Catalytic cyanation of aryl iodides using DMF and ammonium bicarbonate as the combined source of cyanide: A dual role of copper catalysts

Article abstract of DOI:10.1039/c3cc47926a

Cu(ii)-catalyzed cyanation of aryl iodides has been developed using DMF and ammonium bicarbonate as the combined source of cyanide. It is assumed that copper is involved both in the generation of CN units from DMF-ammonia and in the cyanation of aryl halides. A range of electron-rich and fused (hetero)aryl iodides underwent cyanation resulting in moderate to good yields.

Full text of DOI:10.1039/c3cc47926a

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Catalytic cyanation of aryl iodides using DMF and
ammonium bicarbonate as the combined source
of cyanide: a dual role of copper catalysts†
Cite this:DOI: 10.1039/c3cc47926a
Received 15th October 2013,
Accepted 30th October 2013
ab
ab
Amit B. Pawar and Sukbok Chang*
DOI: 10.1039/c3cc47926a
www.rsc.org/chemcomm
Cu(II)-catalyzed cyanation of aryl iodides has been developed using reported the Cu-mediated cyanation of aryl C–H bonds using nitro-
25
DMF and ammonium bicarbonate as the combined source of methane as a cyano precursor. In this regard, we discovered that the
cyanide. It is assumed that copper is involved both in the generation cyano unit ‘‘CN’’ can be generated in situ from the combined source
of ‘‘CN’’ units from DMF–ammonia and in the cyanation of aryl of DMF and aqueous ammonia under copper-mediated oxidative
halides. A range of electron-rich and fused (hetero)aryl iodides conditions for the cyanation of the aryl C–H bond using a palladium
26a
underwent cyanation resulting in moderate to good yields.
catalyst. An isotope study disclosed that the carbon atom of -CN
comes from the dimethyl amino group of DMF and the nitrogen
Nitrile is a ubiquitous building unit used in synthetic chemistry, atom originates from ammonia. Subsequently, NH I and DMF were
4
and it can readily be converted to various functional groups such as also utilized as the combined source of cyanide in the cyanation of
26b
26c
aldehydes, amides, amines, amidines, tetrazoles, or other carboxy aryl boronic acids and electron-rich arenes, indoles and organo-
1
26d
variants. Nitriles are also present in diverse natural products and silanes. In this case, ammonium iodide plays a dual role as an
industrially important compounds such as pharmaceuticals, agro- iodinating reagent as well as the nitrogen source of the ‘‘CN’’ unit.
2
3
4
chemicals, and dyes. Sandmeyer and Rosenmund-von Braun
Although our cyanation approach was proved to be unique and
reactions are the classical methods for the introduction of cyano versatile, one of the main drawbacks was the requirement of more
groups, in which CuCN is employed as a cyanating agent in than stoichiometric amounts of copper species in each procedure.
5
stoichiometric amounts. Procedures based on transition metals
Some additional elegant cyanation approaches have also been
27
28
including Pd, Ni, or Cu species also serve as attractive and reported by others by employing DMF, formamide or analogous
29
economical synthetic routes to the preparation of nitriles. In this combined sources to produce the cyano group in situ. Again, the
6
7
approach, the anionic cyanide sources used include NaCN, KCN,
main limitation of the above-mentioned procedures is the use of
]. A major drawback of this process is the more than stoichiometric amounts of copper species. This led us to
requirement of toxic cyanating agents along with the formation of investigate the development of a cyanation method, being catalytic
8
9
2 4 6
Zn(CN) , and K [Fe(CN)
30
metal wastes in a stoichiometric amount. This issue has recently in copper. Herein, we describe our preliminary results of the
been addressed in a new approach that employs non-metallic Cu-catalyzed cyanation of aryl iodides using NH HCO and DMF
4
3
organic precursors bearing a cyano unit in their molecular struc- as the combined source of ‘‘CN’’ units.
1
0
11
ture. These organo precursors include acetone cyanohydrine,
We initiated our studies by examining a catalytic reaction of
TMSCN, acetonitrile, malononitrile, benzyl cyanide, benzyl p-iodoanisole (1a) using NH HCO and DMF as the combined
12
13
14
15
4
3
16
17
18
19
20
thiocyanate, phenyl cyanate, DDQ, AIBN, ethyl isocyanate,
source of ‘‘CN’’ units using Cu(NO ) Á3H O (20 mol%). We envi-
3
2
2
2
1
22
tert-butyl isocyanide,
N-cyanobenzimidazole,
bromide, or N-cyano-N-phenyl-p-toluenesulfonamide (NCTS).
On the other hand, in the past few years, an additional research the ESI† for details). We were pleased to observe that Ag CO worked
cyanogen sioned that the key to success would be the choice of a suitable
23
24
oxidant, and therefore, a wide range of oxidants were screened (see
2
3
direction for cyanation has been scrutinized by utilizing organic as an effective oxidant under the initial catalytic conditions (Table 1,
compounds that generate ‘‘CN’’ units in situ. For instance, Yu et al. entry 1). It was also found that a sub-stoichiometric amount of silver
species could facilitate cyanation under an O atmosphere using
2
a
Center for Catalytic Hydrocarbon Functionalizations (IBS), Daejeon 305-701,
1
0 mol% of copper(II) nitrate (entry 2). While the reaction was best
performed at 150 1C, lowering the reaction temperature resulted in a
decreased product yield (entry 3). Various silver salts such as Ag O,
AgOAc and AgOTf were less effective when compared to Ag CO
(entries 4–6). In addition, copper species (e.g. CuI or CuSO ) other
Korea. E-mail: sbchang@kaist.ac.kr
b
Department of Chemistry, Korea Advanced Institute of Science & Technology
2
(
KAIST), Daejeon 305-701, Korea
†
Electronic supplementary information (ESI) available: Experimental details and
2
3
copies of spectra. See DOI: 10.1039/c3cc47926a
4
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a
Table 1 Optimization of reaction conditions
(1)
b
Entry
[Cu] (mol%)
Oxidant (equiv.)
Yield (%)
was found that the reaction efficiency was still maintained high
using these substrates (2d–2g). However, cyanation of aryl bro-
mides did not occur under the present conditions.
We subsequently scrutinized the cyanation of electronically
neutral or deficient (hetero)aryl iodides. When the above optimal
conditions were applied to 1-iodonaphthalene (3) as a model
substrate, cyanation was observed to be sluggish, leading to only
moderate product yield [4a, 50%, eqn (1)]. As a result, we decided
to search for any accelerating effects of certain suitable external
ligands. After screening various monodendate and bidentate
1
2
3
4
5
6
7
8
9
Cu(NO
Cu(NO
Cu(NO
Cu(NO
Cu(NO
Cu(NO
3
3
3
3
3
3
)
)
)
)
)
)
2
2
2
2
2
2
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
2
2
2
2
2
2
O (20)
O (10)
O (10)
O (10)
O (10)
O (10)
Ag
Ag
Ag
Ag
2
2
2
2
CO
CO
CO
3
3
3
(1.5)
(0.4)
(0.4)
85
c
80(76)
d
66
O (0.4)
67
44
62
26
16
AgOAc (0.4)
AgOTf (0.4)
CuI (10)
CuSO (10)
Ag
Ag
Ag
Ag
Ag
—
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
(0.4)
(0.4)
(0.4)
(0.4)
(0.4)
4
e
Cu(NO
Cu(NO
—
3
)
)
2
Á3H
2
2
O (10)
O (10)
50
f
10
11
12
3
2
Á3H
9
0
16
Cu(NO
3
)
2
Á3H
2
O (10)
a
Reaction conditions: 1a (0.3 mmol), NH
balloon at 150 1C. H NMR yield
4 3
HCO
(2.0 equiv.), oxidant, and nitrogen ligands (see the ESI† for details), it was found that
b 1
[
Cu] in DMF (1.5 mL) under an O
2
2-aminopyridine displayed the highest ligand effects in the
c
(internal standard: 1,1,2,2-tetrachloroethane). Isolated yield in parenth-
d
e
f
presence of an excess amount of silver species.
2
eses. Run at 140 1C. Under an air atmosphere. Under a N atmosphere.
The new cyanation conditions containing an external ligand,
than Cu(NO ) Á3H O displayed significantly reduced reactivity 2-aminopyridine, were subsequently applied to a wide range of
3
2
2
(
entries 7 and 8). When the reaction was carried out under an air or pertinent substrates (Table 3). The reaction of fused aryl iodides
nitrogen atmosphere, the desired product 2a was obtained in 50% took place smoothly to afford the corresponding nitriles in good
and 9% yields, respectively, suggesting that O
plays an important yields (4a–4d). 2-Iodofluorenone was reacted under the present
2
role in this transformation (entries 9 and 10). As predicted, cyana- conditions to deliver 4e in moderate yield. Aryl iodides substituted
tion did not take place in the absence of copper species (entry 11). with a phenyl group at different positions were cyanated without
Cyanation was observed to be catalytic only in the presence of Ag
2
CO
3
difficulty (4f–4g). p-Iodobenzophenone and 2-iodoanthraquinone
(
entry 12). In addition, although different carbon sources were tested, underwent the desired cyanation in acceptable yields (4h and 4i,
they were much less effective for catalytic cyanation under otherwise respectively). However, the reaction of aryl iodides bearing an ester
identical conditions: DMSO (o5%), N,N-dimethylacetamide (DMA,
2
2%), N-methyl-2-pyrrolidone (NMP, 11%) and 1,3-dimethyl-3,4,5,6-
a
Table 3 Cu-catalyzed cyanation of various aryl iodides
tetrahydro-2-pyrimidinone (DMPU, 27%) (see the ESI† for details).
With the optimized catalytic conditions in hand, we next investi-
gated the substrate scope of electron-rich aryl iodides (Table 2). The
reaction proceeded efficiently with o-iodoanisole to furnish
the corresponding nitrile 2b in 72% yield using 10 mol% of
Cu(NO ) Á3H O and 0.4 equiv. of Ag CO . p-Benzyloxyiodobenzene
3
2
2
2
3
underwent cyanation with 67% yield, but the yield of 2c was
further improved to 75% by employing 1.0 equiv. of Ag CO . Aryl
2
3
iodides bearing multiple substituents were also examined, and it
a
Table 2 Cu-catalyzed cyanation of electron-rich aryl iodides
a
a
Reaction conditions: 1 (0.3 mmol), Cu(NO
3
)
2
Á3H
c
2
O (20 mol%), NH
4
HCO
3
Reaction conditions: 3 (0.3 mmol), NH
CO (2.0 equiv.), 2-aminopyridine (20 mol%) in DMF
(1.5 mL) under an O
4
HCO
3
(2.0 equiv.), Cu(NO
3
)
2
Á3H
2
O
(2.0 equiv.), Ag
2
CO (1.0 equiv.) in DMF (1.5 mL) under an O
3
2
balloon at (20 mol%), Ag
(40 mol%).
2
3
b
1
50 1C for 24 h. Cu(NO
3
)
2
2
Á3H O (10 mol%). Ag
2
CO
3
2
balloon at 150 1C for 24 h.
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0 J. Kim, H. J. Kim and S. Chang, Angew. Chem., Int. Ed., 2012, 51, 11948.
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7–9
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(
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4 3
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2
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2
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2 3
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1
4
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3
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4 3
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This research was supported by the Institute for Basic Science (IBS).
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