proceeded with satisfactory yields for aryl derivatives bearing
electron-donating groups (entry 5), as well as for activated
chlorides (entries 16 and 17). At this point in time, unacti-
vated aryl chlorides remain problematic. ortho-Substituted
substrates (entries 11, 16, and 17) also afforded good yields
of the coupling products. Moreover, many functional groups
Finally, the presence of R-substitution in the organoboron
partner (entry 3) was studied. In this manner, potassium
isopropenyltrifluoroborate (1c) proved to be a very efficient
reagent for the introduction of an isopropenyl group.
A key question remains as to whether the trifluoroborates
remain intact during the coupling, or whether they react with
the alcohol or water during the course of the reactions
forming boronic acids or esters that subsequently couple.
Mechanistic studies are underway to resolve this issue.
In summary, palladium-catalyzed cross-coupling reactions
of potassium alkenyltrifluoroborates with aryl and alkenyl
halides and triflates have been achieved with good yields.
The reaction proceeded with ortho-substituted substrates and
also with electron-rich derivatives. A variety of functional
groups were tolerated in the coupling reaction. The orga-
noboron derivatives can be prepared by different routes,
including transmetalation and both catalyzed and noncata-
lyzed hydroboration. The trifluoroborates are monomeric
solids that possess several advantages over the corresponding
boronic acids and esters. The ease of isolation, purification,
storage, and handling makes them highly attractive inter-
mediates for laboratory scale and industrial processes and
especially for combinatorial chemistry. A variety of func-
tionalized and structurally diverse organotrifluoroborates can
be synthesized and stored for coupling when needed. The
full scope of this method is currently under further investiga-
tion in our laboratories.
(ketone, nitro, ether, nitrile, aldehyde) were tolerated in the
reaction. In certain cases (entries 5, 13, 14, 16, and 17), yields
of the products were modest because the products were
relatively easily oligomerized.
These coupling conditions have been found to be of
general use. Consequently, it is possible to couple an alkenyl
group not only onto aryl or heteroaryl halides, but also onto
alkenyl derivatives (entries 13 and 14) affording the conju-
gated diene in good yield.
Having demonstrated that 1a can act as an efficient
vinylating agent of organic halides and triflates, we briefly
investigated the scope of the coupling reaction using more
highly substituted potassium alkenyltrifluoroborates.
Thus, as outlined in Table 2, potassium styryltrifluoro-
1
5
borate (1b) reacted with 4-bromoacetophenone (entry 1)
Table 2. Cross-Coupling of Aryl Bromides with Potassium
Alkenyltrifluoroborates 1b-c
Acknowledgment. We thank Merck Research Labora-
tories for financial support and Aldrich Chemical Co. for
their support. M.R.R. thanks the Ministerio de Educaci o´ n y
Cultura for a predoctoral fellowship. Finally, we acknowl-
edge the tremendous efforts provided by Dr. Fouzia Mach-
rouhi in the execution of this project.
Supporting Information Available: Full experimental
details. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0169729
(
14) Chambers, R. D.; Chivers, T.; Pyke, D. A. J. Chem. Soc. 1965,
933-3939.
15) Petasis, N. A.; Yudin, A. K.; Zavialov, I. A.; Prakash, G. K. S.;
3
(
and also with 2-bromopyridine (entry 2) leading to the
corresponding stilbene derivatives in high yields.
Olah, G. A. Synlett 1997, 606-608.
(16) Representative Procedure for the Cross-Coupling Reaction of
Potassium Alkenyltrifluoroborates. 4-Acetylstyrene. A solution of potas-
sium vinyltrifluoroborate (1a) (60 mg, 0.448 mmol), PdCl2(dppf)‚CH2Cl2
(6 mg, 0.007 mmol), 4-acetylphenyltriflate (100 mg, 0.373 mmol), and Et3N
(37.7 mg, 0.373 mmol) in n-PrOH (6 mL) was heated at reflux under an
N2 atmosphere. The reaction mixture was stirred at reflux for 3 h, then
cooled to room temperature, and diluted with water (10 mL) followed by
extraction with ether (10 mL × 3). The ethereal solution was washed with
brine (20 mL) and dried over MgSO4. The solvent was removed in vacuo,
and the crude product was purified by silica gel chromatography (eluting
with hexane/ethyl acetate 10:1) to yield 4-acetylstyrene (52 mg, 0.356 mmol,
95%).
(
9) (a) Darses, S.; Michaud, G.; Gen eˆ t, J.-P. Eur. J. Org. Chem. 1999,
1
1
875-1883. (b) Darses, S.; Michaud, G.; Gen eˆ t, J.-P. Tetrahedron Lett.
998, 39, 5045-5048. (c) Darses, S.; Michaud, G.; Gen eˆ t, J.-P.; Brayer,
J.-L.; Demoute, J.-P. Tetrahedron Lett. 1997, 38, 4393-4396.
(10) Chambers, R. D.; Clark, H. C.; Willis, C. J. J. Am. Chem. Soc.
1
960, 82, 5298-5301.
(
(
(
11) Xia, M.; Chen, Z.-C. Synth. Commun. 1999, 29, 2457-2465.
12) Puentener, K.; Scalone, M. Eur. Pat. App. EP 1,057,831 A2, 2000
13) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393-396.
Org. Lett., Vol. 4, No. 1, 2002
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