Suzuki-Miyaura coupling of alkynylboronic esters generated in situ from acetylenic derivatives

Article abstract of DOI:10.1021/ol006439d

(equation presented) A new effective Suzuki-Miyaura coupling reaction between alkynylboronic esters (generated in situ from acetylenic derivatives) and arylbromides or vinylbromides is reported.

Full text of DOI:10.1021/ol006439d

ORGANIC
LETTERS
2000
Vol. 2, No. 23
3559-3561
Suzuki−Miyaura Coupling of
Alkynylboronic Esters Generated in Situ
from Acetylenic Derivatives
,†
Anne-Sophie Castanet,† Franc¸oise Colobert,* and Thierry Schlama‡
Laboratoire de ste´re´ochimie E.C.P.M., 25 rue Becquerel, 67087 Strasbourg Cedex 2,
France, and Rhodia Recherches, Centre de recherches de Lyon, 85 aVenue des Fre`res
Perret, 69192 Saint-Fons Cedex, France
fcolober@chimie.u-strasbg
Received August 10, 2000
ABSTRACT
A new effective Suzuki−Miyaura coupling reaction between alkynylboronic esters (generated in situ from acetylenic derivatives) and arylbromides
or vinylbromides is reported.
Suzuki cross-coupling reactions of organoboron compounds
and organic halides or triflates represent a versatile, prag-
matic, and intensively used method for the formation of
carbon-carbon bonds.1
Among such organoboron compounds, alkynylboronic
derivatives were never used in the Suzuki coupling, although
alkynyl boranes were known for a long time to be useful
synthetic intermediates.2 They readily undergo addition to
aldehydes and ketones, giving the propargylic alcohols.3
More recently an enantioselective synthesis of propargylic
alcohols has been developed by using alkynylboranes.4
Diels-Alder cycloadditions have also been reported with
these derivatives.5
fore, their use in the Suzuki-Miyaura coupling, which
requires a base (commonly aqueous Na2CO3, Ba(OH)2, etc.)
could be problematic.6
This difficulty has been overcome with B-methoxy-9-
borabicyclo[3.3.1]nonane. J. A. Soderquist et al. have found
that the addition of B-methoxy-9-borabicyclo[3.3.1]nonane
to alkynyllithium reagents gave stable methoxy(alkynyl)-
borate complexes which undergo efficient Suzuki coupling
to produce a variety of alkynyl derivatives.7 At the same
time, A. Fu¨rstner and G. Seidel have reported that the borate
complexe can be prepared from B-methoxy-9-borabicyclo-
[3.3.1]nonane and a polar organometallic reagent RM. This
approach allowed cross-couplings of aryl halides with
alkynyl, methyl, and TMSCH2 groups.8
In this paper we report a Suzuki-Miyaura coupling
between alkynylboronic esters and aryl halides in quantitative
yields.
We first studied the coupling reaction between 1-octynyl-
boronic ester (prepared as described by H. C. Brown)9 and
Compared to other organoboranes, alkynylboronic esters
are stronger Lewis acids and are easily hydrolyzed. There-
† Laboratoire de ste´re´ochimie E.C.P.M.
‡ Rhodia Recherches.
(1) (a) Suzuki, A. In Metal-Catalyzed Cross Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998;
Chapter 2, pp 49-89. (b) Suzuki, A.; J. Organomet. Chem. 1999, 576,
147.
(2) Pelter, A.; Smith, K.; Brown, H. C. In Borane Reagents; Academic
Press: London, 1988; Chapter 2.
(3) Brown, H. C.; Molander, G. A.; Singh, S. M.; Racherla, U. S. J.
Org. Chem. 1985, 50, 1577.
(4) Corey, E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151.
(5) Singleton, D. A.; Leung, S. W. J. Org. Chem. 1992, 57, 4796.
(6) (a) Suzuki, A. Pure Appl. Chem. 1991, 63, 419. (b) Miyaura, N.;
Yameda, K.; Suginome, H.; Suzuki, A. J. Am. Chem. Soc. 1985, 107, 972.
(c) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513.
(d) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 36, 3437.
(7) Soderquist, J. A.; Matos, K.; Rune, A.; Ramos, J. Tetrahedron Lett.
1995, 36, 2401.
(8) Fu¨rstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165.
10.1021/ol006439d CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000

p-bromotoluene in the presence of 3% Pd(PPh3)4 and
different fluorides (2 equiv) at reflux of various solvents
(Table 1). The best fluoride was a solution of tetrabutyl-
(1) Influence of fluoride anions: the reaction in DME
without TBAF in THF (entry 2) did not work as well as the
reaction in DME with KF-Me4NCl (entry 3).
(2) Influence of the solvent: the reaction in a mixture of
DME/THF (10/1) without fluoride anion (entry 4) gave the
coupling product in quantitative yield. The use of pure THF
as solvent (entry 5) lowered the yield to 30%.
Table 1. Effect of Fluoride in the Suzuki-Miyaura
Cross-Coupling Reactiona
These results led to the conclusion that THF was essential
to solubilize the “ate-complex”, which is not soluble in pure
DME, and DME was necessary for the Suzuki coupling. In
this one-pot Suzuki coupling the use of a base is not
necessary. The “ate-complex” obtained by formation of
alkynylboronic ester can directly transfer its organic ligand
to the aryl-PdBr species to give the desired coupling product
after reductive elimination.
entry
F-
CsF
CsF
KF
TBAFd
TBAFd
time (h) solvent
GCb
20/65
48/42
no coupling
0/80
yield (%)c
50
1
2
3
4
5
4
16
16
DME
DMF
DME
DME
THF
The conditions established above were applied to the
palladium-catalyzed arylation or vinylation of alkynylboronic
esters starting from the alkynyllithium reagents. Table 3
2.5
16
60
41/44
a Reaction conditions: p-bromotoluene (1 equiv), 1-octynylboronic ester
(1.3 equiv). b GC analysis: (% starting material)/(% coupling product).
c Isolated yield. d TBAF 1 M in THF.
Table 3. Palladium-Catalyzed Arylation or Vinylation of
Alkynyllithium Reagents Mediated by B(OiPr)3
c
ammonium fluoride (1 M in THF) in refluxing DME (entry
4). The use of THF as solvent for the coupling reaction
decreased the yield (entry 5).
We then tried the coupling reaction without isolating the
alkynylboronic ester, which is very sensitive to atmospheric
oxygen. Treatment of octynyllithium with triisopropoxy-
borane in DME at -78 °C afforded the “ate-complex”. In
situ addition of Bu4NF (1 M in THF) and p-bromotoluene
in the presence of Pd(PPh3)4 (3 mol %) afforded after reflux
the coupling product in 70% isolated yield (entry 1, Table
2).
Table 2. Optimization of the One-Pot Cross-Coupling Reaction
a Formation of ditolylacetylene(40%). b DME/THF: 2.5/1 c Reaction
conditions: alkyne (1.3 equiv), BuLi (1.4 equiv), B(OiPr)3 (1.3 equiv),
bromide (1 equiv), Pd(PPh3)4 (0.03 equiv), DME/THF 10/1, reflux.
entry
solvent
DME
DME
DME
DME/THF, 10/1
THF
F-
yield (%)
1
2
3
4
5
TBAF 1 M in THF
without
KF + Me4NCl
without
70
0
0
98
30
summarizes the preparative results obtained. High yields were
also obtained with orthosubstituted and unactivated aryl-
bromides (entries 5 and 6). Uncharacterized decomposition
products were observed for the Suzuki coupling between
bromostyrene and 1-octyne (entry 7).
without
In conclusion, these results demonstrated that all kinds of
boronic acids or esters including alkyl-, aryl-, and now
alkynyl-boronic esters can be successfully employed as cross-
coupling partners in the Suzuki-Miyaura coupling reactions.
Numerous examples of organometallic acetylide deriva-
tives with metals such as copper (Sonogashira), tin (Stille),
To demonstrate that the “ate-complex” (formed by addition
of alkynyllithium with triisopropoxyborane) was the active
species in the coupling reaction, we tried several experiments:
(9) (a) Brown, H. C.; Cole, T. E. Organometallics 1983, 2, 1316. (b)
Brown, H. C.; Bhat, N. G.; Srebnik, M. Tetrahedron Lett. 1988, 29, 2631.
3560
Org. Lett., Vol. 2, No. 23, 2000

zinc (Negishi), and magnesium have been reported.10 All
have been shown to couple efficiently with organic electro-
philes in the presence of palladium. Our Suzuki-type
methodology presents also the ability to generate nucleophilic
acetylides in situ, avoiding the necessity of preparing and
storing large quantities of potentially unstable reagents.
Unactivated arylbromides are not often employed in
Sonogashira coupling because of lower yields and homo-
coupling of terminal alkynes, a side reaction with such
organic halides.11 Therefore this Suzuki aryl-alkynyl cou-
pling could be an alternative to the Sonogashira coupling
especially in the case of orthosubstituted and unactivated
arylbromides; yields of 75% were obtained in the Suzuki
coupling of o-bromotoluene and o-bromoanisole with 1-
octyne. Further studies to optimize the reaction conditions
are now in progress.
All of these methodologies can indeed complement each
other in the synthetic chemistry of enyne derivatives.
Acknowledgment. Financial support from Rhodia Re-
cherches is gratefully acknowledged as well as J. R. Desmurs
(Rhodia). We would like also to thank Prof. Guy Solladie´
for stimulating discussions.
Supporting Information Available: General experimen-
tal procedure for the coupling reactions. This material is
available free of charge via the Internet at http://pubs.acs.org.
(10) Sonogashira, K. In Metal-Catalyzed Cross Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998;
Chapter 5, pp 203-227.
(11) Singh, R.; Just, G. J. Org. Chem. 1989, 54, 4453.
OL006439D
Org. Lett., Vol. 2, No. 23, 2000
3561