Au(I)/Au(III)-catalyzed Sonogashira-type reactions of functionalized terminal alkynes with arylboronic acids under mild conditions

Article abstract of DOI:10.3762/bjoc.7.92

A straightforward, efficient, and reliable redox catalyst system for the Au(I)/Au(III)-catalyzed Sonogashira cross-coupling reaction of functionalized terminal alkynes with arylboronic acids under mild conditions has been developed.

Full text of DOI:10.3762/bjoc.7.92

Au(I)/Au(III)-catalyzed Sonogashira-type reactions of
functionalized terminal alkynes with arylboronic
acids under mild conditions
Deyun Qian1 and Junliang Zhang*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 808–812.
1Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, Department of Chemistry, East China Normal University,
3663 N, Zhongshan Road, Shanghai 200062 (P. R. China) and 2State
Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, Ling Ling Road
345 Shanghai 200032 (P. R. China)
doi:10.3762/bjoc.7.92
Received: 28 March 2011
Accepted: 23 May 2011
Published: 15 June 2011
This article is part of the Thematic Series "Gold catalysis for organic
synthesis".
Email:
Deyun Qian - 51100606057@ecnu.cn; Junliang Zhang* -
jlzhang@chem.ecnu.edu.cn
Guest Editor: F. D. Toste
* Corresponding author
© 2011 Qian and Zhang; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
arylboronic acid; gold-catalysis; Sonogashira cross-coupling
Abstract
A straightforward, efficient, and reliable redox catalyst system for the Au(I)/Au(III)-catalyzed Sonogashira cross-coupling reaction
of functionalized terminal alkynes with arylboronic acids under mild conditions has been developed.
Introduction
The Sonogashira reaction has become the most important and ples have recently been reported for the palladium-catalyzed
widely used method for the synthesis of arylalkynes and conju- Sonagashira-type cross-coupling of terminal alkynes with aryl-
gated enynes, which are precursors for natural products, boronic acids [13], and the Pd(0)/Pd(II) catalytic cycles have
pharmaceuticals and other materials [1-3]. In the past decade, been well studied. Nevertheless, this transformation catalyzed
considerable efforts have been made to enhance the efficiency by gold, involving Au(I)/Au(III) catalytic cycles has, as yet,
and generality of this reaction. All kinds of palladium catalyst been less explored [15-22]. In the few examples already docu-
systems [4-10] and other metal catalyst systems [3] have been mented some conditions, such as rather high reaction tempera-
developed for facilitating the Sonogashira cross-coupling, as tures (130 °C), high catalysis loading or special reagents were
well as expanding the substrate scope [11-14]. Various exam- required [23]. Herein, we report a straightforward, efficient and
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Beilstein J. Org. Chem. 2011, 7, 808–812.
robust catalyst system for the Sonogashira-type cross-coupling,
in which Au(I)/Au(III) catalyzed Csp2–Csp bond formation of
terminal alkynes from arylboronic acids under mild conditions.
Table 1: Initial screenings of Au(I)/Au(III)-catalyzed Sonogashira
couplinga.
By analogy with other d10 species, Au(I) has the same elec-
tronic structure as Pd(0) and can easily interact with the
acetylenic group, and has the ability to undergo the Au(I)/
Au(III) redox cycles [24,25]. In addition, with an increasing
interest in the chemistry of gold(I) and gold(III) compounds,
more and more studies have provided strong evidence for the
existence of Au(I)/Au(III) catalytic cycles [26-32]. For instance,
Zhang and co-workers have developed a gold-catalyzed oxida-
tive cross-coupling reaction of arylboronic acids with propargyl
esters [27], and Selectfluor® – a source of electrophilic fluorine
– was used to oxidize the resulting Au(I) intermediate to Au(III)
species. Recently, Toste reported the first experimental evi-
dence for alkylgold(III) fluorides undergoing C–C bond
forming reactions with arylboronic acids [32]. Inspired by these
results, we envisioned that terminal alkynes would react with
arylboronic acids in the presence of oxidant (Selectfluor®) and
base, and undergo a Au(I)/Au(III)-catalyzed Sonogashira-type
cross-coupling reaction (Scheme 1).
Entry AuL (5 mol %) AgX (mol %) Time (h) Yield (%)b
1
2
Ph3PAuCl
Ph3PAuCl
—
—
18
22
24
24
24
22
22
10
10
24
16
16
12
12
trace
56
AgOTf (5)
AgOTf (5)
AgOTf (5)
AgOTf (15)
AgOTf (5)
AgOTf (5)
AgBF4 (5)
AgSbF4(5)
AgOTf (5)
AgOTf (5)
—
3
0
4
AuCl
21
5
AuCl3
37c
0
6d
7e
8
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
(XPhos)AuCl
dppm(AuCl)2
dppm(AuBr)2
Ph3PAuCl
Ph3PAuCl
41
65
9
62
10
11f
12f
13f,g
14f
0
83c
trace
72 (73c)
75 (80c)
AgOTf (5)
AgBF4 (5)
aReaction conditions: The reaction was carried out by using 1a (0.4
mmol) and phenylboronic acid (0.8 mmol, 2.0 equiv), and 1.05 equiv of
Et3N in 2 mL of CH3CN stirred at room temperature. bIsolated yields.
cYield determined by 1H NMR with dibromomethane as an internal
standard. dSelectfluor® (0 equiv). ePhB(OH)2 (1.5 equiv). fUnder an
atmosphere of nitrogen (N2). gThe reaction temperature was 50 °C.
produced in the absence of Ph3PAuCl (Table 1, entry 3).
Without the phosphine ligand, both AuCl/AgOTf or AuCl3/
AgOTf could catalyze this reaction, but the efficiency was quite
low (Table 1, entries 4, 5). Without Selectfluor® as additive, the
cross-coupling reaction did not occur (Table 1, entry 6), indi-
cating that it was crucial for this transformation via oxidation of
gold(I) to the gold(III) species [26-32]. Reducing the amount of
phenylboronic acid resulted in a lower yield (Table 1, entry 7).
The counter ion effect was then examined on cross-coupling
reaction by variation of the silver salts. Alternative catalyst
systems led to better yields (Table 1, entries 8, 9 and notably 11
vs entry 2). To optimize the reaction conditions, commonly
employed well recognized and commercially available phosphi-
ne ligands [17,18], such as dppm, dppe, dppp, dppf, and XPhos,
were screened to test the feasibility of this gold-catalyzed cross-
coupling (Table 1, entries 10–12, see also Supporting Informa-
tion File 1). In addition, a series of inorganic and organic bases
was also investigated: K2CO3, K3PO4, K3PO4·3H2O, NaHCO3,
NaOAc were substantially less effective, whilst organic bases
such as iPr2NH, Et2NH, TMEDA, Bu3N, PhNMe2 were not
effective bases in this catalytic system (see Supporting Informa-
tion File 1). These results indicated that Et3N might also play an
Scheme 1: Previous work and our projected gold-catalyzed Sono-
gashira-type cross-coupling.
Results and Discussion
We embarked on developing a general protocol for Sono-
gashira-type cross-coupling by using propargyl tosylamide (1a)
and phenylboronic acid as the model substrates because of their
stability, availability, and broad spectrum of nucleophilicity
(Table 1). With commercially available Ph3PAuCl as the cata-
lyst, we treated 1a and phenylboronic acid in CH3CN at room
temperature for 18 h (Table 1, entry 1). Disappointedly, only
trace amounts of product was observed under the above condi-
tions. Taking into account the counter ion effects in gold-
catalyzed reactions [33-35], Ph3PAuOTf, produced from a
combination of Ph3PAuCl and AgOTf in a 1:1 ratio, was
investigated. To our delight, the expected product 2a could be
isolated in 56% yield (Table 1, entry 2). Moreover, a control
experiment was carried out to determine whether AgOTf by
itself could catalyze this transformation. However, no 2a was
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Beilstein J. Org. Chem. 2011, 7, 808–812.
important role in this process. Furthermore, it was also found acid produced the lowest yield, likely due to a competing oxi-
that neither slow addition nor a significant excess of alkyne was dation of the boronic acid by Selectfluor® [27,30]. Gratifyingly,
required to obtain selective and almost quantitative conversion a number of potentially reactive functionalities, such as tertiary
(see Supporting Information File 1). When the reaction was amine, 4-methylbenzenesulfonate, 1,6-enyne and 1,6-diyne,
carried out under an atmosphere of nitrogen (N2) there was a were compatible and remained unaffected, which illustrated the
10% increase in yield (Table 1, entry 8 vs 14). Although the robustness of the catalyst system (Scheme 2, 3–8).
conditions (Table 1, entry 11) seemed the best, this was not the
general case for other substrates. Therefore, the optimum condi- On the basis of these results, a plausible mechanism is outlined
tions were chosen as Ph3PAuCl/AgBF4 as the catalyst, Et3N as in Scheme 3. Initially, unlike traditional C–X oxidative add-
the base and under an atmosphere of nitrogen (Table 1, entry ition as shown by Pd in cross-coupling reactions, the active
14) .
cationic gold(I) species A is oxidized by Selectfluor® to give a
gold(III) species B [26-32,36]. With the aid of base, the reac-
By using the above optimized conditions, the reaction scope tion between B and alkyne affords intermediate C. The weak
was next studied by varying arylboronic acids. As shown in Au–F bond and the strong B–F bond drive the trans-metalation
Scheme 2, functional groups including methyl, chloro, fluoro to produce intermediate D [29,36,37]. Finally, D undergoes
and ester in the para positions of the phenyl ring were tolerated. reductive elimination to give the desired product and gold(I)
Reduced yields were observed with both electron-rich and elec- species A. In addition, C also could experience a five-centered
tron-poor coupling partners (Scheme 2, 2a–f). Arylboronic transition state D', which leads to the C–C bond-forming reac-
acids with electron-withdrawing groups afforded 2c–2e in tion through a bimolecular reductive elimination [30-32].
moderate to good yields. Notably, the slightly electron-defi- Notably, we believed that the key step of this mechanism is the
cient 4-chlorophenylboronic acid gave the best yield. On the generation of cationic gold species B by Selectfluor®. In the
other hand, the more electron-rich 4-methoxyphenylboronic absence of Selectfluor®, no coupling is possible (Table 1, entry
Scheme 2: Scope of the Sonogashira-type cross-coupling reaction (isolated yield). aAgOTf in place of AgBF4. bYield determined by 1H NMR, the
prouduct could not be separated from the unreacted starting material. cAgOTf in place of AgBF4, RT, 36 h.
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Beilstein J. Org. Chem. 2011, 7, 808–812.
6). In a current study, Xu and co-workers have provided strong Acknowledgements
evidence for the oxidation of Au(I) to Au(III) by Selectfluor® in We are grateful to National Natural Science Foundation of
their XPS measurements [36].
China (20972054), the Ministry of Education of China (NCET)
and the Fundamental Research Funds for the Central Universi-
ties.
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