Heterobimetallic cobalt/rhodium nanoparticle-catalyzed carbonylative cycloaddition of 2-alkynylanilines to oxindoles

Article abstract of DOI:10.1021/ol801978n

(Chemical Equation Presented) The cobalt-rhodium heterobimetallic nanoparticle-catalyzed synthesis of oxindoles from 2-alkynylanilines in the presence of carbon monoxide is described.

Full text of DOI:10.1021/ol801978n

ORGANIC
LETTERS
2008
Vol. 10, No. 21
4719-4721
Heterobimetallic Cobalt/Rhodium
Nanoparticle-Catalyzed Carbonylative
Cycloaddition of 2-Alkynylanilines to
Oxindoles
Ji Hoon Park, Eunha Kim, and Young Keun Chung*
Intellectual Textile System Research Center, and Department of Chemistry,
College of Natural Sciences, Seoul National UniVersity, Seoul 151-747, Korea
ykchung@snu.ac.kr
Received June 6, 2008
ABSTRACT
The cobalt-rhodium heterobimetallic nanoparticle-catalyzed synthesis of oxindoles from 2-alkynylanilines in the presence of carbon monoxide
is described.
The transition-metal-catalyzed carbonylative cyclization of
unsaturated hydrocarbons using carbon monoxide1 is among
the most important and synthetically useful catalytic trans-
formations. Recently, considerable research efforts have
focused on the carbonylative cyclization to heterocycles.2
However, in some cases, the usefulness of the transition-
metal-catalyzed carbonylation is debased because of the
requirement for high temperatures, high carbon monoxide
pressure or specially designed ligands.3 It would be desirable
to develop new carbonylation catalysts that can be carried
out under mild reaction conditions.
Recently, transition metal nanoparticles have been widely
used as catalysts for organic synthesis because to their high
catalytic activity and recyclability.4 We recently found cobalt/
rhodium nanoparticles (Co2Rh2) derived from Co2Rh2(CO)12
to be useful catalysts in carbonylation related reactions.5 In
the context of our studies on the use of transition metal
nanoparticles in organic reactions, we found that Co2Rh2 was
quite effective for the carbonylative cycloaddition of 2-alky-
nylanilines. This reaction permits the formation of oxindoles,
which are versatile synthetic intermediates as well as
important structural units in a variety of biologically active
natural products.6 Many useful synthetic methods have been
published.7 Among them, one of the most popular methods
is based on a palladium-catalyzed arylation.8 A transition-
metal-catalyzed carbonylation is highly recommendable in
the synthesis of oxindoles. However, there has only been a
limited amount of research in this area until now.9-11 In
(1) For recent papers, see: (a) Matsuda, T.; Tsuboi, T.; Murakami, M.
J. Am. Chem. Soc. 2007, 129, 12596. (b) Harada, Y.; Nakanishi, J.; Fujihara,
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106, 4644. (b) Csende, F.; Stajer, G. Curr. Org. Chem. 2005, 9, 1737. (c)
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Chem. Res. 2003, 36, 638. (e) Nanoparticles: From Theory to Application;
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Aranzaes, J. R. Angew. Chem., Int. Ed. 2005, 44, 7852.
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Chem. Commun. 2007, 657. (b) D´ıaz, D. J.; Darko, A. K.; Mc-Elwee-White,
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therein.
10.1021/ol801978n CCC: $40.75
Published on Web 10/11/2008
2008 American Chemical Society

1995, Takahashi et al. reported9 a Rh6(CO)16-catalyzed
carbonylation of 2-alkynylanilines under water-gas shift
reaction conditions (100 atm of CO) to give oxindoles in
good yields along with a small amount of 2-quinolones. Here
we report the Co2Rh2-catalyzed cyclization of 2-alkynyla-
nilines in the presence of carbon monoxide to give oxindoles.
This is the first use of transition metal nanoparticles as
catalysts in the synthesis of oxindoles. The catalytic system
does not require any additives or promoters and can be
recycled several times without any significant loss of its
catalytic activity. For the catalytic synthesis of oxindoles,
the catalytic reaction can be carried out under relatively low
CO pressure (20 atm).
of activity even after being recycled six times (90%, 89%,
91%, 92%, 89%, and 91%, respectively). In order to recycle
the catalyst, it was filtered from the reaction mixture and
dried in vacuum. It could then be reused for further catalytic
reactions.
To examine the scope of the present reaction, various
2-alkynylanilines were screened under the optimized reaction
conditions. The results are summarized in Table 2, which
Table 2. Co2Rh2-Catalyzed Synthesis of Oxindoles from
2-Alkynylanilinesa
A catalytic synthesis of oxindoles was studied using
2-alkynylaniline 1a as a model substrate and Co2Rh2 as a
catalyst. 2-Alkynylanilines were easily synthesized by the
palladium-catalyzed cross-coupling between 2-haloanilines
and acetylenes. The treatment of 1a (58 mg, 0.3 mmol) with
20 atm of carbon monoxide in the presence of Co2Rh2 (3
mol %, 15 mg) in 5 mL of toluene at 100 °C for 5 h gave
an oxindole 1b in 29% with the concomitant formation of
an indole 1c10 in 71% yield (eq 1).11 The formation of the
1
oxindoles was confirmed by H and 13C NMR and HRMS
studies. We were pleased to find that the desired product 1b
was obtained in 29% in the initial study.
Encouraged by the formation of 1b, we further optimized
the reaction conditions. The representative optimization
experiments are summarized in Table 1. The yield was highly
Table 1. Screening of Catalyst Systems for the Formation of
1ba
entry CO (atm) solvent temp (°C) isolated yield of 1b (%)b
1
2
3
4
5
6
7
1
5
toluene
toluene
toluene
toluene
THF
100
100
130
100
100
130
90
0 (>99)
0 (>99)
13 (87)
29 (71)
71 (29)
52 (48)
90 (10)
20
20
20
20
20
THF
THF
a 0.3 mmol of 1a and 5 mL solvent were used. b The numbers in
parentheses are the isolated yields of the corresponding indole 1c.
a 0.3 mmol of a and 3 mol % of Co2Rh2 catalyst were used in 5 mL
THF for 5 h. b Isolated yield. c Decomposed.
dependent upon the reaction temperature, the pressure of CO,
and the reaction solvent. The best yield of 1b was 90%.
Compound 1b was a mixture of E/Z isomers (ca. 10:1) with
a slightly different isomer ratio for each experiment. The
optimized reaction conditions were established as follows:
20 atm of CO, 90 °C, and 5 h.
shows that oxindoles b were obtained in satisfactory yields
for all 2-alkynylanilines with an internal alkyne bearing a
hydrogen, alkyl, or aryl substituent on the amine moiety. In
addition to the formation of b, formation of c was observed
for all the cases with slightly different yields (ca. 10-20%).
To check for recyclability, the catalyst was separated and
reused several times. The catalyst maintained its high level
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Org. Lett., Vol. 10, No. 21, 2008

However, in the case of entries 2 and 5, 3c and 6c were
obtained in 48% and 42% yields, respectively. When
2-alkynylaniline with a terminal alkyne was used as a
substrate (entry 12), no characterizable compounds were
isolated. Several years ago, Gabriel and co-workers re-
ported12 a palladium-catalyzed oxidative carbonylation of
2-alkynylanilines to oxindoles. However, when the reaction
was applied to 2-alkynylanilines with internal triple bonds,
carbamates were obtained as a product. Very recently, Li
and co-workers reported13 the palladium-catalyzed carbo-
nylative annulation of 2-(1-alkynyl)benzenamines to 3-(ha-
lomethylene)indolin-2-ones under mild reaction conditions.
However, the N-substituted substrates were not suitable for
their reaction conditions. Thus, our reactions are unique and
can be used as a supplement to other methods.
hydrogenated product. Thus, a mixture of H2O/Et3N was
added to the reaction mixture. However, no reaction was
observed. Instead, when a wet THF was used a reaction
medium, a reduced oxindole and oxindole were isolated in
78% and 7% yields, respectively (Scheme 1). However, the
Scheme 1. Reaction under Water-Gas Shift Reaction Condition
Interestingly, treatment of 2-alkynylaniline (14a) with
bearing TMS under the opimized reaction conditions gave a
quite different result (eq 2). Instead of an oxindole derivative,
a quinolinone 14d was isolated in 52% with a concomitant
formation of indoles, 14c and 14c′. The formation of
quinolinone from 2-alkynylaniline was quite unusal observa-
tion.
addition of water led to a slight decrease in the yield and a
lengthening of the reaction time to up to 18 h. The maximum
reusability of the catalytic system was not tested. The
catalytic system can be reused at least three times without
loss of catalytic activity.
In conclusion, we demonstrated that Co2Rh2 can be used
as an effective catalyst in the carbonylative cycloaddition
of 2-alkynylanilines in the presence of carbon monoxide. This
reaction permits the formation of oxindoles, which are
versatile synthetic intermediates as well as important struc-
tural units in a variety of biologically active natural products.
Acknowledgment. This work was supported by the Korea
Research Foundation grant funded by the Korean Govern-
ment (MOEHRD) (KRF-2008-341-C00022 and KRF-2005-
070-C00072), the Korea Science & Engineering Foundation
(KOSEF, grant R01-2005-000-10548-0) and the SRC/ERC
program of MOST/KOSEF (R11-2005-065). J.H.P. and E.K.
are grateful for a BK21 fellowship.
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carbonylation under water-gas shift reaction conditions (in
the presence of carbon monoxide, water, and an amine) leads
to a mixture of a carbonylated and a carbonylated/
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Supporting Information Available: Experimental pro-
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OL801978N
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