2
452
E. C. Dunne et al. / Tetrahedron Letters 43 (2002) 2449–2453
+
Ph3P
+
Ph3P
+
Ph3P
H
O
H
O
H
O
Hal
Hal
Hal
Hal
moderate Z
moderate E
high Z
+
Ph3P
+
Ph3P
+
Ph3P
H
O
H
O
H
O
Hal
Hal Hal
Hal
Hal
Hal
Hal
high E
v. high E
moderate E
+
Ph3P
+
Ph3P
H
O
H
O
Hal
Hal
Hal
Hal
Hal Hal
Hal
moderate E
v. high E
Chart 1. Approximate selectivities in the Wittig reaction to give ortho-halo substituted stilbenes: moderate: 70–85; high: 85–95;
very high: 95–99%
References
10. Zhang, X.; Schlosser, M. Tetrahedron Lett. 1993, 34,
925.
1
1
. Wittig, G.; Geissler, G. Justus Liebigs Ann. Chem. 1953,
11. Cushman, M.; Nagarathnam, D.; Gopal, D.;
Chakraborti, A. K.; Lin, C. M.; Hamel, E. J. J. Med.
Chem. 1991, 34, 2579–2588.
5
80, 44.
2
. (a) Johnson, A. W. Ylides and Imines of Phosphorus;
Wiley: NY, 1993; Chapters 8 and 9, pp. 221–305; (b)
Kolodiazhnyi, O. I. Phosphorus Ylides: Chemistry and
Application in Organic Synthesis; Wiley: New York, 1999;
12. Experimental procedure: the bromide (0.020 mol) and
benzaldehyde (0.020 mol) were dissolved in chloroform
3
3
(150 cm ) and 50% w/v aqueous NaOH (8.8 cm ; 0.100
mol) added to the rapidly stirring solution. The ylidic
color was noted shortly after addition and gradually
faded. Stirring was maintained overnight, after which the
(c) Gosney, I.; Rowley, A. G. In Organophosphorus
Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.;
Academic Press, 1979; Chapter 2, pp. 17–153.
3
. (a) Vedejs, E.; Snoble, K. A. J. J. Am. Chem. Soc. 1973,
layers were separated, the organic washed with water
3
9
5, 5778; (b) Vedejs, E.; Marth, C. F. J. Am. Chem. Soc.
(3×50 cm ) and dried over MgSO . The chloroform was
4
1
1
988, 110, 3948; (c) Vedejs, E.; Fleck, T. J. J. Am. Chem.
evaporated and a H NMR spectrum (CDCl , 300 MHz)
3
Soc. 1989, 111, 5861; (d) Vedejs, E.; Marth, C. F. J. Am.
Chem. Soc. 1990, 112, 3905; (e) Vedejs, E.; Peterson, M.
J. Top. Stereochem. 1994, 21, 1.
. Stabilized ylides have a carbonyl or similar group conju-
gated to the PꢀC bond. Semi-stabilized (moderated)
ylides have phenyl or similar group and unstabilized have
no such groups.
. (a) Maryanoff, B. E.; Reitz, A. B.; Mutter, M. S.; Inners,
R. R.; Almond, H. R.; Whittle, R. R.; Olofson, R. A. J.
Am. Chem. Soc. 1986, 108, 7664; (b) Maryanoff, B. E.;
Reitz, A. B. Chem. Rev. 1989, 89, 863.
taken of the resulting crude oil. Treatment with pet. spirit
(40–60°C) (100 cm ) caused triphenylphosphine oxide to
3
precipitate and the solid was washed with 4–6 portions of
3
4
5
6
pet. spirit (40–60°C) (50 cm ) to remove all the stilbene.
These washings were combined and the solvent evapo-
rated to give an oil (generally yellow) which often crystal-
lized slowly on standing. The yield at this point was
>70%, except entries 8=60, 11=61, 17=59, 6=52, 2=
67%. Separation of the isomers was achieved using flash
chromatography on neutral alumina with elution by pen-
tane. The E/Z ratios were then calculated by comparing
1
. (a) Yamataka, H.; Nagase, S. J. Am. Chem. Soc. 1998,
the alkene peaks of the isomers in the crude H NMR.
1
20, 7530; (b) Yamataka, H.; Takatsuka, T.; Hanafusa,
Yields quoted are of the crude stilbene. All reduced yields
were accounted for by the remaining aldehyde and in
some cases hydrolysis of the phosphonium salt or ylide to
give the substituted toluene was noted. No other products
were detected. The aldehydes were checked for the pres-
ence of the carboxylic acid prior to use (Ref. 3e).
T. J. Org. Chem. 1996, 61, 722; (c) Yamataka, H.;
Nagareda, K.; Takatsuka, T.; Ando, K.; Hanafusa, T.;
Nagase, S. J. Am. Chem. Soc. 1993, 115, 8570.
. Yamataka, H.; Nagareda, K.; Ando, K.; Hanafusa, T. J.
Org. Chem. 1992, 57, 2865.
7
8
. (a) McEwen, W. E.; Janes, A. B.; Knapczyk, J. W.;
Kyllingstad, V. L.; Shiau, W.-I.; Shore, S.; Smith, J. H. J.
Am. Chem. Soc. 1978, 100, 7304–7311 and references
cited therein; (b) Keldsen, G. L.; McEwen, W. E. J. Am.
Chem. Soc. 1978, 100, 7312–7317.
13. Great care had to be taken to determine the correct Z/E
ratio because of isomerization on chromatography. Even
on neutral alumina, we noted isomerization leading to
loss of the Z-isomer on chromatography in a number of
cases with Z-2,2%-difluorostilbene being especially prone.
This sensitivity presented some difficulty in obtaining the
data for entry 3 because there was almost complete
9. McEwen, W. E.; Cooney, J. V. J. Org. Chem. 1983, 48,
9
83.