Palladium-catalysed annulation reaction of allenyltins with β-iodo vinylic acids: Selective synthesis of α-pyrones

Article abstract of DOI:10.1039/b005886f

Palladium-catalysed regio- and stereoselective annulation of allenyl stannanes by β-iodo vinylic acids gives the corresponding α-pyrones in high yields. This annulation most probably proceeds through a Stille reaction/cyclisation sequence.

Full text of DOI:10.1039/b005886f

Palladium-catalysed annulation reaction of allenyltins with b-iodo vinylic
acids: selective synthesis of a-pyrones
a
a
a
a
b
Séverine Rousset, Mohamed Abarbri, Jérôme Thibonnet, Alain Duchêne* and Jean-Luc Parrain*
a
Laboratoire de Physicochimie des Interfaces et des Milieux Réactionnels, Faculté des Sciences de Tours, Parc de
Grandmont, 37200 Tours, France. E-mail: duchene@delphi.phys.univ-tours.fr
Laboratoire de Synthèse Organique associé au CNRS (ESA 6009), Faculté des Sciences de Saint Jérôme, Avenue
Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France. E-mail: jl.parrain@lso.u-3mrs.fr
b
Received (in Liverpool, UK) 18th July 2000, Accepted 1st September 2000
First published as an Advance Article on the web 21st September 2000
Palladium-catalysed regio- and stereoselective annulation of
allenyl stannanes by b-iodo vinylic acids gives the corre-
sponding a-pyrones in high yields. This annulation most
probably proceeds through a Stille reaction/cyclisation
sequence.
nature of the carboxylic acid derivative on conversion rates was
examined. In DMF and in the presence of 1% of tetra-
kis(triphenylphosphine)palladium,† the ethyl ester of 1a
yielded exclusively ethyl hex-2-en-4-ynoate. The use of
tributyltin carboxylate (Table 1 entry 4) under identical
conditions to those used for the synthesis of tributyltin
methylidenebutenolides, led to 52% yield of 6-methylpyran-
2-one 3a, without any trace of hexa-2,4,5-trienoic acid. Finally,
we found that an 83% yield of 3a could also be obtained from
1a at rt in DMF using 5% palladium acetate, triphenylphos-
phine, sodium carbonate and tetrabutylammonium bromide.
Next the nature of the solvent and of the palladium complexes
were examined. THF was found to be ineffective whereas
acetonitrile afforded a very poor yield ( < 25%) of cyclised
product. We also observed that phosphine-liganded palladium
appeared to be more efficient than other palladium salts such as
Five- and six-membered ring unsaturated lactones (butenolides
or pyrones) constitute an important class of biologically active
compounds and their synthesis has been the focus of consider-
1
able attention in synthetic organic chemistry as well as in
2
medicinal chemistry. Numerous methods reported in the last
decade for the synthesis of these structures involve transition
metal (Ag, Hg, Rh, Pd) promoted intramolecular additions of
carboxylic acids to alkynes.3 In general, the lactonisation
reaction of alk-4-ynoic acids proceeds through a stereoselective
trans addition reaction via a 5-exo process. In addition to the
formation of g-alkylidenebutenolides, in some cases six-
membered lactones resulting from the 6-endo mode have been
obtained as minor products. This problem of regioselectivity
was recently solved by Larock et al. who demonstrated that
substituted isocoumarins or a-pyrones could be prepared by
treating b-halogeno a,b-unsaturated esters with internal alkynes
Table 1 Synthesis of apyrones
4
in the presence of a palladium catalyst. Nevertheless, two a-
pyrone regioisomers were obtained in the case of non-
symmetric alkynes. On the other hand, we have previously
described the synthesis of dienoic acids or enynes bearing a
carboxylic acid function from b-iodovinylic acids and vinyltin
5
or alkynylzinc reagents. This methodology was then applied to
6
the synthesis of g-tributyltin methylidenebutenolides. To
broaden our synthesis strategy and to design a system suitable
for 6-endo lactonization, we planned the preparation of allenyl
substituted alkenoic acids which we thought would exclusively
undergo 6-endo mode cyclisation mediated by a palladium
complex (Scheme 1).7
We report here the selective one pot synthesis of a-pyrones
under palladium complex catalysis. Our investigation began
8
with the coupling of tributylstannylallene with (Z)-3-iodoprop-
5
2
-enoic acid under conditions previously defined by our
6
group. Unfortunately, neither allenyl substituted propenoic
acid nor cyclised products (5- or 6-membered ring lactones)
were detected. Only a large amount of tin by-products were
recovered, among them the tributylstannyl ester of the starting
iodovinylic acid. In order to avoid the proteolysis of allenyl-
stannane and to promote the cross coupling reaction, we
examined the reaction under various conditions (solvent,
catalyst, presence of additives,...). First the influence of the
Scheme 1
DOI: 10.1039/b005886f
Chem. Commun., 2000, 1987–1988
This journal is © The Royal Society of Chemistry 2000
1987

philes are currently under way and will be reported in due
course.
Notes and references
2 3 2 3 4
Scheme 2 Pd(OAc) (5%), PPh (10%), Na CO (4 eq.), n-Bu NBr (1 eq.),
DMF, rt.
†
General procedure for the heteroannulation summarised in Table 1:
palladium acetate (112 mg, 0.5 mmol), triphenylphosphine (131 mg, 0.5
mmol), tetrabutylammonium bromide (3.2 g, 10 mmol) and sodium
carbonate (5.3 g, 50 mmol) were progressively added to a degassed solution
of 3-substituted-3-iodopropenoic acid 1 (10 mmol) in anhydrous DMF (40
mL). The mixture was stirred at rt for 10 min and allenylstannane 2 (10
mmol) was then added. The reaction mixture was stirred for 4 h. After
conversion was complete (checked by TLC; reaction time < 10 h), the
palladium acetate (without additional triphenylphosphine) or
bis(acetonitrile)palladium chloride. Tetrakis(triphenylphosphi-
ne)palladium gave approximately identical yields to the
2 3
Pd(OAc) /PPh couple.
The reaction of tributylstannylallene with a range of (Z)-
-substituted 3-iodoprop-2-enoic acids under regio- and stereo-
4
reaction was quenched with aqueous NH Cl solution. After ether extraction
3
(3 3 20 mL) and usual treatments, the crude products were chromato-
graphed on silica gel to obtain compounds 3a–k. All new compounds were
fully characterised spectroscopically.
control gave good yields of 4-substituted-6-methylpyranones
a–f as the sole products (Table 1 entries 1–6) (Scheme 2).
3
‡
Selected data for 3k: d
H
(200 MHz, CDCl
(50.3 MHz, CDCl
8.9, 109.7, 138.5, 154.2, 154.6, 162.4. MS (70 ev): m/z = 184 (M, 23%),
69 (22), 141 (22), 45 (14), 43 (100), 39 (14).
3
) 2.18 (3H, s), 3.40 (3H, s), 3.59
Other allenylstannanes were used under similar conditions in
order to determine the scope of the reaction. High regio-
selectivity was observed in each case. The use of 3-alkylallenyl-
stannanes (entries 7–10) showed that the regioselective hetero-
annulation reaction occurred only on carbons 1 and 2 of the
allenyltin. On the other hand, g-alkylidenepyranones previously
obtained by Larock et al. from a reaction of allenes with (Z)-
(3H, s), 4.27 (2H, s), 6.15 (1H, s); d
C
3
) 15.3, 59.7, 62.5,
6
1
1 For reviews on butenolides see: (a) Y. S. Rao, Chem. Rev., 1976, 76,
625; (b) Y. S. Rao, Chem. Rev., 1964, 64, 353; (c) D. W. Knight,
Contemp. Org. Synth., 1994, 1, 287. For a discussion of the chemistry of
a-pyrones see: (d) J. Staunton, in Comprehensive Organic Chemistry,
ed. P. G. Sammes, Pergamon Press, Oxford, England, 1979, 4, 629–646.
3
-iodopropenoic acids were not observed. This almost certainly
indicates a different mechanism to those proposed by Larock
2
2
7
H-Pyran-2-one and its derivatives are commonly referred to as
-pyrones or a-pyrones; (e) G. H. Posner, Acc. Chem. Res., 1987, 20,
2.
and Yamamoto respectively.9
,10
A plausible mechanism for the heteroannulation reaction is
shown in Scheme 3. First, a Stille mechanism11 would yield
2
3
M. T. Davies-Coleman and D. E. A. Rivett, Progress in the Chemistry
of Organic Natural Products, 1989, 55, 1; V. Kvita and W. Fischer,
Chimia, 1992, 46, 457; V. Kvita and W. Fischer, Chimia, 1993, 47, 3;
G. H. Posner, T. Nelson, C. Kinter and N. Johnson, J. Org. Chem., 1992,
3-allenylpropenoic acid 6 by oxidative addition, transmetalla-
tion (formation of 5) and reductive elimination. Cyclisation
would then occur via an attack on the carboxylate function at the
b-position of the allenyl moiety, which would give the p-
allylpalladium intermediate. The latter would subsequently
provide a-pyrone and regenerate the palladium(0) catalyst.12
5
7, 4083.
For recent synthesis of butenolides using Pd or Ag catalysts see C. Xu
and E. Negishi, Tetrahedron Lett., 1999, 40, 431; S. Ma and Z. Shi,
J. Org. Chem., 1998, 63, 6387; R. Rossi, F. Bellina, M. Biagetti and L.
Mannina, Tetrahedron Lett., 1998, 39, 7799; R. Rossi, F. Bellina, M.
Biagetti and L. Mannina, Tetrahedron Lett., 1998, 39, 7599; R. Rossi, F.
Bellina and L. Mannina, Tetrahedron Lett., 1998, 39, 3017; R. Rossi, F.
Bellina, C. Bechini, L. Mannina and P. Vergamini, Tetrahedron, 1998,
5
1
4, 135; J. A. Marshall, M. A. Wolf and E. M. Wallace, J. Org. Chem.,
997, 62, 367; J. A. Marshall, M. A. Wolf and E. M. Wallace, J. Org.
Chem., 1995, 60, 796; J. A. Marshall, M. A. Wolf and E. M. Wallace,
J. Org. Chem., 1996, 61, 3238; Y. Ogawa, M. Maruno and T.
Wakamatsu, Heterocycles, 1995, 41, 2587; Y. Ogawa, M. Maruno and
T. Wakamatsu, Synlett, 1995, 871.
4
5
R. C. Larock, M. J. Doty and X. Han, J. Org. Chem., 1999, 64, 8770.
A. Duchêne, M. Abarbri, J.-L. Parrain, M. Kitamura and R. Noyori,
Synlett, 1994, 524; M. Abarbri, J.-L. Parrain and A. Duchêne,
Tetrahedron Lett., 1995, 36, 2469; M. Abarbri, J.-L. Parrain, J.-C.
Cintrat and A. Duchêne, Synthesis, 1996, 82.
6
7
8
S. Rousset, M. Abarbri, J. Thibonnet, A. Duchêne and J.-L. Parrain,
Org. Lett., 1999, 1, 701.
B. Cazes, Pure Appl. Chem., 1990, 62, 1867 and references cited
therein.
Allenyltin reagents were prepared from 3-bromoprop-1-yne, magne-
sium and tributyltin chloride under lead(II) bromide catalysis. H.
Tanaka, A. K. M. A. Hai, H. Ogawa and S. Torii, Synlett, 1993, 835.
R. C. Larock, Y. He, W. W. Leon, X. Han, M. D. Refvik and M. J.
Zenner, J. Org. Chem., 1998, 63, 2154.
Scheme 3 Postulated mechanism for heteroannulation.
An alternative pathway involving the attack of 4 on the
central carbon atom of the stannylallene 2a could be excluded
on the basis of the experiments conducted with 1 or 3-substi-
tuted allenylstannanes since other regioisomers should have
been obtained rather than 3h–g‡.9
In conclusion, under palladium complex catalysis, b-iodo-
vinylic a,b-unsaturated acids react with allenyl stannanes via
heteroannulation selectively to provide diverse a-pyrones.
Studies to extend this reaction to other g-halogeno pronucleo-
9
1
1
0 Y. Yamamoto, M. Al-Masum and N. Fujiwara, Chem. Commun., 1996,
81.
1 J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508; T. N. Mitchell,
Synthesis, 1992, 803.
3
12 M. Al-Masum and Y. Yamamoto, J. Am. Chem. Soc., 1998, 120,
3809.
1988
Chem. Commun., 2000, 1987–1988