Manganese-catalyzed Sonogashira coupling of aryl iodides

Article abstract of DOI:10.1016/j.tetlet.2016.03.014

An interesting manganese-catalyzed Sonogashira coupling reaction of aryl iodides has been developed. With PEG-400 as the green solvent and under mild reaction conditions, a variety of diarylacetylenes were obtained in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2016.03.014

Accepted Manuscript
Manganese-Catalyzed Sonogashira Coupling of Aryl Iodides
Xinxin Qi, Li-Bing Jiang, Xiao-Feng Wu
PII:
S0040-4039(16)30237-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.03.014
TETL 47402
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
15 February 2016
3 March 2016
4 March 2016
Please cite this article as: Qi, X., Jiang, L-B., Wu, X-F., Manganese-Catalyzed Sonogashira Coupling of Aryl
Iodides, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.03.014
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Graphical Abstract
Manganese-Catalyzed Sonogashira Coupling
of Aryl Iodides
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Xinxin Qi, Li-Bing Jiang, Xiao-Feng Wu*

1
Tetrahedron Letters
Manganese-Catalyzed Sonogashira Coupling of Aryl Iodides
Xinxin Qia , Li-Bing Jianga and Xiao-Feng Wu a,b
a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China.
b Leibniz-Institut für Katalyse e.V. an der Universit Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An interesting manganese-catalyzed Sonogashira coupling reaction of aryl iodides has been
developed. With PEG-400 as the green solvent and under mild reaction conditions, a variety of
diarylacetylenes were obtained in moderate to good yields.
2016 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Manganese
Sonogashira Coupling
Aryl iodides
Cross coupling
Nanoparticles
———
 Corresponding author. e-mail: xiao-feng.wu@catalysis.de

2
Tetrahedron
13
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
DABCO
DABCO
DABCO
DABCO
CH3CN
DMF
1,4-dioxane
0
14
8
Transition metal-catalyzed cross-coupling reactions are
14
15
16
found to be extremely powerful in constructing new carbon-
carbon bonds.1 In all the known name reactions, Sonogashira
coupling reaction,2 which was discovered in the early 1970s has
been emerged as one of the most potent transformations.3 The
corresponding acetylenic products are important synthetic units
in preparation of natural products and biologically active
molecules as well.4 Concerning the importance of this reaction,
tremendous efforts have been put in developing new catalyst
systems during the past decades. In addition to the well-
established palladium-catalyzed systems,5 many other non-
expensive metal catalysts have also been explored and applied
include Cu,6 Fe,7 and Ni catalysts8. However, to our surprise,
manganese as an abundant and toxicologically benign catalyst
was not reported in Sonogashira coupling.9 On the other hand,
poly(ethylene glycol)s (PEGs) have recently drawn much
attention for their applications as green solvents in oxidation,
reduction, substitution, and organometallic reactions.10 As
environmental benign and readily available compounds, PEGs
can substitute volatile or halogenated organic solvents and even
give a better catalytic reactivity than the traditional organic
solvents. Under this background, taking the advantages of
manganese catalysts and PEG solvent into consideration and the
interesting of Sonogashira coupling, we become interested in
filling this missed gap. Herein, we wish to report our recent
developed manganese-catalyzed Sonogashira coupling reaction
with PEG-400 as the solvent. To the best of our knowledge, we
here report the first example of manganese-catalyzed
Sonogashira reaction.
EtOH
14
a Reaction conditions: iodobenzene (1.0 mmol), phenylacetylene (1.0 mmol),
b
Catal. (10 mol%), base (2.5 equiv.), solvent (2 mL), 24 h. GC yield, with
dodecane as the internal standard. c base (2 equiv.).
With the optimized reaction conditions in hand,11 we then
performed the generality and limitation testing (Table 2). Firstly,
a variety of aryl iodides were examined (Table 2, entries 1-18).
Substrates with methyl group substituted at meta-, and para-
position provided the desired products in higher yield while
methyl substituted ortho- at the position gave 31% yield which
due to the steric hindrance (Table 2, entries 2, 4 vs. 3). Ethyl
substitution gave similar yield as the methyl group (Table 2,
entry 5). Electron-deficient groups such as ketone, ester, nitro,
nitrile, and trifluoromethyl groups furnished the corresponding
products in high to excellent yields (Table 2, entries 7-11). Poly-
substituted fluoro group also worked well and gave the desired
diarylacetylene product in 82% yield (Table 2, entry 12). Halo-
substitutions were investigated as well, 78% and 68% yield were
obtained with para-fluoro and ortho-chloro groups while the
para-bromo group gave 20% yield which might due to the
activation of the C-Br bond by the manganese catalyst (Table 2,
entries 13-15). We found that heteroaryl group like pyridyl can
also be tolerated well; the desired product was isolated in
moderate to good yields (Table 2, entries 16 and 17).
Furthermore, biphenyl and naphthyl substitutions can also be
applied as the substrates and achieve the desired diaryl alkynes in
53% and 58% isolated yields (Table 2, entries 18-19).
Encouraged by these results, we went on our study with various
aryl alkynes (Table 2, entries 20-22). Good yields can be
obtained with both methyl- or chloro- substituted
phenylacetylenes. 1-Ethynylcyclohex-1-ene was tested instead of
phenyl acetylene and gave the corresponding (cyclohex-1-en-1-
ylethynyl)benzene in 35% yield (Table 2, entry 23). However,
propargylic substrates failed under our conditions.
Initially, this Sonogashira coupling reaction was carried out
with iodobenzene and phenyl acetylene as the model substrates
using Mn(OAc)2.2H2O as the catalyst in PEG-400 at 70°C with
Et3N as the base (Table 1, entry 1). To our delight, 11% yield of
the desired diphenylacetylene was obtained. Then, different bases
were examined (Table 1, entries 2-5). Notably, DABCO gave the
best result among the tested bases (Table 1, entry 3). The yield of
the desired product can be further improved by increasing the
amount of DABCO to 2.5 equivalents (Table 1, entry 6). While
no better results could be obtained by continuing to increase the
loading of DABCO to 3 equivalents. Subsequently, some other
commonly applied manganese catalysts were tested. Among
them, Mn(OAc)2 afforded the corresponding product in 28%
yields (Table 1, entry 7). No product could be observed neither
with MnF3, MnBr2, MnCl2, Mn(acac)2, nor Mn2(CO)10 as the
catalyst in PEG (Table 1, entries 8-12). Finally, the effects of
organic solvents including CH3CN, DMF, 1,4-dioxane, and
C2H5OH were also tested and no better results can be obtained
compared with PEG-400 (Table 1, entries 13-16). Remarkably,
both air and moisture are tolerable by this new developed
manganese based catalytic system. The same results can be
obtained as well when the reaction was performed under nitrogen
atmosphere.
Table 2. Sonogashira coupling reaction of aryl iodides and terminal aryl alkynes.a
Entry
1
1
2
3
Yield (%)b
65
2
3
4
31
61
70
Table 1. Screening of reaction conditions.a
Entry
1c
Catalyst
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
Mn(OAc)3
Mn(OAc)2
MnF3
MnBr2
MnCl2
Mn(acac)2
Mn2(CO)10
Base
Et3N
DBU
Solvent
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
Yield (%)b
11
1
59
22
1
66
28
0
0
0
0
0
2 c
3 c
4 c
5 c
6
5
6
68
30
DABCO
NaOAc
KOH
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
7
8
9
10
11
12

3
In conclusion, we have developed the first manganese-
catalyzed Sonogashira coupling reaction. Compared with the
traditional Sonogashira reaction conditions, this strategy utilized
a cheap and environmental benign manganese catalyst, and the
reaction was performed with PEG-400 as the green solvent at the
open air under mild reaction conditions. Catalyzed by the in situ
formed manganese nanoparticles, various of substituted
diphenylacetylenes were obtained in moderate to good yields
under standard conditions.
7
8
55
59
9
73
98
Acknowledgments
10
The authors thank NSFC (21472174) and Zhejiang Natural
Science Fund for Distinguished Young Scholars (LR16B020002)
for their financial support. X. -F Wu appreciates the general
support from Professor Matthias Beller in LIKAT.
11
12
75
82
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a
Reaction conditions: aryl iodides (1.0 mmol), aryl acetylenes (1.0 mmol),
Mn(OAc)3.2H2O (10 mol%), DABCO (2.5 equiv.), PEG-400 (2 mL), 70 oC, 19-
24 h. b Isolated yield.

4
Tetrahedron
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7.
11. General procedure: In a 25 mL reaction tube, Mn(OAc)3.2H2O (10
mol%), DABCO (2.5 equiv.) and a stirring bar were added. Then
iodobenzene (1 mmol), phenylacetylene (1 mmol) and PEG-400
(2 mL) were injected by syringe. The reaction tube was closed and
transferred to a 70 oC oil bath for 19-24 hours. After the reaction
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was extracted with ethyl acetate and then concentrated and
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5
1. Manganese-Catalyzed Sonogashira Coupling
2. With PEG-400 as the green solvent
3. Good functional group tolerance and good yields