Bis-cyclometallated gold(iii) complexes as efficient catalysts for synthesis of propargylamines and alkylated indoles

Article abstract of DOI:10.1039/c3cc44828b

Stable bis-cyclometallated gold(iii) complexes were developed as efficient catalysts for organic transformation reactions by using two strategies: (1) construction of distorted square planar gold(iii) complexes and (2) dual catalysis by gold(iii) complexes and silver salts. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc44828b

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Bis-cyclometallated gold(III) complexes as efficient
catalysts for synthesis of propargylamines and
alkylated indoles†
Cite this: Chem. Commun., 2013,
49, 8869
Received 27th June 2013,
Accepted 1st August 2013
Hok-Ming Ko, Karen Ka-Yan Kung, Jian-Fang Cui and Man-Kin Wong*
DOI: 10.1039/c3cc44828b
www.rsc.org/chemcomm
Stable bis-cyclometallated gold(III) complexes were developed as coordinatively saturated distorted square planar gold(III) com-
efficient catalysts for organic transformation reactions by using two plexes using bulky C,N donor ligands and (2) gold–silver dual
strategies: (1) construction of distorted square planar gold(III) catalysis for substrate activation.
complexes and (2) dual catalysis by gold(III) complexes and silver salts.
Bis-cyclometallated gold(III) complexes [Au(C4N)2][BF4] 1
(HC4N = 2-phenylquinoline) and 2 (HC4N = 3-phenylisoquinoline)
Gold catalysis has attracted significant attention in catalysis were synthesized by transmetallation of KAuCl4 with their corre-
research due to its superior reactivity, excellent selectivity and sponding organomercury complexes in 75% and 42% yields, respec-
high functional group tolerance.1 Studies on the use of simple tively (Fig. 1). Notably, a distorted square planar geometry9 of 1 was
gold salts (e.g. AuCl and AuCl3) as catalysts for organic synthesis revealed by X-ray crystallography (Fig. 2). The two 2-phenylquinoline
have been widely reported.2 However, the instability of simple ligands in 1 were tilted to give a dihedral angle of 431. The Au–N
gold salts in catalytic cycles leading to low product turnovers is bond length is elongated (up to 0.141 Å) when compared with
an unresolved issue.3 In this connection, gold(I) complexes literature-known square planar cyclometallated gold(III) complexes10
have been largely developed as efficient catalysts to achieve (Table S2, ESI†). Probably due to the steric repulsion between the
novel synthetic transformations.1,4 However, the development quinoline rings, the Au–N bond length is elongated and a non-planar
of gold(III) complexes for catalysis remains largely unexplored. geometry is adopted in order to maintain coordination of ligands to
Gold(III) complexes have a square planar geometry with four the gold(III) centre. On the basis of NMR spectroscopy and literature
coordination sites, and in principle the reactivity of the gold(III) reports, a typical square planar geometry is expected for complex 2.
reaction centre can be easily fine-tuned by diverse ligand design The gold(III) complexes 1 and 2 were characterized by 1H NMR,
in a modular approach.5 However, a significant challenge in the 13C NMR, and ESI-MS, and were found to be air- and water-stable.
development of gold(III) complexes as efficient catalysts is to
strike a balance between stability and reactivity. In general, the
stability of gold(III) ions significantly increases upon complexation
with ligands. However, stable gold(III) complexes generally exhibit
poor catalytic activity. We envision that novel ligand design and
substrate activation strategies are of importance in the pursuit of
gold(III) catalysis for organic synthesis.
Over the years, we have been developing gold catalysis for
Fig. 1 Bis-cyclometallated gold(III) complexes 1 and 2.
organic transformation reactions.6 In particular, we are interested
in employing cyclometallated gold(III) complexes7 as catalysts for
organic synthesis.8 Recently, we found that stable bis-cyclometallated
gold(III) catalysts are able to exhibit high catalytic activity in
organic synthesis through two novel strategies: (1) formation of
State Key Laboratory of Chirosciences and Department of Applied Biology and
Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon,
Hong Kong, China. E-mail: mankin.wong@polyu.edu.hk; Fax: +852 2364-9932
† Electronic supplementary information (ESI) available: Experimental details,
NMR spectra of new compounds, and crystallographic data of complex 1. CCDC
Fig. 2 Crystal structure of 1 in top view (left) and side view (right). Anions were
946727. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3cc44828b
omitted for clarity.
c
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Table 1 Bis-cyclometallated gold(III) complex-catalyzed three-component cou-
pling reaction for propargylamine synthesisa
Table 2 Screening of catalysts for synthesis of alkylated indolesa
Entry
Catalyst (mol%)
Isolated yieldb (%)
Entry
Catalyst (mol%)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
1 (2.5) + AgBF4 (5)
2 (2.5) + AgBF4 (5)
1 (2.5) + Zn(OTf)2 (5)
1 (2.5) + Yb(OTf)3 (5)
1 (5)
2 (5)
AgBF4 (5)
80
47
76
39
13c
0
1
1 (1)
1 (0.1)
1 (1)
2 (5)
2 (1)
83
60
25
8
2
3b
4
5
0
a
10c
0
Reaction conditions: 3a (0.5 mmol), 4a (0.55 mmol) and 5a
b
(0.75 mmol) in H2O (1 mL). Room temperature.
Zn(OTf)2 (5)
Yb(OTf)3 (5)
0
a
Results of studies on the catalytic activities of 1 and 2 in the
three-component coupling reaction of aldehydes, amines and
alkynes for propargylamine synthesis11 are given in Table 1.
Using 1 mol% of complex 1 with a distorted square planar
Reaction conditions: 7a (0.24 mmol) and 8a (0.2 mmol) in CH2Cl2
(2 mL). Isolated yield. Determined by 1H NMR using 1,3,5-tri-
methoxybenzene as an internal standard.
b
c
geometry, propargylamine 6a was obtained in 83% isolated yield followed by C–H addition of indole 8a to the enol ether. Through
at 40 1C in 24 h under air (entry 1). As shown in entry 2, 6a was systematic screening, we found that silver salts are able to work
obtained in 60% isolated yield even with 0.1 mol% of 1, which was
found to be comparable with our previous studies.6a,8a,c Note that
complex 1 (1 mol%) was able to catalyze the reaction at room
temperature (entry 3). In contrast, complex 2 exhibited poor
catalytic activity. Using 5 mol% of 2 only gave 8% isolated yield
(entry 4) while no reaction was observed with 1 mol% of 2 (entry 5).
synergistically with bis-cyclometallated gold(III) complexes in the
indole alkylation.
Using 1 (2.5 mol%) with AgBF4 (5 mol%), alkynyl alcohol 7a
reacted with indole 8a to give alkylated indole 9a in 80% isolated
yield at room temperature in 2 h (entry 1). The reaction using
complex 2 (2.5 mol%) with AgBF4 (5 mol%) gave 47% isolated yield
The significantly higher catalytic activity of 1 than that of 2 (entry 2). Combination of 1 with Zn(OTf)2 or Yb(OTf)3 could also
could be attributed to their difference in geometry. Complex 1 catalyze the reaction to afford 76% and 39% isolated yields, respec-
has a distorted square planar geometry with elongated bond
lengths. Hence, ligand dissociation of 1 to generate a highly
reactive gold(III) reaction centre for alkyne activation would be
more favorable than that of complex 2. It is envisioned that
such design of distorted gold(III) complexes would be applicable
in catalyzing other classes of organic reactions.
tively (entries 3 and 4). In the control experiments (entries 5–9), poor
yields (10–13%) or no product formation were found when only a
single metal catalyst was used. Catalyst screening using various
metal salts was also conducted (see ESI†). These findings indicate
that appropriate combination of dual metal catalysts15 is a feasible
approach to render stable bis-cyclometallated gold(III) complexes as
Next, complex 1 was used in stereoselective synthesis efficient catalysts in organic transformation reactions.
of propargylamines 6b–6h with 70–90% isolated yields and
diastereomeric ratio (dr) of up to >99 : 1 (Fig. 3). In addition,
complex 1 was able to promote selective modification of
D-raffinose aldehyde with 85% aldehyde conversion.8b
In the next section, a gold–silver cooperative dual catalysis
strategy12 was used in bis-cyclometallated gold(III) complex-catalyzed
indole alkylation13 (Table 2). According to the proposed reaction
The substrate scope of the dual metal catalysis for indole
alkylation was demonstrated by using alkynyl alcohols of different
chain lengths 7a–7g and indoles with different substituents 8a–8j to
afford alkylated indoles 9a–9p with up to 94% isolated yields
(Table 3). The reactivity and regioselectivity of the present reaction
were found to be consistent with literature reports.14,16
An important advantage of using gold(III) complexes over
mechanism,14 alkylated indole 9a was formed by metal-catalyzed simple gold(III) salts is the recyclability in catalysis. The recycl-
cyclization of alkynyl alcohol 7a to generate enol ether in situ ability experiments of catalyst 1 in propargylamine synthesis
were conducted (Table 4). Catalyst 1 could be repeatedly used
for 7 cycles leading to 638 product turnovers in total. However,
the conversion when using KAuCl4 decreased significantly
leading to only 29% conversion in the 7th cycle. These findings
clearly indicate the recyclability of catalyst 1.
Next, we set out to examine the recyclability of catalyst 1 in the
dual catalysis of indole alkylation (Table 5). Catalyst 1 could be
repeatedly used for 11 cycles to give 73–88% conversions with
addition of AgBF4 at the 6th and 11th cycles. At the end of the
10th cycle, complex 1 was found to remain intact by ESI-MS analysis
of the reaction mixture. These results suggest that catalyst 1 is stable
under the reaction conditions and could be reused with further
addition of AgBF4. Yet, the recyclability experiments conducted using
Fig. 3 (a) Substrate scope of propargylamine synthesis catalyzed by 1.
(b) Modification of D-raffinose aldehyde via three-component coupling reaction.
c
8870 Chem. Commun., 2013, 49, 8869--8871
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Table 3 Gold(III) complex-silver catalyzed cyclization–addition reactions of alkynyl
alcohols 7a–7g and substituted indoles 8a–8ja
We are thankful for the financial support from the Hong Kong
Research Grants Council (PolyU 5031/11p) and The Hong Kong
Polytechnic University (SEG PolyU01). We also thank Prof. Chun-Yu
Ho of South University of Science & Technology of China for his
comments on the bis-cyclometallated gold(III) complexes.
Notes and references
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Entry
n
R1
R2
R3
X
Product Isolated yield (%)
2 Reviews: (a) N. Krause and C. Winter, Chem. Rev., 2011, 111, 1994;
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1
2
3
4
5
6
7
8
1
1
1
1
2
3
3
1
1
1
1
1
1
1
1
1
CH3
C2H5 CH3
C3H7 CH3
Ph
Ph
C4H9 CH3
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
9a
9b
9c
9d
9e
9f
80
74
78
CH3
CH3
75
74b
84c
94c
80
CH3
CH3
CH3
CH3
9g
9h
9
OMe 9i
NO2
H
H
Br
OMe 9n
NO2
H
80
10
11
12
13
14
15
16
9j
9k
9l
67d
40
CH3 CH3
H
H
H
H
H
H
H
H
H
75
9m
71e
53
9o
9p
70d
58
CH3
´
´
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a
Reaction conditions: 7a–7g (0.24 mmol) and 8a–8j (0.2 mmol) in
b
c
CH2Cl2 (2 mL). 5-Exo-dig cyclized product was formed. 6-Exo-dig
cyclized products were formed. 16 h. 4 h.
d
e
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Cycle
1
2
3
4
5
6
7
Conversionb (%) by 1
99
99
97
94
93
82
85
65
89
51
86
38
89
29
Conversionb (%) by KAuCl4
a
Reaction conditions: 3a (1 mmol), 4a (1.1 mmol) and 5a (1.5 mmol) in
H2O (1 mL). Determined by 1H NMR.
b
Table 5 Recyclability experiment of ‘‘1 + AgBF4’’ in the reaction of 7a and 8a at
a
room temperature in CDCl3
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Cycle
1
2
3
4
5
6c
7
8
9
10 11c
Conversionb (%) 85 81 81 78 73 88 87 85 81 74 83
a
Reaction conditions: 7a (0.24 mmol) and 8a (0.2 mmol) in CDCl3 (2 mL).
b Determined by 1H NMR. c Additional AgBF4 (5 mol%) was added.
KAuCl4 or ‘‘KAuCl4 + AgBF4’’ as catalysts gave no product in the
2nd cycle.
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2007, 13, 8285.
rendering stable bis-cyclometallated gold(III) complexes as
efficient catalysts in organic synthesis by (1) ligand design
15 (a) A. S. K. Hashmi, Chem.–Eur. J., 2013, 19, 1058; (b) Y.-Z. Wang,
L.-Z. Liu and L.-M. Zhang, Chem. Sci., 2013, 4, 739.
and (2) dual catalysis.
16 A. Zanardi, J. A. Mata and E. Peris, Chem.–Eur. J., 2010, 16, 13109.
c
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Chem. Commun., 2013, 49, 8869--8871 8871