1884
A. Costa et al.
LETTER
(15) The sequence alkylation- -elimination-Heck/coupling
237 L, 0.72 mmol for compound 7; 7 L, 0.02 mmol for
compounds 6ad and 6bd) in dry THF (3 mL), at 0 °C, the
corresponding electrophile (0.24 mmol) was added. After
stirring at this temperature, for reaction times depicted in
Table, an aqueous 2 M solution of hydrochloric acid (2 mL)
was poured into the flask. The aqueous phase was extracted
with EtOAc (3 10 mL) and the combined organic layers
were washed successively with aqueous 2 M HCl (2 10
mL) and brine (10 mL), dried (Na2SO4) and evaporated
under vacuo. The crude products were purified by flash
chromatography (silica gel) using mixtures of n-hexane/
ethyl acetate as eluent, obtaining products 6 or 7 in yields
showed in Table.
reaction gave slightly lower yields because a little
intramolecular Heck reaction onto o-halocinnamic ester
occurred.
(16) For a recent review, see: Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2000, 100, 3009.
(17) For recent publications regarding the efficiency of
tetraalkylammonium salts in Heck reaction, see: (a) Jeffery,
T. Tetrahedron Lett. 1999, 40, 1673. (b) Jeffery, T.
Tetrahedron 1996, 52, 10113; and references cited therein.
(18) Symmetrical ortho-distyrylbenzenes have been obtained by
a double Heck reaction: (a) Chao, B.; Dittmer, D. C.
Tetrahedron Lett. 2000, 41, 6001. (b) Voigt, K.; Lansky, A.;
Noltemeyer, M.; de Meijere, A. Liebigs Ann. 1996, 899.
(c) Lansky, A.; Reiser, O.; de Meijere, A. Synlett 1990, 405.
(d) Tao, W.; Nesbitt, S.; Heck, R. F. J. Org. Chem. 1990, 55,
63.
(19) As well, symmetrical ortho-distyrylbenzenes have been
obtained by a double Wittig or a double Horner-Wadsworth-
Emmons reaction from the corresponding phthalaldehydes:
(a) Kaupp, G.; Frey, H.; Behmann, G. Chem. Ber. 1988, 121,
2135. (b) Darby, N.; Cresp, T. M.; Sondheimer, F. J. Org.
Chem. 1977, 42, 1960. (c) Tavares, D. F.; Ploder, W. H.
Tetrahedron Lett. 1970, 1567.
(20) (a) Martínez, G. R.; Gooding, O. W.; Repke, D. B.;
Teitelbaum, P. J.; Walker, K. A. M.; Whiting, R. L. U. S.
Patent 19960723, 1996. (b) Chem. Abstr. 1996, 125,
195657. (c) Martínez, G. R.; Repke, D. B.; Teitelbaum, P. J.;
Walker, K. A. M.; Gooding, O. W.; Whiting, R. L.; Bansal,
R. P.; Muehldorf, A. V.; O’yang, C. U. S. Patent 19951102,
1995. (d) Chem. Abstr. 1995, 124, 176116.
(21) (a) Bousard, M.-F.; Guette, J. P.; Wierzbicki, M.; Beal, P.;
Fournier, J.; Boulanger, M.; Della-Zuana, O.; Duhault, J.
Arzneim.-Forsch. 2000, 50, 1084. (b) Wierzbicki, M.;
Hugon, P.; Duhault, J.; Lacour, F. FR. Patent 19900105,
1990. (c) Chem. Abstr. 1990, 113, 230948.
A typical procedure for compounds 8 follows:
To a solution of the benzyl sulfone 5 (0.2 mmol) and P2-Et
(79 L, 0.24 mmol)in dry THF (3 mL), at -78 °C, under an
inert atmosphere (N2) was added the corresponding aldehyde
(0.24 mmol). After stirring at this temperature, for reaction
times depicted in Table, an aqueous 2 M solution of
hydrochloric acid (2 mL) was poured into the flask. The
aqueous phase was extracted with EtOAc (3 10 mL) and
the combined organic layers were washed successively with
aqueous 2 M HCl (2 10 mL) and brine (10 mL), dried
(Na2SO4) and evaporated under vacuo. The crude products
were purified by flash chromatography (silica gel) using
mixtures of n-hexane/ethyl acetate as eluent, obtaining
aldols 8 in yields showed in Table.
A typical procedure for compounds 9 follows:
To a solution of paraformaldehyde (34 mg, 1.08 mmol) and
benzyl sulfone 5 (0.2 mmol) in dry THF (10 mL), at 0 ºC,
was slowly added (2 h) a solution of P2-Et (145 L, 0.43
mmol) in dry THF (5 mL). The resulting mixture was stirred
at room temperature overnight and an aqueous 2 M HCl
solution (2 mL) was added. The mixture was treated as
described previously affording, after purification by flash
chromatography (silica gel), compound 9a or 9b in 54% and
70% yield, respectively (see Table).
(22) For reviews, see: (a) Suzuki, A. J. Organomet. Chem. 1999,
576, 147. (b) Suzuki, A. Metal Catalyzed Cross Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-V.C.H.:
Weinheim, 1998, Chap. 2, 49–97.
(23) In the case of ortho-iodobenzyl chloride Cu-thiophene-2-
carboxylate (CuTC)-mediated coupling of boronic acids
under non-basic/room temperature conditions has been
reported as alternative to the traditional Suzuki–Miyaura
conditions: Savarin, C.; Liebeskind, L. S. Org. Lett. 2001, 3,
2149.
9a: 1H NMR (300 MHz, CDCl3) : 2.41 (s, 3 H, CH3Ar),
5.93, 6.82 (2 s, 2 H, CH2=C), 7.19–7.31 (m, 4 H, ArH) and
7.42–7.52 (m, 4 H, ArH). 13C NMR (75 MHz, CDCl3) :
21.6 (CH3Ar), 124.4 (ArCBr), 127.6, 128.7, 129.1, 130.4,
131.0, 134.7, 136.7, 139.7, 140.1, 144.7 and 148.9 (ArC and
CH2=C). IR (neat): 3101, 1596, 1316, 1303, 1149, 800
cm–1. MS (EI, 70 eV) m/z: 338, 336 (M+, 3%), 259 (11), 258
(80), 257 (96), 199 (54), 197 (49), 184 (39), 182 (78), 181
(100), 140 (27), 103 (31), 102 (44)and 101 (45).
(12) Truce, W. E.; Klingler, T. C. J. Org. Chem. 1970, 35, 1834.
(13) Chinchilla, R. private communication.
(14) Compound 10a was obtained from the crude reaction
mixture as a 5:1 mixture of diastereomers.
(24) Sonogashira, K. Metal Catalyzed Cross Coupling Reactions;
Diederich, F.; Stang, P. J., Eds.; Wiley-V.C.H.: Weinheim,
1998, Chap. 5, 203–229.
Synlett 2001, No. 12, 1881–1884 ISSN 0936-5214 © Thieme Stuttgart · New York