Rhodium-catalyzed direct C-H bond cyanation of arenes with isocyanide

Article abstract of DOI:10.1021/jo500087g

An efficient rhodium-catalyzed regioselective C-H bond cyanation of arenes was developed using tert-butyl isocyanide as the cyanide source. A wide range of (hetero)aryl and cycloalkenyl nitriles could be afforded with high regioselectivity and good functional group tolerance.

Full text of DOI:10.1021/jo500087g

Note
pubs.acs.org/joc
Rhodium-Catalyzed Direct C−H Bond Cyanation of Arenes with
Isocyanide
Xiaohu Hong,† Hao Wang,† Guangyin Qian,† Qitao Tan,† and Bin Xu*,†,‡,§
†School of Materials Science and Engineering, Department of Chemistry, Innovative Drug Research Center, Shanghai University,
Shanghai 200444, China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
§Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University,
Shanghai 200062, China
S
* Supporting Information
ABSTRACT: An efficient rhodium-catalyzed regioselective
C−H bond cyanation of arenes was developed using tert-
butyl isocyanide as the cyanide source. A wide range of
(hetero)aryl and cycloalkenyl nitriles could be afforded with
high regioselectivity and good functional group tolerance.
Scheme 1. Metal-Catalyzed C−H Bond Cyanation Using
tert-Butyl Isocyanide
ryl nitriles are structural motifs that frequently occurred as
Athe core structures of many pharmaceuticals and agro-
chemicals.1 In addition, the widespread synthetic utility of
nitrile moiety is highlighted by serving as a versatile building
block and by its possible nitrile transformations leading to the
formation of aldehydes, amides, amidines, amines, carboxyl
derivatives and heterocycles.2,3 The early synthetic efforts for
the preparation of organonitriles include two traditional
methods such as the Sandmeyer reaction4 and Rosenmund−
von Braun reaction,5 which use stoichiometric amounts of
copper cyanide as “CN” source. Recently, a variety of protocols
on the basis of transition metal-catalyzed cyanation of aryl
halides6−11 or direct cyanation of C−H bonds12−28 have been
developed. Among them, however, some of these trans-
formations suffered from their intrinsic drawbacks, including
use of toxic reagents, poor functional group tolerance, and the
need for tedious and costly preactivation steps. Compared with
some toxic metal cyanide sources M−CN (M = K, Na, Zn) and
user-friendly cyanation reagent K4[Fe(CN)6], nonmetallic
cyano-group sources have been fully disclosed such as using
DMF,22,23 DMSO24 and N-cyano-N-phenyl-p-methylbenzene-
sulfonamide (NCTS)25,26 as the cyano sources, which would
avoid producing stoichiometric metal waste and hazardous
HCN gas.21−30 Recently, we have reported a palladium-
catalyzed oxidative cyanation reaction using tert-butyl iso-
cyanide as the cyanide source, in which a regioselective C2 and
C3 cyanation of indoles could be achieved (Scheme 1).31
Independently, Zhu and co-workers also disclosed the similar
C3 cyanation of indoles.32 In contrast to many reports on
palladium-catalyzed and copper-mediated cyanation reactions,
rhodium(III)-catalyzed C−H cyanation reaction has been much
less explored,26,33 which has proved to be a good complement
to other transition metals in terms of substrate scope and
functional group compatibility. In this event, to expand the
scope and utility of C−H cyanation reactions using nonmetallic
cyano-group sources, the development of rhodium-catalyzed
highly efficient, selective, and practical C−H bond cyanation
methods continues to be an active and rewarding research area.
Pyrimidines and their derivatives have attracted many
attentions as important motifs in materials and medicinal
chemistry.34,35 Thus, the development of readily available
functionalized arylpyrimidines in a regioselective manner would
find significant application in preparing this class of molecules.
Previously, we have successfully demonstrated the feasibility of
specific chelation effect of a pyrimidyl group in the metal-
catalyzed C−H bond functionalization reactions to afford
Received: January 14, 2014
Published: March 7, 2014
© 2014 American Chemical Society
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Note
halogenated36,37 and acetoxylated38 arylpyrimidines regioselec-
tively, as well as C2 cyanated N-pyrimidyl indoles31 and
unsymmetrical N-pyrimidyl ureas39 in good to excellent yields.
However, attempting to achieve cyanated arylpyrimidine
products in the previous palladium-catalyzed cyanation reaction
gave unsatisfactory results; for instance, ortho-monocyanated
phenylpyrimidine 2a was afforded in only 27% yield with 54%
conversion of 2-phenylpyrimidine 1a after reacting for 24 h at
130 °C.31 In this context, a general, direct and selective C−H
bond cyanation method would be highly desirable. Herein, we
report a novel rhodium-catalyzed regioselective cyanation of
(hetero)arylpyrimidines using tert-butyl isocyanide as an
effective “CN” source. Furthermore, this protocol could be
successfully applied to the vinyl C−H bond cyanation of
cycloalkenes with high regioselectivity which, to our knowledge,
represents the first example of metal-catalyzed direct C−H
cyanation reaction of olefinic double bonds using isocyanide
(Scheme 1).
while DMF, dioxane or anisole gave much lower yields (entries
5−7), and toluene or acetic acid failed to give any product
(entries 8−9). Lowering the reaction temperature gave
diminished yields with lower reaction conversion (entries
10−11). Decreased yield was afforded without using AgSbF6
(entry 12), and the reaction became sluggish to give 2a in 32%
yield in the absence of [RhCp*Cl2]2 and AgSbF6, which
indicated that rhodium catalyst was crucial for this cyanation
reaction (entry 13).
With the optimized reaction conditions in hand, we sought
to explore the reaction with a range of substrates as summarized
in Scheme 2. In general, this reaction was highly efficient and
showed excellent monoselectivity when substrates bearing
para-, meta-, ortho-, or multisubstitutions on the aryl ring
were employed. Substrates with electron-donating substitution
at para- or meta-position could afford ortho-cyanated products
in good to excellent yields in short reaction time (2b−2d, 2j−
2k), while longer time was needed to complete the reaction for
those substrates with electron deficient groups (2e−2i, 2l−2n).
The presence of a ortho-methyl group on the phenyl ring
resulted in the corresponding cyanated product 2o in 47% yield
and disubstituted substrate could also give 2p in 86% yield.
Furthermore, this cyanation reaction could proceed well for
trisubstituted substrate with high steric hindrance, for which the
combination of Cu(OAc)2·H2O (2.0 equiv), PivOH (1.0 equiv)
and H2O (2.5 equiv) was found to be superior to Cu(TFA)2
and AgSbF6, affording cyanated product 2q in 90% yield after
reacting for 36 h.
At the outset of this investigation, we commenced our study
by exploring the reaction of 2-phenylpyrimidine (1a) with tert-
butyl isocyanide in the presence of [RhCp*Cl2]2 (2.0 mol %) in
DCE using Cu(OAc)2·H2O as an oxidant. Intriguingly, the
ortho-cyanated product 2a was isolated in 51% yield with 57%
conversion of 1a after reacting for 48 h at 130 °C (Table 1,
a
Table 1. Optimization of Reaction Conditions
To further explore the generality and scope of this approach,
a variety of substrates were investigated. As illustrated in
Scheme 3, substrates with substituents on the pyrimidinyl ring
also afforded cyanated products in moderate to good yields
(4a−4d). This cyanation protocol was not limited to phenyl
ring, the α- and β-pyrimidyl naphthalenes could afford 2- and 3-
cyanation products 4e and 4f in 65% and 63% yield,
respectively, and phenanthrene could be functionalized in the
10-position to give cyanated product 4g. Heteroarenes such as
pyrrole, indole and carbazole were also found to be suitable
substrates and afforded the cyanated products in good yields
(4h−4j). Moreover, this newly established protocol could
extend to benzo[h]quinoline and gave the corresponding cyano
product 4k in 98% yield. However, 2-phenyl substituted
adenine or its derivatives such as 9-benzyl-2-phenyl-9H-purin-
6-amine failed to give any cyanated products. Notably, no
significant double cyanation products or regioisomers could be
isolated under the standard conditions.
It should be noted that the substrate 3c, which has two
potential ortho-cyanation positions derived from the coordina-
tion of rhodium and two nitrogen atoms, gave exclusive
product 4c in 41% yield (Scheme 4). The identity of 4c was
determined by spectra analysis and further confirmed by X-ray
crystallographic analysis.40
Although there are many reports involving C−H cyanation
of arenes under the assistance of various directing groups, fewer
examples were successfully investigated through direct C−H
cyanation of olefinic double bonds, which need prefunctional-
ized substrates or multistep reactions.41,42 We were pleased to
find that the vinyl C−H bond in 2-cyclohexenylpyrimidine 5a
could be also cyanated selectively to give its corresponding
cyanide product 6a in 64% yield (Scheme 5). The substrate
scope was extended further to include 2-cycloalkenylpyridines
providing direct access to corresponding cycloalkenyl nitriles in
good yields that incorporate cyclopentenyl (6b) and cyclo-
b
additive
time
(h)
yield
(%)
entry
Cu source
(mol %)
solvent
c
1
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
−
DCE
48
38
3
51
2
PivOH (100)
PivOH (100)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
AgSbF6 (8)
−
DCE
82
3
DCE
62
4
DCE
3
84
5
DMF
dioxane
anisole
toluene
HOAc
DCE
8
22
6
8
33
7
4
17
8
24
24
24
24
3
trace
trace
9
d
10
11
12
13
23
e
DCE
69
DCE
79
f
−
DCE
6
32
a
Reaction conditions: 1a (0.2 mmol), t-BuNC (2.0 equiv),
[RhCp*Cl2]2 (2 mol %), Cu salt (2.0 equiv) and additive (8 mol
%) in solvent (1.0 mL), air, sealed tube, 130 °C. Cu(TFA)2 = cupric
trifluoroacetate. DCE = 1,2-dichloroethane. Isolated yield. With 57%
b
c
d
e
conversion of 1a. At 80 °C, with 48% conversion of 1a. At 120 °C,
f
with 86% conversion of 1a. In the absence of [RhCp*Cl2]2.
entry 1). Better result could be achieved by addition of 1.0
equiv of PivOH after reacting for 38 h (entry 2). The use of
Cu(TFA)2 instead of Cu(OAc)2·H2O could significantly reduce
the reaction time from 38 to 3 h although with decreased yield
(entry 3). However, the use of AgSbF6 instead of PivOH as an
additive could dramatically promote this reaction and afford 2a
in 84% yield within 3 h (entry 4). Among all other solvents
tested, DCE proved to be the most efficient one (entry 4),
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Note
a b
,
Scheme 2. Cyanation of Various Arylpyrimidines
a
Reaction Conditions: 1a−q (0.4 mmol), t-BuNC (2.0 equiv), [RhCp*Cl2]2 (2 mol %), AgSbF6 (8 mol %), Cu(TFA)2 (2.0 equiv), DCE (2.0 mL),
b
c
air, sealed tube, at 130 °C. Isolated yield. Cu(OAc)2·H2O (2.0 equiv), PivOH (1.0 equiv), and H2O (2.5 equiv) were used instead of Cu(TFA)2
and AgSbF6.
hexenyl (6c) functionality (Scheme 5). This reaction protocol
could be very useful in the synthesis of natural products using
cycloalkenyl carbonitriles as key intermediates.43
dimethylphenyl-isocyanide and cyclohexylisocyanide were
employed, while tertiary isocyanide bearing a β-hydrogen
such as 1-adamantanylisocyanide (AdNC) could afford
cyanation product 2a in 56% yield (eq 4), which indicated
that tertiary isocyanides (AdNC vs t-BuNC) might be crucial to
give cyanation products through β-alkyl elimination.
Although the detailed reaction mechanism remains to be
clarified, a plausible mechanism for this reaction was proposed
on the basis of the above results (Scheme 7). With the direction
of pyrimidyl group, electrophilic rhodation at the ortho position
affords a rhodacycle A.46 Then the following insertion of
isocyanide generates an intermediate B,47 which undergoes β-
tert-butyl elimination to give the product 2a together with
expulsion of isobutene.31,32 The formed Rh(I) species is
reoxidized by Cu(II), which could be derived from the
oxidation of Cu(I) with oxygen and regenerating the Rh(III)
catalyst.
To define the possible intermediates and pathway of this
reaction, several control experiments were carried out (Scheme
6). When 1a was reacted with tert-butyl cyanide under the
standard reaction conditions, only trace amount of 2a was
observed (eq 1), which suggested that the reaction might not
go through the tert-butyl cyanide intermediate.44,45 When 2
equiv of CuCN was used instead of t-BuNC and Cu(TFA)2
during the reaction, 2a was afforded in only 27% yield (eq 2),
and this result implied that the reaction did not mainly proceed
via the CuCN intermediate, which may be generated from t-
BuNC and Cu(TFA)2. However, when a copper carboxylate-
isonitrile complex [CF3COO·Cu(I)CNBu-t] (2.0 equiv)
was used instead of t-BuNC and Cu(TFA)2, only trace amount
of 2a was detected (eq 3), which indicated that this complex
might not be the key intermediate during the reaction.31 To
further confirm the origin of cyano group, aromatic isocyanide
and aliphatic isocyanides were used as cyanide sources in the
reaction. The cyanation reaction did not proceed when 2,6-
In summary, we have developed a rhodium-catalyzed C−H
bond cyanation of (hetero)arylpyrimidines using tert-butyl
isocyanide as an efficient “CN” source with good regioselec-
tivity and functional group tolerance. The present rhodium
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Note
ab
,
Scheme 3. Cyanation of Aromatic Heterocycles
a
Reaction Conditions: 3a−k (0.4 mmol), t-BuNC (2.0 equiv), [RhCp*Cl2]2 (2.0 mol %), AgSbF6 (8 mol %), Cu(TFA)2 (2.0 equiv), DCE (2.0
b
c
mL), air, sealed tube, at 130 °C. Isolated yield. Yield based on 57% conversion.
Scheme 4. Regioselective C−H Bond Cyanation of 3c
EXPERIMENTAL SECTION
General Information. All solvents were purified before use
■
according to standard procedure. All melting points were taken on a
digital melting point apparatus without correction. Infrared spectra
were obtained using an FT-IR spectrometer. H, 13C, and 19F NMR
1
spectra were recorded at 500, 125, and 470 MHz, respectively, with
chemical shift values being reported in ppm relative to chloroform (δ =
7.26 ppm), dimethyl sulfoxide (δ = 2.50 ppm), or TMS (δ = 0.00
ppm) for 1H NMR, chloroform (δ = 77.16 ppm) or dimethyl sulfoxide
(δ = 39.52 ppm) for 13C NMR, and C6F6 (δ = −164.9 ppm) for 19F
NMR. Mass spectra and high resolution mass spectra (HRMS) were
recorded using electron impact (EI) or electrospray ionization (ESI)
techniques. Elemental analyses were carried out on an elemental
analyzer. X-ray structure was performed on an X-ray diffractometers.
Silica gel plates GF254 were used for thin layer chromatography
(TLC), and silica gel H or 300−400 mesh were used for flash column
chromatography. Yields refer to chromatographically and spectroscopi-
cally pure compounds, unless otherwise indicated.
Scheme 5. Cyanation of Cycloalkenes
Synthesis of Starting Materials. Arylpyrimidines (1a−1c, 1e−1l,
1o−1q, 3b, 3f),36 3h−3i,31 and 5b−5c48 were synthesized as reported
in the literature. Arylpyrimidines (1m, 3a, 3d−3e)36 and 3j31 were
prepared according to literature reported procedures. 3k was
purchased from commercial source.
2-(4-Ethoxyphenyl)-pyrimidine (1d) (General Procedure). To
a round-bottom flask was added 2-chloropyrimidine (343.5 mg, 3.0
mmol), 4-ethoxyphenylboronic acid (597.6 mg, 3.6 mmol), Pd-
(PPh3)2Cl2 (42.1 mg, 0.06 mmol), Na2CO3 (2 M, 10 mL), and
dioxane (10 mL). The reaction mixture was heated at 90 °C until the
2-chloropyrimidine was consumed completely (monitored by TLC).
The heterogeneous aqueous was concentrated under reduced pressure,
and the residue was diluted with EtOAc (15 mL), washed by H2O (20
mL), and brine (20 mL). The organic layer was dried over Na2SO4,
concentrated, and purified by column chromatography on silica gel
(petroleum ether/EtOAc = 20/1) to afford 1d (558.0 mg, 93%) as a
white solid: mp 120−121 °C; IR (KBr, cm−1) 3441, 3046, 2972, 1606,
1569, 1420, 1244, 854, 797, 641; 1H NMR (500 MHz, CDCl3) δ 8.74
(d, J = 5.0 Hz, 2H), 8.34 (dd, J = 7.0, 2.0 Hz, 2H), 7.10 (t, J = 5.0 Hz,
catalyst system was also successfully applied to the direct C−H
cyanation of olefinic double bonds leading to cycloalkenyl
nitriles in good yields. This approach offers a unique strategy
and alternative route for preparation of organonitriles in good
to excellent yields.
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Note
Scheme 6. Mechanistic Studies
21.8; EI-MS m/z (%) 326 (41) [M+], 155 (44), 143 (30), 91 (100);
HRMS (EI-TOF) m/z calcd for C17H14N2O3S [M+] 326.0725, found
326.0724.
Scheme 7. Plausible Mechanism for Synthesis of 2a from 1a
2,4-Bis(4-methoxyphenyl)pyrimidine (3c). The same proce-
dure was used as for 1d with 2,4-dichloropyrimidine (447.0 mg, 3.0
mmol), 4-methoxyphenylboronic acid (1094.4 mg, 7.2 mmol),
Pd(PPh3)2Cl2 (42.1 mg, 0.06 mmol), Na2CO3 (2 M, 10 mL) and
dioxane (10 mL). After the reaction was over, purification by column
chromatography on silica gel (petroleum ether/EtOAc = 20/1)
afforded 3c (753.4 mg, 86%) as a white solid: mp 141−143 °C; IR
(KBr, cm−1) 3067, 2964, 2841, 1608, 1511, 1249, 1178, 1024, 832,
820, 797, 576, 541; 1H NMR (CDCl3, 500 MHz) δ 8.85 (d, J = 5.0 Hz,
1H), 8.56 (dd, J = 7.0, 2.0 Hz, 2H), 8.23−8.20 (m, 2H), 7.49 (d, J =
5.0 Hz, 1H), 7.07−7.03 (m, 4H), 3.92 (s, 3H), 3.91 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 163.9, 163.4, 162.1, 161.9, 157.0, 129.9, 129.4,
128.8, 114.2, 113.8, 112.9, 55.5, 55.4; EI-MS m/z (%) 292 (100) [M+],
277 (10), 214 (9), 132 (17); HRMS (EI-TOF) m/z calcd for
C18H16N2O2 [M+] 292.1212, found 292.1210.
2-(Phenanthren-9-yl)pyrimidine (3g). The same procedure was
used as for 1d with 2-chloropyrimidine (343.5 mg, 3.0 mmol),
phenanthren-9-ylboronic acid (799.2 mg, 3.6 mmol), Pd(PPh3)2Cl2
(42.1 mg, 0.06 mmol), Na2CO3 (2 M, 10 mL) and dioxane (10 mL).
After the reaction was over, purification by column chromatography
on silica gel (petroleum ether/EtOAc = 5/1) afforded 3g (176.6 mg,
23%) as a yellow solid: mp 95−97 °C; IR (KBr, cm−1) 3033, 1566,
1549, 1414, 813, 744, 720; 1H NMR (CDCl3, 500 MHz) δ 8.97 (d, J =
5.0 Hz, 2H), 8.79 (d, J = 8.0 Hz, 1H), 8.73 (d, J = 8.0 Hz, 1H), 8.60
(d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 8.00 (d, J = 8.5 Hz, 1H), 7.73−7.61
(m, 4H), 7.32 (t, J = 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
167.3, 157.3, 134.6, 131.3, 131.2, 131.1, 131.0, 129.7, 129.6, 127.8,
127.0, 126.9, 126.7, 126.6, 123.0, 122.6, 119.1; EI-MS m/z (%) 256
(62) [M+], 255 (100), 176 (26). Anal. Calcd. for C18H12N2: C, 84.35;
H, 4.72; N, 10.93. Found: C, 84.24; H, 4.52; N, 10.73.
2-(Cyclohex-1-en-1-yl)pyrimidine (5a). The same procedure
was used as for 1d with 2-chloropyrimidine (343.5 mg, 3.0 mmol),
cyclohex-1-en-1-ylboronic acid (453.6 mg, 3.6 mmol), Pd(PPh3)2Cl2
(42.1 mg, 0.06 mmol), Na2CO3 (2 M, 10 mL) and dioxane (10 mL).
After the reaction was over, purification by column chromatography
on silica gel (petroleum ether/EtOAc = 20/1) afforded 5a (388.8 mg,
81%) as a colorless oil: IR (KBr, cm−1) 3030, 2932, 2857, 1567, 1552,
1H), 6.99−6.97 (m, 2H), 4.10 (q, J = 7.0 Hz, 2H), 1.44 (t, J = 7.0 Hz,
3H); 13C NMR (CDCl3, 125 MHz) δ 164.5, 161.5, 157.2, 129.9,
118.4, 114.6, 63.7, 14.9; EI-MS m/z 200 (59) [M+], 172 (100), 119
(80); HRMS (EI-TOF) m/z calcd for C12H12N2O [M+] 200.0950,
found 200.0948.
3-(Pyrimidin-2-yl)phenyl 4-methylbenzenesulfonate (1n).
The same procedure was used as for 1d with 2-chloropyrimidine
(343.5 mg, 3.0 mmol), 3-(tosyloxy)- phenylboronic acid (1051.2 mg,
3.6 mmol), Pd(PPh3)2Cl2 (42.1 mg, 0.06 mmol), Na2CO3 (2 M, 10
mL) and dioxane (10 mL). After the reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 20/
1) afforded 1n (811.7 mg, 83%) as a white solid: mp 127−129 °C; IR
(KBr, cm−1) 3048, 1555, 1411, 1367, 1194, 1086, 899, 802, 790, 726;
1H NMR (CDCl3, 500 MHz) δ 8.78 (d, J = 5.0 Hz, 2H), 8.34 (d, J =
7.5 Hz, 1H), 8.16 (t, J = 2.0 Hz, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.39 (t,
J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 4.5 Hz, 1H), 7.08
(m, 1H), 2.43 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 163.4, 157.4,
150.2, 145.5, 139.7, 132.6, 129.9, 128.7, 126.8, 124.5, 122.4, 119.7,
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Note
1
1419, 923, 786, 632; H NMR (CDCl3, 500 MHz) δ 8.66 (d, J = 5.0
1H), 7.27 (t, J = 5.0 Hz, 1H), 7.21 (dd, J = 9.0, 2.5 Hz, 1H), 4.14 (q, J
= 7.0 Hz, 2H), 1.48 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz)
δ 162.6, 160.2, 157.2, 132.4, 132.0, 120.3, 119.5, 119.2, 118.9, 112.9,
64.2, 14.6; EI-MS m/z 225 (63) [M+], 197 (100), 144 (87), 116 (25);
HRMS (EI-TOF) m/z calcd for C13H11N3O [M+] 225.0902, found
225.0904.
Hz, 2H), 7.29−7.27 (m, 1H), 7.05 (t, J = 5.0 Hz, 1H), 2.59−2.55 (m,
2H), 2.32−2.27 (m, 2H), 1.80−1.75 (m, 2H), 1.70−1.65 (m, 2H); 13C
NMR (CDCl3, 125 MHz) δ 166.0, 156.5, 136.1, 134.2, 118.2, 26.1,
25.3, 22.6, 21.9. LC-MS (ESI) m/z 161 [M+H]; HRMS (ESI-TOF)
m/z calcd for C10H13N2 [M+H]+ 161.1079, found 161.1077.
General Procedure for the Synthesis of Cyanated Products.
Caution! Use safety glasses and nitrile gloves under a well-ventilated hood
since isocyanides such as tert-butyl isocyanide have pungent odors and are
known to be toxic. To a 15 mL sealed tube was added substrates (0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). The reaction mixture was stirred at 130 °C
under air atmosphere. Upon completion, the reaction was diluted by
EtOAc (10 mL) and quenched with aqueous ammonia solution (3 M,
10 mL). The aqueous layer was extracted with EtOAc (3 × 10 mL),
and the combined extract was dried over Na2SO4, filtered, and
concentrated in vacuo. The given residue was purified by column
chromatography to give the cyanated product.
5-Chloro-2-pyrimidin-2-yl-benzonitrile (2e). The general
procedure was followed with 2-(4-chloro-phenyl)-pyrimidine 1e
(76.2 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2e (69.0 mg, 80%) as a white solid: mp
212−214 °C; IR (KBr, cm−1) 3083, 3032, 2231, 1573, 1415, 1383,
1
807, 634; H NMR (CDCl3, 500 MHz) δ 8.91 (d, J = 4.5 Hz, 2H),
8.36 (d, J = 8.5 Hz, 1H), 7.81 (d, J = 2.5 Hz, 1H), 7.68 (dd, J = 9.0, 2.5
Hz, 1H), 7.33 (t, J = 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
161.9, 157.4, 138.6, 136.5, 134.6, 132.9, 131.7, 120.3, 117.6, 113.2; EI-
MS m/z 217 (22) [M+ (37Cl)], 215 (74) [M+ (35Cl)], 162 (100), 127
(33), 100 (35); HRMS (EI-TOF) m/z calcd for C11H6ClN3 [M+]
215.0250, found 215.0249.
2-Pyrimidin-2-yl-benzonitrile (2a).31 The general procedure was
followed with 2-phenylpyrimidine 1a (62.4 mg, 0.4 mmol),
[RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 2a (57.9 mg, 80%) as a white solid: mp 134−136 °C; IR
5-Fluoro-2-(pyrimidin-2-yl)benzonitrile (2f). The general
procedure was followed with 2-(4-fluorophenyl)pyrimidine 1f (69.6
mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0
mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4
mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2f (58.9 mg, 74%) as a white solid: mp
172−174 °C; IR (KBr, cm−1) 3043, 2228, 1559, 1416, 1397, 903, 807;
1H NMR (CDCl3, 500 MHz) δ 8.90 (d, J = 5.0 Hz, 2H), 8.42 (dd, J =
9.0, 5.5 Hz, 1H), 7.54 (dd, J = 8.0, 2.5 Hz, 1H), 7.43−7.39 (m, 1H),
7.32 (t, J = 5.0 Hz, 1H); 19F NMR (CDCl3, 470 MHz) −108.7 (m,
1
(KBr, cm−1) 3071, 3040, 2224, 1565, 1554, 1413, 818, 758, 628; H
NMR (CDCl3, 500 MHz) δ 8.91 (d, J = 5.0 Hz, 2H), 8.35 (dd, J = 7.5,
1.0 Hz, 1H), 7.84 (dd, J = 8.0, 1.0 Hz, 1H), 7.70 (td, J = 7.5, 1.0 Hz,
1H), 7.56 (td, J = 8.0, 1.0 Hz, 1H), 7.32 (t, J = 5.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) δ 162.8, 157.3, 140.3, 135.0, 132.5, 130.4, 130.2,
120.1, 118.9, 111.8; EI-MS m/z 181 (100) [M+], 128 (95).
5-Methyl-2-pyrimidin-2-yl-benzonitrile (2b).49 The general
procedure was followed with 2-(p-tolyl)pyrimidine 1b (68.0 mg, 0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 2b (59.3 mg, 76%) as a white solid: mp 172−174 °C; IR
1
Ar−F); 13C NMR (CDCl3, 125 MHz) δ 163.1 (d, JC−F = 252.5 Hz),
4
3
162.0, 157.4, 136.7 (d, JC−F = 3.7 Hz), 132.9 (d, JC−F = 8.7 Hz),
2
2
122.0 (d, JC−F = 25.0 Hz), 120.3, 120.2 (d, JC−F = 20.0 Hz), 117.8,
113.7 (d, 3JC−F = 10.0 Hz); EI-MS m/z 199 (30) [M+], 147 (39), 146
(65), 52 (100); HRMS (EI-TOF) m/z calcd for C11H6FN3 [M+]
199.0546, found 199.0547.
1
Toluene-4-sulfonic Acid 3-Cyano-4-pyrimidin-2-yl-phenyl
ester (2g). The general procedure was followed with 4-(pyrimidin-
2-yl)phenyl 4-methylbenzenesulfonate 1g (130.4 mg, 0.4 mmol),
[RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032 mmol),
Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8 mmol) and
DCE (2.0 mL). After reaction was over, purification by column
chromatography on silica gel (petroleum ether/EtOAc = 3/1) afforded
2g (108.1 mg, 77%) as a white solid: mp 135−137 °C; IR (KBr, cm−1)
3073, 3035, 2222, 1576, 1553, 1418, 1376, 1190, 1175, 817, 783, 714,
552; 1H NMR (CDCl3, 500 MHz) δ 8.89 (d, J = 5.0 Hz, 2H), 8.35 (d,
J = 8.5 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.43−7.32 (m, 5H), 2.46 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 161.7, 157.4, 150.4, 146.2,
138.9, 132.1, 131.5, 130.1, 128.5, 128.4, 126.9, 120.3, 113.1, 21.8; EI-
MS m/z 351 (29) [M+], 155 (52), 91 (100), 65 (32); HRMS (EI-
TOF) m/z calcd for C18H13N3O3S [M+] 351.0678, found 351.0680.
3-Cyano-4-pyrimidin-2-yl-benzoic Acid Ethyl Ester (2h). The
general procedure was followed with 4-pyrimidin-2-yl-benzoic acid
ethyl ester 1h (91.2 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008
mmol), AgSbF6 (11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8
mmol), t-BuNC (66.4 mg, 0.8 mmol) and DCE (2.0 mL). After
reaction was over, purification by column chromatography on silica gel
(petroleum ether/EtOAc = 5/1) afforded 2h (70.8 mg, 70%) as a
white solid: mp 128−130 °C; IR (KBr, cm−1) 3089, 2991, 2224, 1720,
(KBr, cm−1) 3081, 3035, 2959, 2225, 1561, 1413, 816, 801, 634; H
NMR (CDCl3, 500 MHz) δ 8.89 (d, J = 5.0 Hz, 2H), 8.26 (d, J = 8.5
Hz, 1H), 7.65 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.29 (t, J = 5.0 Hz,
1H), 2.45 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 162.9, 157.3,
140.9, 137.6, 135.5, 133.5, 130.4, 119.9, 119.2, 111.7, 21.0; EI-MS m/z
195 (100) [M+], 143 (27), 115 (43).
5-Methoxy-2-pyrimidin-2-yl-benzonitrile (2c). The general
procedure was followed with 2-(4-methoxyphenyl)pyrimidine 1c
(74.4 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2c (71.7 mg, 85%) as a white solid: mp
128−129 °C; IR (KBr, cm−1) 3079, 2979, 2222, 1606, 1552, 1416,
1289, 1054, 889, 803, 719; 1H NMR (CDCl3, 500 MHz) δ 8.89 (d, J =
5.0 Hz, 2H), 8.36 (d, J = 8.5 Hz, 1H), 7.34 (d, J = 2.5 Hz, 1H), 7.28 (t,
J = 5.0 Hz, 1H), 7.23 (dd, J = 9.0, 2.5 Hz, 1H), 3.92 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 162.5, 160.8, 157.2, 132.6, 132.0, 119.8, 119.5,
118.9, 118.7, 112.9, 55.8; EI-MS m/z 211 (100) [M+], 158 (67), 128
(18), 115 (24); HRMS (EI-TOF) m/z calcd for C12H9N3O [M+]
211.0746, found 211.0744.
5-Ethoxy-2-(pyrimidin-2-yl)benzonitrile (2d). The general
procedure was followed with 2-(4-ethoxyphenyl)-pyrimidine 1d
(80.0 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2d (54.9 mg, 61%) as a white solid: mp
180−181 °C; IR (KBr, cm−1) 3440, 2977, 2225, 1602, 1567, 1551,
1416, 1285, 1054, 827, 816, 799, 623; 1H NMR (CDCl3, 500 MHz) δ
8.88 (d, J = 5.0 Hz, 2H), 8.34 (d, J = 9.0 Hz, 1H), 7.32 (d, J = 2.5 Hz,
1
1554, 1413, 1278, 1179, 824, 759, 633; H NMR (DMSO-d6, 500
MHz) δ 9.06 (d, J = 5.0 Hz, 2H), 8.47 (d, J = 8.5 Hz, 1H), 8.40 (d, J =
1.5 Hz, 1H), 8.34 (dd, J = 8.0, 1.5 Hz, 1H), 7.65 (t, J = 5.0 Hz, 1H),
4.38 (d, J = 7.5 Hz, 2H), 1.36 (t, J = 7.5 Hz, 3H); 13C NMR (DMSO-
d6, 125 MHz) δ 164.3, 161.4, 158.4, 143.6, 135.9, 133.8, 132.2, 131.3,
121.9, 118.1, 111.7, 62.1, 14.5; EI-MS m/z 253 (56) [M+], 208 (100),
155 (27), 127 (47), 100 (29); HRMS (EI-TOF) m/z calcd for
C14H11N3O2 [M+] 253.0851, found 253.0852.
3233
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Note
2-(Pyrimidin-2-yl)-5-(trifluoromethyl)benzonitrile (2i). The
general procedure was followed with 2-(4-(trifluoromethyl)phenyl)-
pyrimidine 1i (89.6 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008
mmol), AgSbF6 (11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8
mmol), t-BuNC (66.4 mg, 0.8 mmol) and DCE (2.0 mL). After
reaction was over, purification by column chromatography on silica gel
(petroleum ether/EtOAc = 5/1) afforded 2i (63.7 mg, 64%) as a white
solid: mp 122−123 °C; IR (KBr, cm−1) 3066, 2231, 1559, 1418, 1331,
(t, J = 5.0 Hz, 1H), 7.31−7.28 (m, 1H); 19F NMR (CDCl3, 470 MHz)
−103.0 (m, Ar−F); 13C NMR (CDCl3, 125 MHz) δ 164.9 (d, 1JC−F
=
253.7 Hz), 161.7 (d, 4JC−F = 2.5 Hz), 157.5, 143.3 (d, 3JC−F = 8.8 Hz),
3
2
137.5 (d, JC−F = 8.8 Hz), 120.7, 118.3, 118.0 (d, JC−F = 23.8 Hz),
117.9 (d, 2JC−F = 21.2 Hz), 108.0 (d, 4JC−F = 3.8 Hz); EI-MS m/z (%)
199 (79) [M+], 146 (100), 119 (25).
4-Cyano-3-(pyrimidin-2-yl)phenyl 4-Methylbenzenesulfo-
nate (2n). The general procedure was followed with 3-(pyrimidin-
2-yl)phenyl 4-methylbenzenesulfonate 1n (130.4 mg, 0.4 mmol),
[RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032 mmol),
Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8 mmol) and
DCE (2.0 mL). After reaction was over, purification by column
chromatography on silica gel (petroleum ether/EtOAc = 3/1) afforded
2n (78.6 mg, 56%) as a white solid: mp 162−163 °C; IR (KBr, cm−1)
1
1179, 1129, 822; H NMR (CDCl3, 500 MHz) δ 8.95 (d, J = 4.5 Hz,
2H), 8.56 (d, J = 9.0 Hz, 1H), 8.10 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H),
7.39 (t, J = 5.0 Hz, 1H); 19F NMR (CDCl3, 470 MHz) −63.1 (s, Ar−
CF3); 13C NMR (CDCl3, 125 MHz) δ 161.5, 157.5, 143.2, 132.5 (q,
3
3
2JC−F = 32.5 Hz), 131.9 (q, JC−F = 3.8 Hz), 131.1, 129.2 (q, JC−F
=
3.8 Hz), 122.9 (q, 1JC−F = 271.3 Hz), 120.8, 117.6, 112.7; EI-MS m/z
249 (82) [M+], 196 (99), 177 (29), 146 (58), 52 (100); HRMS (EI-
TOF) m/z calcd for C12H6F3N3 [M+] 249.0514, found 249.0515.
4-Methyl-2-(pyrimidin-2-yl)benzonitrile (2j). The general
procedure was followed with 2-(m-tolyl)pyrimidine 1j (68.0 mg, 0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 2j (68.6 mg, 88%) as a white solid: mp 93−94 °C; IR (KBr,
cm−1) 3064, 3037, 2966, 2923, 2217, 1570, 1557, 1422, 1398, 816,
728; 1H NMR (CDCl3, 500 MHz) δ 8.90 (d, J = 5.0 Hz, 2H), 8.15 (s,
1H), 7.72 (d, J = 8.0 Hz, 1H), 7.37 (dd, J = 8.0, 1.0 Hz, 1H), 7.32 (t, J
= 5.0 Hz, 1H), 2.48 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 163.0,
157.3, 143.6, 140.1, 135.0, 131.1, 131.0, 120.1, 119.2, 108.9, 21.8; EI-
MS m/z 195 (100) [M+], 142 (54), 115 (27); HRMS (EI-TOF) m/z
calcd for C12H9N3 [M+] 195.0796, found 195.0795.
1
3091, 3048, 2922, 2223, 1558, 1421, 1378, 1163, 919, 784, 668; H
NMR (CDCl3, 500 MHz) δ 8.92 (d, J = 4.5 Hz, 2H), 8.19 (d, J = 2.5
Hz, 1H), 7.79 (dd, J = 8.5, 5.5 Hz, 3H), 7.37 (t, J = 5.0 Hz, 3H), 7.20
(dd, J = 8.5, 2.5 Hz, 1H), 2.47 (s, 3H); 13C NMR (CDCl3, 125 MHz)
δ 161.6, 157.5, 152.5, 146.2, 142.5, 136.7, 132.0, 128.6, 124.7, 124.1,
120.7, 110.5, 21.9; EI-MS m/z (%) 351 (35) [M+], 207 (30), 155
(82), 91 (100); HRMS (EI-TOF) m/z calcd for C18H13N3O3S [M+]
351.0678, found 351.0681.
3-Methyl-2-(pyrimidin-2-yl)benzonitrile (2o). The general
procedure was followed with 2-(o-tolyl)pyrimidine 1o (68.0 mg, 0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 2o (36.7 mg, 47%) as a white solid: mp 179−181 °C; IR
(KBr, cm−1) 2959, 2224, 1556, 1406, 819, 782, 737; 1H NMR (CDCl3,
500 MHz) δ 8.93 (d, J = 5.0 Hz, 2H), 7.63 (d, J = 7.5 Hz, 1H), 7.52
(d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.36 (d, J = 5.0 Hz, 1H),
2.31 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 165.0, 157.4, 141.8,
138.0, 135.1, 131.0, 129.2, 120.1, 118.1, 112.7, 20.1; EI-MS m/z (%)
195 (70) [M+], 194 (100), 168 (36), 114 (30); HRMS (EI-TOF) m/z
calcd for C12H9N3 [M+] 195.0796, found 195.0791.
4,5-Dimethoxy-2-pyrimidin-2-yl-benzonitrile (2p). The gen-
eral procedure was followed with 2-(3,4-dimethoxyphenyl)pyrimidine
1p (86.4 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2p (82.9 mg, 86%) as a white solid: mp
169−170 °C; IR (KBr, cm−1) 3098, 3061, 2967, 2844, 2213, 1598,
1555, 1411, 1389, 1151, 1216, 1038, 812, 734, 634; 1H NMR (CDCl3,
500 MHz) δ 8.89 (d, J = 5.0 Hz, 2H), 7.94 (s, 1H), 7.29 (t, J = 5.0 Hz,
1H), 7.25 (s, 1H), 4.05 (s, 3H), 3.99 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 162.5, 157.3, 152.2, 150.4, 134.4, 119.8, 119.5, 116.6, 112.5,
103.9, 56.5, 56.4; EI-MS m/z 241 (100) [M+], 226 (47), 210 (33), 198
(32), 195 (36). Anal. Calcd. For C13H11N3O2: C, 64.72; H, 4.60; N,
17.42. Found: C, 64.73; H, 4.47; N, 17.20.
3-Methoxy-2,5-dimethyl-6-(pyrimidin-2-yl)benzonitrile (2q).
The general procedure was followed with 2-(4-methoxy-2,5-
dimethylphenyl)pyrimidine 1q (85.6 mg, 0.4 mmol), [RhCp*Cl2]2
(4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032 mmol), Cu-
(OAc)2·H2O (159.6 mg, 0.8 mmol), PivOH (40.8 mg, 0.4 mmol),
H2O (18.0 mg, 1.0 mmol), t-BuNC (66.4 mg, 0.8 mmol) and DCE
(2.0 mL). After reaction was over, purification by column
chromatography on silica gel (petroleum ether/EtOAc = 5/1) afforded
2q (86.0 mg, 80%) as a white solid: mp 91−93 °C; IR (KBr, cm−1)
3096, 2971, 2925, 2226, 1594, 1563, 1554, 1420, 1280, 1156, 1108; 1H
NMR (CDCl3, 500 MHz) δ 8.90 (d, J = 5.0 Hz, 2H), 7.31 (t, J = 5.0
Hz, 1H), 6.91 (s, 1H), 3.88 (s, 3H), 2.42 (s, 3H), 2.27 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 165.4, 157.6, 157.1, 136.3, 133.8, 129.5,
119.5, 117.1, 115.9, 114.0, 55.8, 20.2, 14.1; EI-MS m/z 239 (100)
[M+], 224 (36), 210 (28), 196 (42); HRMS (EI-TOF) m/z calcd for
C14H13N3O [M+] 239.1059, found 239.1062.
4-Methoxy-2-(pyrimidin-2-yl)benzonitrile (2k). The general
procedure was followed with 2-(3-methoxyphenyl)pyrimidine 1k (74.4
mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0
mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4
mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2k (53.2 mg, 63%) as a white solid: mp
130−131 °C; IR (KBr, cm−1) 3020, 2976, 2211, 1598, 1559, 1030,
1
826, 808, 635; H NMR (CDCl3, 500 MHz) δ 8.90 (d, J = 5.0 Hz,
2H), 7.87 (d, J = 3.0 Hz, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.33 (t, J = 5.0
Hz, 1H), 7.06 (dd, J = 8.5, 2.5 Hz, 1H), 3.94 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 162.8, 162.7, 157.3, 142.3, 136.7, 120.3, 119.3,
116.6, 115.3, 103.6, 55.8; EI-MS m/z 211 (72) [M+], 210 (100), 181
(70); HRMS (EI-TOF) m/z calcd for C12H9N3O [M+] 211.0746,
found 211.0742.
4-Chloro-2-(pyrimidin-2-yl)benzonitrile (2l). The general
procedure was followed with 2-(3-chlorophenyl)pyrimidine 1l (76.2
mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0
mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4
mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2l (50.0 mg, 58%) as a white solid: mp
1
126−128 °C; IR (KBr, cm−1) 2924, 2226, 1570, 1552, 1419, 821; H
NMR (CDCl3, 500 MHz) δ 8.93 (d, J = 5.0 Hz, 2H), 8.41 (d, J = 2.0
Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.55 (dd, J = 8.5, 2.0 Hz, 1H), 7.36
(t, J = 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 161.6, 157.4,
141.7, 139.3, 136.1, 130.7, 130.5, 120.6 (2C), 110.1; EI-MS m/z (%)
217 (18) [M+ (37Cl)], 215 (50) [M+ (35Cl)], 164 (22), 162 (67), 52
(100); HRMS (EI-TOF) m/z calcd for C11H6ClN3 [M+] 215.0250,
found 215.0252.
4-Fluoro-2-(pyrimidin-2-yl)benzonitrile (2m).50 The general
procedure was followed with 2-(3-fluorophenyl)pyrimidine 1m (69.6
mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0
mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4
mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 2m (41.4 mg, 52%) as a white solid: mp
154−156 °C; IR (KBr, cm−1) 3112, 3085, 3053, 2226, 1606, 1560,
2-(5-Ethylpyrimidin-2-yl)benzonitrile (4a). The general proce-
dure was followed with 5-ethyl-2-phenylpyrimidine 3a (73.6 mg, 0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
1
1423, 1209, 826; H NMR (CDCl3, 500 MHz) δ 8.95 (d, J = 5.0 Hz,
2H), 8.15 (dd, J = 9.5, 2.5 Hz, 1H), 8.15 (dd, J = 8.5, 2.5 Hz, 1H), 7.38
3234
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The Journal of Organic Chemistry
Note
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 4a (60.2 mg, 72%) as a white solid: mp 40−42 °C; IR (KBr,
Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 164.4, 157.5, 142.2, 135.0,
130.5, 130.1, 128.8, 128.4, 128.2, 127.0, 126.4, 120.3, 118.4, 110.2; EI-
MS m/z 231 (83) [M+], 230 (100), 204 (23), 151 (43); HRMS (EI-
TOF) m/z calcd for C15H9N3 [M+] 231.0796, found 231.0802.
3-(Pyrimidin-2-yl)-2-naphthonitrile (4f). The general procedure
was followed with 2-(naphthalen-2-yl)pyrimidine 3f (82.4 mg, 0.4
mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 4f (58.2 mg, 63%) as a white solid: mp 202−204 °C; IR (KBr,
cm−1) 3050, 2223, 1556, 1411, 816, 749; 1H NMR (CDCl3, 500 MHz)
δ 8.94 (d, J = 5.0 Hz, 2H), 8.85 (s, 1H), 8.41 (s, 1H), 8.00 (d, J = 8.0
Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 7.68−7.62 (m, 2H), 7.32 (t, J = 5.0
Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 163.2, 157.4, 137.6, 134.7,
134.3, 132.7, 131.2, 129.5, 129.1, 128.8, 128.1, 120.0, 119.4, 108.9; EI-
MS m/z 231 (50) [M+], 178 (100), 152 (15), 52 (62); Anal. Calcd. for
C15H9N3: C, 77.91; H, 3.92; N, 18.17. Found: C, 77.85; H, 3.82; N,
17.93.
10-(Pyrimidin-2-yl)phenanthrene-9-carbonitrile (4g). The
general procedure was followed with 2-(phenanthren-9-yl)pyrimidine
3g (102.4 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol),
AgSbF6 (11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-
BuNC (66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was
over, purification by column chromatography on silica gel (petroleum
ether/EtOAc = 3/1) afforded 4g (30.1 mg, 47% yield based on 57%
conversion of 3g) as a yellow solid: mp 139−140 °C; IR (KBr, cm−1)
3074, 3039, 2215, 1554, 1416, 748, 717; 1H NMR (CDCl3, 500 MHz)
δ 9.10 (d, J = 5.0 Hz, 2H), 8.80 (d, J = 7.5 Hz, 2H), 8.45 (dd, J = 8.0,
1.0 Hz, 1H), 7.86−7.80 (m, 3H), 7.74 (d, J = 8.5 Hz, 1H), 7.63 (t, J =
8.0 Hz, 1H), 7.54 (t, J = 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
165.0, 157.6, 143.6, 132.0, 129.6, 128.7, 128.6, 128.4, 127.7, 126.7,
123.1, 123.0, 120.5, 116.7, 110.1; EI-MS m/z (%) 281 (64) [M+], 280
(44), 254 (23); HRMS (EI-TOF) m/z calcd for C19H11N3 [M+]
281.0953, found 281.0959.
1
cm−1) 2971, 2935, 2217, 1544, 1425, 761; H NMR (CDCl3, 500
MHz) δ 8.74 (s, 2H), 8.31 (d, J = 8.0 Hz, 1H), 7.82 (dd, J = 8.0, 1.0
Hz, 1H), 7.67 (td, J = 7.5, 1.0 Hz, 1H), 7.53 (td, J = 7.5, 1.0 Hz, 1H),
2.71 (q, J = 7.5 Hz, 2H), 1.32 (t, J = 7.5 Hz, 3H); 13C NMR (CDCl3,
125 MHz) δ 160.6, 156.7, 140.4, 135.4, 134.9, 132.5, 130.2, 129.8,
119.0, 111.6, 23.5, 14.7; EI-MS m/z 209 (100) [M+], 194 (29), 181
(33), 129 (79); HRMS (EI-TOF) m/z calcd for C13H11N3 [M+]
209.0953, found 209.0948.
2-(4-Phenylpyrimidin-2-yl)benzonitrile (4b). The general
procedure was followed with 2,4-diphenylpyrimidine 3b (92.8 mg,
0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg,
0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 4b (57.6 mg, 56%) as a white solid: mp 108−110 °C; IR
(KBr, cm−1) 3061, 2217, 1544, 1426, 1375, 754, 685; 1H NMR
(CDCl3, 500 MHz) δ 8.91 (d, J = 5.5 Hz, 1H), 8.50 (d, J = 8.0 Hz,
1H), 8.34−8.32 (m, 2H), 7.88 (dd, J = 7.5, 1.0 Hz, 1H), 7.74−7.70
(m, 2H), 7.59−7.53 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 164.6,
162.7, 158.1, 140.7, 136.3, 135.3, 132.6, 131.5, 130.6, 130.3, 129.2,
127.8, 119.5, 115.5, 111.9; EI-MS m/z 257 (22) [M+], 256 (100), 128
(29); Anal. Calcd. for C17H11N3: C, 79.36; H, 4.31; N, 16.33. Found:
C, 79.17; H, 4.15; N, 15.98.
5-Methoxy-2-(4-(4-methoxyphenyl)pyrimidin-2-yl)-
benzonitrile (4c). The general procedure was followed with 2,4-
bis(4-methoxyphenyl)pyrimidine 3c (116.8 mg, 0.4 mmol),
[RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032
mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 4c (52.0 mg, 41%) as a white solid: mp 117−119 °C; IR
(KBr, cm−1) 3072, 2960, 2851, 2222, 1606, 1582, 1413, 1256, 1029,
815; 1H NMR (CDCl3, 500 MHz) δ 8.83 (d, J = 5.0 Hz, 1H), 8.56 (d,
J = 8.5 Hz, 1H), 8.35 (dd, J = 7.0, 2.0 Hz, 2H), 7.63 (d, J = 5.0 Hz,
1H), 7.38 (d, J = 2.5 Hz, 1H), 7.25 (dd, J = 9.0, 2.5 Hz, 1H), 7.09 (dd,
J = 7.0, 2.0 Hz, 2H), 3.94 (s, 3H), 3.91 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 163.8, 162.3, 162.1, 160.7, 157.5, 133.1, 132.0, 129.3,
128.8, 119.8, 119.5, 118.7, 114.4, 113.9, 112.8, 55.8, 55.4; EI-MS m/z
(%) 317 (30) [M+], 316 (100), 302 (16), 273 (12); HRMS (EI-TOF)
m/z calcd for C19H14N3O2 [M+-H] 316.1086, found 316.1083.
N-(2-(2-Cyanophenyl)pyrimidin-4-yl)acetamide (4d). The
general procedure was followed with N-(2-phenylpyrimidin-4-yl)-
acetamide 3d (85.2 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008
mmol), AgSbF6 (11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8
mmol), t-BuNC (66.4 mg, 0.8 mmol) and DCE (2.0 mL). After
reaction was over, purification by column chromatography on silica gel
(petroleum ether/EtOAc = 2/1) afforded 4d (38.0 mg, 40%) as a
white solid: mp 203−205 °C; IR (KBr, cm−1) 3265, 2219, 1690, 1574,
1-(Pyrimidin-2-yl)-1H-pyrrole-2-carbonitrile (4h).31 The gen-
eral procedure was followed with 2-(1H-pyrrol-1-yl)pyrimidine 3h
(58.4 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 4h (54.4 mg, 80%) as a white solid: mp
115−118 °C; IR (KBr, cm−1) 3131, 2224, 1581, 1564, 1450, 1423,
1337, 1267, 1178, 828, 814, 748; 1H NMR (CDCl3, 500 MHz) δ 8.74
(d, J = 4.5 Hz, 2H), 7.99 (dd, J = 3.0, 2.0 Hz, 1H), 7.23 (t, J = 4.5 Hz,
1H), 7.08 (dd, J = 4.0, 1.5 Hz, 1H), 6.38 (t, J = 4.5 Hz, 1H); 13C NMR
(DMSO-d6, 125 MHz) δ 159.4, 154.3, 126.4, 125.5, 119.9, 113.8,
112.2, 101.7; LC-MS (ESI) m/z 171 [M+H].
1-(Pyrimidin-2-yl)-1H-indole-2-carbonitrile (4i).31 The general
procedure was followed with 1-(pyrimidin-2-yl)-1H-indole 3i (78.4
mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0
mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4
mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 4i (51.0 mg, 58%) as a white solid: mp
120−121 °C; IR (KBr, cm−1) 3101, 2225, 1572, 1531, 1449, 1427,
1
1246, 763, 558; H NMR (CDCl3, 500 MHz) δ 8.75 (d, J = 5.5 Hz,
1H), 8.37 (d, J = 8.0 Hz, 1H), 8.29 (br, 1H), 8.14 (d, J = 5.5 Hz, 1H),
7.81 (dd, J = 7.5, 1.0 Hz, 1H), 7.68 (td, J = 7.5, 1.0 Hz, 1H), 7.55 (td, J
= 7.5, 1.0 Hz, 1H), 2.27 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
169.6, 161.8, 158.9, 157.2, 139.5, 135.0, 132.6, 130.3, 130.3, 111.5,
108.8, 24.8; EI-MS m/z (%) 238 (4) [M+], 43 (100); HRMS (EI-
TOF) m/z calcd for C13H10N4O [M+] 238.0855, found 238.0851.
1-(Pyrimidin-2-yl)-2-naphthonitrile (4e). The general proce-
dure was followed with 2-(naphthalen-1-yl)pyrimidine 3e (82.4 mg,
0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg,
0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 4e (60.1 mg, 65%) as a white solid: mp 228−230 °C; IR
(KBr, cm−1) 3052, 2227, 1557, 1375, 810, 742; 1H NMR (CDCl3, 500
MHz) δ 9.03 (d, J = 5.0 Hz, 2H), 8.01 (d, J = 8.5 Hz, 1H), 7.94 (d, J =
8.5 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.64
(td, J = 8.0, 1.0 Hz, 1H), 7.56 (td, J = 8.0, 1.0 Hz, 1H), 7.47 (t, J = 5.0
1
1256, 812, 739, 625; H NMR (500 MHz, CDCl3) δ 8.83 (d, J = 5.0
Hz, 2H), 8.69 (d, J = 8.5 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.52−7.48
(m, 1H), 7.47 (s, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 5.0 Hz,
1H); 13C NMR (CDCl3, 125 MHz) δ 158.5, 156.8, 136.8, 128.0,
127.8, 123.7, 122.2, 121.2, 118.2, 116.4, 114.4, 109.1; LC-MS (ESI) m/
z 221 [M+H].
9-(Pyrimidin-2-yl)-9H-carbazole-1-carbonitrile (4j). The gen-
eral procedure was followed with 9-(pyrimidin-2-yl)-9H-carbazole 3j
(98.0 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 4j (59.4 mg, 55%) as a white solid: mp
183−185 °C; IR (KBr, cm−1) 3050, 2961, 2924, 2221, 1562, 1452,
3235
dx.doi.org/10.1021/jo500087g | J. Org. Chem. 2014, 79, 3228−3237

The Journal of Organic Chemistry
Note
1
1430, 1208, 739; H NMR (CDCl3, 500 MHz) δ 9.00 (d, J = 5.0 Hz,
ASSOCIATED CONTENT
■
2H), 8.34 (t, J = 8.0 Hz, 2H), 8.12 (d, J = 8.0 Hz, 1H), 7.83 (dd, J =
7.5, 1.0 Hz, 1H), 7.56 (td, J = 7.0, 1.0 Hz, 1H), 7.45−7.42 (m, 2H),
7.36 (t, J = 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 158.6, 157.0,
140.1, 138.2, 132.4, 127.8, 127.1, 124.6, 123.8, 122.8, 121.6, 120.0,
119.0, 117.7, 113.3, 98.5; EI-MS m/z (%) 270 (100) [M+], 245 (25),
217 (9), 192 (20), 164 (14); HRMS (EI-TOF) m/z calcd for
C17H10N4 [M+] 270.0905, found 270.0903.
S
* Supporting Information
1
Copies of H NMR, 13C NMR, and 19F NMR spectra for all
compounds, X-ray structure of compound 4c (CIF), and details
for mechanistic studies. This material is available free of charge
via the Internet at http://pubs.acs.org.
Benzo[h]quinoline-10-carbonitrile (4k).15 The general proce-
dure was followed with benzo[h]quinoline 3k (71.6 mg, 0.4 mmol),
[RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg, 0.032 mmol),
Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8 mmol) and
DCE (2.0 mL). After reaction was over, purification by column
chromatography on silica gel (petroleum ether/EtOAc = 5/1) afforded
4k (80.0 mg, 98%) as a white solid: mp 143−145 °C; IR (KBr, cm−1)
3440, 3047, 2207, 1424, 832, 716, 664; 1H NMR (CDCl3, 500 MHz) δ
9.12 (dd, J = 4.5, 1.5 Hz, 1H), 8.22 (dd, J = 8.0, 1.5 Hz, 1H), 8.14 (dd,
J = 7.5, 1.5 Hz, 1H), 8.11 (dd, J = 9.0, 1.0 Hz, 1H), 7.82−7.76 (m,
2H), 7.71 (t, J = 7.5 Hz, 1H), 7.63−7.60 (m, 1H); 13C NMR (CDCl3,
125 MHz) δ 148.5, 144.5, 136.2, 135.7, 134.0, 132.7, 130.7, 127.4,
127.2, 127.1, 126.9, 123.0, 120.8, 108.9; EI-MS m/z (%) 204 (100)
[M+], 176 (11), 150 (13).
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: xubin@shu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(No. 21272149), Innovation Program of Shanghai Municipal
Education Commission (No. 14ZZ094), and Science and
Technology Commission of Shanghai Municipality (No.
13ZR1416400) for financial support. The authors thank Prof.
Hongmei Deng (Laboratory for Microstructures, SHU) for
assistance with spectral measurements.
2-(Pyrimidin-2-yl)cyclohex-1-enecarbonitrile (6a). The gen-
eral procedure was followed with 2-(cyclohex-1-en-1-yl)pyrimidine 5a
(64.0 mg, 0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6
(11.0 mg, 0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC
(66.4 mg, 0.8 mmol) and DCE (2.0 mL). After reaction was over,
purification by column chromatography on silica gel (petroleum
ether/EtOAc = 5/1) afforded 6a (47.4 mg, 64%) as a colorless oil: IR
REFERENCES
■
(1) Kleemann, A.; Engel, J.; Kutscher, B.; Reichert, D. Pharmaceutical
Substances: Syntheses, Patents, Applications, 4th ed.; Georg Thieme:
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(KBr, cm−1) 3036, 2944, 2860, 2197, 1555, 1415, 824, 799; H NMR
1
(CDCl3, 500 MHz) δ 8.83 (d, J = 5.0 Hz, 2H), 7.27 (t, J = 5.0 Hz,
1H), 2.79−2.76 (m, 2H), 2.55−2.52 (m, 2H), 1.85−1.76 (m, 4H); 13
C
NMR (CDCl3, 125 MHz) δ 164.1, 156.8, 150.7, 120.2, 119.4, 113.2,
29.7, 27.8, 21.4, 21.3. LC-MS (ESI) m/z 186 [M+H]; HRMS (ESI-
TOF) m/z calcd for C11H12N3 [M+H] 186.1031, found 186.1026.
2-(Pyridin-2-yl)cyclopent-1-enecarbonitrile (6b). The general
procedure was followed with 2-(cyclopentenyl)pyridine 5b (58.0 mg,
0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg,
0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 6b (32.6 mg, 48%) as a white solid: mp 126−128 °C; IR
(KBr, cm−1) 3059, 2973, 2949, 2206, 1577, 1473, 1426, 1345, 989,
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1
791, 742, 610; H NMR (Acetone-d6, 500 MHz) δ 8.69−8.68 (m,
1H), 7.91 (td, J = 8.0, 2.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.42−7.40
(m, 1H), 3.09−3.05 (m, 2H), 2.88−2.84 (m, 2H), 2.15−2.09 (m, 2H);
13C NMR (Acetone-d6, 125 MHz) δ 157.8, 152.6, 150.4, 137.5, 124.9,
122.8, 117.9, 110.6, 37.3, 35.5, 22.9; EI-MS m/z (%) 170 (58) [M+],
169 (100), 142 (13), 117 (8); HRMS (EI-TOF) m/z calcd for
C11H10N2 [M+] 170.0844, found 170.0843.
2-(Pyridin-2-yl)cyclohex-1-enecarbonitrile (6c). The general
procedure was followed with 2-(1-cyclohexenyl)pyridine 5c (63.6 mg,
0.4 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), AgSbF6 (11.0 mg,
0.032 mmol), Cu(TFA)2 (232.0 mg, 0.8 mmol), t-BuNC (66.4 mg, 0.8
mmol) and DCE (2.0 mL). After reaction was over, purification by
column chromatography on silica gel (petroleum ether/EtOAc = 5/1)
afforded 6c (38.3 mg, 52%) as a colorless oil: IR (KBr, cm−1) 3051,
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1
2925, 2854, 2208, 1584, 1464, 1260, 1082, 1022, 802, 783; H NMR
(DMSO-d6, 500 MHz) δ 8.65−8.63 (m, 1H), 7.89 (td, J = 8.0, 2.0 Hz,
1H), 7.61 (dt, J = 7.5, 2.0 Hz, 1H), 7.43−7.40 (m, 1H), 2.61−2.59 (m,
2H), 2.42−2.39 (m, 2H), 1.74−1.67 (m, 4H); 13C NMR (DMSO-d6,
125 MHz) δ 156.7, 154.2, 149.6, 137.4, 124.3, 122.8, 119.8, 109.3,
29.1, 28.5, 21.5, 21.3; EI-MS m/z (%):184 (99) [M+], 183 (100), 169
(47), 155 (41); HRMS (EI-TOF) m/z calcd for C12H12N2 [M+]
184.1000, found 184.0997.
3236
dx.doi.org/10.1021/jo500087g | J. Org. Chem. 2014, 79, 3228−3237

The Journal of Organic Chemistry
Note
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9933.
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