Method for the Vinylation of Aromatic Halides
A R T I C L E S
These donors include boron-,11 tin-,12 and magnesium-based13
reagents and have been demonstrated to react with a range of
organic acceptors. Boron-based reagents, including vinylboronic
acid,11a its related esters,11b,c and cyclic anhydrides,11d as well
as potassium trifluoroborates,11e-g cross-couple with a range of
aryl bromides at elevated temperatures. Despite the utility of
these vinylboron species, there are difficulties associated with
their preparation. For example, the parent vinylboronic acid must
be either trapped immediately as one of the aforementioned
derivatives or freshly prepared prior to each use.11a Although
the vinylboronic acid derivatives are significantly more stable
and are commercially available, their greater cost14 likely reflects
the problems associated with their preparation.15 Additionally,
these reagents often require elevated temperatures and/or higher
pressures for reaction.11 The vinylboron reagents are generally
used with aryl bromides, whereas the vinyltributyltin reagents
react with a broader scope of electrophiles, including aryl
iodides, aryl and vinyl bromides, aryl and vinyl chlorides, and
triflates, to afford high yields of the corresponding vinylated
products.16 Unfortunately, vinyltributyltin suffers from the heavy
metal toxicity generally associated with organotin species,17
which, taken together with its cost,18 can significantly deter its
use on a larger scale. The Kumada-type coupling of vinylmag-
nesium bromide and chloride is more limited in the scope of
electrophilic partner because of the basicity and nucleophilicity
of the vinylating agent. For compatible substrates, however,
good yields of the corresponding styrene are observed.13
Alternatively, dibromoethane has been used as a vinyl bromide
precursor for the preparation of styrenes from arylboronic acids,
in a process that inverts the acceptor/donor relationship.19
Each of these vinylmetallic reagents has one or more
limitations. An ideal vinylation method would involve an
inexpensive and nontoxic donor capable of transferring a vinyl
group to a wide range of acceptors under mild conditions and
be compatible with many functional groups.
tions. In particular, organosilicon reagents are nontoxic21 and
the silicon containing byproducts are easily removed. Moreover,
the organosilicon subunit can be installed by a wide range of
reactions, such that the cross-coupling event can be combined
with other powerful carbon-carbon bond forming processes,
such as ring-closing metathesis,22 silylformylation,23 and silyl-
carbocyclization.24 The initial reports of silicon-based, pal-
ladium-catalyzed cross-coupling reactions involved the use of
highly reactive, in-situ generated pentacoordinate silicon re-
agents such as fluorosilicates or bis(catechol)silicates.25 Since
those reports, a variety of alternative organosilicon donors have
been developed, including trimethyl- and difluoromethyl-
alkenylsilanes developed by Hiyama. These donors successfully
react with aryl iodides, although they suffered from low
reactivity and water sensitivity, respectively.26 Alkenyltrialkoxy-
silanes27,28 and dimethylsilanols29 are inherently more stable,
and, with proper activation (typically a fluoride or hydroxide
source), do participate in cross-coupling processes. Tetra-
butylammonium fluoride trihydrate (TBAF) is the most com-
monly employed fluoride source because of its solubility in
organic solvents.
Recently, the use of Brønsted base activation (that avoids
the requirement for fluoride activation) of alkenyldimethyl-
silanols in cross-coupling reactions has been developed in these
and other laboratories.30 Initially, potassium trimethylsilanoate
(KOSiMe3) served as the Brønsted base activator that facilitated
the palladium-catalyzed cross-coupling between alkenyldi-
methylsilanols and aryl iodides.31 In addition, alkali carbonates30a
and alkali hydroxides30b are also competent bases for the cross-
coupling reactions. More recently, alkali metal alkenyl-, aryl-,
and heteroaryldimethylsilanolates, prepared from the corre-
sponding dimethylsilanols with a metal hydride, have been used
directly in cross-coupling reactions without additional activa-
tors.32 Alkenylsilanolates cross-couple effectively with aryl
iodides, bromides, and chlorides, to afford excellent yields under
mild reaction conditions.33
Background
The transfer of a simple vinyl group using organosilicon-
based, palladium-catalyzed cross-coupling was first demon-
strated by Hiyama and co-workers.26 The combination of
vinyltrimethylsilane and 1-iodonaphthalene provided the cor-
responding styrene in excellent yield. In this case, the silicon
moiety was activated for vinyl transfer using tris(dimethyl-
amino)sulfonium difluorotrimethylsilicate (TASF) and HMPA
as the solvent. Jeffrey and co-workers have shown that a
combination of potassium fluoride and tetrabutylammonium
Silicon-based donors, first reported by Kumada and Tamao,20
offer a number of advantages as compared to other organo-
metallic reagents in palladium-catalyzed cross-coupling reac-
(11) (a) Peyroux, E.; Berthiol, F.; Doucet, H.; Santelli, M. Eur. J. Org. Chem.
2004, 1075-1082. (b) Stewart, S. K.; Whiting, A. J. Organomet. Chem.
1994, 482, 293-300. (c) Lightfoot, A. P.; Twiddle, S. J. R.; Whiting, A.
Synlett 2005, 529-531. (d) Kerins, F.; O’Shea, D. F. J. Org. Chem. 2002,
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1999, 1875-1883.
(12) (a) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343-6348. (b) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119-122.
(c) McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K. J. Org.
Chem. 1987, 52, 422-424.
(13) Bumagin, N. A.; Luzikova, E. V. J. Organomet. Chem 1997, 532, 271-
273.
(21) Cragg, S. T. In Patty’s Toxicology; Bingham, E., Cohrssen, B., Powell, C.
H., Eds.; Wiley: Hoboken, 2001; DOI: 10.1002/0471435139.tox.093.
(22) (a) Denmark, S. E.; Yang, S.-M. Org. Lett. 2001, 3, 1749-1752. (b)
Denmark, S. E.; Yang, S.-M. J. Am. Chem. Soc. 2002, 124, 2102-2103.
(c) Denmark, S. E.; Yang, S.-M. J. Am. Chem. Soc. 2002, 124, 15196-
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(14) Vinylboronic acid pinacol ester, (Aldrich, catalog no. 63348), $2757/mol
($18/g); 2,4,6-trivinylcyclotriboroxane (Aldrich, catalog no. 637998), $3822/
mol ($17/g); potassium vinyltrifluoroborate (Aldrich, catalog no. 655228),
$2364/mol ($18/g).
(15) The preparation of potassium vinyltrifluoroborate does not involve vinyl-
boronic acid as an intermediate, although the vinylboronic acid dimethyl
ester is used. For its preparation, see ref 11e.
(23) Denmark, S. E.; Kobayashi, T. J. Org. Chem. 2003, 68, 5153-5159.
(24) Denmark, S. E.; Liu, J. H.-C. J. Am. Chem. Soc. 2007, 129, 3737-3744.
(25) Hosomi, A.; Kohra, S.; Tominga, Y. Chem. Pharm. Bull. Jpn. 1988, 36,
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(26) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918-920.
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E.; Najera, C. AdV. Synth. Catal. 2006, 348, 2085-2091.
(16) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 3-652.
(17) (a) National Institute of Occupational Health and Safety; Pub. No. 77-115;
Government, U.S. Printing Office: Washington. (b) Lassiter, D. V.; Stewart,
J. H. In Patty’s Toxicology, 5th ed.; Bingham, E., Cohrssen, B., Powell, C.
H., Eds.; Wiley: Hoboken, 2001; 1976, Vol. 2, pp 576-598.
(18) Tributyl(vinyl)tin (Aldrich, catalog no. 271438): $3032/mol.
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(20) Yoshida, J.; Tamao, K.; Yamamoto, H.; Kakui, T.; Uchida, T.; Kumada,
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