pubs.acs.org/joc
such as antibacterial and antifungal effects.1 Several useful
The Scope and Limitation of Nickel-Catalyzed
Aminocarbonylation of Aryl Bromides from
Formamide Derivatives
synthetic methods have been reported.2 Among them, palla-
dium-catalyzed aminocarbonylation, which was developed
by Heck, is a powerful method for the synthesis of amides
from the reaction of aryl halides and amines in the presence
of carbon monoxide, and is one of the most frequently used
in organic synthesis.3 This transformation has been used for
the synthesis of simple building blocks and bioactive materi-
als.4 The reaction mechanism of palladium-catalyzed ami-
nocarbonylation was well established, and carbon monoxide
was employed as the carbonyl source.
Youngshin Jo,† Jinhun Ju,† Jaehoon Choe,‡
Kwang Ho Song,*,§ and Sunwoo Lee*,†
†Department of Chemistry, Chonnam National University,
300 Yongbong-dong, Buk-gu, Gwangju 500-757, Republic of
Korea, ‡LG Chem Research Park, Daejeon 305-380, Republic
of Korea, and §Department of Chemical & Biological
Engineering, Korea University, Seoul 136-713,
Republic of Korea
However, the use of carbon monoxide requires instru-
ments such as high-pressure vessels, and is cumbersome in
the organic laboratory. To address the handling of toxic
carbon monoxide gas, a variety of other sources such as Mo-
(CO)6 and formamides have been reported. Larhed et al.
reported the use of Mo(CO)6 as a carbon monoxide source in
the aminocarbonylations of aryl halides.5 They showed that
Cr(CO)6 and W(CO)6 were also able to be employed as
surrogates.5c Despite their suitability for high-throughput
organic synthesis, these inorganic materials are relatively
expensive. Carbamoylstanne6 and carbamoylsilane7 were
reacted with aryl halides in the presence of a palladium
catalyst to afford the product to which the corresponding
carbamoyl group directly bonded. However, they are not
commercially available, and are limited to the synthesis of
only the N,N-dimethyl-substituted amide derivatives. In
addition, carbamoylstanne is thermal unstable. DMF de-
composes to release carbon monoxide in the presence of
strong base at high temperature and has been utilized for the
preparation of inorganic metal-carbonyl complexes.8 Hall-
berg et al. employed DMF as a CO surrogate in the palla-
dium-catalyzed aminocarbonylation.9 They showed that the
addition of amine to the reaction mixture delivered the
corresponding aryl amides. However, imidazole was re-
quired as an additive and the reaction temperature was very
high (180-190 °C). Hiyama et al. reported aminocarbonyla-
tion using DMF as an amide source.10 Although their
method offered the advantage of functional group tolerance,
khsong@korea.ac.kr; sunwoo@chonnam.ac.kr
Received May 21, 2009
Nickel-catalyzed aminocarbonylation of aryl halides is
described. A well-defined air-stable nickel-phosphite
catalytic system (Ni(OAc)2 4H2O/phosphite 1) effec-
tively promoted the aminocarbonylation of aryl bromides
with a range of formamides to give the corresponding aryl
amide products in moderate to good yields. The less
hindered formamide required lower catalytic loading
for full conversion and produced higher yields than the
more hindered one. It also exhibited base-dependent
activity toward formamides.
3
(3) (a) Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327–3331.
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Oxford, UK, 1995; Vol. 12, pp 249-251. (c) Tsuji, J. Palladium Reagents and
Catalysis; Wiley: Chichester, UK, 1995; pp 196-198. (d) Colguhoun, H. M.;
Thompson, D. J.; Twigg, M. V. Carbonylation; Plenum: New York, 1991; pp
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The amide is a very important functional group in organic
compounds. Some amide derivatives exhibit biological activities
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*To whom correspondence should be addressed.
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Arpaci, O.; Yalcin, I.; Altanlar, N. Farmaco 2000, 55, 469–476. (c) Kobayashi, I.;
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R. J. Antimicrob. Chemother. 2002, 50, 129–132. (d) Humphrey, J. M.; Cham-
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Published on Web 07/02/2009
DOI: 10.1021/jo901065y
r
2009 American Chemical Society