Regio- and stereoselective preparation of γ-alkylidenebutenolides or α-pyrones using a Stille reaction and palladium-catalysed oxacyclisation sequence

Article abstract of DOI:10.1016/j.tetlet.2003.08.043

Synthesis of butenolides or α-pyrones from substituted tributylstannyl acetylides is highly dependant on the nature of the acetylide.

Full text of DOI:10.1016/j.tetlet.2003.08.043

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7633–7636
Regio- and stereoselective preparation of g-alkylidenebutenolides
or a-pyrones using a Stille reaction and palladium-catalysed
oxacyclisation sequence
a
a
a,b
b,
S e´ verine Rousset, Mohamed Abarbri, J e´ r oˆ me Thibonnet, Jean-Luc Parrain * and
a,
Alain Duch eˆ ne *
a
Laboratoire de Physicochimie des Interfaces et des Milieux R e´ actionnels, Facult e´ des Sciences de Tours, Parc de Grandmont,
3
7200 Tours, France
b
Laboratoire de Synth e` se Organique, UMR 6009, Facult e´ des Sciences de Saint J e´ r oˆ me, 13397 Marseille Cedex 20, France
Received 27 June 2003; revised 12 August 2003; accepted 12 August 2003
Abstract—Synthesis of butenolides or a-pyrones from substituted tributylstannyl acetylides is highly dependant on the nature of
the acetylide.
©
2003 Elsevier Ltd. All rights reserved.
The heterocyclisation reaction is one of the most impor-
tant reactions in organic synthesis. The synthesis of
five- and six-membered ring unsaturated lactones
tive conversion of (Z)-2-en-4-ynoic acids to a-pyranone
in the presence of a catalytic amount of ZnBr (10%) or
2
5
to furanone in the presence of silver salts. In order to
(
butenolides or a-pyrones) constitutes an important
prepare a-pyranone selectively, we recently reported
two different approaches using palladium-catalysed
sequences involving a functional vinylstannane and acyl
7
class of biologically active compounds and has been a
focus of considerable attention in synthetic organic
chemistry and in medicinal chemistry. Numerous
methods reported for the synthesis of these structures in
the last decade utilise transition metals (Ag, Hg, Rh,
Pd) to promote intramolecular addition of carboxylic
1
2
6
chlorides or b-iodovinylic acids and allenylstannanes.
In addition, we previously described the synthesis of
dienoic acids or enynes bearing a carboxylic acid func-
tion from b-iodovinylic acids and vinyltin or alkynyl-
3
acid to alkynes. In general, the lactonisation reaction
8
zinc reagents. This methodology was then applied to
of 4-alkynoic acids involves a stereoselective trans-addi-
tion reaction via a 5-exo process. In addition to the
formation of g-alkylidene butenolides, in some cases
six-membered lactones have been obtained resulting
from the 6-endo mode. In each case the synthesis suffers
from a lack of selectivity. The problem of regioselectiv-
ity was recently studied by Larock et al. who demon-
strated that substituted isocoumarins or a-pyrones
could be prepared by treating b-halogeno a,b-unsatu-
rated esters with internal alkynes in the presence of a
the synthesis of g-tributyltinmethylidene butenolides
which constitute useful intermediates in the selective
9
synthesis of arylmethylidene butenolides (Scheme 1).
To broaden our synthesis strategy and by designing a
system suitable for 5- or 6-endo lactonisation, we
4
palladium catalyst. Nevertheless, in the case of non-
symmetric alkynes two a-pyrone regioisomers were
obtained. More recently Negishi et al. proposed selec-
Keywords: butenolides; pyran-2-one; palladium catalyst; heteroannu-
lation.
*
Corresponding authors. Tel.: 33 (0)2 47 36 69 59; fax: 33 (0)2 47 36
0 40; e-mail: duchene@delphi.phys.univ-tours.fr
7
Scheme 1.
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.043

7
634
S. Rousset et al. / Tetrahedron Letters 44 (2003) 7633–7636
planned to examine the reactivity of diverse substituted
Compared to Sonogashira and Negishi processes,
minor secondary by-products such as alkyne dimers or
Michael adducts were not detected. Although the pro-
cedure described does not respond to the atom econ-
omy criteria, the clean access to only one lactone
prompted us to examine the origin of the regioselectiv-
ity observed.
alkynyltin reagents with (Z)-b-iodoacrylic acids medi-
1
0
ated by a palladium complex (Scheme 2).
Our investigation began with the coupling of phenyl-
alkynyltributylstannane with (Z)-3-iodoprop-2-enoic
acid protected as tributyltinester under conditions pre-
8
e
viously defined in our group.
A plausible mechanism for the heteroannulation reac-
1
1
tion is shown in Scheme 3. First, a Stille mechanism
Compared to our initial results, no enynoic acid or its
tributyltinester was recovered. Only compound 2a was
obtained as a sole isomer. Contrary to the results
starting from tributyltin acetylide, we did not observe
any tin metallated lactones. Moreover, the selective
formation of a five- or a six-membered ring of unsatu-
rated lactones seems to depend on the nature of the
substituent on the alkynyltin reagent. Compared to
other conditions reported in the literature [both in a
palladium-catalysed one-pot procedure and metal salt
would yield 3-enynoic acid by oxidative addition,
transmetallation (formation of 5) and reductive elimi-
nation. Cyclisation would then occur via an attack on
the carboxylate function at the a- or b-position of the
alkynyl moiety, which would give the palladium(II)
intermediate. The latter would subsequently provide
stannylpyrones or stannylalkylidenebutenolides and
12
regenerate the palladium(0) catalyst. At this stage the
stannyllactones obtained would certainly be very sensi-
tive to the work-up or during the silica gel purification
(
Zn or Ag) promoted oxacyclisation], each attempt
1
3
process affording hydrolysed lactones 2 or 3.
yielded only a single lactone (Table 1).
At this point, factors affecting the pyranone/furanone
ratio are not yet very clear. It is nevertheless tempting
to speculate that the stereoelectronic effect of the sub-
stituent of the unsaturated bonds in tin (Z)-2-en-4-
ynoate would lead to the formation of 2H-pyran-2-ones
via an inductive donating effect. In contrast, aryl or
potentially chelating palladium atom substituants may
stereoelectronically lead to 5-exo-mode cyclisation.
In addition, bearing in mind the mechanism evoked in
Scheme 3, we decided to trap the stannyllactones with
electrophiles. The reaction of tributylstannyl acetylide
reagents with a range of tributylstannyl (Z)-3-substi-
tuted 3-iodoprop-2-enoates followed by addition of a
solution of iodine in ether, proceeded with regio- and
stereocontrol to give fair yields of (E)-5-iodoalkylidene-
Scheme 2.
Table 1.
5
H-furan-2-ones or 5-iodo-2H-pyran-2-ones (Scheme 4,
14
Table 2). Similar regiochemical trends were again
observed.
Scheme 3.
Scheme 4.

S. Rousset et al. / Tetrahedron Letters 44 (2003) 7633–7636
7635
Table 2.
References
1. For reviews on butenolides, see: (a) Rao, Y. S. Chem.
Rev. 1964, 64, 353; (b) Rao, Y. S. Chem. Rev. 1976, 76,
625; (c) Knight, D. W. Contemp. Org. Synth. 1994, 1,
287; (d) Negishi, E.; Kotora, M. Tetrahedron 1997, 53,
6707; (e) Br u¨ ckner, R. Curr. Org. Chem. 2001, 5, 679; (f)
Rossi, R.; Bellina, F. Targets Heterocyclic Syst. 2001, 5,
69; (g) Br u¨ ckner, R. Chem. Commun. 2001, 141. For a
1
discussion of the chemistry of a-pyrones, see: (h)
Staunton, J. In Comprehensive Organic Chemistry; Sam-
mes, P. G., Ed.; Pergamon Press: Oxford, England, 1979;
Vol. 4, pp. 629–646. 2H-Pyran-2-one and its derivatives
are commonly referred to as 2-pyrones or a-pyrones: (i)
Posner, G. H. Acc. Chem. Res. 1987, 20, 72–78.
2
. (a) Davies-Coleman, M. T.; Rivett, D. E. A. Progr.
Chem. Org. Nat. Prod. 1989, 55, 1; (b) Kvita, V.; Fischer,
W. Chimia 1992, 46, 457; (c) Kvita, V.; Fischer, W.
Chimia 1993, 47, 3; (d) Posner, G. H.; Nelson, T.; Kinter,
C.; Johnson, N. J. Org. Chem. 1992, 57, 4083.
3. For recent synthesis of butenolides using Pd or Ag cata-
lysts, see: (a) Hanisch, I.; Br u¨ ckner, R. Synlett 2000, 374;
(
(
b) Br u¨ ckner, R.; Ohe, F. v d. New J. Chem. 2000, 659;
c) Siegel, K.; Br u¨ ckner, R. Synlett 1999, 1227; (d) Xu,
C.; Negishi, E. Tetrahedron Lett. 1999, 40, 431; (e) Ma,
S.; Shi, Z. J. Org. Chem. 1998, 63, 6387; (f) G o¨ rth, F. C.;
Umland, A.; Br u¨ ckner, R. Eur. J. Org. Chem. 1998, 1055;
(
g) Rossi, R.; Bellina, F.; Biagetti M.; Mannina, L.
Tetrahedron Lett. 1998, 39, 7799; (h) Rossi, R.; Bellina,
F.; Biagetti, M.; Mannina, L. Tetrahedron Lett. 1998, 39,
7599; (i) Rossi, R.; Bellina, F.; Mannina, L. Tetrahedron
Lett. 1998, 39, 3017; (j) Rossi, R.; Bellina, F.; Bechini, C.;
Mannina, L.; Vergamini, P. Tetrahedron 1998, 54, 135;
(
k) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J. Org.
Chem. 1997, 62, 367; (l) Kotora, M.; Negishi, E. Synthesis
997, 201; (m) Marshall, J. A.; Wolf, M. A.; Wallace, E.
1
M. J. Org. Chem. 1996, 61, 3238; (n) Marshall, J. A.;
Wolf, M. A.; Wallace, E. M. J. Org. Chem. 1995, 60, 796;
(
o) Ogawa, Y.; Maruno, M.; Wakamatsu, T. Heterocy-
cles 1995, 41, 2587; (p) Ogawa, Y.; Maruno, M.; Waka-
matsu, T. Synlett 1995, 871.
Scheme 5.
4
. (a) Larock, R. C.; He, Y.; Leon, W. W.; Han, X.; Refvik,
M. D.; Zenner, M. J. J. Org. Chem. 1998, 63, 2154; (b)
Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett.
Finally, Stille cross-coupling of 4f with styryltributyl-
stannane in the presence of a catalytic amount of
dichlorobis (bistriphenylphosphine)palladium(II) (5%)
in DMF yielded 72% of the desired arylbutenolide
1
998, 39, 5713 and references cited therein.
5. Anastasia, L.; Xu, C.; Negishi, E. Tetrahedron Lett. 2002,
43, 5673.
6. Thibonnet, J.; Abarbri, M.; Parrain, J.-L.; Duch eˆ ne, A. J.
Org. Chem. 2002, 67, 3941.
. Rousset, S.; Abarbri, M.; Thibonnet, J.; Duch eˆ ne, A.;
Parrain, J.-L. Chem. Commun. 2000, 1987.
(
Scheme 5) but with complete retention of the configu-
ration of the exocyclic double bond with respect to the
15
7
stereochemistry of the starting iodoalkene.
8
. (a) Abarbri, M.; Parrain, J.-L.; Kitamura, M.; Noyori,
R.; Duch eˆ ne, A. J. Org. Chem. 2000, 65, 7475; (b)
Thibonnet, J.; Abarbri, M.; Duch eˆ ne, A.; Parrain, J.-L.
Synlett 1999, 141; (c) Pri e´ , G.; Thibonnet, J.; Abarbri,
M.; Duch eˆ ne, A.; Parrain, J.-L. Synlett 1998, 839; (d)
Thibonnet, J.; Abarbri, M.; Parrain, J.-L.; Duch eˆ ne, A.
Synlett 1997, 771; (e) Thibonnet, J.; Abarbri, M.; Parrain,
J.-L.; Duch eˆ ne, A. Main Group Met. Chem. 1997, 20, 195;
In conclusion, under palladium complex catalysis, we
prepared by selective sequence Stille and heterocyclisa-
tion reactions butenolides or a-pyrones from alkynyltin
reagents.
Acknowledgements
(
f) Abarbri, M.; Parrain, J.-L.; Cintrat, J.-C.; Duch eˆ ne,
A. Synthesis 1996, 82; (g) Abarbri, M.; Parrain, J.-L.;
Duch eˆ ne, A. Tetrahedron Lett. 1995, 36, 2469; (h) Duch-
eˆ ne, A.; Abarbri, M.; Parrain, J.-L.; Kitamura, M.; Noy-
ori, R. Synlett 1994, 524.
We thank the CNRS and MESR for providing financial
support and the Service d’analyse chimique du vivant
de Tours for recording NMR and mass spectra.

7
636
S. Rousset et al. / Tetrahedron Letters 44 (2003) 7633–7636
9. Rousset, S.; Abarbri, M.; Thibonnet, J.; Duch eˆ ne, A.;
to precipitate the tributyltin iodide formed. After strongly
Parrain, J.-L. Org. Lett. 1999, 1, 701.
0. Cazes, B. Pure Appl. Chem. 1990, 62, 1867 and references
cited therein.
stirring for 1 h, the reaction mixture was filtered and
extracted with diethyl ether. The organic layer was
washed with a 5% solution of sodium thiosulfate. After
usual work-up, 4a–f and 5a–b were purified by column
chromatography on silica (petroleum ether/Et O/Et N;
1
1
1. (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25,
5
1
08; (b) Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987,
09, 813; (c) Mitchell, T. N. Synthesis 1992, 803; (d)
2
3
80/18/2).
1
Farina, V. In Comprehensive Organometallic Chemistry
II; Abel, E. W.; Stone, F. G.; Wilkinson, G., Eds.;
Elsevier: Oxford, 1995; Vol. 12, Chapter 3.4; pp. 161–241;
(
(
(
2a): Mp: 82–84°C. H NMR (CDCl , 200 MHz) l
ppm): 6.02 (s, 1H), 6.20 (d, J=5.3 Hz, 1H), 7.31–7.42
m, 3H), 7.49 (d, J=5.3 Hz, 1H), 7.74–7.81 (m, 2H).
3
13
C
(
e) Farina, V.; Roth, G. P. In Advances in Metal-Organic
Chemistry; Liebeskind, L. S., Ed.; JAI Press: New York,
996; Vol. 5, pp. 1–53; (f) Farina, V.; Krishnamurthy, V.;
Scott, W. J. Org. React.; Paquette, L. A., Ed.; John Wiley
Sons, 1997; Vol. 50, Chapter 1, pp. 1–652; (g) Farina,
NMR (CDCl , 50 MHz) l (ppm): 114.8, 118.7, 129.4,
3
129.9 (2C), 131.3 (2C), 133.4, 145.8, 149.0, 170.8. MS (70
1
eV): m/z=172 (M, 100), 144 (33), 118 (14), 116 (52), 115
(
(
(
68), 90 (42), 89 (46), 86 (14), 72 (10), 64 (11), 63 (33), 62
13), 58 (24), 57 (19), 51 (17), 50 (12), 45 (14), 39 (25), 38
10). (3a): IR (neat): 2982, 2865, 1747, 1652, 1567, 1125.
&
V.; Krishnamurthy, V. In The Stille Reaction; Wiley:
New York, 1999; (h) Campagne, J.-M.; Prim, D. In Les
Complexes du palladium en synth e` se organique; CNRS
Editions: Paris, 2001.
1
H NMR (CDCl , 200 MHz) l (ppm): 0.95 (s, 9H), 2.03
3
(
5
s, 3H), 2.59 (t, J=6.1 Hz, 2H), 3.89 (t, J=6.1 Hz, 2H),
13
.88 (bs, 2H). C NMR (CDCl , 50 MHz) l (ppm): 12.3,
3
1
1
2. Yamamoto, Y.; Al-Masum, M.; Fujiwara, N. Chem.
Commun. 1996, 381.
3. We unambiguously established the structure and stereo-
chemistry of these new compounds by NMR techniques.
See also Ref. 6 and Ref. 7.
18.3 (3C), 37.8, 60.7, 108.0, 112, 156.5, 162.5, 163.6. MS
(
70 eV): m/z=226 (M, 13), 136 (66), 184 (16), 183 (100),
1
2
55 (52), 75 (55), 45 (13). (4f): Mp: 103°C. IR (KBr):
975, 2965, 2880, 1760, 1655, 1600, 1225. H NMR
1
(
6
CDCl , 200 MHz) l (ppm): 2.37 (s, 2H), 3.95 (s, 2H),
.12 (q, J=1.5 Hz, 1H), 7.31–7.13 (m, 5H). C NMR
3
1
4. Typical procedure: A dry three-necked flask equipped
13
with magnetic stirring and septum was charged with
(
CDCl , 50 MHz) l (ppm): 18.3, 36.6, 42.6, 88.4, 121.3,
3
(
Z)-tributylstannyl-3-iodobut-2-enoate (3.2 g, 3.6 mmol)
1
27.0, 128.4 (2C), 129 (2C), 137.6, 149.4, 155.3, 166.3.
MS (70 eV): m/z=372 (M, 16), 245 (97), 227 (29), 91
100), 39 (13). (5a): IR (neat): 3070, 2980, 2975, 1755,
in DMF (20 mL) and 5.4 mmol of 1-tributylstannyl-2-
phenylethynyl. 208 mg (5% mol) of Pd(PPh3)4 were
added. The resulting solution was then stirred under
argon for 12 h at room temperature.
(
1
1625, 1230. H NMR (CDCl , 200 MHz) l (ppm): 0.9 (t,
3
J=7.3 Hz, 3H), 1.66–1.27 (m, 8H), 2.51 (s, 3H), 2.94 (t,
(a) The reaction mixture was then quenched with a
13
J=7.1 Hz, 2H), 6.16 (s, 1H). C NMR (CDCl , 50
3
saturated NH Cl solution at 0°C and Et O was added.
4
2
MHz) l (ppm): 14.5, 19.0, 23.0, 28.6, 29.6, 32.0, 41.5,
After filtration over Celite, the organic layer was sepa-
92.0, 121.0, 149.0, 155.7, 167.5. MS (70 eV): m/z=320
rated, extracted with Et O, washed with brine and dried
2
(
(
M, 32), 193 (13), 175 (13), 124 (100), 55 (22), 43 (25), 41
36), 39 (35).
over MgSO . After evaporation of solvents, the crude
4
products 2a–c and 3a–c were purified by column chro-
matography on silica (petroleum ether/Et O/Et N; 80/18/
1
5. For compounds 4 or 5, the structure and stereochemistry
were also confirmed by NMR techniques and by some
Stille cross-coupling reactions; it is well known that these
reactions occur always with retention of configuration. A
full paper describing all these new compounds will
reported in due course.
2
3
2
).
(b) Iodine (1.27 g, 5 mmol) diluted in 20 mL of Et O was
2
added. Stirring was then maintained for 2 h at room
temperature. The mixture was hydrolysed with 30 mL of
1
M solution of potassium fluoride and 25 mL of acetone