Angewandte
Chemie
DOI: 10.1002/anie.201300881
Synthetic Methods
Rhodium(III)-Catalyzed Redox-Neutral Coupling of
N-Phenoxyacetamides and Alkynes with Tunable Selectivity**
Guixia Liu,* Yangyang Shen, Zhi Zhou, and Xiyan Lu*
À
Transition-metal-catalyzed functionalization of arene C H
bonds has been developed as a powerful and straightforward
synthetic approach for complex molecules from less-function-
alized substrates.[1] Directing groups and stoichiometric
amounst of oxidants are often required to achieve chemo-
selectivity and catalytic turnover. To meet the demand of
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green chemistry, a C H functionalization should: 1) minimize
the cost and waste associated with stoichiometric additives,
and 2) avoid harsh reaction conditions which may be incom-
patible with sensitive functionalities. The development of
innovative directing groups, which enable novel transforma-
tions to deliver valuable structures under mild and simple
reaction conditions, are highly desirable.
Recently, rhodium(III) was used as an efficient catalyst
À
for direct arene C H functionalization under mild reaction
conditions.[1c,d,i,2] In particular, rhodium(III)-catalyzed oxida-
tive couplings of various aromatic substrates with alkynes by
À
À
C H and X H (X = N or O) double activation has been
widely investigated (Scheme1).[2,3] This kind of reaction
typically uses heteroatoms to direct cyclometalation at the
Scheme 1. The formation of C-C/C-X (X=N or O) bonds through
rhodium(III)-catalyzed direct coupling of aromatic substrates with
alkynes.
À
À
ortho C H bond. After alkyne insertion and subsequent C X
bond reductive elimination, the desired heterocycles are
produced along with a rhodium(I) species. Thus stoichiomet-
ric amounts of external oxidants are necessary to regenerate
the catalyst. To address this drawback, an attractive redox-
neutral strategy employing an oxidizing directing group,[4–8]
which acts as a directing group and internal oxidant, has been
used in the elegant works from many groups.[6]
À
ment of a mild rhodium(III)-catalyzed redox-neutral C H
functionalization of N-phenoxyacetamides with alkynes for
the synthesis of ortho-hydroxyphenyl-substituted enamides,[9]
a highly atom-economical process (Scheme1). Furthermore,
an unexpected synthesis of valuable benzofuran derivatives
À
through C-C/C O bond formation was accomplished by
Oxidizing directing groups reported in the transition-
simply switching the reaction conditions.
In preliminary experiments, N-phenoxyacetamide (1a)[10]
was treated with [{Cp*RhCl2}2] (2.5 mol%), CsOAc
(25 mol%), and diphenylacetylene (2a, 1.2 equiv) in MeOH
(0.4m) at room temperature for 16 hours, and the desired
product 3a was obtained in 82% yield (Table 1, entry 1). The
structure of 3a was confirmed by NMR spectroscopy, as well
as IR, HRMS, and X-ray crystallography.[11] The reaction was
not sensitive to air or moisture and the addition of water did
not affect the yield (Table 1, entry 2). No product formation
was observed in the absence of the rhodium catalyst or
CsOAc additive (Table 1, entries 3 and 4). Some other acetate
additives[1g] were tested. Slightly lower yields were obtained
with AgOAc and NaOAc (Table 1, entries 5 and 6). Other
alcoholic solvents such as EtOH were not as good as MeOH
(Table 1, entry 7). Employing [Cp*Rh(OAc)2] as the catalyst
gave a result similar to that obtained with the [{Cp*RhCl2}2]/
CsOAc system (Table 1, entry 8).
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metal-catalyzed C H functionalization typically contain an
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N O bond, such as an N-oxide, N-acyloxy, and N-methoxy
group.[4–8] Normally, the oxidation of a low-valent metal by
these internal oxidants will result in cleavage of an N O bond
accompanied by the departure of the oxygen-atom-containing
unit. We envisioned that the rational design of an oxidizing
directing group may enable all atoms in the starting material
to be transformed into the product, and thus realize a highly
atom-economical process. Herein, we disclose the develop-
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[*] Prof. G. Liu, Y. Shen, Z. Zhou, Prof. X. Lu
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic chemistry, Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032 (China)
E-mail: guixia@sioc.ac.cn
[**] We thank the National Basic Research Program of China
(2009CB825304), the National Natural Science Foundation of China
(21202184, 21242001), and the Chinese Academy of Sciences for
financial support.
With the optimized reaction conditions in hand, we first
explored the reaction scope for the synthesis of ortho-
hydroxyphenyl-substituted enamides (3; Scheme 2). Several
functional groups, such as hydroxy (3 f), ester (3g, 3h, 3i), and
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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