A homogeneous, recyclable rhodium(l) catalyst for the hydroarylation of michael acceptors

Article abstract of DOI:10.1021/ol802927v

A robust and practical polymer-supported, recyclable biphephos rhodium(l) catalyst has been developed. Control of polymer molecular weight allowed the tuning of solubility such that the polymer-supported catalyst is soluble in nonpolar solvents and not soluble in polar solvents. Thus, catalytic addition of aryl- and vinylboronic acids to enones occurs under completely homogeneous conditions and catalyst recycle can be achieved by simple precipitation and filtration.

Full text of DOI:10.1021/ol802927v

ORGANIC
LETTERS
2
009
Vol. 11, No. 4
71-974
A Homogeneous, Recyclable Rhodium(I)
Catalyst for the Hydroarylation of
Michael Acceptors
9
Ranjan Jana and Jon A. Tunge*
Department of Chemistry and Center for EnVironmentally Beneficial Catalysis at the
UniVersity of Kansas, Lawrence, Kansas 66045
tunge@ku.edu
Received December 19, 2008
ABSTRACT
A robust and practical polymer-supported, recyclable biphephos rhodium(I) catalyst has been developed. Control of polymer molecular weight
allowed the tuning of solubility such that the polymer-supported catalyst is soluble in nonpolar solvents and not soluble in polar solvents.
Thus, catalytic addition of aryl- and vinylboronic acids to enones occurs under completely homogeneous conditions and catalyst recycle can
be achieved by simple precipitation and filtration.
A recent survey reveals an extreme rise in the market price
of rhodium such that it is by far the most expensive transition
heterogeneous catalytic system that facilitates recycle, but
ultimately reduces the catalytic efficiency and/or selectivity
in synthetic transformations. Since homogeneous catalysts
are often more selective than heterogeneous catalysts and
are not impeded by mass-transfer effects that reduce activities
of heterogeneous catalysts, the development of recyclable,
homogeneous supports is expected to provide more syntheti-
cally tunable and practical catalysts. Here we report the
design and development of a homogeneous polymer support
and its successful application to the rhodium-catalyzed 1,4-
additions of aryl- and vinylboronic acids to enones. Exploit-
ing the property of the polymers’ differential solubility, phase
trafficking by simple precipitation with an antisolvent can
be used to recover and reuse the catalyst without appreciable
1
metal (28 172 USD/mol). Since rhodium catalysts have
2
-4
wide-ranging utility in organic synthesis,
extensive at-
tention has been paid to the development of methods for the
5
recycle of the costly rhodium catalyst. Immobilization of
6
the catalyst on solid supports like silica leads to a
(
1) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008,
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002, 43, 5905. (g) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara,
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Gosberg, A. Org. Lett. 2001, 4083
3) (a) Oi, S.; Moro, M.; Ono, S.; Inoue, Y. Chem. Lett. 1998, 83. (b)
loss of catalytic efficiency.
Previously, several research groups have developed
.
5,8
(
Huang, T.; Meng, Y.; Venkatraman, S.; Wang, D.; Li, C.-J. J. Am. Chem.
Soc. 2001, 123, 7451. (c) Li, C.-J.; Meng, Y. J. Am. Chem. Soc. 2000, 122,
polystyrene supports that facilitate the recycle of rhodium
9
531
4) (a) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed. 1998,
7, 3279. (b) Lautenes, M.; Dockendorff, C.; Fagnou, K.; Malicki, A. Org.
.
(
(5) (a) Uozumi, Y.; Nakazono, M. AdV. Synth. Catal. 2002, 344, 274.
(b) Otomaru, Y.; Senda, T.; Hayashi, T. Org. Lett. 2004, 6, 3357. (c) Miao,
S.; Liu, Z.; Zhang, Z.; Han, B.; Miao, Z.; Ding, K.; An, G. J. Phys. Chem.
C 2007, 111, 2185.
3
lett. 2002, 4, 1311. (c) Murakami, M.; Igawa, H. J. Chem. Soc., Chem.
Commun. 2002, 390. (d) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara,
M. J. Am. Chem. Soc. 2001, 123, 9918. (e) Nakamura, K.; Nakamura, H.;
Yamamoto, Y. J. Org. Chem. 1999, 64, 2614. (f) Jang, H.-Y.; Krische,
(6) Mcdonald, A. R.; Muller, C.; Vogt, D.; van Klink, G. P. M.; van
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.
(7) Flynn, D. L. Med. Res. ReV. 1999, 19, 408.
10.1021/ol802927v CCC: $40.75
Published on Web 01/26/2009
 2009 American Chemical Society

catalysts. However, the typical polymer supports suffer from
serious limitations like insolubility, gel formation, tedious
procedures to swell the polymer, and limited loading of the
phosphorus ligand in the polymer backbone (e.g., 0.17 mmol/
Scheme 1. Synthesis of Polymer-Supported Ligand
5
b
g). Many of these issues relate to the fact that polymers
that are purchased commercially, or are prepared by con-
ventional radical polymerization of styrene, have high
molecular weight and/or broad molecular weight distribution.
Thus, they have poor solubility properties. The slower
kinetics of reactions catalyzed by gel-phase or solid-phase
catalysts have important practical effects as well. For
instance, the conjugate addition of arylboronic acids to
enones suffers from competing hydrolysis of the costly
boronic acids: the slower the catalyst is, the more hydrolysis
occurs. Thus, when a heterogeneous polystyrene-supported
catalyst is used for the conjugate addition, a 4-5-fold excess
5
of boronic acid is required. We hypothesized that problems
such as this could be solved by synthesis of soluble polymer-
supported rhodium catalysts that have a narrow molecular
weight distribution yet can be readily recycled by precipita-
tion and filtration. In addition to molecular weight control,
it was important to design a polymer support that could bind
Rh in a bidentate fashion. Such binding was expected to
better site-isolate the rhodium catalysts as well as prevent
leaching of rhodium from the polymer.
indicating that the polymer can support 0.32 mmol of
rhodium per gram of polymer.
11
The polymer-supported phosphite is quite soluble in
tetrahydrofuran, dichloromethane, and toluene (e.g., 60 mg/
ml in toluene), but is insoluble in methanol. Thus, it is
recovered quantitatively by simple precipitation with MeOH
and filtration.
Next, we turned our attention to the examination of the
supported rhodium complexes in catalytic hydroarylations
of enones. The typical experimental procedure is straight-
forward and simple to operate. A mixture of enone (1 mmol)
and arylboronic acid (1.3 equiv) was placed in a round-
bottomed flask and a toluene solution (3 mL) containing
Ultimately, we have been able to synthesize a well-
characterized polymer having comparatively low molecular
weight and a narrow molecular weight distribution (∼1.2 ×
4
9
1
0 , PDI ) 1.3, Scheme 1). Control of the molecular weight
and distribution was achieved by adopting a living free
radical polymerization technique that is mediated by the
9
stable nitroxyl radical, TEMPO. Conducting the copolym-
erization of the functional monomer 1 and styrene (1:10 ratio)
at 123 °C produced a functional polymer whose ligand
incorporation into the polystyrene backbone was estimated
2
Rh(acac)(CO) and JanaPhos was added to it under an inert
1
at 10% from the H NMR spectrum. Interestingly, end group
atmosphere. Finally, a solution of methanol and water (1:1,
0.5 mL) was added to it via syringe and the resulting reaction
mixture was heated at 50 °C. As can be seen from Table 1,
enals, aliphatic enones, chalcones, and cyclic enones all give
1
analysis of the vinyl region of the H NMR spectrum suggests
that the polymer is not cross-linked under these conditions.
In other words, a single alkene in the bis-alkene 1 undergoes
polymerization. The resulting polymer was deprotected and
the phosphite ligands introduced onto the polymer backbone.
The result is a polymer-supported Biphephos derivative that
1
2
high yields of hydroarylation products with our ligand.
Importantly, these high yields are obtained when using just
.3 equiv of boronic acid partners; related reactions with
1
1
0
polymer-supported rhodium catalysts require 4-5-fold excess
we call JanaPhos. If incorporation of the phosphite into
the polymer was perfect, one would expect a P-loading of
5
of boronic acids. In fact, our recyclable catalyst performs
as well as, or better than, typical small-molecule catalysts
1
.10 mmol/g and thus the ligand loading would be 0.55
2
a,5
3
1
which typically utilize 1.3-10 equiv of boronic acid.
It is important to note that the MeOH/H O cosolvent used
mmol/g. Estimation of the P loading by P NMR spectros-
copy shows that the P-loading is 0.65 mmol/g. This value
was further confirmed by ICP-OES analysis of the polymer,
2
in the hydroarylations was not enough to cause precipitation
of the catalyst. In fact, the use of water as a cosolvent has a
marked positive effect on the reaction yield; in the absence
of protic cosolvent, the hydroarylation of cyclohexenone
proceeds to only 35% conversion after 15 h.
(
8) (a) Grubbs, R. H.; Kroll, L. C. J. Am. Chem. Soc. 1971, 93, 3062.
(
b) Nozaki, K.; Itoi, Y.; Shibahara, F.; Shirakawa, E.; Ohta, T.; Takaya,
H.; Hiyama, T. J. Am. Chem. Soc. 1998, 120, 4051. (c) Nozaki, K.;
Shibahara, F.; Itoi, Y.; Shirakawa, E.; Ohta, T.; Takaya, H.; Hiyama, T.
Bull. Chem. Soc. Jpn. 1999, 72, 1911. (d) Shibahara, F.; Nozaki, K.; Hiyama,
T. J. Am. Chem. Soc. 2003, 125, 8555.
(11) Recent reaction improvements have led to phosphorus loadings of
1.06 mmol/g; however, the experiments reported in this paper utilized
polymer with lower (0.65 mmol/g) phosporus loading.
(
9) Since our functional monomer proved to be equally active toward
polymerization as styrene, the PDI is expected to be similar to that reported
for pure polystyrene: Dollin, M.; Szkurhan, A. R.; Georges, M. K. J. Polym.
Sci., Part A 2007, 45, 5487.
(12) A control experiment wherein cyclohexenone was treated with
phenylboronic acid without added Rh(acac)(CO)
product under identical conditions.
2
and did not produce any
(
10) Cuny, G. D.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115, 2066.
972
Org. Lett., Vol. 11, No. 4, 2009

Table 1. Conjugate Addition of Phenylboronic Acid
Table 2. Rh-Catalyzed 1,4-Addition of Boronic Acids
Next, the scope of boronic acids that can be utilized was
briefly examined. Simple aryl and biaryl boronic acids all
provided good yields of arylated products with a variety of
enals and enones (Table 2). Moreover, dibenzylidene acetone
undergoes selective monoarylation, generating only 5% of
the double-addition product (Table 2, entry 4). Lastly,
vinylboronic acids were suitable reaction partners, allowing
access to γ,δ-unsaturated ketones (Table 2, entries 7 and 8).
Having explored the general scope of the reaction, our
attention turned to recycle of the catalyst. Here, the reaction
was run as previously described. Then, upon completion of
the hydroarylation, excess methanol was added to the reaction
mixture and the catalyst precipitated out as a white solid
a
2
equiv of the boronic acid was used.
(
Figure 1). While the white solid is somewhat unusual for a
31
103
rhodium-containing catalyst, the P- Rh coupling present
in the P NMR of isolated catalyst confirms that Rh remains
bound to the polymer.
31
1
3
The catalyst was then isolated by filtration and used for
subsequent reactions. It was observed that performing the
filtration under air was associated with the gradual loss of
catalytic activity as gauged by the yield of product (Table
3
). However, filtration under an inert atmosphere allowed
recycle with no appreciable loss of catalytic activity (Table
).
Next, to examine the utility of the catalyst on a somewhat
Figure 1. Recycle of catalyst.
3
larger scale, the reaction of cyclohexenone with phenylbo-
ronic acid was performed on a 20 mmol scale and the product
ligands described herein may have practical application in
larger scale reactions.
Finally, with the goal of demonstrating the broad utility
of the soluble polymer-bound ligand reported herein, a
variety of standard rhodium-catalyzed reactions were per-
2-phenylcyclohexanone was isolated in identical yield (83%)
to the small-scale reaction (Table 1, entry 5). Thus, the
(
13) See the Supporting Information for details.
Org. Lett., Vol. 11, No. 4, 2009
973

Table 3. Catalyst Recycle
Scheme 2. Applicability of JanaPhos
filtration under air
filtration under argon
run
yield (%)
run
yield (%)
1
2
3
4
5
83
83
85
73
68
1
2
3
4
5
83
83
82
82
83
formed with the JanaPhos ligand (Scheme 2). As is evident
from Scheme 2, good yields of product are obtained in the
1
0
hydroformylation of 1-octene, conjugate addition of an
1
4
4a,15
alkyne to acrolein, arylation of an aldehyde,
and
4
d
arylation of an alkyne. Broader substrate scope studies of
these reactions are ongoing and will be reported in due
course.
In conclusion, we have developed a recyclable polymer-
supported rhodium(I) catalyst for the efficient 1,4-addition
of aryl- and vinylboronic acids to enones. In addition the
catalyst is active for a number of other rhodium-catalyzed
reactions, including hydroformylation. The catalyst operates
under homogeneous catalytic conditions, thus avoiding
typical problems associated with heterogeneous catalysts.
Finally, the supported catalyst can be readily recycled by
simple precipitation and filtration.
Acknowledgment. We thank the University of Kansas
Center for Environmentally Beneficial Catalysis (EEC-
0310689) and the National Institute of General Medical
Sciences (1R01GM079644).
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
(
14) Nikishin, G. I.; Kovalev, I. P. Tetrahedron Lett. 1990, 31, 7063.
15) Ueda, M.; Saito, A.; Miyaura, N. Synlett 2000, 1637. Furstner, A.;
Krause, H. AdV. Synth. Catal. 2001, 343
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Org. Lett., Vol. 11, No. 4, 2009