
Pattenden, G. J. Chem. Soc., Chem. Commun. 1978, 60. (c) Ito, M.; Iwata,
T.; Tsukida, K. Heterocycles 1982, 19, 1385. (d) Ito, M.; Iwata, T.; Tsukida,
K. Chem. Pharm. Bull. 1984, 32, 1709. (e) Ito, M.; Shibata, Y.; Sato, A.;
Tsukida, K. J. Natr. Sci. Vitaminol. 1987, 33, 313.
(
(
Kotora, M.; Negishi, E. Synthesis 1997, 121. (c) Kotora, M.; Negishi, E.
Tetrahedron Lett. 1996, 37, 9041.
1
0.1021/ol9900764 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/28/1999

a few traces of stannylated methylidenebutenolide 1a were
obtained in mixture with a large amount of tin byproducts
and the starting iodovinylic acid.
Scheme 1
To obtain good yields of 1, we examined the reaction
under various conditions (solvent, catalyst, presence of
additives, . . .). The results are summarized in Table 1. In
the first step, the influence of the nature of the carboxylic
acid function on conversion rates was examined.
construction of the exocyclic double bond. The fourth one,
a transition metal (Pd, Ag) catalyzed lactonization allows
Table 1. Experimental Conditions for the Synthesis of 1aa
entryb
1
R2
[Pd]
A
add.
solvent
DMF
yield, %
5
1
0,11
complete control of exocyclic alkene geometry.
In
addition, we have previously described the synthesis of dienic
acids or enynes bearing a carboxylic acid function from
H
CuI (10%)
Et3N
12
2
3
4
5
6
7
8
9
Et
Na
A
A
A
A
A
B
C
C
A
DMF
DMF
DMF
MeCN
THF
DMF
DMF
DMF
DMF
c
0
67
0
â-iodovinylic acid and vinyltin or alkynylzinc reagents. This
methodology was then applied to the synthesis of retinoic
acids and certain analogues.13 To broaden our synthetic
strategy, we planned to prepare γ-alkylidenebutenolides 1
and 2 which we though would allow more flexibility in the
construction of the above natural products and could
theoretically be obtained from â-iodo vinylic acids and
tributylstannylacetylene (Scheme 1).
SnBu3
SnBu3
SnBu3
SnBu3
SnBu3
SnBu3
SnBu3
0
13
54
57
60
PPh3
CuI
1
0
a
b
A ) Pd(PPh3)4; B) PdCl2(MeCN)2; C) PdCl2(PPh3)2. These attempts
1
c
were performed with (Z)-3-iodoprop-2-enoic acid (R ) H). Ethyl pent-
-en-4-ynoate was obtained in 73% yield.
2
Scheme 2
In DMF and in the presence of 1% tetrakis(triphenylphos-
phine)palladium, free carboxylic acid (entry 1), ester (entry
), and sodium salt derivatives (entry 3) did not yield the
2
desired tin butenolides 1. Surprisingly, the use of tributyltin
carboxylate (entry 4), under identical conditions to those
above, gave in 67% yield 1a with a clean configuration of
the double bond. Next were examined the nature of the
solvent and of the palladium complexes. Acetonitrile and
THF (entries 5 and 6) were found to be ineffective while
DMF (or dimethylacetamide) afforded cyclized product in
fair yields. We equally observed that phosphine ligated
palladium appeared to be more efficient than other palladium
salts such as palladium acetate or bis(acetonitrile)palladium
chloride (entry 7). Attempts to further improve the yield by
using copper salt met with no success (entry 10).
Herein, we report a stereoselective synthesis of (E)-γ-
tributylstannylmethylidene)butenolides under palladium com-
plex catalysis and the preliminary results about their reac-
tivity.
(
Our investigation began with the coupling of tributyl-
stannylacetylene with (Z)-3-iodoprop-2-enoic acid under
14
4b
conditions defined by Lu or Negishi. Unfortunately, only
(
10) Grundman, C.; Kober, E. J. Am. Chem. Soc. 1955, 77, 2332.
1
a was easily purified by column chromatography, and
(11) For recent synthesis of butenolides using Pd or Ag catalysts, see:
1
13
(
a) Xu, C.; Negishi, E. Tetrahedron Lett. 1999, 40, 431. (b) Ma, S.; Shi, Z.
its structure was attributed by H and C NMR. According
to the above authors, a (Z)-isomer of 1a was expected.
Analysis of tin-carbon coupling constants, which was
previously reported to be a good tool to attribute the
stereochemistry of trisubstituted vinystannanes, revealed
a very low JSn-C4 (17 Hz) coupling constant, indicating a
J. Org. Chem. 1998, 63, 6387. (c) Rossi, R.; Bellina, F.; Biagetti, M.;
Mannina, L. Tetrahedron Lett. 1998, 39, 7799. (d) Rossi, R.; Bellina, F.;
Biagetti, M.; Mannina, L. Tetrahedron Lett. 1998, 39, 7599. (e) Rossi, R.;
Bellina, F.; Mannina, L. Tetrahedron Lett. 1998, 39, 3017. (f) Rossi, R.;
Bellina, F.; Bechini, C.; Mannina, L.; Vergamini, P. Tetrahedron 1998,
4, 135. (g) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J. Org. Chem.
997, 62, 367. (h) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J. Org.
Chem. 1995, 60, 796. (i) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J.
Org. Chem. 1996, 61, 3238. (j) Ogawa,Y.; Maruno, M.; Wakamatsu, T.
Heterocycles 1995, 41, 2587. (k) Ogawa,Y.; Maruno, M.; Wakamatsu, T.
Synlett 1995, 871.
15
5
1
3
preference for the (E)-isomer. A NOESY experiment con-
ducted on 1a gave a strong cross-peak between H
of Bu Sn group and no cross-peak between H
confirmed the E configuration.
4
and R-CH
and H and
2
3
4
6
(12) (a) Duch eˆ ne, A.; Abarbri, M.; Parrain, J.-L.; Kitamura, M.; Noyori,
R. Synlett 1994, 524. (b) Abarbri, M.; Parrain, J.-L.; Duch eˆ ne A.
Tetrahedron Lett. 1995, 36, 2469. (c) Abarbri, M.; Parrain, J.-L.; Cintrat,
J.-C.; Duch eˆ ne A. Synthesis 1996, 82. (d) Thibonnet, J.; Abarbri, M.;
Parrain, J.-L.; Duch eˆ ne, A. Main Group Metal Chem. 1997, 20, 195.
Reaction of tributylstannyl acetylene with a range of
tributylstannyl (Z)-3-substituted 3-iodoprop-2-enoates pro-
(
13) (a) Thibonnet, J.; Abarbri, M.; Parrain, J.-L.; Duch eˆ ne, A. Synlett
1
997, 771. (b) Pri e´ , G.; Thibonnet, J.; Abarbri, M.; Duch eˆ ne A.; Parrain,
J.-L. Synlett 1998, 839. (c) Thibonnet, J.; Abarbri, M.; Duch eˆ ne, A.; Parrain,
J.-L. Synlett 1999, 141.
(14) Lu, X.; Huang, X.; Ma, S. Tetrahedron Lett. 1993, 34, 5963.
(15) Ardisson, J.; F e´ r e´ zou, J.-P.; Li, Y.; Pancrazi, A. Bull. Soc. Chim.
Fr. 1992, 129, 401.
702
Org. Lett., Vol. 1, No. 5, 1999

1
7
ceeded with regio- and stereocontrol to give (E)-5-tributyl-
stannylmethylidene-5H-furan-2-ones 1a-e in fair yields
Finally, Stille cross-coupling of 1a with iodobenzene in
the presence of a catalytic amount of dichlorobis(aceto-
nitrile)palladium(II) (5%) in DMF gave the desired aryl-
butenolide in 72% yield (Scheme 4) but with an inversion
of the configuration of the exocyclic double bond with
respect to the stereochemistry of the starting tin product.
(Table 2).
Table 2. Synthesis of
(E)-5-(Tributylstannylmethylidene)-3-substituted-5H-furan-2-ones
Scheme 4
This can be explained by the greater thermodynamic
stability of the (Z)-isomer of 3. The AM1 semiempirical
calculation method applied to both isomers of 3 reveals for
the isomer (E)-3 (certainly formed during the cross-coupling)
a substantial interaction of the hydrogen borne by the C4
carbon of the furanone cycle and the hydrogens in the ortho
No isomerization of the double bond was observed and
18
position of the benzenic ring. In contrast, an identical
no cyclization, affording pyranones, occurred as previously
observed under Sonogashira conditions.3b,16 Moreover, Stille
cross-coupling products derived from 1a and the starting
iodopropenoic acid were not detected. It is clear from these
preliminary experiments, although somewhat difficult to
rationalize, that all the desired compounds 1a-e were
obtained with full preference for the (E)-isomer (the stereo-
chemistry was assigned on each case via the C- Sn
coupling constants).
Attention was next directed to the reactivity of tin
butenolides 1a-e. The iododestannylation of 1a occurred
stereospecifically in ether at 0 °C in good yield. (Scheme
attempt performed with 2-iodothiophene led to the desired
thienyl methylidene butenolide 4 with a clean E configuration
of the exocyclic double bond, again demonstrating that Stille
coupling occurs with retention of configuration.
In conclusion, we have demonstrated that the palladium-
catalyzed tandem cross-coupling/cyclization reactions of
tributylstannyl 3-iodopropenoate with tributyltinacetylene
affords with fixed configuration of the double bond (E)-γ-
tributylstannylmethylidene butenolides which are the poten-
tial precursors of numerous alkylidenes butenolides. Current
studies are aimed at increasing our mechanistic understanding
of butenolide formation as well as broadening the application
of such reagents toward the synthesis of natural alkylidene
butenolides.
1
3
119
3).
Acknowledgment. We thank the CNRS and MENRT for
providing financial support and the Service d’analyse
chimique du vivant de Tours for recording NMR and mass
spectra.
Scheme 3
Supporting Information Available: Typical experimen-
tal procedure for the preparation of 1a-e, 2, and 3-4.
1
13
119
Tabulated H, C,and Sn NMR and mass data for 1a-e,
2, 3, and 4. H, C, and 119Sn NMR spectra for 1a-e and
NOESY or NOE difference spectra of 1a, 3, and 4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
13
Nevertheless, the iodobutenolide (E)-2 was found to be
unstable and quantitatively isomerized into the (Z)-isomer.
Attempts to stabilize (E)-2 by lowering the temperature or
changing the solvent (toluene, chloroform, or dichloro-
methane) were unsuccessful and yielded mixtures of isomers
which, after few hours, led to the thermodynamically more
stable (Z)-isomer.
OL9900764
(
17) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Mitchell, T. N. Synthesis 1992, 803.
18) AM1 calculations were performed by the Hyperchem package on a
(
-
1
(16) Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39,
PC computer. (Z)-3: E ) -2418.816 kcal‚mol . (E)-3: E ) -2416.067
-1
5
713 and references therein.
kcal‚mol (rms energy gradient <0.001).
Org. Lett., Vol. 1, No. 5, 1999
703