Efficient palladium-catalyzed cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6] in t-BuOH-H2O using tris(2-morpholinophenyl)phosphine as a ligand

Article abstract of DOI:10.1039/c3ra43279c

A practical method for the synthesis of various aryl/heteroaryl nitriles using non-toxic K₄[Fe(CN)₆] as the cyanide source is described. The cyanation of aryl/heteroaryl bromides with K₄[Fe(CN) ₆] proceeded smoothly in the presence of a Pd/tris(2- morpholinophenyl)phosphine (L5) catalyst under mild conditions. The corresponding aryl/heteroaryl nitriles were produced in good to excellent yields. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra43279c

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Efficient palladium-catalyzed cyanation of aryl and heteroaryl bromides was successfully
achieved by utilizing air-stable and sterically bulky phosphine ligand
tris(2-morpholinophenyl)phosphine (L5).

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DOI: 10.1039/C3RA43279C
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ARTICLE TYPE
Efficient palladium-catalyzed cyanation of aryl/heteroaryl bromides
with K4[Fe(CN)6] in t-BuOH/H2O using tris(2-
morpholinophenyl)phosphine as a ligand
Tao Zou,a Xiujuan Feng,*a Hesong Liu,b Xiaoqiang Yu,a Yoshinori Yamamotoa,c and Ming Bao*a
5
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
(diꢀtertꢀbutylphosphino)ꢀ1ꢀ(2ꢀ(trimethylsilyl)phenyl)ꢀ1Hꢀ
pyrrole.6
A
practical method for the synthesis of various
aryl/heteroaryl nitriles using non-toxic K4[Fe(CN)6] as the
cyanide source is described. The cyanation of aryl/heteroaryl
Based on the above, the development of inexpensive, airꢀ
stable, and readily available bulky phosphane ligands is necessary
50 for aryl/heteroaryl nitrile synthesis through the crossꢀcoupling of
aryl halides with K4[Fe(CN)6]. The sterically bulky P,Nꢀbidentate
ligands L2–L5 with a unique coordination chemistry and
promising effects in the selective synthesis of δꢀlactone have been
recently reported by our group.13 These inexpensive, airꢀstable,
55 and readily available P,Nꢀbidentate ligands were examined in the
palladiumꢀcatalyzed crossꢀcoupling of aryl/heteroaryl bromides
with K4[Fe(CN)6]. The results of such examination are reported
in this paper.
10 bromides with K4[Fe(CN)6] proceeded smoothly in the
presence of a Pd/tris(2-morpholinophenyl)phosphine (L5)
catalyst under mild conditions. The corresponding
aryl/heteroaryl nitriles were produced in good to excellent
yields.
15 1. Introduction
Aryl/heteroaryl nitriles are highly common structural motifs in a
variety of natural products, agrochemicals, pharmaceuticals, dyes,
etc.1 In addition, the cyano group is regarded as a highly valuable
functional group for various chemical transformations, such as
20 hydroformylation, amination, amidination, etc.2 Traditional
synthesis methods for aromatic nitriles are the Sandmeyer
reaction of aryl diazonium salts and the Rosenmundꢀvon Braun
reaction of aryl halides. These reactions require a stoichiometric
amount of CuCN at an elevated temperature (typically 150 °C–
25 250 °C) and usually involve complicated workup procedures.3
Significant achievements have been made for the crossꢀcoupling
of aryl halides or pseudohalides with various cyanide sources
[KCN, NaCN, Zn(CN)2, CuCN, (CH3)2C(OH)CN, (CH3)3SiCN,
and K4[Fe(CN)6] catalyzed by transition metal catalysts (Pd, Ni,
30 Cu).4 Compared with other cyanation reagents, K4[Fe(CN)6], first
introduced by Beller and coꢀworkers,5 exhibits excellent
properties such as low cost and nonꢀtoxicity, and can be handled
without special precautions.6 However, similar to other cyanide
sources, K4[Fe(CN)6] is a potent catalyst poison.7 In fact, an
35 excess amount of cyanide ion can produce CN3PdꢀAr (Scheme 1,
route a), which leads to process termination.8 A sterically bulky
phosphine ligand is highly effective in inhibiting contact between
the transition metal center and the cyanide ions, thus enhancing
the activity of the catalyst at relatively low temperature (Scheme
40 1, route b). To the best of our knowledge, there are limited
literature reports concerning the cyanation of aryl halides using
60 Scheme 1 Ligand steric effects in palladium-catalyzed cross-coupling
of aryl bromides with K4[Fe(CN)6].
2. Results and discussion
In our initial studies, the reaction of 1ꢀbromonaphthalene (1v)
with K4[Fe(CN)6] was chosen as a model to optimize the reaction
65 conditions. The results are shown in Table 1. The commercially
available triphenylphosphine (PPh3, L1) and our previously
developed P,Nꢀbidentate ligands (L2–L5) were initially tested in
tꢀBuOH/H2O (1:1) at 85 °C in the presence of Pd2(dba)3 and
K3PO4 as the catalyst precursor and base, respectively (entries 1–
70 5). Almost no reaction was observed with the ligand L1 (entry 1).
As expected, the use of sterically bulky P,Nꢀbidentate ligands
L2–L5 led to the occurrence of the desired cyanation reaction to
produce 1ꢀnaphthonitrile (2v) in 23%–88% yields (entries 2–5).
Among ligands L2–L5, the more sterically bulky ligand L5
75 proved to be the best ligand. The catalyst precursors [Pd2(dba)3,
Pd(OAc)2, and PdCl2] and bases (K3PO4, Cs2CO3, Na2CO3, and
K2CO3)14 were then screened (entries 5–10). The combination of
Pd2(dba)3 as the catalyst precursor and K2CO3 as the additive was
sterically
bulky
phosphine
ligands
such
as
1,8ꢀ
bis(diisopropylphosphino)triptycene,9 1,1'ꢀbinaphthylꢀ2ꢀyldiꢀtertꢀ
butylphosphine,10
2ꢀ(2ꢀ(dicyclohexylphosphino)phenyl)ꢀ1ꢀ
45 methylꢀ1Hꢀindole,11 di(1ꢀadamantyl)ꢀ1ꢀbutylphosphine,12 and 2ꢀ
This journal is © The Royal Society of Chemistry [year]
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found to display the best activity for the desired cyanation
bromides with K4[Fe(CN)6] were performed in the presence of
reaction and 2v was obtained in 89% yield (entry 10). The effect 35 Pd2(dba)3 as the precatalyst using L5 and K2CO3 as the ligand
of the solvent on the 2v yield was subsequently examined. Trace
amount of 2v was obtained when tertiary butanol (tꢀBuOH) was
used as a single solvent owing to the low solubility of the cyanide
source K4[Fe(CN)6] (entry 11). Low yield of 2v was observed
and the base, respectively, in tꢀBuOH/H2O (1:1) at 85 °C.
The scope of aryl/heteroaryl bromide substrates was then
determined under the optimized reaction conditions (Table 2).
The reactions of aryl bromides 1a–1c bearing electronꢀ
5
when water (H2O) was used instead of tꢀBuOH as the solvent 40 withdrawing groups formyl (CHO), aminocarbonyl (NH2CO),
(entry 12, 14% yield).
and Cl on para position, respectively, were completed within 10
h to produce the corresponding aryl nitriles 2a–2c in 80%–95%
yields (entries 1–3). The reaction of 1,4ꢀdibromobenzene (1d)
needed prolonged reaction time (24 h) to complete. The double
45 cyanation product, terephthalonitrile (2d), was obtained in good
yield (entry 4, 80%). Aryl bromide substrates 1e–1l bearing
strong electronꢀwithdrawing groups [such as F, acetyl (CH3CO),
NO2, CF3, CN, and ethoxycarbonyl (EtO2C)] on para or meta
position exhibited higher reactivities than aryl bromides 1a–1c. It
50 was noteworthy that the desired cyanide products 2d–2h and 2j–
2l were obtained in good to excellent yields even by the use of
0.5 mol% Pd2(dba)3 (entries 5–12, 80%–95%). The reactions of
aryl bromide substrates 1m–1t bearing electronꢀdonating groups
[such as Me, normal butyl (nBu), OH, MeO, NH2, and Me2N] on
55 para or meta position required a relatively long reaction time to
complete. Also good to excellent yields of cyanide products 2m–
2t were observed (entries 13–20, 79%–92%). As expected, 4ꢀ(Nꢀ
acetylamino)phenyl bromide (1u) exhibited higher reactivity in
this type of cyanation reaction than its parent substrate 1s (entry
60 21 vs. entry 19). The reaction of 1u was completed within 5 h to
produce the corresponding product 2u in 92% yield. Naphthyl
and anthryl bromides were then used as substrates to determine
the scope of aryl bromides under the optimized reaction
conditions. The reactions of 1ꢀbromonaphthalene (1v), 1ꢀbromoꢀ
65 4ꢀmethylnaphthalene (1w), 2ꢀbromonaphthalene (1x), and 9ꢀ
bromophenanthrene (1y) proceeded smoothly to give the
corresponding products 2v–2y in 88%–94% yields (entries 22–
25). The reactivities of 5ꢀindolyl bromide substrates were finally
investigated. Both Nꢀfree and Nꢀmethyl 5ꢀindolyl bromides 1z
70 and 1A proved to be suitable substrates for this type of cyanation
reaction. 5ꢀIndolyl nitriles 2z and 2A were obtained in 92% and
86% yields, respectively (entries 26 and 27).
Table 1 Screening of reaction conditionsa
10
Entry Cat. precursor / L Coꢀcat.
Solvent
Yield (%)b
1
2
3
4
5
6
7
Pd2(dba)3 / L1
Pd2(dba)3 / L2
Pd2(dba)3 / L3
Pd2(dba)3 / L4
Pd2(dba)3 / L5
Pd(OAc)2 / L5
PdCl2 / L5
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
none
tꢀBuOH/H2O trace
tꢀBuOH/H2O 23
tꢀBuOH/H2O 48
tꢀBuOH/H2O 72
tꢀBuOH/H2O 88
tꢀBuOH/H2O 45
tꢀBuOH/H2O trace
tꢀBuOH/H2O 88
tꢀBuOH/H2O 85
tꢀBuOH/H2O 89
8
9
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
Pd2(dba)3 / L5
10
11
12
13c
14d
15e
16f
17
18f,h
tꢀBuOH
H2O
trace
14
tꢀBuOH/H2O 89
tꢀBuOH/H2O 90
tꢀBuOH/H2O 92
tꢀBuOH/H2O 94
tꢀBuOH/H2O NRg
tꢀBuOH/H2O 86
K2CO3
a
Reaction conditions: 1ꢀbromonaphthalene (1v, 0.5 mmol, 103.0 mg),
K4[Fe(CN)6] (0.22 mmol, 92.9 mg), Pd catalyst (0.01 mmol, 2 mol%),
ligand (0.02 mmol, 4 mol%), base (1.0 mmol) in tꢀBuOH/H2O (1:1,
b
c
2.0 mL) at 85 °C for 15 h under N2 atmosphere. Isolated yield.
15 0.5 mmol of K2CO3 (69.0 mg) was used. d 0.25 mmol of K2CO3 (34.5 mg)
e
f
was used. 0.125 mmol of K2CO3 (17.3 mg) was used. 0.063 mmol of
g
h
K2CO3 (8.6 mg) was used. No reaction. The reaction was performed
under air.
The successful acquisition of aryl nitriles from the Pdꢀ
catalyzed cyanation of aryl bromides encouraged us to examine
75 the cyanation of heteroaryl bromides. The results are summarized
in Eqs.(1) and (2). The reactions of Nꢀ and Sꢀcontaining
heteroaryl bromides 2ꢀbromopyridine (1B), 3ꢀbromopyridine
(1C), and 3ꢀbromothiophene (1D) occurred under the optimized
reaction conditions to produce the corresponding products 2B,
80 2C, and 2D in 72%, 82%, and 82% yields, respectively.
20 Therefore, the mixed solvent of tꢀBuOH and H2O (1:1) was
employed in the subsequent investigation. The effect of the base
loading on the cyanation reaction was finally examined. Similar
yield as obtained for 2v was observed even though the basic
additive was decreased from an excess to an equimolar ammount
25 (89% yield; entry 13 vs. entry 10). Surprisingly, the yield of 2v
slightly increased with further decreasing base loading (entries
14–16). However, no reaction was observed in the absence of
K2CO3 (entry 17). These results indicated that the use of basic
additive is necessary for the palladiumꢀcatalyzed crossꢀcoupling
30 of aryl halides with K4[Fe(CN)6]. Slightly decreased yield of 2v
was observed when the cyanation reaction was performed under
air (entry 18, 86% yield). Therefore, the subsequent palladiumꢀ
catalyzed crossꢀcoupling reactions of various aryl/heteroaryl
Table 2 Pdꢀcatalyzed crossꢀcoupling of various aryl/heteroaryl bromides
with K4[Fe(CN)6]a
Time/
Entry
1
Substrate 1
Product 2
Yieldb
1a
2a
5 h/95%
2
|
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Br
27
1A
2A
10 h/86%
2
1b
2b
10 h/82%
N
Me
Reaction conditions: aryl bromides (1a–1A, 0.5 mmol), K4[Fe(CN)6]
(0.22 mmol, 92.9 mg), Pd2(dba)3 (0.005 mmol, 1 mol%, 4.6 mg), L5
(4 mol%, 10.3 mg), K2CO3 (12.5 mol%, 8.6 mg) in tꢀBuOH/H2O (1:1,
3
1c
1d
1e
2c
2d
2e
10 h/80%
24 h/80%
10 h/87%
4c
5d
b
c
2.0 mL) at 85 °C under N2 atmosphere. Isolated yield. 0.44 mmol of
d
5
K4[Fe(CN)6] (185.8 mg) was used. 0.5 mol% Pd2(dba)3 (2.3 mg) and
2 mol% L5 (5.2 mg) were used, respectively.
Pd2(dba)3/L5
+
K4[Fe(CN)6]
Br
CN
(1)
(2)
6d
1f
2f
5 h/95%
t-BuOH/H2O (1:1)
N
N
K2CO3, 85 °C, 15 h
1B, 2-Br
1C, 3-Br
2B, 2-CN, 72%
2C, 3-CN, 82%
7 d
8 d
9d
1g
1h
1i
2g
2h
2d
2j
5 h/90%
5 h/92%
5 h/85%
5 h/90%
CN
Br
Pd2(dba)3/L5
+
K4[Fe(CN)6]
t-BuOH/H2O (1:1)
K2CO3, 85 °C, 15 h
S
S
1D
2D, 82%
3. Conclusions
10d
1j
A general and efficient Pdꢀcatalyzed cyanation of aryl/heteroaryl
10 bromides by utilizing the environmentally benign cyanide source
K4[Fe(CN)6] is demonstrated in this work. The novel, sterically
bulky ligand tris(2ꢀmorpholinophenyl)phosphine (L5) proved to
be an effective ligand for this type of Pdꢀcatalyzed cyanation of
aryl/heteroaryl bromides. This ligand is airꢀstable and can be
15 conveniently stored and handled under ambient conditions. The
mild reaction conditions, experimental simplicity, and broad
substrate scope are the features of the general catalytic method
proposed in this paper. Further efforts to extend the application of
these P,Nꢀbidentate ligands in the Pdꢀcatalyzed cyanation of aryl
20 chlorides are currently underway in our laboratory.
11d
12 d
13
1k
1l
2k
2l
5 h/89%
5 h/80%
15 h/82%
1m
2m
14
1n
2n
12 h/88%
15
16
17
18
1o
1p
1q
1r
2o
2p
2q
2r
15 h/79%
12 h/89%
15 h/92%
12 h/84%
4. Experimental section
General Information
CN
All reactions were carried out under a nitrogen atmosphere unless
otherwise noted. Solvents were purified by standard techniques
25 without special instructions. The ligands L2–L5 were prepared
according to the our reported procedures.13 1H and 13C NMR
spectra were recorded on either a Varian Inovaꢀ400 spectrometer
NH2
19
20
1s
1t
2s
2t
12 h/90%
15 h/83%
1
(400 MHz for H, 100 MHz for 13C) or a Bruker Avance IIꢀ400
spectrometer (400 MHz for 1H, 100 MHz for 13C); CDCl3 (or
30 DMSOꢀd6) and TMS were used as a solvent and an internal
standard, respectively. The chemical shifts are reported in ppm
downfield (δ) from TMS, the coupling constants J are given in
Hz. The peak patterns are indicated as follows: s, singlet; d,
doublet; t, triplet; m, multiplet; q, quartet. TLC was carried out on
35 SiO2 (silica gel 60 F254, Merck), and the spots were located with
UV light, iodoplatinate reagent or 1% aqueous KMnO4. Flash
chromatography was carried out on SiO2 (silica gel 60, 200ꢀ300
mesh).
21
22
1u
1v
2u
2v
5 h/92%
15 h/94%
23
1w
2w
15 h/88%
24
25
1x
1y
2x
2y
15 h/90%
15 h/92%
General Procedure for Obtaining Products 2
40 Pd2(dba)3 (4.6 mg, 1 mol%), tris(2ꢀmorpholinophenyl)phosphine
(L5) (10.3 mg, 4 mol%), K2CO3 (8.6 mg, 0.063 mmol), aryl or
heteroaryl bromide (1, 0.5 mmol), and K4[Fe(CN)6]ꢁ3H2O
(92.9 mg, 0.22 mmol) were placed in a 25 mL Schlenk tube with
a magnetic stir bar. The Schlenk tube was evacuated and purged
45 with nitrogen gas three times. Afterward, tꢀBuOH (1.0 mL) and
26
1z
2z
10 h/92%
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H2O (1.0 mL) were sequentially added. The reaction mixture was
7.26 (d, J = 7.8 Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.5, 131.8, 129.6, 119.0, 109.0, 21.6.
heated to 85 ºC. Upon completion of the reaction, the resultant
mixture was allowed to cool to room temperature. Water (10 mL)
was added to the mixture, and the product was extracted with
ethyl acetate (10 mL × 3). The combined extracts were washed
with brine (10 mL × 2), dried over Na2SO4, and evaporated in
vacuo. The residue obtained was purified via silica gel
chromatography (eluent: ethyl acetate/petroleum ether = 1:10, 1:5
or 1:1) to afford aryl or heteroaryl cyanide 2.
60
4-Butylbenzonitrile (2n).18 White solid (70.8 mg, 88% yield).
1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.27 (d, J
= 8.0 Hz, 2H), 2.68–2.64 (m, 2H), 1.60–1.56 (m, 2H), 1.38–1.30
(m, 2H), 0.93 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
148.4, 131.9, 129.0, 119.0, 109.3, 35.6, 32.9, 22.1, 13.7.
5
65
4-Hydroxybenzonitrile (2o).19 White solid (47.8 mg, 79%
1
yield). H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.6 Hz, 2H),
10
4-Formylbenzonitrile (2a).15 White solid (63.2 mg, 95%
6.92 (d, J = 8.6 Hz, 2H), 6.16 (bs, 1H); 13C NMR (100 MHz,
CDCl3) δ 159.7, 134.3, 119.2, 116.4, 103.6.
1
yield). H NMR (400 MHz, CDCl3) δ 10.11 (s, 1H), 8.01 (d, J =
8.0 Hz, 2H), 7.86 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 190.6, 138.7, 132.9, 129.8, 117.7, 117.6.
4-Methoxybenzonitrile (2p).15 Yellow oil (60.1 mg, 89%
1
70 yield). H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.4 Hz, 2H),
6.92 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.9, 134.0, 119.3, 114.8, 103.9, 55.6.
4-Cyanobenzamide (2b).16 Yellow solid (60.7 mg, 82%
1
15 yield). H NMR (400 MHz, DMSOꢀd6) δ 8.21 (s, 1H), 8.01 (d, J
= 8.2 Hz, 2H), 7.93 (d, J = 8.2 Hz, 2H), 7.67 (s, 1H); 13C NMR
(100 MHz, DMSOꢀd6) δ 166.5, 138.3, 132.4, 128.3, 118.4, 113.7.
3-Methoxybenzonitrile (2q).20 White solid (62.1 mg, 92%
1
yield). H NMR (400 MHz, CDCl3) δ 7.28 (dd, J = 7.9 Hz, 1H),
4-Chlorobenzonitrile (2c).15 White solid (55.6 mg, 80% 75 7.10 (d, J = 7.9 Hz, 1H), 7.05 (d, J = 2.0 Hz, 1H), 6.82 (dd, J =
1
yield). H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.4 Hz, 2H),
20 7.47 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 139.3,
133.2, 129.5, 117.8, 110.6.
7.9, 2.0 Hz, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.9, 142.7, 129.8, 119.8, 113.0, 112.9, 55.4.
2-Aminobenzonitrile (2r).20 Yellow solid (50.4 mg, 84%
Terephthalonitrile (2d).15 White solid (55.3 mg, 85% yield).
yield). H NMR (400 MHz, CDCl3) δ 7.40–7.31 (m, 2H), 6.76–
1
1H NMR (400 MHz, CDCl3) δ 7.73 (s, 4H); 13C NMR (100 MHz, 80 6.72 (m, 2H), 4.41 (bs, 2H); 13C NMR (100 MHz, CDCl3) δ 149.5,
CDCl3) δ 133.0, 117.2, 116.9.
134.0, 132.3, 118.0, 117.6, 115.1, 96.0.
25
4-Fluorobenzonitrile (2e).17 Yellow oil (53.5 mg, 87% yield).
1H NMR (400 MHz, CDCl3) δ 7.44–7.40 (m, 2H), 7.07–7.03 (m,
4-Aminobenzonitrile (2s).20 Yellow solid (54.0 mg, 90%
1
yield). H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 8.7 Hz, 2H),
2H); 13C NMR (100 MHz, CDCl3) δ 162.6 (d, JCꢀF = 244.7 Hz),
6.64 (d, J = 8.7 Hz, 2H), 4.20 (s, 2H); 13C NMR (100 MHz,
85 CDCl3) δ 150.4, 133.7, 120.1, 114.3, 99.9.
1
136.6, 128.7 (d, 3JCꢀF = 8.0 Hz), 115.9 (d, 2JCꢀF = 21.3 Hz), 114.9.
4-Acetylbenzonitrile (2f).15 Yellow solid (69.8 mg, 95%
4-(Dimethylamino)benzonitrile (2t).15 White solid (61.4 mg,
1
1
30 yield). H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.5 Hz, 2H),
7.79 (d, J = 8.5 Hz, 2H), 2.66 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 196.5, 139.9, 132.5, 128.6, 117.9, 116.3, 26.7.
4-Nitrobenzonitrile (2g).15 Yellow solid (67.5 mg, 90% yield).
1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.4 Hz, 2H), 7.92 (d, J
35 = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 150.1, 133.6,
124.4, 118.4, 116.9.
83% yield). H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 9.2 Hz,
2H), 6.62 (d, J = 9.2 Hz, 2H), 3.03 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 152.3, 133.3, 120.7, 111.3, 97.1, 39.9.
90
N-(4-cyanophenyl)acetamide (2u).10 Yellow solid (74.5 mg,
92% yield). 1H NMR (400 MHz, DMSOꢀd6) δ 10.35 (s, 1H),
7.76–7.70 (m, 4H), 2.08 (s, 3H); 13C NMR (100 MHz, DMSOꢀd6)
δ 169.0, 143.4, 133.0, 119.0, 118.9, 104.7, 24.1.
4-(Trifluoromethyl)benzonitrile (2h).17 Yellow solid (79.6
1-Naphthonitrile (2v).15 Yellow oil (71.9 mg, 94% yield). 1H
1
mg, 92% yield). H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 95 NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J =
Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
8.4 Hz, 1H), 7.89–7.85 (m, 2H), 7.65–7.56 (m, 2H), 7.50–7.46 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 133.3, 132.9, 132.6, 132.3,
128.7, 128.6, 127.6, 125.1, 125.0, 117.9, 110.2.
2
40 143.3, 130.4 (q, JCꢀF = 32.4 Hz), 127.7, 126.1, 126.0, 124.2 (q,
1JCꢀF = 270.4 Hz).
Ethyl 4-cyanobenzoate (2j).15 Yellow solid (79.7 mg, 90%
4-Methyl-1-naphthonitrile (2w).21 Yellow oil (73.5 mg, 88%
1
1
yield). H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 100 yield). H NMR (400 MHz, CDCl3) δ 8.13–8.11 (m, 1H), 7.95–
7.73 (d, J = 8.4 Hz, 2H), 4.41 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 7.2
45 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.9, 134.2, 132.1,
130.0, 118.0, 116.2, 61.7, 14.2.
7.93 (m, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.58–7.52 (m, 2H), 7.22
(d, J = 7.4 Hz, 1H), 2.63 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
141.1, 132.4, 132.3, 132.2, 128.2, 127.4, 125.9, 125.8, 124.8,
3-(Trifluoromethyl)benzonitrile (2k).17 Yellow oil (77.0 mg,
118.2, 108.4, 20.0.
1
1
89% yield). H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.90– 105 2-Naphthonitrile (2x).17 Yellow oil (68.9 mg, 90% yield). H
7.87 (m, 2H), 7.70–7.66 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.4 Hz, 1H), 8.07 (d, J =
8.4 Hz, 1H), 7.93–7.89 (m, 2H), 7.69–7.59 (m, 2H), 7.51 (dd, J =
7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 133.4, 133.0, 132.8,
132.5, 128.8, 128.7, 127.7, 125.3, 125.0, 118.0, 110.3.
2
50 135.3, 131.9 (q, JCꢀF = 33.5 Hz), 129.9, 129.4, 129.4, 128.9,
122.8 (q, 1JCꢀF = 271.0 Hz), 117.3, 113.4.
3-Nitrobenzonitrile (2l).7 White solid (60.0 mg, 80% yield).
1H NMR (400 MHz, CDCl3) δ 8.47–8.46 (m, 1H), 8.43–8.40 (m, 110 Phenanthrene-9-carbonitrile (2y).22 Yellow oil (93.4 mg,
1H), 7.96–7.94 (m, 1H), 7.72–7.67 (m, 1H); 13C NMR (100 MHz,
55 CDCl3) δ 137.8, 130.8, 127.7, 127.3, 122.2, 116.7, 114.2.
4-Methylbenzonitrile (2m).15 Colorless oil (48.8 mg, 82%
92% yield). H NMR (400 MHz, CDCl3) δ 8.50–8.48 (m, 2H),
8.14–8.12 (m, 1H), 8.03 (s, 1H), 7.75–7.73 (m, 1H), 7.67–7.51
(m, 4H); 13C NMR (100 MHz, CDCl3) δ 135.6, 131.7, 129.9,
129.8, 129.7, 129.5, 128.9, 128.3, 128.1, 127.7, 126.1, 123.1,
115 122.9, 118.0, 109.4.
1
1
yield). H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.8 Hz, 2H),
4
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DOI: 10.1039/C3RA43279C
1H-indole-5-carbonitrile (2z).7 Yellow solid (65.3 mg, 92%
yield). 1H NMR (400 MHz, CDCl3) δ 8.73 (bs, 1H), 7.89 (s, 1H),
7.38 (d, J = 8.4 Hz, 1H), 7.33–7.30 (m, 1H), 7.26–7.24 (m, 1H),
6.50 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 137.7, 127.7, 126.7,
126.5, 124.9, 121.1, 112.2, 103.4, 102.6.
2008, 3351; (d) See Ref. 3b; (e) H. Jiang, J. Jiang, H. Wei and C. Cai,
Catal. Lett., 2013, DOI 10.1007/s10562ꢀ013ꢀ1057ꢀ8; (f) G.ꢀY.
Zhang, J.ꢀT. Yu, M.ꢀL. Hu and J. Cheng, J. Org. Chem., 2013, 78,
2710; (g) M. Guo, J. Ge, Z. Zhu and X. Wu, Lett. Org. Chem., 2013,
10, 213; (h) Z. Wang and S. Chang, Org. Lett., 2013, 15, 1990.
T. Schareina, A. Zapf and M. Beller, Chem. Commun., 2004, 1388.
T. Schareina, R. Jackstell, T. Schulz, A. Zapf, A. Cotté, M. Gotta and
M. Beller, Adv. Synth. Catal., 2009, 351, 643.
65
70
5
5
6
1-Methyl-1H-indole-5-carbonitrile (2A).17 Yellow solid (67.1
mg, 86% yield). 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H),
7.33–7.20 (m, 2H), 7.07 (d, J = 3.2 Hz, 1H), 6.45 (d, J = 3.2 Hz,
1H), 3.70 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 138.2, 131.4,
7
8
M. Shevlin, Tetrahedron Lett., 2010, 51, 4833.
(a) K. D. Dobbs, W. J. Marshall and V. V. Grushin, J. Am. Chem.
Soc., 2007, 129, 30; (b) M. Sundermeier, A. Zapf and M. Beller,
Angew. Chem., Int. Ed., 2003, 42, 1661.
10 128.2, 126.5, 124.5, 121.1, 110.2, 102.3, 102.2, 33.2.
Picolinonitrile (2B).23 White solid (37.4 mg, 72% yield). H
NMR (400 MHz, CDCl3) δ 8.76 (d, J = 4.8 Hz, 1H), 7.97–7.93
(m, 1H), 7.79–7.77 (m, 1H), 7.64–7.61 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 150.7, 136.9, 133.3, 128.3, 126.8, 116.9.
1
9
O. Grossman and D. Gelman, Org. Lett., 2006, 8, 1189.
75 10 A. Littke, M. Soumeillant, R. F. Kaltenbach III, R. J. Cherney, C. M.
Tarby and S. Kiau, Org. Lett., 2007, 9, 1711.
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Int. Ed., 2010, 49, 8918; (b) P. Y. Yeung, C. M. So, C. P. Lau and F.
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80 12 T. Schareina, A. Zapf, W. Mägerlein, N. Müller, M. Beller,
Tetrahedron Lett., 2007, 48, 1087–1090.
13 Y. Dai, X. Feng, B. Wang, R. He and M. Bao, J. Organomet. Chem.,
2012, 696, 4309.
14 Base was often regarded as effective additive in Pdꢀcatalyzed
cyanation. See: Ref. 3b.
15. R. S. Jensen, A. S. Gajare, K. Toyota, M. Yoshifujia and F. Ozawa,
Tetrahedron Lett., 2005, 46, 8645.
16 K. Ramesh, S. N. Murthy, K. Karnakar, K. H. V. Reddy, Y. V. D.
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20 A. V. Ushkov and V. V. Grushin, J. Am. Chem. Soc., 2011, 133,
10999.
1
15
Nicotinonitrile (2C).17 Yellow oil (42.6 mg, 82% yield). H
NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.77–8.76 (m, 1H),
7.92–7.91 (m, 1H), 7.40–7.37 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 153.1, 152.6, 139.4, 123.8, 116.6, 110.3.
Thiophene-3-carbonitrile (2D).17 Yellow oil (44.7 mg, 82%
1
85
90
20 yield). H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 3.0, 1.1 Hz,
1H), 7.43 (dd, J = 5.1, 3.0 Hz, 1H), 7.30 (dd, J = 5.1, 1.1 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 135.4, 128.6, 127.2, 115.1, 110.6.
Acknowledgements
We are grateful to the National Natural Science Foundation of
25 China (21073025) for financial support. This work was partly
supported by the Fundamental Research Funds for the Central
Universities (DUT13LK03).
21 J. Y. Lan and G. B. Schuster, J. Am. Chem. Soc., 1985, 107, 6710.
22 L.ꢀH. Li, Z.ꢀL. Pan, X.ꢀH. Duan and Y.ꢀM. Liang, Synlett, 2006, 13,
Notes and references
a State Key Laboratory of Fine Chemicals, Dalian University of
30 Technology, Dalian 116023, China. Fax: +86ꢀ0411ꢀ84986180; Tel: +86ꢀ
0411ꢀ84986181; Eꢀmail: fengxiujuan@dlut.edu.cn, mingbao@dlut.edu.cn
b Department of Dermatology & Venereology, The First Hospital of Jilin
University, Changchun 130021, China
100
2094.
23 H.ꢀJ. Cristau, A. Ouali, J.ꢀF. Spindler and M. Taillefer, Chem. Eur.
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c WPIꢀAIMR (WPIꢀAdvanced Institute for Materials Research), Tohoku
35 University, Sendai 980ꢀ8577, Japan
† Electronic Supplementary Information (ESI) available: Experimental
procedures and spectroscopic data for isolated compounds. See
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4
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