Intermolecular rhodium-catalyzed carbometalation/Heck-type reaction in water

Article abstract of DOI:10.1002/anie.200602585

(Chemical Equation Presented) Only in water: A fully intermolecular rhodium-catalyzed domino coupling reaction, in which aryl boronic acids react with alkynes and acrylates to afford substituted 1,3-dienes, can only be successfully carried out in water. The reaction predominantly provides 1,4-addition products in aqueous THF and Heck-type addition products in a homogenized system with sodium decyl sulfate. cod = 1,5-cyclooctadiene.

Full text of DOI:10.1002/anie.200602585

Communications
Heterogenous Catalysis
formed as the major product in 58% yield in organic solvents
such as wet THF and dioxane. The reaction in a biphasic
system (water/diisopropyl ether) yielded the Heck-type
product 5aa as the major product in 61% yield. Curiously,
however, when the same reaction was conducted in aqueous
media, a three-component assembly reaction took place to
afford 1,3-diene 6aaa in 81% yield along with the simple
Heck-type product 5aa (11%) and 1,4-addition product 4aa
(3%; Scheme 1): an emulsion of phenylboronic acid (1a),
DOI: 10.1002/anie.200602585
Intermolecular Rhodium-Catalyzed
Carbometalation/Heck-Type Reaction in Water**
Takuya Kurahashi, Hiroshi Shinokubo,* and
Atsuhiro Osuka
In recent years, organic reactions in aqueous media have
received particular attention for environmental and safety
reasons. Furthermore, water often exhibits profound effects
on the rate and selectivity of organic reactions through
enhanced hydrophobic interactions and the enrichment of
organic substrates in the local environment as a result of its
unique physical and chemical properties.[1,2] Arecent report
by Sharpless and co-workers clearly demonstrates that water
can accelerate some types of intermolecular addition reac-
tions, even under heterogeneous conditions with insoluble
organic components.[3] Such an intriguing effect should also be
valid for transition-metal-catalyzed reactions, thus leading to
novel transformations that are difficult in conventional
reaction media. Herein, we wish to describe a novel rho-
dium-catalyzed coupling reaction of aryl boronic acids with
internal alkynes and acrylates in water to afford functional-
ized dienes through an aryl rhodation/Heck-type addition
sequence. Although a number of rhodium-catalyzed domino
processes with organoboron reagents and unsaturated func-
tionalities have been reported,[4–6] a fully intermolecular
version is quite rare.
a,b-Unsaturated carbonyl compounds are highly reactive
substrates in the rhodium-catalyzed addition of boronic acid
derivatives. Aryl rhodation also occurs to alkynes, but the
reactivity is lower than that of conjugated enones and enoates.
The rhodium-catalyzed addition of aryl boronic acids to a,b-
unsaturated carbonyl compounds can proceed at room
temperature, whereas the addition to alkynes often requires
elevated temperatures.[7] Consequently, one can anticipate
that an aryl rhodium intermediate predominantly adds to
unsaturated carbonyl compounds, even in the presence of
alkynes. Not surprisingly, the 1,4-addition product 4aa was
Scheme 1. Addition of phenylboronic acid to methyl acrylate and
5-decyne.
5-decyne (2a), methyl acrylate (3a), and 4 mol% of
[{Rh(OH)(cod)}2] (cod = 1,5-cyclooctadiene) in water was
allowed to stand at ambient temperature for 12 h without
stirring to provide 4-butyl-5-phenylnona-2,4-dienoic acid
methyl ester (6aaa; see Supporting Information).[8] Note
that arylation proceeds at ambient temperature with an
unactivated alkyne. Importantly, the domino reaction takes
place only in an emulsion of substrates with water, as far as we
investigated. As Lautens et al. already reported, the use of
surfactants (i.e., sodium decyl sulfate) to homogenize the
reaction system resulted in the exclusive formation of the
Heck product 5aa.[9] Water-soluble phosphine ligands, such as
trisodium triphenylphosphine-3,3’,3’’-trisulfonate, disodium
triphenylphosphine-4,4’-disulfonate, and cyclohexyl amphos
chloride, were not effective. Thus, the course of the reaction
was found to be quite sensitive to the conditions.
Boronic acids with electron-donating (1b and 1c) or
-withdrawing groups (1d) gave the corresponding product 6
as the predominant product in moderate yields (Table 1).
2-Naphthylboronic acid (1e) also reacted with 2a and 3a to
furnish the corresponding diene 6eaa in 45% yield. In this
case, the emulsion of the substrates in water seemed not to be
as stable as that obtained from 1a. The reactions of 1a and 3a
with various alkynes were also examined. Alkynes, such as 4-
octyne, 6-dodecyne, and 7-tetradecyne, reacted to furnish the
corresponding dienes 6. The sparingly water-soluble tolane
(2e) sluggishly reacted to give 6bea in 31% yield. The
miscibility of substrates seems to be critical for the successful
reaction.[10] The configuration of diene 6bea was unambigu-
ously confirmed by an X-ray crystal structure analysis (see
Supporting Information). Consequently, the arylation of
alkynes in this reaction proceeds in a syn fashion.
[*] Dr. T. Kurahashi, Prof. Dr. H. Shinokubo, Prof. Dr. A. Osuka
Department of Chemistry
Graduate School of Science
Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan)
and
PRESTO
Japan Science and Technology Agency (JST)
Fax: (+81)75-753-3970
E-mail: hshino@kuchem.kyoto-u.ac.jp
[**] We thank Yasuhide Inokuma for X-ray analysis and Katsuhiro
Shimono for the mass spectrometric measurements. H.S.
acknowledges the Takeda Science Foundation for Science and
Technology and the Kurata Memorial Hitachi Science and Technol-
ogy Foundation for financial support.
We propose the following mechanism for this domino
reaction (Scheme 2). Both the alkyne and acrylate coordinate
to the aryl–rhodium species B, which is generated through the
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
6336
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Angew. Chem. Int. Ed. 2006, 45, 6336 –6338

Angewandte
Chemie
Table 1: Rhodium-catalyzed domino carbometalation/Heck-type reac-
rhodium species F, which is hydrolyzed to complete the
tion of aryl boronic acids to alkynes and methyl acrylate in water.[a]
catalytic cycle. This mechanism is consistent with fact that
quantitative formation of the 1,4-reduction product, methyl
propanoate, was observed by 1H NMR spectroscopic analysis
in the reaction mixture.[12]
Although conclusive discussion of the role of water in this
reaction is difficult at present, we performed several experi-
ments to obtain some information. Whereas the reaction
under solvent-free conditions provided the three-component
coupling product 6aaa in only 15% yield and Heck product
5aa as the major product (31%), application of high pressure
(140 atm) doubled the yield of 6aaa under the same
conditions but produced 5aa (33%) in an unchanged yield
(Scheme 3). The domino reaction is more pressure-dependent
Ar
R1
Yield [%]
6[b]
4[c]
5[c]
Ph (1a)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
Pr (2b)
C5H11 (2c)
C6H13 (2d)
Ph (2e)
81 (6aaa)
66 (6baa)
50 (6caa)
72 (6daa)
45 (6eaa)
61 (6aba)
53 (6aca)
57 (6ada)
31 (6bea)
3 (4aa)
5 (4ba)
10 (4ca)
12 (4da)
3 (4ea)
3 (4aa)
11 (4aa)
6 (4aa)
3 (4ba)
11 (5aa)
5 (5ba)
14 (5ca)
11 (5da)
44 (5ea)
7 (5aa)
8 (5aa)
5 (5aa)
59 (5ba)
4-Me-C6H4 (1b)
4-MeO-C6H4 (1c)
4-CF3-C6H4 (1d)
2-Naphthyl (1e)
Ph (1a)
Ph (1a)
Ph (1a)
4-Me-C6H4 (1b)
[a] The reaction was carried out with 1 (0.2 mmol), 2 (0.1 mmol), and 3
(0.2 mmol) in water (1 mL) in the presence of [{RhOH(cod)}2]
(0.004 mmol) at ambient temperature for 12 h. [b] Yield of the isolated
products. [c] Yields were determined by the 1H NMR signals of the crude
products with dibromomethane as an internal standard.
Scheme 3. Pressure dependence under neat conditions.
than the Heck-type reaction. This fact indicates that the rate-
determining step of the domino reaction, which would be the
ꢀ
C C bond-forming step of the reaction of aryl rhodium with
alkyne and acrylate species (C!D), has a negative activation
volume (DV°). Importantly, water often enhances reaction
rates for reactions, such as the Diels–Alder reaction and
Claisen rearrangement, for which the activation volumes are
negative.[13] This behavior implies that high internal pressure
of water may be one of reasons for this phenomenon.
However, the heterogeneous nature of the present reaction
may call for other explanations, such as specific interactions
between hydrophobic molecules at the microscopic water–oil
phase boundary.
In summary, we have demonstrated that the reaction of
aryl boronic acids with internal alkynes and acrylate units can
be performed by rhodium catalysis in water to give the
domino coupling products. Although the role of water is
unclear at this stage, the present reaction demonstrates that
water offers us not only the possibility to optimize known
reactions but also to discover novel transformations. Inves-
tigations to expand the scope and limitations of this procedure
along with the mechanistic elucidation are currently in
progress.
Scheme 2. A plausible mechanism for the rhodium-catalyzed domino
reaction.
Received: June 29, 2006
Published online: August 28, 2006
transmetalation of hydroxo–rhodium species A with aryl
boronic acid 1. The resulting complex C then undergoes an
addition to the carbon–carbon triple bond of alkyne 2 and the
double bond of acrylate 3 in either a concerted or stepwise
manner to yield alkyl–rhodium species D.[11] We suppose that
acrylate 3 acts not only as the third coupling component but
also as a good p-acid ligand to promote the addition of aryl
boronic acids to alkynes, as the reaction of 1a and 2a without
3 under the same conditions provided a trace of the phenyl-
ation product of 2a. Compound D affords product 6 and
hydrido–rhodium species E through b-hydride elimination.
The hydrido–rhodium E reacts with 3 to form oxa-p-allyl–
Keywords: alkynes · aqueous media · boron · domino reactions ·
.
rhodium
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