A stereoselective access to functional dienes containing a trifluoromethyl group via stille cross coupling of ethyl 4,4,4-trifluoro-3-iodobutenoate

Article abstract of DOI:10.1055/s-1998-1787

Stereoselective construction of 3-trifluoromethyl conjugated dienoates or enynoates was achieved from ethyl (Z)-4,4,4-trifluoro-3-iodobutenoate and alkenyltin or alkynyltin reagents through the Stille reaction. Reduction of ethyl 3-trifluoromethyldienoate

Full text of DOI:10.1055/s-1998-1787

August 1998
SYNLETT
839
A Stereoselective Access to Functional Dienes Containing a Trifluoromethyl Group via Stille
Cross Coupling of Ethyl 4,4,4-Trifluoro-3-iodobutenoate
a
a
a
a
b
Gildas Prié, Jérôme Thibonnet, Mohamed Abarbri, Alain Duchêne, * Jean-Luc Parrain *
a
Laboratoire de Physicochimie des Interfaces et des Milieux Réactionnels, Faculté des Sciences de Tours, Parc de Grandmont, F-37200 Tours, France
Fax 33 2 47 36 69 59 e-mail duchene@delphi.phys.univ-tours.fr
b
Laboratoire de Synthèse Organique associé au CNRS, D12, Faculté des Sciences de Saint Jérôme, Avenue Escadrille Normandie-Niemen, F-13397
Marseille Cedex 20, France
Fax 33 4 91 98 38 65 e-mail jl.parrain@lso.u-3mrs.fr
Received 27 March 1998
Abstract: Stereoselective construction of 3-trifluoromethyl conjugated
dienoates or enynoates was achieved from ethyl (Z)-4,4,4-trifluoro-3-
iodobutenoate and alkenyltin or alkynyltin reagents through the Stille
reaction. Reduction of ethyl 3-trifluoromethyldienoates using DIBAL-H
selectively afforded allylic alcohols.
Vinyltin compounds were used with 3% of dichlorobis-
(acetonitrile)palladium(II) using DMF as solvent. The mild
experimental conditions of the Stille cross-coupling reaction resulted in
good yields of dienes 3 and no polymerisation products were detected.
Results are shown in Table 1. NMR studies on 3a confirmed the
retention of the Z stereochemistry of the α-double bond.14 Cross
coupling of 2 with (E)-1,2-bis(tributylstannyl)ethylene (1.6 eq.) (entry
Functionalized molecules bearing fluorine atoms, which modify their
bioactivity by enhancement of both nucleophilicity and electronic
6
) under the same experimental conditions, provided a separable
mixture of dienyltin compound 3f and bis coupling product 3g. When
.51 equivalent of (E)-1,2-bis(tributylstannyl)ethylene was used (entry
7), 3g was obtained as the sole product, indicating the high reactivity of
towards vinyltin in comparison with our previous results where no bis-
1
,2,3
properties, are often required in medicinal chemistry.
Among these
0
molecules, trifluoromethyl substituted α,β-unsaturated esters are
4
,5
important. Trifluoromethyl substituted polyenes have previously been
obtained by Wittig Horner olefination of trifluoromethyl ketones or
2
cross-coupling product was obtained.17 Finally, to extend this
methodology to other tin reagents, we found that alkynyltin reagents led
to functional enynes (entries 8 and 9) in good yields and with a complete
retention of the double bond configuration.
6
7
phosphonates, or through sulfone-based cross coupling. These major
routes have been successfully applied to the synthesis of
a
8
9
trifluoromethyl substituted juvenile hormone, retinal or retinoic acid.
Nevertheless, the weak E/Z selectivity of the created trisubstituted
double bond containing a trifluoromethyl group constitutes the major
drawback of such approaches.
The synthetic potential of compounds 3a-i has not been completely
studied to date. However, saponification reaction with lithium hydroxide
in a 1/1 water/ethanol mixture at 20°C gave the corresponding acids in
fair yields [3c’(83%), 3d’(73%), 3e’(69%)].18 Finally, selective
reduction of the ester function into the primary alcohol was investigated
in order to preserve the trifluoromethyl diene moiety. Treatment of
dienes 3 with DIBAL-H (2 eq.) at -78° C afforded quantitatively dienyl
alcohols 4 (Scheme 3).19
Following our previous work describing the synthesis of (Z)- or (E)-3-
1
0
methylalk-2-enoic or 3-substituted but-3-enoic acids, we decided to
examine the possibility of extending this methodology to the direct
synthesis from 4,4,4-trifluoro-3-iodobutenoate esters of dienoic esters
bearing a trifluoromethyl group. Moreover, a recent paper describing the
synthesis of trifluoromethyl substituted enynes from 2 under Heck-
Sonogashira conditions prompted us to report our results in this field.11
In this paper we report the stereoselective synthesis of functional dienes
from ethyl (Z)-4,4,4-trifluoro-3-iodobutenoate 2 via the Stille reaction.
The starting ethyl (Z)-4,4,4-trifluoro-3-iodobutenoate 2 was obtained by
1
2
13
addition of hydroiodic acid on 1.
Scheme 3
DIBAL-H treatment of 2 under the same experimental conditions also
gave the corresponding (Z)-4,4,4-trifluoro-3-iodobutenol in 50 % yield.
Scheme 1
In summary, we have shown that Stille cross-coupling of ethyl (Z)-4,4,4-
trifluoro-3-iodobutenoate with tin reagents constitutes a facile method
for a selective synthesis of functional dienes or enynes bearing a
trifluoromethyl group. Application to the synthesis of trifluoroterpenoic
structures are in progress and will be reported in due course.
The addition on the triple bond occurs with clean Z-stereoselectivity.14
It should be noted that temperature, reaction time and purity of
hydroiodic acid are critically important parameters in obtaining a pure
Z-stereoisomer. Because of the high volatility of 1, the use of a
hydroiodic solution at 0°C instead of the sodium iodide/acetic acid
Acknowledgements: We thank CNRS and MESR for providing
financial support, the "Service d'analyse chimique du vivant de Tours"
for recording NMR and mass spectra, and the "Conseil Régional de la
Région Centre" for awarding a fellowship to one of us (J.T.).
1
5
system was an appealing procedure.
Attention was next directed to the synthesis of trifluorodienoates by
palladium complex mediated cross-coupling between 2 and organotin
1
6
reagents as described in Scheme 2.
Scheme 2

8
40
LETTERS
SYNLETT
9
1
Mead, D.; Asato, A.E.; Denny, M.; Liu, R.S.H.; Hanzawa,Y.;
Taguchi, T.; Yamada, A.; Kobayashi, N.; Hosoda, A.; Kobayashi,
Y. Tetrahedron Lett. 1987, 28 , 259-262 and references cited
therein.
0
a) Abarbri, M.; Parrain, J.L.; Duchêne A. Tetrahedron Lett. 1995,
3
6, 2469-2472; b) Abarbri, M.; Parrain, J.L.; Cintrat, J.C.;
Duchêne A. Synthesis 1996, 82-86; c) Thibonnet, J.; Abarbri, M.;
Parrain, J.L.; Duchêne, A. Tetrahedron Lett. 1996, 37, 7507-7510.
1
1
2
Qing, F.L.; Zhang, Y. Tetrahedron Lett. 1997, 38 , 6729-6732.
1
a) Chalcat, J.C.; Théron, F.; Vessière, R. C. R. Acad Sci. série C
1
971, 273, 763-765. b) Preparation of 2: 14.6 mL (0.065 mol) of
an aqueous solution of hydroiodic acid(57%) are added dropwise
to 8.3 g (0.05 mol) of 1 with stirring at 0,-5 °C. After work-up (5%
aq. Na S 0 , brine solution, MgSO ), 2 (11.8 g, 0.04 mol, 80%) is
2
2
3
4
pure enough and can be used without purification.
1
3
4
Hamper, B.C. Org. Synth. 1991, 70, 246-253.
1
For assignment of Z stereochemistry see: a) Camps, F.; Canela, R.;
Coll, J.; Messeguer, A.; Roca, A. Tetrahedron 1978, 34, 2179-
2182; b) Begue, J;-P.; Bonnet-Delpon, D.; Mesureur, D.;
Ourevitch, M. Magn. Reson. Chem. 1991, 29, 675-678; c) Tamura,
K.; Ishihara, T.; Yamanaka, H. J. Fluorine Chem. 1994, 68, 25-31;
d) Bouillon, J.-P.; Maliverney, C.; Janousek, Z.; Viehe, H.G. Bull.
3
Soc. Chim. Fr. 1997, 134, 47-57. All the coupling constants J
C-F
for carbon 2 of compounds 3a-f are up to 5.1 Hz. This strongly
supports the Z stereochemistry of the double bond (ref. 14b).
1
1
5
6
a) Ma, S.; Lu, X.; Li, Z. J .Org. Chem. 1992, 57, 709; b) Ma, S.;
Lu, X. J. Chem. Soc., Chem. Commun. 1990, 1643; c) Lu, X.;
Wang, Z.; Ji, J. Tetrahedron Lett. 1995, 35, 613-616.
a) Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524;
b) Stille, J.K.; Groh, B.L. J. Am. Chem. Soc. 1987, 109, 813-817;
c) Labadie, J.W.; Stille, J.K. J. Am. Chem. Soc. 1983, 105, 669-
6
70; d) Mitchell, R.N. Synthesis 1992, 803-815.
Thibonnet, J.; Abarbri, M.; Parrain, J.-L.; Duchêne, A. Synlett
997, 771-772.
1
7
8
1
19
1
F NMR δ (ppm) (183.3 MHz, CDCl ) (using CF COOH as
3
3
external standard, upfield positive): -9.85 (3b), -9.75 (3c), -9.45
3d), -4.85 (3d), -9.45 (3g), -5.55 (3h), -9.45 (3d’), -4.85 (3e’)
(
References and Notes
1
2
9
0
Sen, S.E.; Ewing, G.J. J. Org. Chem. 1997, 62, 3529-3536.
1
a) Welch, J.T. Tetrahedron 1987, 4, 3123-3136 and references
Typical procedure: Preparation of compound 3c. To a DMF
solution (15mL) of 2 (1.77 g, 7 mmol), (E)-2-tributylstannyl-1-
trimethylsilylethene (2.81 g, 7.2 mmol) and 55 mg (0.21 mmol) of
dichlorobis(acetonitrile)palladium(II) were added. The mixture
was stirred for 6h at 20°C, then hydrolysed with 25 mL of a 0.5M
solution of potassium fluoride and 25 mL of ethyl acetate to
precipitate the tribuyltin fluoride formed. After strongly stirring
for 2h, the reaction mixture was filtered and extracted with diethyl
ether (3x30 mL). After usual work-up, the crude ester 3c was
purified by column chromatography (hexane/diethylether = 97/3
cited therein; b) Organofluorine Compounds in Medicinal
Chemistry and Biomedical Applications, Filler, R.; Kobayashi, Y.;
Yagupolskii, L.; Eds., Elsevier, Amsterdam, 1993.
2
3
Fluorine in Bioorganic Chemistry, Welch J.T., Eswara-Krishnan
S., Eds., Wiley, New York, 1991.
a) Francesch, A.; Alvarez, R.; Lopez, S.; de Lera, A.R. J. Org.
Chem. 1997, 62, 310-319; b) Groesbeck, M.; Smith, S.O. J. Org.
Chem. 1997, 62, 3638-3641.
4
5
6
Fluorine-Containing Aminoacids, Synthesis and Properties,
Kukhar VP, Soloshonok VA, Eds., Wiley, New York, 1995.
-
1
1
to 70/30). IR (cm ): 3060, 2963, 1725, 1637, 1251; H NMR δ
3
(
(
ppm) (200 MHz): 0.19 (9H, s), 1.37 (3H, t, J = 7.1Hz), 4.3
2H, q, J3H = 7.1Hz), 6.31 (1H, s), 6.62 (1H, dq, J = 20Hz,
JH-F = 2.2Hz), 7.65 (1H, bd, 3J1H = 20Hz); C NMR δ (ppm) (50
MHz): -1.2, 14.7, 61.7, 121.2 (q, JC-F = 6Hz), 123.1 (q, JC-F =
77Hz), 132.7, 141.3 (q, JC-F = 28Hz), 143.5, 165.2; MS (70
2H
Bensadat, A.; Félix, C.; Laurent, A.; Laurent, E.; Faure, R.;
Thomas, T. Bull. Soc. Chim. Fr. 1996, 133, 509-514.
3
3
1H
4
13
Poulter, C.D.; Wiggins, P.L.; Plummer, T.L. J. Org. Chem. 1981,
3
1
46, 1532-1538.
2
2
7
8
Welch, S.C.; Gruber, J.M. J. Org. Chem. 1982, 47, 385-389.
eV): m/z = 251 (M-Me, 1), 237 (15), 174 (23), 146 (38), 129 (11),
81 (13), 79 (15), 77 (56), 75 (78), 73 (100), 59 (10), 45 (19), 43
(13)
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