.
Angewandte
Communications
DOI: 10.1002/anie.201107605
Gold Catalysis
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A Highly Efficient Gold-Catalyzed Oxidative C C Coupling from C H
Bonds Using Air as Oxidant**
Jin Xie, Huamin Li, Jiecong Zhou, Yixiang Cheng, and Chengjian Zhu*
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The construction of C C bond is a perennial subject of
interest for the synthetic chemist. Lately, the homogeneous
In our initial study, the oxidative C C coupling reaction of
N-phenyl tetrahydroisoquinoline 7a with nitromethane 8a
was chosen as a model reaction.[10] The results are summar-
ized in Table 1. To our delight, the aerobic oxidative C C
coupling reaction could occur under the catalysis of 1a
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gold-catalyzed C C coupling reaction has emerged as a
powerful method for the synthesis of intricate scaffolds.[1] In
the methods reported, the introduction of a highly function-
alized group or a sacrificial external oxidant was usually
required, thus diminishing the overall sustainability of the
gold-catalyzed process. In recent years, the direct use of two
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Table 1: Optimization of the aerobic oxidative C C coupling reaction of
amines with nitromethane.[a]
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C H bonds for C C coupling has become a promising
strategy, as C H bonds are ubiquitous in organic molecules.
[2]
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In 2009 and 2010, the groups of Tse and Nevado reported the
gold-catalyzed oxidative homocoupling of simple arenes and
oxidative ethynylation of arenes with terminal alkynes using
PhI(OAc)2 as an oxidant.[3] However, the gold-catalyzed
oxidative C C coupling of Csp3 H bonds under aerobic
oxidative conditions is still a challenge.[4–5] Directed toward
such goals, we became interested in the gold-catalyzed
Entry
Catalyst (mol%)
Solvent
t [h]
Yield [%][b]
À
À
1
2
3
4
5
6
7
8
1a (6)
1b (6)
2a (6)
2b (6)
3 (6)
4 (6)
NaAuCl4 5 (6)
Ph3PAuCl 6 (6)
–
1b (6)
1b (6)
1b (3)
1b (3)
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeNO2
MeNO2
MeNO2
MeNO2
6
6
6
6
6
6
6
6
6
3
3
3
3
48
71
56
52
45
47
38
trace
trace
82
86
86
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H
oxidative C C coupling of amines with various Csp3
coupling partners. Although some notable progress has
been achieved in this area, a stoichiometric amount of
dangerous oxidants or pure oxygen (ꢀ 1.0 atm), and even
specialized reaction conditions are usually necessary.[6,7]
These disadvantages have seriously limited the utility of
such methods. Therefore, the development of a more environ-
mentally benign and convenient catalytic system for amine
functionalization is highly desirable. Following the principle
of sustainable chemistry, air is a favorable oxidant, with water
as the only waste product, and it has received considerable
attention in modern oxidation chemistry.[8] To the best of our
knowledge, there is no successful example of a gold-catalyzed
9
10
11[c]
12[c]
13[c,d]
12
[a] Reaction conditions: 7a (0.1 mmol, 0.1m), 8a (0.20 mL), catalysts 1–
6 (3–6 mol%), solvent (0.8 mL), air, 608C. [b] Yields of the isolated
products. [c] 100 mL MeOH was added. [d] The reaction was carried out
in Ar (1.0 atm).
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a-C H functionalization of amines using air as the sole
oxidant.[5,9] Herein, we wish to report an unprecedented
homogeneous gold-catalyzed amine functionalization proto-
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col involving the oxidative C C coupling of two different C
H bonds with air as a sustainable and efficient oxidant.
[*] J. Xie, H. Li, J. Zhou, Prof. Y. Cheng, Prof. C.-J. Zhu
State Key Laboratory of Coordination Chemistry
School of Chemistry and Chemical Engineering
Nanjing University, Nanjing 210093 (P. R. China)
E-mail: cjzhu@nju.edu.cn
(6 mol%) with methanol as solvent at 608C under air, to
afford 9a in 48% yield (Table 1, entry 1). Among the AuIII
catalysts screened 1b showed the best catalytic activity
(Table 1, entries 1–7). The utilization of Ph3PAuCl 6 instead
of a AuIII catalyst resulted in the formation of only a trace
amount of product (Table 1, entry 8). Interestingly, a trace
amount of the desired product 9a was obtained in the absence
of any catalyst (Table 1, entry 9). When the aerobic oxidative
Prof. C.-J. Zhu
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Shanghai 200032 (P. R. China)
[**] We gratefully acknowledge the National Natural Science Foundation
of China (20832001, 20972065, 21074054, 21172106) and the
National Basic Research Program of China (2010CB923303) for
their financial support.
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C C coupling reaction was performed without a solvent at
608C under air, it led to a satisfactory yield of 82% (Table 1,
entry 10). Notably, the yield could be improved to 86% by
adding a small amount of methanol (Table 1, entry 11).
Supporting information for this article is available on the WWW
1252
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1252 –1255