Mendeleev Commun., 2002, 12(5), 178–179
†
workup, product 4 was obtained as a yellow oil in 85% yield.
Desilylation with tetrabutylammonium fluoride and oxidative
decomplexation afforded alcohol 5, which was converted into
stilbene 2.6
When the reaction time of the treatment of 8 with LiSEt was
extended to 12 h, resveratrol 1 was formed in 30% yield. Note
1
13
that all reaction products were fully characterised by H,
C
NMR and IR spectroscopy and mass spectrometry.
In conclusion, we found a new strategy for the synthesis
of substituted stilbenes such as trans-resveratrol exploiting the
In the second set of experiments, we prepared stilbene 7
from phosphonate 6 by means of a Wittig–Horner olefination.
While some related reactions have been described in arene
chromium chemistry, it has never been reported that the
required phosphonates (such as 6) can be directly prepared
from the benzylic deprotonated intermediates by reaction with
specific reactivity of 3,5-dimethoxybenzene-Cr(CO) complexes.
3
1
6
Moreover, the surprisingly selective conversion of trimethoxy-
stilbene 2 into pinostilbene deserves attention as it opens
possibilities for the preparation of novel resveratrol analogues
with potentially interesting properties. The described route could
also be extended for the preparation of other plant hydroxy-
stilbenes, for instance, piceatannol (3,5,4',5'-tetrahydroxystil-
bene) and tunalbene (3,3'-dihydroxy-5-methoxystilbene).19
‡
diethylchlorophosphate. Interestingly, phosphonate 6 could be
synthesised through the deprotonation of complex 3 with
n-BuLi in dry THF at –40 °C in a nitrogen atmosphere and the
subsequent addition of diethylchlorphosphate to the deep red
solution of the deprotonated intermediate at –30 to 0 °C. The
Wittig–Horner reaction between phosphonate 6 and p-anisalde-
hyde was then achieved through the deprotonation of 6 with
n-BuLi followed by the addition of the reaction partner at a low
temperature (–30 °C) and warming up to 0 °C. The complexed
References
1
(a) N. A. Tyukavkina, A. S. Gromova, V. I. Lutskii and V. K. Voronov,
§
stilbene 7 was obtained as red needles in 80% yield.
2002, 56, 84; (c) K. P. L. Bhat and J. M. Pezzuto, Ann. N. Y. Acad. Sci.,
The synthesis of key complex 3 from 1,3-dimethoxybenzene
has been conducted in three steps in 61% overall yield.13 While
the first method described for the conversion of 3 into stilbene
2
2
(via 4 and 5) proceeded in four steps with 51% yield, the
same overall transformation was achieved (via 6 and 7) in 46%
overall yield using the Wittig–Horner reaction as a key step. In
the latter case, both the desilylation and decomplexation steps
proceeded cleanly with almost quantitative yields.
3
4
V. Pont and R. Pezet, J. Phytopathol., 1990, 130, 1.
D. R. Kanis, M. A. Ratner and T. J. Marks, J. Am. Chem Soc., 1992,
As a final step for the synthesis of resveratrol 1, the triple
demethylation of trimethoxystilbene 2 had to be performed.
The described methods for this transformation (using BBr3,
MeMgI or LiPPh as a reagent) afforded the product in 30–60%
yield. As a consequence of our positive experience employing
lithium thioethylate (LiSEt) for the double demethylation of
8
V. N. Kalinin, Usp. Khim., 1987, 56, 1190 (Russ. Chem. Rev., 1987, 56,
2
682).
1
7
1
,2-dimethoxybenzene derivatives, we treated 2 (a DMF solu-
9
L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic
Molecules, University Science Books, Mill Valley, 1994, ch. 10.
tion of 2) with an excess of LiSEt at 160 °C for 2 h. We were
surprised and delighted to find that monomethoxystilbene 8
was formed under these conditions in 98% yield. Actually,
compound 8 is a well-known natural product called pino-
stilbene,1 which is found in the bark of Pinus sibericahas
and exhibits interesting biological properties as an inhibitor of
cyclooxygenase (COX-1). It has never been synthesised before.
Thus, the selective conversion of 2 to 8 with LiSEt opens an
efficient synthetic access to pinostilbene and its derivatives.19
1
0 H.-G. Schmalz and S. Siegel, in Transition Metals for Fine Chemicals
and Organic Synthesis, eds. C. Bolm and M. Beller, VCH, Weinheim,
1998, ch. 6.
,18
11 H.-G. Schmalz, M. Arnold, J. Hollander and J. W. Bats, Angew. Chem.,
994, 106, 77 (Angew. Chem., Int. Ed. Engl., 1994, 33, 109).
2 H.-G. Schmalz and K. Schellhaas, Angew. Chem., 1996, 108, 2277
1
1
†
6
Tricarbonyl-[2-(h -3,5-dimethoxy-4-trimethylsilylphenyl)-1-(4'-methoxy-
phenyl)ethanol]-chromium(0) 4: mp 120 °C. H NMR (400 MHz, CDCl )
d: 0.34 (s, 9H, MeSi), 2.04 (d, 1H, OH, J 3 Hz), 2.85 (dd, 1H, CH , J
4 Hz, J 5 Hz), 2.93 (dd, 1H, CH , J 14 Hz, J 8 Hz), 3.61, 3.64 (s, 6H,
OMe), 3.82 (s, 3H, OMe), 4.58, 4.65 (s, 2H, 2-C, 6-C), 4.93 (m, 1H,
CHOH), 6.91 (d, 2H, 2'-C, 6'-C, J 9 Hz), 7.29 (d, 3'-C, 5'-C, J 2 Hz, J
Hz). C NMR (67.7 MHz, CDCl ) d: 1.5 (q, MeSi), 26.9 (d, CHOH),
5.4 (t, CH ), 55.4, 55.29, 55.27 (q, OMe), 73.2, 74.6 (d, 2-C, 6-C),
08.3 (s), 114.0 (d, 3'-C, 5'-C), 127.2 (d, 2'-C, 6'-C), 135.3 (s), 148.1 (s),
59.5 (s), 234.5 [s, Cr(CO) ]. IR (KBr, n/cm ): 3586 (OH), 2954, 1950,
865 [C=O, Cr(CO) ]. MS (EI, 70 eV), m/z (%): 496 (8) [M] , 412 (100).
Tricarbonyl-[1-(h -3,5-dimethoxy-4-trimethylsilylphenyl)-methyldiethyl-
phosphonate]-chromium(0) 6: mp 130 °C. H NMR (400 MHz, CDCl )
d: 0.32 (s, 9H, MeSi), 1.34 (t, 6H, Me, J 7 Hz), 2.96 (d, 2H, CH , JPH,
J 20.5 Hz), 3.69 (s, 6H, OMe), 4.13 (m, 4H, OCH ), 4.74 (s, 2H, 2-C,
-C). C NMR (67.7 MHz, CDCl ) d: 1.5 (q, MeSi), 16.4, 16.5 (q, Me),
1
3
2
1
2
1
3
9
4
1
1
3
2
1537; (c) H.-G. Schmalz and A. Majdalani, Synlett, 1997, 1303.
–1
18 (a) A. S. Gromova, N. A. Tyukavkina, V. I. Lutskii, G. A. Kalabin and
D. F. Kushnarev, Khim. Prir. Soedin., 1975, 677 [Chem. Nat. Compd.
(Engl. Transl.), 1975, 11, 715]; (b) A. S. Gromova, V. I. Lutskii and
N. A. Tyukavkina, Khim. Prir. Soedin., 1977, 275 [Chem. Nat. Compd.
(Engl. Transl.), 1977, 13, 236]; (c) A. S. Gromova, V. I. Lutskii and
N. A. Tyukavkina, Khim. Drevesiny, 1979, 103 (in Russian).
3
+
1
3
6
‡
1
3
2
2
2
19 (a) N. H. Shin, S. Y. Ryu, H. S. Lee, K. R. Min and Y. S. Kim, Planta
1
3
6
3
1
7
3
Medica, 1998, 64, 283; (b) C. H. Rolfs and H. Kindl, Plant Physiol.,
2.7, 34.9 (t, OCH ), 62.5 (t, CH P), 72.27, 72.31 (d, 2-C, 6-C), 79.3 (s,
-C), 102.3 (s, 4-C), 148.0 (s, 3-C, 5'-C), 234.2 [s, Cr(CO) ]. MS (EI,
0 eV), m/z (%): 496 (2) [M] , 412 (100), 285 (68). IR (KBr, n/cm ):
2
2
1984, 75, 489.
3
+
-1
2
903, 1951, 1866 [C=O, Cr(CO) ], 1230.
Tricarbonyl-[1-(h -3,5-dimethoxy-4-trimethylsilylphenyl)-2-(4'-methoxy-
3
§
6
1
phenyl)ethene]-chromium(0) 7: mp 202 °C. H NMR (400 MHz, CDCl )
3
d: 0.45 (s, 9H, Me-TMS), 3.76 (s, 6H, OMe), 3.83 (s, 3H, OMe), 4.93
(s, 2H, 2-C, 6-C), 6.72 (d, 1H, olefin, J 17 Hz), 6.91 (d, 2H, 2'-C, 6'-C,
J 9 Hz), 6.98 (d, 1H, olefin, J 17 Hz), 7.44 (d, 2H, 3'-C, 5'-C, J 9 Hz).
13
C NMR (67.7 MHz, CDCl ) d: 1.5 (q, Me-TMS), 55.2, 55.3, 55.4 (q,
3
OMe), 68.9 (d, 2-C, 6-C), 79.4 (s), 106.5 (s), 114.4 (d, 3'-C, 5'-C), 123.9
(
d, olefin), 128.3 (d, 2'-C, 6'-C), 128.4 (s), 131.8 (d, olefine), 148.3 (s),
–1
1
60.2 (s), 234.0 [s, Cr(CO) ]. IR (KBr, n/cm ): 2978, 2956, 1935, 1843
3
+
[C=O, Cr(CO) ], 1605. MS (EI, 70 eV), m/z (%): 478 (1) [M] , 394 (8)
3
+
+
[
M – 3CO] , 342 (92) [M – 3CO – Cr] , 267 (100).
Received: 17th June 2002; Com. 02/1942
–
179 –