J. McNulty, P. Das
SHORT COMMUNICATION
[3] E. Vedejs, M. J. Peterson, Top. Stereochem. 1994, 21, 1–157.
[4] B. E. Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863–927.
[5] a) R. Robiette, J. Richardson, V. K. Aggarwal, J. N. Harvey, J.
Am. Chem. Soc. 2006, 128, 2394–2409; b) M. Edmonds, A.
Abell, in Modern Carbonyl Olefination (Ed.: T. Takeda), Wiley-
VCH, Weinheim, 2004, pp. 1–17.
Conclusion
We show that semi-stabilized ylides can be formed solely
in aqueous media from the reaction of a trialkylbenzylphos-
phonium salts and a metal hydroxide and that these ylides
react with aromatic aldehydes in water to precipitate (E)-
stilbenes with high selectivity. As the triethylphosphane ox-
ide side product is water-soluble, we also show that the (E)-
stilbene product can be isolated pure simply by filtration
and washing with water. The same ylides react with enoliz-
able aliphatic aldehydes providing 1-phenylalkenes with
good selectivity. Overall, this direct, high-yielding synthesis
of (E)-stilbenes and alkenes in aqueous media is technically
simple, general and provides high yields of valuable phar-
macological and photo-active materials with high configu-
rational selectivity under environmentally benign condi-
tions. In fact, the aqueous stilbene synthesis elevates the
Wittig reaction of trialkylphosphane-derived semi-stabi-
lized ylides into the realm of “Click” chemistry, satisfying
most of the stringent criteria.[30] Extension of the scope of
the aqueous Wittig chemistry and mechanistic investi-
gations are under study.
[6]
a) F. Orsini, L. Verotta, M. Lecchi, R. Restano, G. Curia, E.
Redaelli, E. Wanke, J. Nat. Prod. 2004, 67, 421–426; b) M.
Cushma, N. Dhanapalan, D. Gopal, A. K. Chakraborti, C. M.
Lin, E. Hamel, J. Med. Chem. 1991, 34, 2579–2588; c) D. Si-
moni, M. Roberti, F. P. Invidiata, E. Aiello, S. Aiello, P. March-
etti, R. Baruchello, M. Eleopra, A. Di Cristina, S. Grimaudo,
N. Gebbia, L. Crosta, F. Diele, M. Tolomeo, Bioorg. Med.
Chem. Lett. 2006, 16, 3245–3248.
a) G. R. Pettit, A. Thornhill, N. Melody, J. C. Knight, J. Nat.
Prod. 2009, 72, 380–388; b) A. Shirali, M. Sriram, J. J. Hall,
B. L. Nguyen, R. Guddneppanavar, M. B. Hadimani, J. F. Ack-
ley, R. Siles, C. J. Jelinek, P. Arthasery, R. C. Brown, V. L.
Murrell, A. McMordie, S. Sharma, D. J. Chaplin, K. G. Pinney,
J. Nat. Prod. 2009, 72, 414–421.
[7]
[8]
a) C. J. Li, Chem. Rev. 1993, 93, 2023–2035; b) C. J. Li, Chem.
Rev. 2005, 105, 3095–3165 .
[9]
[10]
U. M. Lindstrom, Chem. Rev. 2002, 102, 2751–2772.
S. Naraya, J. Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb,
K. B. Sharpless, Angew. Chem. Int. Ed. 2005, 44, 3275–3279.
J. E. Klijn, J. B. F. N. Engberts, Nature 2005, 435, 746–747.
a) J. Dambacher, W. Zhao, A. El-Batta, R. Anness, C. Jiang,
M. Bergdahl, Tetrahedron Lett. 2005, 46, 4473–4477; b) J. Wu,
D. Zhang, S. Wei, Synth. Commun. 2005, 35, 1213–1222; c) F.
Orsini, G. Sello, T. Fumagalli, Synlett 2006, 1717–1718; d) T.
Thiemann, M. Watanabe, Y. Tanaka, S. Mataka, New J. Chem.
2006, 30, 359–369; e) A. El-Batta, C. Jiang, W. Zhao, R. An-
ness, A. L. Cooksy, M. Bergdahl, J. Org. Chem. 2007, 72, 5244–
5259; f) G. A. Molander, R. A. Oliveira, Tetrahedron Lett.
2008, 49, 1266–1268; g) S. Tiwari, A. Kumar, Chem. Commun.
2008, 4445–4447.
[11]
[12]
Experimental Section
Synthesis of DMU-212 (5): Into a flame-dried flask, containing a
magnetic stirring bar was weighed 4-methoxybenzyl bromide
(1.21 mL, 8.4 mmol) under argon. Triethylphosphane (1.24 mL,
8.4 mmol) was then added slowly at 0 °C. The reaction mixture was
slowly warmed to room temp. and stirred for 30 min. Distilled
water (3.4 mL) was added to make a 2.5 solution. The mixture
was stirred at room temp. for 15 min, whereupon LiOH (814.3 mg,
34 mmol) was added slowly. After 2 min, 3,4,5-trimethoxybenzal-
dehyde (1.65 g, 8.4 mmol) was added slowly to the reaction flask.
The flask was stirred vigorously at 70 °C for 3 h. The oil bath was
removed and the flask cooled to room temp. Water (80 mL) was
added to the reaction mixture, and the flask was stirred for 10 min.
The slurry was vacuum-filtered, washed with water and dried to
yield 2.42 g (96%) of DMU-212 (5) as a yellow solid. M.p. 156–
[13]
a) J. J. Hwang, R. L. Lin, R. L. Shieh, J. J. Jwo, J. Mol. Catal.
A 1999, 142, 125–139; b) J. Wu, D. Li, D. Zhang, Synth. Com-
mun. 2005, 35, 2543–2551; c) S. A. Busafi, W. A. Rawahi, In-
dian J. Chem., Sect. B 2007, 46, 370–374.
[14]
[15]
a) M. G. Russel, S. Warren, J. Chem. Soc. Perkin Trans. 1 2000,
505–513; b) C. Huo, X. He, T. K. Chan, J. Org. Chem. 2008,
73, 8583–8586.
a) B. G. James, G. Pattenden, J. Chem. Soc. Perkin Trans. 1
1976, 1476–1479; b) R. Tamura, M. Kato, K. Saegusa, M.
Kakihana, D. Oda, J. Org. Chem. 1987, 52, 4121–4124; c) R.
Tamura, K. Saegusa, M. Kakihana, D. Oda, J. Org. Chem.
1988, 53, 2723–2728; d) Q. Wang, M. E. Khoury, M. Schlosser,
Chem. Eur. J. 2000, 6, 420–426.
1
157 °C. H NMR (600 MHz, CDCl3): δ = 3.81 (s, 3 H), 3.85 (s, 3
H), 3.91 (s, 6 H), 6.88 (d, JHH = 16.1 Hz, 1 H), 6.89 (JHH = 8.8 Hz,
2 H, 2 H), 6.99 (d, JHH = 16.1 Hz, 1 H), 7.43 (d, JHH = 8.8 Hz, 2
H) ppm. 13C NMR (50 MHz, CDCl3): δ = 55.2, 56.0, 60.8, 103.1,
114.3, 126.5, 127.5, 127.7, 129.9, 133.3, 137.4, 153.3, 159.1 ppm.
HRCI MS: calcd. for C18H20O4 [M+] 300.1362, found 300.1346.
[16]
[17]
a) B. B. Aggarwal, A. Bhardwaj, R. S. Aggarwal, N. P. Seeram,
S. Shishodia, Y. Takada, Anticancer Res. 2004, 24, 2783–2840;
b) P. Saiko, A. Szakmary, W. Jaeger, T. Szekres, Mutat. Res.
2008, 658, 68–94.
S. Sale, R. D. Verschoyle, D. Boocock, D. J. L. Jones, N.
Wilsher, K. C. Ruparelia, G. A. Potter, P. B. Farmer, W. P.
Steward, A. J. Gescher, Br. J. Cancer 2004, 90, 736–744.
J. A. Baur, D. A. Sinclair, Nature Rev. Drug Discov. 2006, 5,
493–506.
S. Sale, R. G. Tunstall, K. C. Ruparelia, G. A. Potter, W. P.
Steward, A. J. Gescher, Int. J. Cancer 2005, 115, 194–201.
C. Wu, J. Wei, D. Tian, Y. Feng, R. H. Miller, Y. Wang, J. Med.
Chem. 2008, 51, 6682–6688.
B. Stankoff, Y. Wang, M. Bottlaender, M. S. Aigrot, F. Dolle,
Proc. Natl. Acad. Sci. USA 2006, 103, 9304–9309.
C. Wu, D. Tian, Y. Feng, P. Polak, J. Wei, J. Histochem. Cyto-
chem. 2006, 54, 997–1004.
Supporting Information (see footnote on the first page of this arti-
cle): General details, synthetic protocols and characterization data
for phosphonium salts, compounds 4 and 5 and the materials re-
ported in Tables 1 and 2.
[18]
[19]
[20]
[21]
[22]
[23]
[24]
Acknowledgment
We thank the Natural Science and Engineering Research Council
of Canada (NSERC) and Cytec Canada for financial support of
this work.
S. Xun, Q. Zhou, H. Li, D. Ma, L. Wang, X. Jing, F. Wang, J.
Polym. Sci., Part A: Polym. Chem. 2008, 46, 1566–1576.
C. Kim, H. Choi, S. Kim, C. Baik, K. Song, M. S. Kang, S. O.
Kang, J. Ko, J. Org. Chem. 2008, 73, 7072–7079.
[1] G. Wittig, G. Geissler, Justus Liebigs Ann. Chem. 1953, 580,
44–57.
[2] T. Takeda, Modern Carbonyl Olefination, Wiley-VCH,
Weinheim, 2004.
4034
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4031–4035