Reusable and durable immobilized-cationic gold(I) catalysts for environmentally benign bond-forming reactions

Article abstract of DOI:10.1002/adsc.201000753

Polystyrene-immobilized cationic gold catalysts 2a and 2b were synthesized for the first time and found to be highly effective catalysts for the bond-forming reactions via the activation of the Ci￡C triple bonds. The immobilized 2a was easily and quantita

Full text of DOI:10.1002/adsc.201000753

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DOI: 10.1002/adsc.201000753
Reusable and Durable Immobilized-Cationic Gold(I) Catalysts
for Environmentally Benign Bond-Forming Reactions
Masahiro Egi,a Kenji Azechi,a and Shuji Akaia,*
a
School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan
Fax : (+81)-54-264-5672; e-mail: akai@u-shizuoka-ken.ac.jp
Received: October 7, 2010; Revised: November 30, 2010; Published online: February 8, 2011
Abstract: Polystyrene-immobilized cationic gold
catalysts 2a and 2b were synthesized for the first
time and found to be highly effective catalysts for
the bond-forming reactions via the activation of the
Meanwhile, increasing environmental concerns
have recently resulted in the development of new pro-
tocols that can minimize reagent quantity, prevent
waste, or use renewable feedstocks. One of the key
technologies to achieve these objectives is the applica-
tion of the metallic gold immobilized on a support.
Until now, the huge effort has focused on the synthe-
sis of gold nanoparticles finely dispersed on either
metal oxides or organic polymers; however, their util-
ity has been mainly limited to CO oxidation and the
selective oxidation of alcohols,[4] although there are a
few reports on their use for reduction[5] and the
Suzuki–Miyaura cross-coupling reaction.[6] Therefore,
it is highly desirable to develop supported gold cata-
lysts that effectively catalyze bond-forming reactions
by activating carbon-carbon multiple bonds.[7] De-
scribed herein are the first synthesis of recyclable and
ꢀ
C C triple bonds. The immobilized 2a was easily
and quantitatively recovered from the reaction mix-
ture and reused at least seven times while maintain-
ing the original catalytic activity. Furthermore, a
flow reactor containing 2a was developed for a
larger scale continuous production.
Keywords: alkynes; bond formation; gold; green
chemistry; immobilization
For a long time, gold compounds have scarcely re- durable cationic gold(I) catalysts immobilized on a
ceived any attention as a catalyst due to the bias that polymer and their application to environmentally
gold is unreactive. Once it was discovered that gold benign ring forming reactions.
compounds have a significant affinity to carbon-
Aiming to synthesize the immobilized gold com-
carbon multiple bonds, great strides were made using plexes that can activate unsaturated bonds while re-
them in organic synthesis.[1] Among the gold species, taining high catalytic activities, we considered that the
cationic gold(I) complexes have become particularly gold-phosphine coordination would be the most con-
attractive over the past decade because they are re- venient and effective for the immobilization. Readily
sistant to air and moisture and display a high catalytic available polystyrene-bound triphenylphosphines
reactivity with a small loading to promote a variety of were first treated with (Me2S)AuCl[8] in CH2Cl2 at
transformations, such as nucleophilic reactions, intra- room temperature (Scheme 1), and the particle size of
molecular cyclizations, and rearrangements.[2,3]
the supports was found to have a significant influence
on the coordination and/or catalytic activities. For in-
Scheme 1. Synthesis of polystyrene-immobilized gold catalysts 1 and 2.
Adv. Synth. Catal. 2011, 353, 287 – 290
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287

Masahiro Egi et al.
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stance, the polymer resin with a 20–60 mesh poorly reactions of 3b–e with 2a and b afforded the furans
coordinated to (Me2S)AuCl, while the smaller poly- 4b–d and the pyrrole 4e in excellent yields. Thereby,
mer-PPh2 species were successfully involved in the co- it was found that the polymer-attached 2a and b pos-
À
ordination. Among them, the 100–200 mesh polymer sessed a sufficient reactivity for the C O bond forma-
resin[9] was the most effective and useful in view of tion and that the type of counter anion had little in-
easy handling to form the immobilized gold com- fluence on their activities. Another important fact is
pound 1 with a 0.81 mmol gold composition per 1.0 g that the gold pre-catalyst 1 was stable enough to
of the prepared polymer-bound reagent. Subsequent- maintain its high catalytic activity in a refrigerator.
ly, stirring the mixture of 1 and silver compounds, For example, the combination of 1 (0.5 mol%), stored
such as AgOTf and AgNTf2, in toluene for 15 min in for at least 1 year, with AgNTf2 (0.5 mol%) catalyzed
situ generated the cationic gold catalysts 2a and b im- the cyclization of 3a to produce a 95% yield of 4a in
mobilized on the polymer. In addition, the nature of 3 h, which was comparable to that using the freshly
the resin was found to be another important factor prepared 1 (Table 1, entry 2).
because a similar gold catalyst immobilized on the
more flexible polystyrene JandaJelTM[10] exhibited a 2) were also available for other types of Au-catalyzed
low catalytic activity. cyclization reactions. For instance, the oxazolidine-
The polymer-attached cationic gold catalysts (1 and
As part of our ongoing project on the development forming reaction, discovered by Carretero using
of highly potential gold-catalyzed reactions,[11] we Ph3PAuCl and AgSbF6,[12] similarly proceeded with
have recently developed an efficient and rapid synthe- the combination of the pre-catalyst 1 and AgSbF6
sis of furans and pyrroles 4 via the intramolecular cyc- [Eq. (1)]. The activated 2a proved to be efficient for
[13]
À
lization of readily available compounds 3 using homo- Tosteꢁs C C bond forming reaction
to give 6 in
geneous cationic gold catalysts.[11b] We have evaluated 94% yield within only 3 h [Eq. (2)]. Hence, these
the activity of the immobilized gold compounds 2a polymer-bound gold catalysts will be widely applica-
and b for the same intramolecular cyclization of 3 as
a test reaction (Table 1). When 3a was treated with
either 2a or 2b, each containing 0.5 mol% of the Au
component, the expected compound 4a was obtained
in 95% and 98% yields, respectively, though their re-
action times were longer than those under homogene-
ous conditions. We have examined a similar reaction
in the presence of polystyrene-PPh2 and AgOTf
(0.5 mol%) in toluene at room temperature for 3 h to
obtain a trace amount of 4a. The reaction with
5.0 mol% of TfOH did not take place at all. There-
fore, the supported cationic gold species has been
shown to be the true active catalyst.[11b] Similarly, the
Table 1. Intramolecular cyclization of 3 into 4 using the immobilized cationic gold(I) catalysts 2a and b.
Entry
Substrate
2
Time [h]
Product
Isolated yield [%]
R1
R2
R3
(CH2)2Ph
X
1
2
3
4
5
6
7
8
9
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
H
H
H
H
Me
Me
Me
Me
G
O
O
O
O
O
O
O
O
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
3
3
9
6
6
6
6
6
6
6
4a
4a
4b
4b
4c
4c
4d
4d
4e
4e
95
98
79
88
92
95
88
92
80
79
A
2-thienyl
2-thienyl
Ph
Ph
Ph
Ph
N
ACHTUNGTRENNUNG
-(CH2)4-
-(CH2)4-
H
H
H
H
H
H
Me
Me
NBoc
NBoc
10
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Reusable and Durable Immobilized-Cationic Gold(I) Catalysts
ble to various organic reactions that have been con-
ducted using homogeneous gold-based catalysis.
Having established the high catalytic performance
of 2a and b in the ring forming reactions, we next ex-
amined their recyclability. Using 2a (0.5 mol% of the
Au component), the reaction of 3a was conducted
under the conditions described in Table 1. After the
reaction, simple decantation allowed the easy and
almost quantitative recovery of 2a from the reaction
mixture. Catalyst 2a was then dried for 10 min under
reduced pressure and reused for the next reaction run
without the further addition of AgOTf. Its high cata-
lytic activity was maintained up to the fourth run as
shown in Table 2. Moreover, even for the eighth use,
the reaction smoothly proceeded to afford 4a in 94%
yield, although it took a longer time for completion.
The leaching of the Au components was evaluated by
inductively coupled plasma (ICP) spectroscopy of the
each crude product which revealed that 0.47% of Au
Scheme 2. Flow reactor system for the preparation of 4a.
was leached in the first run and 0.12–0.21% for runs toluene (60 mL) was passed at a 1.0 mLminÀ1 flow
2–8. Thus, the coordination binding between the Au rate through the column. Concentration of the efflu-
moiety and the phosphine on the polymer has proved ent, followed by flash filtration through a silica gel
to be strong enough during every reaction and recov- pad with hexanes as eluent gave 4a in 92% yield. At
ery process. The lengthening of the reaction time the higher flow rate of 2.5 mLminÀ1, 4.04 g of 4a were
seems to be attributable to the slight deactivation of produced with a similar yield (89%) and purity within
the immobilized gold catalyst by water formed during 30 min. Therefore, the high efficiency of the flow re-
these reactions.
actor system was demonstrated in terms of a rapid
It is notable that the cationic catalyst 2a was also production and simple operation.
applicable for a larger-scale continuous flow reactor
In summary, we have synthesized, for the first time,
system (Scheme 2). After mixing polymer-PPh2-AuCl polymer-supported cationic gold(I) complexes 2a and
1
(800 mg, 0.65 mmol) with AgOTf (167 mg, b, which exhibited high catalytic activities for the in-
0.65 mmol) in toluene (10 mL) for 15 min at room tramolecular ring-forming reactions leading to hetero-
temperature to generate 2a, the reaction mixture was cycles (4 and 5) and a cycloalkane 6. The reusability
poured into a glass column with a diameter of 12 mm of 2a was also demonstrated without any significant
and a length of 30 mm containing the catalytic phase. loss of reactivity over 8 times. Moreover, 2a was ap-
Subsequently, a solution of 3a (5.00 g, 25 mmol) in plied to a flow reactor system to achieve a rapid and
continuous production with a high quality. Further
improvement of the reactivity and durability of these
immobilized gold catalysts are now in progress.
Table 2. The reuse of 2a for converting 3a into 4a.
Experimental Section
Time [h][a]
Yield [%] of 4a
Au leaching [%][b]
Procedure for the Preparation of 1
Run
To a suspension of polystyrene-supported triphenylphos-
phine[9] (170 mg, 0.170 mmol of the phosphine ligand) in
CH2Cl2 (4.0 mL) was added a solution of (Me2S)AuCl
(50.0 mg, 0.170 mmol) in CH2Cl2 (2.5 mL) at 08C via a
canula. After stirring at room temperature for 6 h, the pre-
cipitate was filtered off, washed with CH2Cl2, and dried
under vacuum. Based on the weight gain of the resin and a
trace amount (<1.0 mg) of the gold compound recovered
from the combined filtrates, the Au moiety was found to
completely coordinate with the phosphine ligand on the
polymer. Thus, the polymer supported-gold catalyst 1 with
0.81 mmol of the Au component per 1.0 g of 1 was obtained.
1st
2
2
2
2
3
5
7
7
98
98
94
98
97
99
98
94
0.47
0.18
0.12
0.16
0.15
0.21
0.14
0.14
2nd
3rd
4th
5th
6th
7th
8th
[a]
Reaction time to consume 3a.
The amount of leached Au based on the starting material
[b]
2a.
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Masahiro Egi et al.
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General Procedure for the Preparation of Furans and
Pyrrole (Table 1)
Under a nitrogen atmosphere, to a suspension of 1 (7.5 mg,
0.0060 mmol of the Au component) in toluene (3.0 mL,
0.4M) was added either AgOTf (1.6 mg, 0.0060 mmol) or
AgNTf2 (2.3 mg, 0.0060 mmol) at room temperature. The
mixture was stirred for 15 min to generate the cationic cata-
lyst 2a or 2b. After the substrate 3 (1.2 mmol) was added,
the reaction mixture was stirred at room temperature until
the complete consumption of 3 and then filtered through a
Celite pad. The filtrate was evaporated under vacuum and
the residue was purified by flash column chromatography
(silica gel, usually hexanes/EtOAc or hexanes) to give the
corresponding product 4.
The spectroscopic data of the obtained products 4 were in
good agreement with those in our previous publication.[11b]
Recovery and Reuse of 2a (Table 2)
To a toluene suspension (2.5 mL) of 2a, generated from 1
(6.2 mg, 0.0050 mmol) and AgOTf (1.3 mg, 0.0050 mmol),
was added 3a (204 mg, 1.0 mmol) at room temperature, and
the mixture was stirred for 2 h under a nitrogen atmosphere.
The solution was separated by decantation, and the remain-
ing 2a was washed with toluene. The combined organic
layers were evaporated under vacuum, and the residue was
purified by column chromatography as above to give 4a.
After drying under vacuum at room temperature for 10 min,
the recovered 2a was reused for another conversion of 3a
(204 mg, 1.0 mmol) into 4a under the same conditions.
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tained from Merck KGaA; 1% cross-linked, 100–200
mesh, containing 1.00 mmol of the phosphine ligand/g.
[10] JandaJelTM, available from the Aldrich Chemical Co., is
a member of lightly cross-linked polystyrene resins in
which the standard cross-linker divinylbenzene is re-
placed with a more flexible 1,4-bis(4-vinylphenoxy)bu-
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Acknowledgements
We are grateful to Dr. Satoshi Mitsunobu and Professor Ma-
sahiro Sakata of Institute for Environmental Sciences, Uni-
versity of Shizuoka for their kind help to measure ICP. This
work was supported by a Grant-in-Aid for Young Scientists
(B) from MEXT and the Uehara Memorial Foundation (for
M.E.).
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Adv. Synth. Catal. 2011, 353, 287 – 290