Highly efficient visible-light-induced aerobic oxidative C-C, C-P coupling from C-H bonds catalyzed by a gold(III)-complex

Article abstract of DOI:10.1039/c3ob27400d

A novel and highly efficient gold(III)-complex catalyzed aerobic oxidative α-C-H functionalization of amines has been developed. The tertiary amines can be directly coupled with various nucleophiles using air as a sustainable oxidant.

Full text of DOI:10.1039/c3ob27400d

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Highly efficient visible-light-induced aerobic oxidative
C–C, C–P coupling from C–H bonds catalyzed by a
gold(III)-complex†
Cite this: Org. Biomol. Chem., 2013, 11,
1606
Received 11th December 2012,
Accepted 18th January 2013
Qicai Xue,a Jin Xie,a Hongming Jin,a Yixiang Chenga and Chengjian Zhu*a,b
DOI: 10.1039/c3ob27400d
www.rsc.org/obc
A novel and highly efficient gold(III)-complex catalyzed aerobic long-chain ketones were employed as coupling partners.7j,11 To
oxidative α-C–H functionalization of amines has been developed. address this challenge, our initial investigation was carried out
The tertiary amines can be directly coupled with various nucleo- on the reaction of N-phenyl tetrahydroisoquinoline 2a with
philes using air as a sustainable oxidant.
2-hexanone 3a. The oxidative coupling product 4a could be
formed using 1a as a photoredox catalyst, and the yield could
increase to 53% by the addition of 10 mol% of L-proline
(Table 1, entry 1). Encouraged by this result, we investigated
different photocatalysts, additives and solvents, and the results
are summarized in Table 1. To compare the relative reactivity,
all the reactions were also performed and stopped at 12 h.
Among the gold catalysts screened in the dual catalytic process
(Scheme 1), 1d showed the best catalytic activity (Table 1, entry 4).
L-Proline was found to play an important role in the catalytic
process. Other additives such as pyrrolidine and piperidine
gave less satisfactory yields (Table 1, entries 4–6). Sub-
sequently, various solvents were evaluated in this
The direct functionalization of C–H bonds has emerged as an
attractive and challenging strategy, as C–H bonds are ubiqui-
tous in organic molecules.1 In recent years, gold-catalyzed C–H
bond activation has aroused more and more interest.2 For the
methods reported, gold catalysts were commonly used as mild
π-acids to activate unsaturated C–H bonds.3 However, gold-
catalyzed oxidative functionalization of the sp3 C–H bond
remains a great challenge,4 since a sacrificial external oxidant
is usually required.5
Visible light photoredox catalysis has become a promising
strategy for the development of novel and sustainable sp3 C–H
activation reactions.6 However, few efforts were dedicated to
developing the other efficient photocatalysts relative to tra-
ditional RuII,6d,7 IrIII,7k,8 or dye-liking catalysts9 for chemical
transformations. Since the 1990s, significant interest has been
paid to developing the photochemical and photocatalytic pro-
perties of gold-complexes, but the successful case for the gold
photocatalytic property is still elusive.10 Very recently, Che and
co-workers have disclosed the first organogold-catalyzed oxi-
dative cyanation reaction enabled by irradiation with a 300 W
xenon lamp under an oxygen atmosphere.4a As part of our
ongoing interest in sp3 C–H activation,4b,c we report a novel
visible-light-induced sp3 C–H bond functionalization protocol
catalyzed by a gold(III)-complex.
Table 1 Survey of different photocatalysts, additives and solventsa
Entry
Catalyst 1
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1d
1d
1d
1d
1d
1d
—
L-Proline
L-Proline
L-Proline
L-Proline
Pyrrolidine
Piperidine
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
—
DMF
DMF
DMF
DMF
DMF
DMF
CH3OH
CH2Cl2
CH3CN
NMP
53
51
47
61
15
10
12
Trace
34
To the best of our knowledge, the oxidative coupling of
amines with unmodified ketones was usually limited to
acetone, and the results are not satisfactory when unmodified
9
aState Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, People’s Republic of China.
E-mail: cjzhu@nju.edu.cn; Fax: (+86)-025-8331-7761; Tel: (+86)-02583317761
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Shanghai 200032, People’s Republic of China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3ob27400d
10
11
12
78
Trace
Trace
NMP
NMP
1d
a Reaction conditions: 2a (0.1 mmol), 3a (0.5 mmol), catalyst 1 (5 mol%),
additive (10 mol%), solvent (1.0 mL), 5 W blue LEDs (λmax = 455 nm),
r.t., air, 12 h. b Isolated yield.
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Table 3 Scope of the photocatalytic oxidative coupling reactiona
Scheme 1 Gold(III)-complexes screened.
Table 2 Further survey of the photocatalytic oxidative coupling conditionsa
Entry
Light source
Time
Yieldb (%)
1
2
3
4
5
6
7
8
Fluorescent light bulb (40 W)
White LEDs (5 W)
Red LEDs (5 W)
Yellow LEDs (5 W)
Blue LEDs (5 W)
Blue LEDs (5 W)
Blue LEDs (5 W)
—
12 h
12 h
12 h
12 h
12 h
24 h
36 h
36 h
66
51
45
56
78
86
91
Trace
a Reaction conditions: 2a (0.1 mmol), 3a (0.5 mmol), 1d (5 mol%),
L-proline (10 mol%), NMP (1.0 mL), light source, r.t., air. b Isolated yield.
photooxidation coupling reaction. It was notable that when
methanol or DCM was used as the solvent, the starting
material 2a was rapidly consumed but with a small amount of
desired product, since enamine nucleophilic attack may be sig-
nificantly slower than over-oxidative amide formation (Table 1,
entries 7, 8). To our delight, the oxidative coupling reaction
proceeded smoothly without generation of other by-products
when it was conducted in NMP, providing the product 4a with
the highest isolated yield 78% (Table 1, entry 10). It should be
pointed out that exclusion of the 1d or L-proline gave trace
amounts of 4a (Table 1, entries 11, 12).
In order to maximize the yields, different light sources were
also tested in the coupling reactions (Table 2). The results
demonstrated that a fluorescent light bulb (40 W) resulted in
decreased yield (66%) accompanied by the amide byproduct
(Table 2, entry 1). Notably, the reaction led to the desired
product in excellent yield with blue LEDs (5 W) as the light
source (Table 2, entry 5). We observed that the yield could
increase to 91% by prolonging the reaction time from 12 h to
36 h (Table 2, entry 7). In addition, the exclusion of the light
gave unsatisfactory results (Table 2, entry 8).
a Standard reaction conditions: 2 (0.1 mmol), 3 (0.5 mmol), 1d (5 mol%),
L-proline (10 mol%), NMP (1.0 mL), 5 W blue LEDs (λmax = 455 nm),
r.t., air, 36 h. Yields are of the isolated products.
With the optimized reaction conditions established
(Table 2, entry 7), we investigated the scope of this protocol
(Table 3). Firstly, a variety of unmodified ketones were sub-
jected to the optimized conditions and they can afford the
desired products in good to excellent yields. Intriguingly, it
was found that long-chain ketones were still very effective in
our catalytic system and can give good results (Table 3, 4a–e).
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Table 4 The oxidative coupling reaction of amines with phosphine oxides and
phosphitesa
Scheme 2 Extended scope of the oxidative C–C coupling reaction.
Subsequently, different N-aryltetrahydroisoquinolines were
examined. All the tertiary amines could be coupled with 2-hexa-
none readily to afford the desired products 4f–n in good yields
under air. It was important to point out that electron-donating
as well as electron-withdrawing groups on the aromatic rings
were compatible in the aerobic oxidative C–C coupling reac-
tion. The N-aryltetrahydroisoquinolines bearing bulky groups
resulted in moderate yields (Table 3, 4o–p). When 6 or 7-pos-
ition substituted isoquinolines were employed, the reaction
could proceed smoothly to furnish the C–C coupling products
with excellent yields (Table 3, 4q–r).
a Standard reaction conditions: 2 (0.1 mmol), 11 (0.3 mmol), 1d (5 mol%),
CH3CN (1.0 mL), 5 W blue LEDs (λmax = 455 nm), r.t., air, 24 h. Yields
are of the isolated products.
convenient and environmentally benign process, as well as
broad substrate-scope, makes this protocol very practical.
Further studies on exploration of the detailed mechanism of
this transformation are currently underway in our laboratory.
We applied this protocol to malonates, cyclic ketones,
linear amines, and the corresponding results are listed in
Scheme 2. Under visible-light irradiation in air, the desired
products (6a–c), α-diester amine derivatives, were obtained in
moderate yields. When cyclopentanone or N,N,4-trimethylani-
line was used, an acceptable yield could also be obtained.
The success of C–C bond formation by using 1d encouraged
us to investigate C–P bond coupling reactions.12 In this work, a
variety of tertiary amines could react with phosphine oxides in
the presence of 1d to give the desired products in good yields
after irradiation by blue light for 24 h (Table 4, 12a–f). Both
electron-donating and electron-withdrawing groups on the aro-
matic rings were compatible in the oxidative C–P coupling
reaction. Moreover, different phosphites also could undergo
the oxidative reaction to provide the desired products in good
to excellent yields (Table 4, 12g–i).
In conclusion, we have reported a novel gold(III)-complex
catalyzed operationally simple method for the oxidative coup-
ling of tertiary amines with unmodified long-chain methyl
ketones, cycloketones, active methylene substrates, phosphine
oxides and phosphites. Gold(III)-complex 1d displayed high
photocatalytic activity in the oxidative coupling reaction high-
lighting the richness of gold(III) photochemistry. The reaction
proceeds in high isolated yield under air. The efficient,
Acknowledgements
We gratefully acknowledge the National Natural Science Foun-
dation of China (21172106, 21074054), the National Basic
Research Program of China (2010CB923303) and the Research
Fund for the Doctoral Program of Higher Education of China
(20120091110010) for their financial support. J. Xie thanks the
academic scholarship for doctoral candidates of MOE.
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