Base-free mizoroki-heck reaction catalyzed by rhodium complexes

Article abstract of DOI:10.1021/ol071098q

A base-free rhodium-catalyzed Mizoroki-Heck (M-H) reaction using potassium aryltrifluoroborates as the arylating agent of alkenes and acetone as a green "oxidant" is described. Thanks to the ready availability of organoboranes, this reaction should consti

Full text of DOI:10.1021/ol071098q

ORGANIC
LETTERS
2007
Vol. 9, No. 17
3213-3216
Base-Free Mizoroki−Heck Reaction
Catalyzed by Rhodium Complexes
Re´mi Martinez, Florina Voica, Jean-Pierre Genet,* and Sylvain Darses*
Laboratoire de Synthe`se Se´lectiVe Organique (UMR 7573, CNRS), Ecole Nationale
Supe´rieure de Chimie de Paris, 11 rue P&M Curie, 75231 Paris cedex 05, France
sylVain-darses@enscp.fr; jean-pierre-genet@enscp.fr
Received May 11, 2007
ABSTRACT
A base-free rhodium-catalyzed Mizoroki
as a green “oxidant” is described. Thanks to the ready availability of organoboranes, this reaction should constitute an interesting alternative
to conventional M H reactions using aryl halides.
−Heck (M−H) reaction using potassium aryltrifluoroborates as the arylating agent of alkenes and acetone
−
The arylation of alkenes, the Mizoroki-Heck reaction (M-
H),1 is now recognized to be of genuine synthetic utility for
preparing aromatic fine chemicals.2 In addition to the
conventional M-H reaction of unsaturated compounds with
organic halides, triflates, or carboxylic acid derivatives,
occurring via oxidative addition, the use of organometallic
reagents, such as silanes, stannanes or boranes, has attracted
much attention.
the presence of many functional groups. Moreover, large
amounts of palladium catalyst are generally required (5-
10%) to achieve acceptable yields of the M-H adduct. A
variant, using a ruthenium(II) catalyst as a precursor, has
been reported, but the reaction still required a regeneration
system based on the association of a base and an oxidant.6
Alternatively, Lautens7 and our group8 have reported M-H
reactions using rhodium(I) catalysts9 for the reaction of
boronic acids with styrenes, in the presence of a base but
without any oxidizing agent. These conditions were extended
The palladium(II)-mediated vinylic substitution of orga-
nometallic reagents was first reported by Heck,3 using
stoichiometric amounts of palladium(II) salts, more than two
decades ago. A catalytic variant, using organoboronic acids,
was reported by Uemura et al. in 1994, requiring the use of
a base.4 Since then, several conditions have been developed
for the so-called palladium-catalyzed oxidative Heck-type
reaction of organometallic reagents with electron-deficient
olefins.5 However, all these reactions require the presence
of both excess base and excess oxidant (copper(II) acetate
or O2) as the reoxidizing agent, conditions incompatible with
(5) Borane: Du, X.; Suguro, M.; Hirabayashi, K.; Mori, A.; Nishikata,
T.; Hagiwara, N.; Kawata, K.; Okeda, T.; Wang, H. F.; Fugami, K.; Kosugi,
M. Org. Lett. 2001, 3, 3313. Jung, Y. C.; Mishra, R. K.; Yoon, C. H.;
Jung, K. W. Org. Lett. 2003, 5, 2231. Andappan, M. M. S.; Nilsson, P.;
Larhed, M. Chem. Commun. 2004, 218. Andappan, M. M. S.; Nilsson, P.;
von Schenck, H.; Larhed, M. J. Org. Chem. 2004, 69, 5212. Yoon, C. H.;
Yoo, K. S.; Yi, S. W.; Mishra, R. K.; Jung, K. W. Org. Lett. 2004, 6,
4037. Enquist, P.-A.; Lindh, J.; Nilsson, P.; Larhed, M. Green Chem. 2006,
8, 338. Silane: Hirabayashi, K.; Nishihara, Y.; Mori, A.; Hiyama, T.
Tetrahedron Lett. 1998, 39, 7893. Hirabayashi, K.; Kondo, T.; Toriyama,
F.; Nishihara, Y.; Mori, A. Bull. Chem. Soc. Jpn. 2000, 73, 749. Hirabayashi,
K.; Ando, J.-i.; Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Bull.
Chem. Soc. Jpn. 2000, 73, 1409. Stannane: Hirabayashi, K.; Ando, J.-i.;
Nishihara, Y.; Mori, A.; Hiyama, T. Synlett 1999, 99. Parrish, J. P.; Jung,
Y. C.; Shin, S. I.; Jung, K. W. J. Org. Chem. 2002, 67, 7127. Others: Inoue,
A.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc. 2003, 125, 1484.
(6) Farrington, E. J.; Brown, J. M.; Barnard, C. F. J.; Rowsell, E. Angew.
Chem., Int. Ed. 2002, 41, 169.
(1) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971,
44, 581. (b) Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320.
(2) Reviews: (a) Heck, R. F. Org. React. 1982, 27, 345. (b) Shibasaki,
M.; Boden, C. O. J.; Kojima, A. Tetrahedron 1997, 53, 7371. (c) Beletskaya,
I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (d) Whitcombe, N.
J.; Hii, K. K.; Gibson, S. E. Tetrahedron 2001, 57, 7449. (e) Littke, A. F.;
Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176. (f) Alonso, F.; Beletskaya,
I. P.; Yus, M. Tetrahedron 2005, 61, 11771.
(7) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martin-Matute, B.
J. Am. Chem. Soc. 2001, 123, 5358.
(8) Amengual, R.; Michelet, V.; Genet, J.-P. Tetrahedron Lett. 2002,
43, 5905.
(9) In some rhodium-catalyzed 1,4-additions, the M-H adduct has been
observed as a byproduct: Cho, C. S.; Motofusa, S.-i.; Ohe, K.; Uemura, S.
J. Org. Chem. 1995, 60, 883.
(3) (a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518. (b) Heck, R. F.
J. Am. Chem. Soc. 1969, 91, 6707. (c) Dieck, H. A.; Heck, R. F. J. Org.
Chem. 1975, 40, 1083.
(4) Cho, C. S.; Uemura, S. J. Organomet. Chem. 1994, 465, 85.
10.1021/ol071098q CCC: $37.00
© 2007 American Chemical Society
Published on Web 07/18/2007

to other activated alkenes by Lautens, but the reaction still
needed added base.10 Mori reported the rhodium(I)-11 and
iridium(I)-catalyzed12 M-H reaction of organosilanes with
electron-deficient olefins, and more recently it has been
shown that RhCl3 could be used in place of Rh(I).13 However,
there are some evident drawbacks in these reactions. First,
the presence of a base and/or an oxidizing agent is required
for maximum efficiency. Second, in the Rh- or Ir-catalyzed
reactions, the Mizoroki-Heck product is generally contami-
nated by the presence of saturated product10-13 (1,4-addition
adduct), and with some electron-deficient olefins, such as
enones, the latter become the major product.
potassium phenyltrifluoroborate (1a, R ) Ph) with butyl
acrylate (2a, EWG ) CO2Bu) using [Rh(d)2Cl]2 in conjunc-
tion with the PPh3 ligand as catalyst afforded quantitative
conversion in alkene 3a (R ) Ph, EWG ) CO2Bu) as the
sole product. Contrary to other Rh- or Ir-catalyzed reactions,
we did not observe any traces of the 1,4-addition/protonation
adduct 4.
These conditions proved to be general, and a great variety
of M-H adducts were obtained from the reaction of
potassium organotrifluoroborates with acrylates (Table 1).
We have recently shown that potassium organotrifluo-
roborates14 were highly suitable organoboron reagents in
either palladium- or rhodium-catalyzed processes.15 More
particularly, we developed an efficient Heck-type reaction
with aldehydes, affording a direct access to ketones.16 We
want to report here a general and efficient process for the
Heck reaction, occurring under very mild conditions, in the
absence of either added base or oxidant17,18 and using easily
available and stable potassium trifluoro(organo)borates
(Scheme 1).
Table 1. Rhodium-Catalyzed Mizoroki-Heck Reaction with
Potassium Organotrifluoroboratesa
Scheme 1. Rhodium-Catalyzed Mizoroki-Heck-Type
Reaction with Potassium Trifluoro(organo)borates
To achieve exclusive formation of the Mizoroki-Heck
adduct 3 at the expense of the 1,4-addition adduct 4, several
conditions were evaluated in the presence of the rhodium
catalyst (Scheme 1). It appeared that, whatever the conditions
evaluated, in the presence of water only the saturated product
4 was obtained, a result similar to that observed by Mori et
al.11 On the other hand, under anhydrous conditions, the
Mizoroki-Heck product became the only observable prod-
uct. Among the tested solvents, a binary mixture of dioxane/
acetone proved to be the most suitable. Indeed, reaction of
(10) Lautens, M.; Mancuso, J.; Grover, H. Synthesis 2004, 2006.
(11) Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am.
Chem. Soc. 2001, 123, 10774.
(12) Koike, T.; Du, X.; Sanada, T.; Danda, Y.; Mori, A. Angew. Chem.,
Int. Ed. 2003, 42, 89.
(13) Zou, G.; Wang, Z.; Zhu, J.; Tang, J. Chem. Commun. 2003, 2438.
(14) Reviews: (a) Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2003, 4313.
(b) Molander, G. A.; Figueroa, R. Aldrichim. Acta 2005, 38, 49.
(15) For some examples, see: (a) Pucheault, M.; Darses, S.; Genet, J.-
P. Eur. J. Org. Chem. 2002, 3552. (b) Pucheault, M.; Darses, S.; Genet,
J.-P. Tetrahedron Lett. 2004, 45, 4729. (c) Navarre, L.; Darses, S.; Genet,
J.-P. Chem. Commun. 2004, 1108. (d) Navarre, L.; Darses, S.; Genet, J.-P.
Eur. J. Org. Chem. 2004, 69. (e) Navarre, L.; Darses, S.; Genet, J.-P. Angew.
Chem., Int. Ed. 2004, 43, 719. (f) Pucheault, M.; Darses, S.; Genet, J.-P.
Chem. Commun. 2005, 4714-4716. (g) Navarre, L.; Darses, S.; Genet, J.-
P. AdV. Synth. Catal. 2006, 348, 317.
a Reactions conducted using 1 mmol of 1, 2 equiv of 2 with 1.5 mol %
of [Rh(CH2CH2)Cl]2, and 6 mol % of PPh3 at 80 °C in 2.5 mL of 1,4-
c
dioxane/acetone 4:1. b Isolated yields of M-H adduct. 10% of debromi-
d
nated product was also obtained. 3 equiv of enone was used.
Good to excellent yields were generally achieved with many
substitution patterns on the reaction partners. It appeared that
the electronic nature of the organoboron reagent did not have
a great influence as similar yields and reaction rates were
obtained with trifluoroborates bearing either electron-
withdrawing or -releasing substituents (entries 3 and 4). It
is also noteworthy that reactions of mono- and di-ortho-
(16) (a) Pucheault, M.; Darses, S.; Genet, J.-P. J. Am. Chem. Soc. 2004,
126, 15356. (b) Mora, G.; Darses, S.; Genet, J.-P. AdV. Synth. Catal. 2007,
349, 1180.
(17) Base-free Heck reaction using aroyl chloride in place of boronic
acid has been reported: Sugihara, T.; Satoh, T.; Miura, M.; Nomura, M.
Angew. Chem., Int. Ed. 2003, 42, 4672.
(18) Under the present conditions, RBF3K is not decomposed to RBF2
and KF, ruling out KF as a base.
3214
Org. Lett., Vol. 9, No. 17, 2007

substituted potassium aryltrifluoroborates (entries 6 and 7)
with ethyl acrylate afforded the expected M-H adducts 3f
and 3g in high yield, whereas such ortho substitution
generally resulted in the formation of high amounts of 1,4-
adduct.10 The reaction is not limited to ethyl acrylate, and
other alkenes such as vinylphosphonates or acrylamides
participated equally well (entries 8-11). For example,
reaction of potassium trifluoro(3-methoxyphenyl)borate with
diethyl(vinyl)phosphonate afforded M-H adduct 3i in 86%
yield, as the only reaction product (entry 8). It is noteworthy
that reaction of vinyl ketones afforded exclusively the M-H
adduct on reaction with aryltrifluoroborates (entries 12 and
13), in sharp contrast with other rhodium-catalyzed processes
described.10,11,13 Indeed, reaction of trifluoro(2-methylphen-
yl)borate with propyl vinyl ketone allowed the formation of
unsaturated ketone 3n in 86% yield (entry 13).
For the present reaction, a Heck-type mechanism2 can be
envisioned after the transmetalation step of the organome-
tallic to rhodium(I): insertion of the olefin bond into the
aryl-rhodium(I) species followed by rotation and â-hydrogen
elimination forms the (E)-olefin and generates a rhodium
hydride species (Scheme 3). To understand the subsequent
transformations of the putative rhodium-hydride and the
crucial part played by acetone in this reaction, labeling
studies were conducted (Scheme 2).
Figure 1. (a) 2H NMR spectrum of the crude reaction mixture of
the rhodium-catalyzed reaction of 1b with 2a. (b) 2H NMR spectrum
after addition of water (benzene-d6, δ ) 7.16 ppm, was used as
the internal reference).
and we observed the appearance of a new signal at 3.51 ppm,
which was assigned to 2-deuteriopropan-2-ol (Figure 1b).
The remainder of the spectra was unchanged. Indeed, the
species observed at 2.61 ppm could be assigned to a boron
alcoholate derived from 2-deuteriopropan-2-ol, which must
be produced during the transmetalation step of potassium
phenyltrifluoroborate to the alkoxo-rhodium, formed upon
reaction of rhodium-hydride with acetone.
Scheme 2
Two other minor signals were also observed at 0.83 and
2.03 ppm, which were attributed to ethyl 3-deuteriopro-
panoate and ethyl 2-deuteriopropanoates, respectively. In-
deed, under these conditions, the starting material also acts
as a hydride acceptor but to a minor extent, the major path
being the hydride transfer to acetone.
The overall mechanism is believed to involve transmeta-
lation of the organometallic reagent to the rhodium(I)
complex followed by the insertion of the activated olefin
into the aryl-rhodium(I) (Scheme 3). Rotation, followed by
To our surprise, the reaction of ethyl (Z)-3-deuteriopro-
penoate (1b) with potassium phenyltrifluoroborate (2a) under
standard conditions afforded not only the expected nondeu-
terated adduct 3o but also a mixture of monodeuterated
adducts 5a and 5b, and deuterium scrambling occurred in
position R and even in position â of the M-H adduct. To
determine the origin of this scrambling, ethyl acrylate 1b
was reacted under identical conditions but in the absence of
potassium phenyltrifluoroborate. Indeed, we observed com-
plete deuterium scrambling of the substrate, with the reaction
mixture after 1 h consisting of an equimolar mixture of the
three possible monodeuterated and nondeuterated acrylates.
Such deuterium-proton exchange must occur via insertion/
â-hydride elimination sequences in the substrate on reaction
with a putative rhodium-hydride species, but we did not study
this exchange process any further.
Scheme 3. Proposed Reaction Mechanism for the
Rhodium-Catalyzed M-H Reaction
The 2H NMR spectra of the crude reaction mixture
(Scheme 2 and Figure 1a) revealed the formation of a major
deuterated compound at 2.61 ppm, along with traces of
monodeuterated products 5a (δ ) 7.49 ppm) and 5b (δ )
6.35 ppm) as well as all three possible double bond
monodeuterated acrylates (δ ) 6.15, 5.93, and 5.66 ppm).
Upon addition of water, the signal at 2.61 ppm disappeared,
syn-â-deuteride elimination from the generated alkyl rhod-
ium(I) complex, would release the M-H adduct and a
rhodium(I) deuteride species. The latter may react with
Org. Lett., Vol. 9, No. 17, 2007
3215

acetone to afford an alkoxo-rhodium(I) complex, which is
suited for transmetalation with the boron reagent. Trans-
metalation of organoboron compounds to the alkoxo or
hydroxo complex of palladium,19 rhodium,16,20 or ruthenium21
has been described, allowing the regeneration of aryl-metal
species. It is worthy to note that the starting alkenes may
also react with rhodium hydride, generating a rhodium
enolate, which may also be suitable for transmetalation with
organoboranes. But the major path remains the hydride
transfer to acetone.
We have thus described for the first time a base-free
rhodium-catalyzed M-H reaction using potassium aryltri-
fluoroborate as the arylating agent of alkenes and acetone
as a green oxidant. This reaction should be an interesting
alternative to conventional M-H reactions using aryl
halides,2 all the more because organoboron compounds, and
organotrifluoroborates, are now easily accessible directly
from alkenes or arenes via rhodium- or iridium-catalyzed
C-H bond activation.22
Acknowledgment. This work was supported by the
Centre National de la Recherche Scientifique (CNRS). R.
Martinez thanks the Ministe`re de l’Education et de la
Recherche for a grant.
(19) Review: Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(20) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am.
Chem. Soc. 2002, 124, 5052.
(21) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am.
Chem. Soc. 2003, 125, 1698. (b) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani,
N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706.
(22) (a) Lawrence, J. D.; Takahashi, M.; Bae, C.; Hartwig, J. F. J. Am.
Chem. Soc. 2004, 126, 15334. (b) Boller, T. M.; Murphy, J. M.; Hapke,
M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005,
127, 14263. (c) Murphy, J. M.; Tzschucke, C. C.; Hartwig, J. F. Org. Lett.
2007, 9, 757 and references therein. (d) Review: Ishiyama, T.; Miyaura,
N. J. Organomet. Chem. 2003, 603, 3.
Supporting Information Available: Experimental pro-
cedures and compound descriptions. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL071098Q
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