1110
A. Giraud et al. / Tetrahedron Letters 49 (2008) 1107–1110
and 3m14 in good yields. Similarly, we succeeded in the one-
pot preparation of known biologically active analogues of
CA-4, 3n15 and 3o16 in good yields and high Z-stereo-
control (entries 12 and 13).
4. (a) Lindlar, H. Helv. Chim. Acta 1952, 35, 446; (b) Lindlar, H.;
Dubuis, R. Org. Synth. 1973, 5, 880.
5. LeBras, G.; Radanyi, C.; Peyrat, J.-F.; Brion, J.-D.; Alami, M.;
Marsaud, V.; Stella, B.; Renoir, J.-M. J. Med. Chem. 2007, 50 http://
On account of the large scope of this one-pot procedure,
we then attempted to synthesize CA-4 from the corre-
sponding 1c having a free phenolic function. Because of
the side silylation of the phenol moiety, the desilylation
step was conducted at 60 °C. As shown in entry 14, CA-4
was obtained with fortunately an excellent Z-stereoselec-
tivity (Z:E/90:10) and in a good yield. Careful separation
on silica gel afforded pure CA-4, which could be used as
reference for biological evaluation of analogues that would
be reported in due course.
In summary, we have developed a new, mild and effi-
cient method for the synthesis of Z-stilbenes from diary-
lalkynes. This method is complementary to the existing
procedures and sometimes could be the method of choice
because of its chemoselectivity, simplicity and its excellent
Z-stereoselectivity. The ease by which several Z-stilbenes
were obtained with a total Z-stereocontrol and in good
yields encouraged us to prepare efficiently the natural stil-
bene CA-4 by this way. Moreover, we also demonstrated
that this hydrosilylation–protodesilylation sequence could
be achieved in a one-pot way from various diarylalkynes.
6. Provot, O.; Giraud, A.; Peyrat, J.-F.; Alami, M.; Brion, J.-D.
Tetrahedron Lett. 2005, 46, 8547.
7. (a) Robinson, J. E.; Taylor, R. J. K. Chem. Commun. 2007, 1617; (b)
Harrowven, D. C.; Guy, I. L.; Howell, M.; Packham, G. Synlett 2006,
2977; (c) Gaukroger, K.; Hadfield, J. A.; Hepworth, L. A.; Lawrence,
N. J.; McGown, A. T. J. Org. Chem. 2001, 66, 8135; (d) Lawrence, N.
J.; Abdul Ghani, F.; Hepworth, L. A.; Hadfield, J. A.; McGown, A.
T.; Pritchard, R. G. Synthesis 1999, 1656; (e) Furstner, A.; Nikolakis,
¨
K. Liebigs Ann. 1996, 2107.
´
8. Lara-Ochoa, F.; Espinosa-Perez, G. Tetrahedron Lett. 2007, 48, 7007.
9. (a) Hamze, A.; Provot, O.; Brion, J.-D.; Alami, M. Synthesis 2007,
2025; (b) Hamze, A.; Provot, O.; Alami, M.; Brion, J.-D. Org. Lett.
2005, 7, 5625.
10. (a) Liron, F.; Le Garrec, P.; Alami, M. Synlett 1999, 246; (b) Alami,
M.; Liron, F.; Gervais, M.; Peyrat, J.-F.; Brion, J.-D. Angew. Chem.,
Int. Ed. 2002, 41, 1578; (c) Liron, F.; Gervais, M.; Peyrat, J.-F.;
Alami, M.; Brion, J.-D. Tetrahedron Lett. 2003, 44, 2789; (d) Bujard,
M.; Ferri, F.; Alami, M. Tetrahedron Lett. 1998, 39, 4243; (e) Hamze,
A.; Provot, O.; Brion, J.-D.; Alami, M. J. Org. Chem. 2007, 72, 3868.
11. Dodd, D. E.; Stuart, B. O.; Rothenberg, S. J.; Kershaw, M.; Mann, P.
C.; James, J. T.; Lam, C. W. Inhal. Toxicol. 1994, 6, 151.
12. Speier’s catalyst is well known to provide cis-addition processes for
internal and terminal alkynes; see: Tsipis, C. A. J. Organomet. Chem.
1980, 187, 427.
13. Procedure for the synthesis of CA-4: In a 10 mL flask, PtO2 (10 mg,
0.0035 mmol) and arylalkyne 1c (0.5 mmol) were placed under
nitrogen atmosphere. Dimethylethoxysilane (304 lL, 2 mmol) was
introduced via syringe and the mixture was stirred at 60 °C in an oil
bath for 1 h. The residue was concentrated and then purified by
column chromatography over silica gel to yield the vinylsilanes as a
mixture of regioisomers (147 mg; 70%). The mixture of vinylsilanes
(147 mg, 0.35 mmol) was treated with TBAF in THF (1 mL, 1 N) at
60 ° C for 1 h. After concentration in vacuo, the crude product was
purified by column chromatography (SiO2, cyclohexane/EtOAc: 70/
30) to afford CA-4 as a single Z-stereoisomer (75 mg; 69%). TLC: Rf
0.46 (cyclohexane/EtOAc: 70/30, 1/1, SiO2). 1H NMR (300 MHz,
CDCl3) d 3.70 (s, 6H), 3.84 (s, 3H), 3.86 (s, 3H), 5.50 (br s, 1H, OH),
6.40 (d, 1H, J = 12.1 Hz), 6.47 (d, 1H, J = 12.1 Hz), 6.53 (s, 2H), 6.72
(d, 1H, J = 8.2 Hz), 6.80 (dd, 1H, J = 8.2 Hz, J = 1.8 Hz), 6.92 (d,
1H, J = 1.8 Hz). 13C NMR (75 MHz, CDCl3) d 55.9 (2C), 56.1, 60.9,
106.0 (2C), 110.3, 115.0, 121.1, 129.0, 129.5, 130.6, 132.7, 137.1, 145.2,
145.8, 152.8 (2C).
Acknowledgements
The CNRS is gratefully acknowledged for financial sup-
port of this research and the MNSER for a doctoral fellow-
ship to A.G.
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