Develop m en t of th e Su zu k i-Miya u r a Cr oss-Cou p lin g Rea ction :
Use of Air -Sta ble P ota ssiu m Alk yn yltr iflu or obor a tes in Ar yl
Alk yn yla tion s
Gary A. Molander,* Bryson W. Katona, and Fouzia Machrouhi
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania,
Philadelphia, Pennsylvania 19104-6323
Received J uly 24, 2002
The palladium-catalyzed cross-coupling reaction of potassium alkynyltrifluoroborates with aryl
halides or triflates proceeds readily with moderate to excellent yields. The potassium alkynyltri-
fluoroborates are air- and moisture-stable crystalline solids that can be stored indefinitely, which
will provide an advantage in applications to combinatorial chemistry. The alkynyl cross-coupling
reaction can be effected using 9 mol % of PdCl
2
(dppf)‚CH
2
Cl
2
2
as catalyst in THF or THF-H O in
the presence of Cs
partners.
2
CO
3
as the inorganic base. A variety of functional groups are tolerated in both
In tr od u ction
Even with these improvements, there will be instances
where the Sonogoshira coupling fails to deliver product
The Sonogashira coupling reaction of terminal alkynes
with aryl or alkenyl halides has emerged as one of the
most straightforward and powerful methods for the
preparation of conjugated alkynes. Many applications
of this method in natural product synthesis and materials
in acceptable yields. In anticipation of these inevitable
shortcomings, complementary methods employing alkyn-
ylmetallic reagents have been developed. Although vari-
ous organometallic acetylide intermediates have been
1
5
6
7
explored [e.g., tin (Stille), zinc (Negishi), and others ],
organoboron compounds (Suzuki-Miyaura) present sev-
eral advantages.8 Thus, organoboron compounds are
2
science have been reported. However, few if any syn-
thetic methods work well in every conceivable situation,
and the Sonogashira coupling as it was initially conceived
is no exception. In the quest for improvements of this
palladium-catalyzed cross-coupling, several recent pub-
lications have illustrated the use of new ligand systems
9
less toxic than organostannane reagents, and unlike
alkynylzincs and -magnesiums many organoboron com-
pounds possess remarkable oxidative and thermal sta-
bilities.10
to accommodate a wider range of coupling partners under
mild conditions. As an example, P(t-Bu)
3
3
or phosphonium
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3
, 4295.
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0.1021/jo0262356 CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/30/2002
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J . Org. Chem. 2002, 67, 8416-8423