Copper-mediated cyanation of aryl boronic acids using benzyl cyanide

Article abstract of DOI:10.1016/j.tet.2013.07.063

An efficient copper-mediated synthesis of aryl nitriles from aryl boronic acids has been achieved using benzyl cyanide as a user-friendly cyanide source. Various aryl boronic acids underwent the reaction smoothly, affording the corresponding aryl nitriles in moderate to good yields. tert-Butyl hydroperoxide (TBHP) was found to be a critical agent facilitating the cyanation reaction.

Full text of DOI:10.1016/j.tet.2013.07.063

Tetrahedron xxx (2013) 1e5
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-mediated cyanation of aryl boronic acids using benzyl
cyanide
*
*
Yan Luo, Qiaodong Wen, Zhiyuan Wu, Jisong Jin, Ping Lu , Yanguang Wang
Department of Chemistry, Zhejiang University, Hangzhou 310027, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient copper-mediated synthesis of aryl nitriles from aryl boronic acids has been achieved using
benzyl cyanide as a user-friendly cyanide source. Various aryl boronic acids underwent the reaction
smoothly, affording the corresponding aryl nitriles in moderate to good yields. tert-Butyl hydroperoxide
(TBHP) was found to be a critical agent facilitating the cyanation reaction.
Received 21 May 2013
Received in revised form 11 July 2013
Accepted 18 July 2013
Available online xxx
Ó 2013 Published by Elsevier Ltd.
Keywords:
Copper catalysis
Cyanation
Benzyl cyanide
Boronic acid
CeH oxidation
1. Introduction
interested due to the good starting material availability and oper-
ational feasibility (Scheme 1). Liebeskind et al. have reported
Aryl nitriles are known to be important organic compounds
widely existing in nature products, pharmaceuticals, dyes, and
herbicides.1 Furthermore, due to the tunable reactivity of the cyano
group, aryl nitriles have been utilized as key synthetic in-
termediates for the preparation of other organic compounds, such
as aldehydes, carboxylic acids, amines, amidines, amides, and
tetrazoles.2
Among various methods, the Sandmeyer and Rosenmund-von
Braun reactions have been widely used in aromatic cyanation.3
However, the most commonly used metal cyanides, such as KCN,
NaCN, CuCN, Zn(CN)2, are extremely toxic.4 In 2004, K4[Fe(CN)6]
was shown to be a safety cyanide reagent by Beller et al. and
thereafter was wildly used for cyanations.5 In addition to inorganic
cyanating reagents, many other CN-containing organic compounds
have also been exploited as CN source, including acetone cyano-
hydrin, trimethylsilyl cyanide (TMSCN), CH3CN, propanedinitrile,
ethyl cyanoacetate, and isocyanide.6 Intriguingly, non-CN-
containing systems, such as CH3NO2, N,N-dimethylformamide
(DMF) only,7 and DMF or dimethyl sulfoxide (DMSO) plus ammo-
nium salts,8 have also been employed as CN sources.
a palladium-catalyzed copper(I)-mediated cyanation of boronic
acids using benzylthiocyanate.10 Hartwig et al. have shown a cop-
per-mediated cyanation of arenes via iridium-catalyzed bor-
ylation.11 Cheng et al. demonstrated a copper-mediated cyanation
of boronic acids with CuCN and TMSCN.12 In addition to the above
mentioned aromatic cyanations using conventional cyanide sour-
ces, Beller et al. disclosed a rhodium-catalyzed cyanation of aryl and
alkenyl boronic using N-cyano-N-phenyl-p-toluenesulfonamide
(NCTS).13 More recently, Chang et al. demonstrated that similar
conversion could also been achieved using a combination of DMF
and NH4I as the cyanide source.8d
Among various Pd and Cu-catalyzed aromatic cyanation re-
actions,9 the cyanation of aryl boronic acids has been increasingly
* Corresponding authors. Tel./fax: þ86 571 87952543; e-mail addresses: pinglu@
Scheme 1. Cyanation of boronic acids using various cyanating agents.
zju.edu.cn (P. Lu), orgwyg@zju.edu.cn (Y. Wang).
0040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.07.063
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2
Y. Luo et al. / Tetrahedron xxx (2013) 1e5
Our group has utilized readily available benzyl cyanide as a vi-
with 82% yield (Table 1, entry 20). It was notable that a nice yield
(70%) of 4-phenylbenzonitrile could be obtained when the reaction
was taken under N2 atmosphere (Table 1, entry 21).
With the optimal conditions in hand, we explored the substrate
scope of the present reaction (Scheme 2). Aryl boronic acids bearing
strong electron-donating and moderate electron-withdrawing
substituents (OR and Cl, respectively) gave the corresponding aryl
able agent for the cyanation of arenes, aryl halides, and indoles.14
Kwong et al. applied this reagent in the cyanation of 3-
cyanoindole derivatives.15 Herein, we disclose a copper-mediated
cyanation of aryl boronic acids using benzyl cyanide.
2. Results and discussion
Our original experiment was taken with 4-biphenylboronic acid
(1a), benzyl cyanide (2a), and cuprous iodide (CuI). Unfortunately,
only trace amount of the expected 4-phenylbenzonitrile (3a) was
detected when the mixture was reacted in DMF at 130 ꢀC under air
(Table 1, entry 1). According to GC analysis of the reaction mixture,
4-iodobiphenyl and biphenyl were identified as the major com-
ponents, which were presumably formed from the iodination and
hydrogenation of 1a, respectively.
Table 1
Optimization of reaction conditions for the preparation of 3aa
Entry
Cu (equiv)
Oxidant (equiv)
Solvent
T (ꢀC)
3a (%)b
1
2
3
4
5
6
7
8
CuI (1.5)
CuI (1.5)
CuBr (1.5)
CuCl (1.5)
Cu2O (1.5)
Cu(OAc)2 (1.5)
CuCl2 (1.5)
CuI (1.5)
CuI (1.5)
CuI (1.5)
CuI (1.5)
CuI (1.5)
CuI (1.5)
CuI (1.0)
CuI (0.4)
CuI (0.2)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
None
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Dioxane
NMP
DMSO
DMAc
DMAc
130
130
130
130
130
130
130
130
130
130
130
110
80
130
130
130
130
130
130
130
130
Trace
78
12
Trace
Trace
Trace
Trace
11
70
61
53
55
22
75
56
17
0
56
74
82
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
DTBP (2.0)
BPO (2.0)
TBHP (1.0)
TBHP (4.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
TBHP (2.0)
9
10
11
12
13
14
15
16
17
18
19
20
21c
a Reaction conditions: 1 (0.5 mmol), 2a (0.75 mmol), CuI (0.5 mmol), TBHP
(aq. 1 mmol), air, DMAc (2 mL), 130 °C, 20 h. b Isolated yields based on 1. c
The reaction was carried out on 6 mmol scale.
70
Scheme 2. Substrate scope of cyanation of aryl boronic acidsa,b
.
a
Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), Cu source, oxidant, air,
solvent (2 mL), 20 h.
b
Isolated yields.
c
Under N2 atmosphere. TBHP¼tert-butyl hydroperoxide, DTBP¼di-tert-butylper-
nitriles in good yields. 4-tert-Butyl-phenyl boronic acid furnished
the cyanation product in only 53% yield. In contrast, the in-
troduction of the NO2 and ester groups onto the aromatic ring led to
dramatic decrease in reaction yields. Both ortho- and para-phenyl
substituted boronic acids underwent reaction smoothly, indicating
the insignificant role of steric effects in reaction yields. For fused
aryl rings, such as naphthalene, anthracene, and fluorene de-
rivatives, moderate to excellent yields were obtained. In addition,
heterocyclic boronic acids could also be used as the substrates,
affording the corresponding aryl nitriles 3o and 3p in relatively
lower yields. To demonstrate the feasibility of the present protocol,
oxide, BPO¼benzoyl peroxide. NMP¼N-methyl-2-pyrrolidone, DMSO¼dimethyl sulf-
oxide, DMAc¼N,N-dimethylacetamide. TBHP represents 70% aqueous solution.
To our delight, the yield of 3a was found to increase to 78% when
we applied 2 equiv of tert-butyl hydroperoxide aqueous solution
(TBHP) as an oxidant to promote the benzylic oxidation of 2a (Table
1, entry 2). Further reaction condition screening showed CuI to be
optimal among different copper sources (Table 1, entries 2e7).
Other oxidants, such as di-tert-butylperoxide (DTBP) and benzoyl
peroxide (BPO), could also serve as oxidizing agents in the reaction,
which, however, led to inferior yields (Table 1, entries 8, 9). Al-
though we tried to alter the reaction temperatures and proportions
of substrates and reagents, such attempts did not provide addi-
tional improvement to reaction yields (Table 1, entries 10e16). We
also examined the solvent effects in this reaction. As expected, low
polar solvents, such as 1,4-dioxane, led to dramatic decrease in
reaction yield possibly due to low solubility of CuI in these solvents
(Table 1, entry 17). In comparison, high reaction yields were gen-
erally enabled by polar solvents, among which N,N-dimethylace-
tamide (DMAc) was found to be the optimal solvent affording 3a
a
gram-scale reaction was carried out with 6 mmol 4-
biphenylboronic acid, which gave desired product in 56% yield. In
addition to aryl boronic acids, we have also attempted the cyana-
tion of aryl boronic esters, which generally demonstrated similar
reactivity to the parent boronic acids (Scheme 3).
To gain mechanistic insight into the reaction, we carried out
cyanation reaction with different benzyl nitriles as the CN sources.
As shown in Scheme 4, the cyanation was sluggish when NO2-
substituted benzyl nitrile was employed. Presumably, the strong
electron-withdrawing ability of the para NO2 group can inhibit the
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Y. Luo et al. / Tetrahedron xxx (2013) 1e5
3
The overall mechanism is illustrated in Scheme 5. Benzyl cya-
nide was oxidized to 2-hydroxy-2-phenylacetonitrile and/or ben-
zoyl cyanide by cuprous iodide and TBHP.16 These species could
release cyanide anion by either b-elimination or nucleophilic acyl
substitution with ‘Nu’, such as H2O, HNMe2, and tert-BuOH. All
these procedures were coupled with the releasing of cyanide anion.
On the other hand, 4-biphenylboronic acid (1a) was firstly activated
by CuI and TBHP to furnish 4-iodobiphenyl and biphenyl byproduct.
4-Iodobiphenyl further coupled with cyanide anion in the presence
of CuI to give 4-phenylbenzonitrile (3a).
Scheme 3. Copper-mediated cyanation of boronic acid ester.
Scheme 5. Plausible mechanism.
Scheme 4. Cyanation of 4-biphenylboronic acid with various benzyl nitriles.
release of cyanide release. The above mentioned result implied that
the cyanide expelling played a critical role in the overall reaction.
We have also performed a control experiment in the absence of
biphenylboronic acid under standard reaction conditions. From
such reaction, tert-butyl benzoate, tert-butyl alcohol, and cyanide
anion were detected (see Supplementary data). This outcome
supported the proposal that the cyanide was released from 2-
hydroxy-2-phenylacetonitrile, an oxidized product from benzyl
cyanide. Given the fact that the reaction proceeded smoothly under
N2 atmospheres, oxygen could be ruled out as major oxidant.
As depicted in Fig. 1, 4-iodobiphenyl was observed as the major
product at the initial stage of the reaction, whose concentration
gradually decreased thereafter. Meanwhile, we also observed an
induction period regarding the formation of 3a. By subjecting 4-
bromobiphenyl to similar reaction conditions, the corresponding
cyanation product was obtained in poor yield. On the basis of these
observations, the iodination products were proposed to be key
reaction intermediates toward desired aryl nitriles. Furthermore,
the GCeMS analysis of the reaction mixture after 10 h showed the
formation of tert-butyl alcohol, benzaldehyde, N,N-dime-
thylbenzamide, biphenyl, 4-iodobiphenyl, and 4-phenylbenzo
nitrile (3a) (Fig. S1), thereby validating our proposed mechanism.
3. Conclusions
In conclusion, we have developed a new copper-mediated
TBHP-oxidized cyanation of aryl boronic acids using benzyl cya-
nide as cyanide source. Compared to conventional cyanation, the
present protocol features ready availability and relative low toxicity
of substrates as well as a broad substrate scope. The synthetic ap-
plication of method is currently underway in our laboratory.
4. Experimental
4.1. General
NMR spectra were obtained on a spectrometer operating at
400 MHz for 1H NMR, 100 MHz for 13C NMR in CDCl3. Chemical
shifts were quoted in parts per million (ppm) referenced to the
appropriate solvent peak or 0.0 ppm for tetramethylsilane. The
following abbreviations were used to describe peak splitting
patterns when appropriate: s¼singlet, d¼doublet, t¼triplet,
m¼multiplet, br¼broad. Coupling constants J, were reported in
€
Hertz unit (Hz). Melting points were recorded on a BUCHI 535. The
high-resolution mass spectrum (HRMS) was recorded on GCT
premier instrument using TOF-EI. All the reagents were either
purchased or synthesized by the published methods. Solvents were
purchased and used without further treatment. Aryl boronic
pinacol esters (1o, 1p, 1q, 1r) were synthesized using the published
procedures.17
2a
100
Biphenyl
3a
4-Iodobiphenyl
80
60
40
20
0
4.2. General procedure for the synthesis of 3
Boronic acid 1 (0.5 mmol), benzyl cyanide 2 (0.75 mmol), CuI
(95 mg, 0.5 mmol), tert-BuOOH (70% aq, 144 mL,1 mmol), and DMAc
(2 mL) were placed in a 25 mL round flask. The reaction mixture
was stirred at 130 ꢀC (oil bath) for 20 h under air. After cooling to
the room temperature, the resulting mixture was poured to 15 mL
water and extracted with dichloromethane (3ꢁ5 mL). The organic
phase was combined and dried over anhydrous Na2SO4. Dichloro-
methane was evaporated under reduced pressure and the residue
was purified by flash column chromatography on a silica gel to give
the product 3.
-2
0
2
4
6
8
10
12
14
16
18
Time (h)
Fig. 1. Reaction progress monitored by GC analysis.
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4
Y. Luo et al. / Tetrahedron xxx (2013) 1e5
4.3. Characterization data
126.4, 123.1, 120.8, 120.2, 119.8, 109.8, 55.5, 40.1, 31.7, 29.8, 28.9,
23.7, 22.5, 14.0. HRMS(TOF-EI): calcd for C28H37N [Mþ], 387.2926;
found, 387.2920.
4.3.1. 4-Phenylbenzonitrile (3a). EtOAc/Petroleum ether¼1:10 (v/
v), Rf¼0.4; white solid; mp 83e84 ꢀC (Lit.18 82.5e83.5 ꢀC). 1H NMR
(400 MHz, CDCl3)
d
7.59 (d, J¼8.4 Hz, 2H), 7.54 (d, J¼7.6 Hz, 2H), 7.44
4.3.11. 4-Chlorobenzonitrile (3k). EtOAc/Petroleum ether¼1:10 (v/
v), Rf¼0.4; white solid; mp 90e91 ꢀC (Lit.22 91e92 ꢀC). 1H NMR
(t, J¼7.6 Hz, 2H), 7.36 (t, J¼7.2 Hz, 1H), 7.32 (d, J¼8.0 Hz, 2H). 13
C
NMR (100 MHz, CDCl3)
118.9, 110.8.
d
145.6,139.1,132.5,129.1,128.6,127.7, 127.2,
(400 MHz, CDCl3)
NMR (100 MHz, CDCl3)
d
7.61 (d, J¼8.0 Hz, 2H), 7.47 (d, J¼8.0 Hz, 2H). 13
C
d 139.5, 133.3, 129.7, 117.9, 110.8.
4.3.2. 4-Methoxybenzonitrile (3b). EtOAc/Petroleum ether¼1:8 (v/
v), Rf¼0.2; white solid; mp 57e58 ꢀC (Lit.14a 60e61 ꢀC). 1H NMR
4.3.12. Methyl 4-cyanobenzoate (3l). EtOAc/Petroleum ether¼1:7
(v/v), Rf¼0.4; white solid; mp 65e67 ꢀC (Lit.10 65e66 ꢀC). 1H NMR
(400 MHz, CDCl3)
d
7.59 (d, J¼8.8 Hz, 2H), 6.95 (d, J¼8.8 Hz, 2H),
(400 MHz, CDCl3)
d
8.14 (d, J¼8.0 Hz, 2H), 7.75 (d, J¼8.0 Hz, 2H),
3.86 (s, 3H). 13C NMR (100 MHz, CDCl3)
103.9, 55.5.
d
162.8, 133.9, 119.2, 114.7,
3.97 (s, 3H). 13C NMR (100 MHz, CDCl3)
117.9, 116.4, 52.7.
d 165.4, 133.9, 132.2, 130.1,
4.3.3. 3,4,5-Trimethoxybenzonitrile (3c). EtOAc/Petroleum ether¼1:7
(v/v), Rf¼0.3; white solid; mp 91e93 ꢀC (Lit.19 92e93 ꢀC). 1H NMR
4.3.13. 4-Nitrobenzonitrile (3m). EtOAc/Petroleum ether¼1:7 (v/v),
Rf¼0.3; white solid; mp 143e145 ꢀC (Lit.19 145e147 ꢀC). 1H NMR
(400 MHz, CDCl3)
(100 MHz, CDCl3)
d
6.87 (s, 2H), 3.91 (s, 3H), 3.88 (s, 6H). 13C NMR
153.6, 142.3, 118.9, 109.4, 106.7, 61.0, 56.4.
(400 MHz, CDCl3)
d
8.36 (d, J¼8.8 Hz, 2H), 7.89 (d, J¼8.8 Hz, 2H). 13
C
d
NMR (100 MHz, CDCl3) d 150.0, 133.5, 124.3, 118.3, 116.8.
4.3.4. 4-Hydroxybenzonitrile (3d). EtOAc/Petroleum ether¼1:5 (v/
v), Rf¼0.2; white solid; mp 110e111 ꢀC (Lit.14a 112e113 ꢀC). 1H NMR
4.3.14. 3-Nitrobenzonitrile (3n). EtOAc/Petroleum ether¼1:7 (v/v),
Rf¼0.2; white solid; mp 114e115 ꢀC (Lit.22 115e116 ꢀC). 1H NMR
(400 MHz, CDCl3)
d
7.56 (d, J¼8.8 Hz, 2H), 6.93 (d, J¼8.8 Hz, 2H),
(400 MHz, CDCl3)
d
8.55 (t, J¼1.6 Hz, 1H), 8.50e8.47 (m, 1H), 8.01
6.21 (br, 1H). 13C NMR (100 MHz, CDCl3)
103.4.
d
159.9, 134.3, 119.2, 116.4,
(dt, J1¼8.0 Hz, J2¼1.2 Hz, 1H), 7.75 (dd, J1¼8.0 Hz, J2¼8.4 Hz, 1H). 13
C
NMR (100 MHz, CDCl3) d 148.2, 137.6, 130.6, 127.5, 127.2, 116.5, 114.1.
4.3.5. 4-(tert-Butyl)benzonitrile (3e). EtOAc/Petroleum ether¼1:10
4.3.15. Benzofuran-2-carbonitrile (3o). EtOAc/Petroleum ether¼1:10
(v/v), Rf¼0.5; colorless liquid.20 1H NMR (400 MHz, CDCl3)
d
7.59 (d,
(v/v), Rf¼0.4; colorless liquid.23 1H NMR (400 MHz, CDCl3)
d 7.68 (d,
J¼8.6 Hz, 2H), 7.48 (d, J¼8.7 Hz, 2H),1.33 (s, 9H). 13C NMR (100 MHz,
J¼8.0 Hz, 1H), 7.56 (dd, J1¼8.4 Hz, J2¼0.8 Hz, 1H), 7.51 (td, J1¼7.2 Hz,
CDCl3)
d 156.6, 131.9, 126.1, 119.2, 109.3, 35.3, 30.9.
J2¼1.2 Hz, 1H), 7.46 (d, J¼0.8 Hz, 1H), 7.37 (td, J1¼7.2 Hz, J2¼0.8 Hz,
1H). 13C NMR (100 MHz, CDCl3)
122.6, 118.4, 112.1, 111.8.
d 155.7, 128.4, 127.3, 125.5, 124.5,
4.3.6. 2-Phenylbenzonitrile (3f). EtOAc/Petroleum ether¼1:10 (v/
v), Rf¼0.4; white solid; mp 33e34 ꢀC (Lit.21 35e37 ꢀC). 1H NMR
(400 MHz, CDCl3)
d
7.76 (dd, J1¼8.0 Hz, J2¼1.2 Hz, 1H), 7.64 (td,
4.3.16. Benzo[b]thiophene-2-carbonitrile (3p). EtOAc/Petroleum
ether¼1:10 (v/v), Rf¼0.4; colorless liquid.23 1H NMR (400 MHz,
J1¼7.6 Hz, J2¼1.2 Hz, 1H), 7.58e7.54 (m, 2H), 7.54e7.40 (m, 5H). 13
C
NMR (100 MHz, CDCl3)
127.5, 118.7, 111.3.
d
145.5,138.1, 133.7, 132.8,130.1, 128.7, 128.7,
CDCl3)
d
7.93e7.84 (m, 3H), 7.54 (td, J1¼6.8 Hz, J2¼1.2 Hz, 1H), 7.48
(td, J1¼7.2 Hz, J2¼1.2 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 141.3,
137.5, 135.0, 127.9, 125.7, 125.3, 122.4, 114.5, 109.7.
4.3.7. 1-Naphthonitrile (3g). EtOAc/Petroleum ether¼1:10 (v/v),
Rf¼0.4; white solid; mp 35e37 ꢀC (Lit.14a 36e37 ꢀC). 1H NMR
4.3.17. tert-Butyl benzoate. Colorless liquid.24 1H NMR (400 MHz,
(400 MHz, CDCl3)
d
8.21 (d, J¼8.0 Hz,1H), 8.05 (d, J¼8.4 Hz,1H), 7.90
CDCl3)
d
7.99 (d, J¼8.0 Hz, 2H), 7.52 (dd, J1¼7.6 Hz, J2¼7.2 Hz, 1H),
(d, J¼8.0 Hz, 1H), 7.88 (d, J¼6.8 Hz, 1H), 7.67 (t, J¼7.6 Hz, 1H), 7.60
7.41 (t, J¼7.6 Hz, 2H),1.60 (s, 9H). 13C NMR (100 MHz, CDCl3)
d 165.8,
(dd, J1¼8.0 Hz, J2¼7.2 Hz, 1H), 7.49 (dd, J1¼8.0 Hz, J2¼7.2 Hz, 1H). 13
C
132.4, 132.0, 129.4, 128.2, 80.9, 28.2.
NMR (100 MHz, CDCl3)
d 133.2, 132.8, 132.5, 132.3, 128.6, 128.5,
127.5, 125.0, 124.8, 117.7, 110.1.
Acknowledgements
4.3.8. 2-Naphthonitrile (3h). EtOAc/Petroleum ether¼1:10 (v/v),
Rf¼0.4; white solid; mp 65e66 ꢀC (Lit.19 68e70 ꢀC). 1H NMR
P.L. and Y.W. thank the National Nature Science Foundation of
China (No. 21032005, 21272203 and J1210042) for financial
support.
(400 MHz, CDCl3)
d 8.22 (s, 1H), 7.92e7.87 (m, 3H), 7.68e7.57 (m,
3H). 13C NMR (100 MHz, CDCl3)
d 134.6, 134.1, 132.2, 129.2, 129.0,
128.4, 128.0, 127.6, 126.3, 119.2, 109.4.
Supplementary data
4.3.9. Anthracene-9-carbonitrile (3i). EtOAc/Petroleum ether¼1:10
(v/v), Rf¼0.3; yellow-green solid; mp 174e175 ꢀC (Lit.14a
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.063. These data include MOL files
and InChiKeys of the most importantcompounds described in this
article.
175e176 ꢀC). 1H NMR (400 MHz, CDCl3)
d 8.60 (s, 1H), 8.37 (dd,
J1¼8.8 Hz, J2¼0.8 Hz, 2H), 8.03 (d, J¼8.8 Hz, 2H), 7.68 (td, J1¼8.0 Hz,
J2¼1.2 Hz, 2H), 7.55 (td, J1¼8.0 Hz, J2¼0.8 Hz, 2H). 13C NMR
(100 MHz, CDCl3)
117.2, 105.4.
d 133.2, 132.7, 130.6, 128.9, 128.9, 126.3, 125.2,
References and notes
1. (a) Gebs, M. H.; Abeles, R. H. J. Med. Chem. 1986, 29, 585; (b) Larock, R. C.
Comprehensive Organic Transformations; Wiley-VCH: New York, NY, 1989; pp.
819e995.
2. (a) Fatiadi, A. J. In Preparation and Synthetic Applications of Cyano Compounds;
Patai, S., Rappoport, Z., Eds.; Wiley-VCH: New York, NY, 1983; (b) Rappoport, Z.
Chemistry of the Cyano Group; John Wiley & Sons: London, UK, 1970; pp.
121e312.
4.3.10. 9,9-Diheptyl-9,9a-dihydro-4aH-fluorene-2-carbonitrile
(3j). EtOAc/Petroleum ether¼1:10 (v/v), Rf¼0.4; colorless liquid. 1H
NMR (400 MHz, CDCl3)
d 7.77e7.73 (m, 2H), 7.65e7.59 (m, 2H),
7.42e7.34 (m, 3H), 1.97 (q, J¼6.0 Hz, 4H), 1.22e1.12 (m, 4H),
1.11e0.98 (m, 12H), 0.79 (t, J¼7.2 Hz, 6H), 0.56 (q, J¼6.1 Hz, 4H). 13
C
3. (a) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 2650; (b) Rosenmund, K. W.;
Struck, E. Ber. Dtsch. Chem. Ges. 1919, 52, 1749.
NMR (100 MHz, CDCl3) d 151.4, 151.4, 145.7, 139.1, 131.2, 128.9, 127.2,
Please cite this article in press as: Luo, Y.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.07.063

Y. Luo et al. / Tetrahedron xxx (2013) 1e5
5
4. For some examples, see: (a) Yang, C.; Williams, J. M. Org. Lett. 2004, 6, 2837; (b)
11. Liskey, C. W.; Liao, X.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 11389.
12. Zhang, G.; Zhang, L.; Hu, M.; Cheng, J. Adv. Synth. Catal. 2011, 353, 291.
13. Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2011, 50,
Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 2890; (c) Jia,
X.; Yang, D.; Zhang, S.; Cheng, J. Org. Lett. 2009, 11, 4716; (d) Buono, F. G.;
Chidambaram, R.; Mueller, R. H.; Waltermire, R. E. Org. Lett. 2008, 10, 5325.
5. (a) Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004, 1388; (b) Yan, G.;
Kuang, C.; Zhang, Y.; Wang, J. Org. Lett. 2010, 12, 1052; (c) Yeung, P. Y.; So, C. M.;
Lau, C. P.; Kwong, F. Y. Angew. Chem. 2010, 122, 9102 Angew. Chem., Int. Ed. 2010,
49, 8918; (d) Ren, Y.; Yan, M.; Zhao, S.; Wang, J.; Ma, J.; Tian, X.; Yin, W. Adv.
Synth. Catal. 2012, 354, 2301.
519.
14. (a) Wen, Q. D.; Jin, J. S.; Hu, B. B.; Lu, P.; Wang, Y. G. RSC Adv. 2012, 2, 6167; (b)
Jin, J. S.; Wen, Q. D.; Lu, P.; Wang, Y. G. Chem. Commun. 2012, 9933; (c) Zhang, L.
P.; Wen, Q. D.; Jin, J. S.; Wang, C.; Lu, P.; Wang, Y. G. Tetrahedron 2013, 69, 4236;
(d) Wen, Q. D.; Jin, J. S.; Mei, Y. C.; Lu, P.; Wang, Y. G. Eur. J. Org. Chem. 2013,
4032.
6. (a) Sundermeier, M.; Zapf, A.; Beller, M. Angew. Chem. 2003, 115, 1700 Angew.
Chem., Int. Ed. 2003, 42, 1661; (b) Schareina, T.; Zapf, A.; Cotte, A.; Gotta, M.;
Beller, M. Adv. Synth. Catal. 2011, 353, 777; (c) Chatani, N.; Hanafusa, T. J. Org.
Chem. 1986, 51, 4714; (d) Luo, F.; Chu, C.; Cheng, C. Organometallics 1998, 17,
1025; (e) Jiang, Z.; Huang, Q.; Chen, S.; Long, L.; Zhou, X. Adv. Synth. Catal. 2012,
354, 589; (f) Zheng, S.; Yu, C.; Shen, Z. Org. Lett. 2012, 14, 3644; (g) Xu, S.;
Huang, X.; Hong, X.; Xu, B. Org. Lett. 2012, 14, 4614; (h) Peng, J.; Zhao, J.; Hu, Z.;
Liang, D.; Huang, J.; Zhu, Q. Org. Lett. 2012, 14, 4966.
15. Yuen, O. Y.; Choy, P. Y.; Chow, W. K.; Wong, W. T.; Kwong, F. Y. J. Org. Chem. 2013,
78, 3374.
16. For some examples of benzylic oxidation using TBHP as an oxidant, see: (a)
Iwata, S.; Hata, T.; Urabe, H. Adv. Synth. Catal. 2012, 354, 3480; (b) Wu, X.;
Bheeter, C. B.; Neumann, H.; Dixneuf, P. H.; Beller, M. Chem. Commun. 2012,
12237; (c) Gephart, R. T.; McMullin, C. L.; Sapiezynski, N. G.; Jang, E. S.; Aguila,
M. J. B.; Cundari, T. R.; Warren, T. H. J. Am. Chem. Soc. 2012, 134, 17350; (d) Feng,
J.; Liang, S.; Chen, S.-Y.; Zhang, J.; Fu, S.-S.; Yu, X.-Q. Adv. Synth. Catal. 2012, 354,
1287; (e) Shi, E.; Shao, Y.; Chen, S.; Hu, H.; Liu, Z.; Zhang, J.; Wan, X. Org. Lett.
2012, 14, 3384.
7. (a) Chen, X.; Hao, X. S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128,
6790; (b) Ding, S. T.; Jiao, N. J. Am. Chem. Soc. 2011, 133, 12374.
8. (a) Kim, J.; Chang, S. J. Am. Chem. Soc. 2010, 132, 10272; (b) Ren, X.; Chen, J.;
Chen, F.; Cheng, J. Chem. Commun. 2011, 6725; (c) Zhang, G. Y.; Ren, X. Y.; Chen,
J. B.; Hu, M. L.; Cheng, J. Org. Lett. 2011, 13, 5004; (d) Kim, J.; Choi, J.; Shin, K.;
Chang, S. J. Am. Chem. Soc. 2012, 134, 2528; (e) Kim, J.; Kim, H.; Chang, S. Org.
Lett. 2012, 14, 3924; (f) Wang, Z.; Chang, S. Org. Lett. 2013, 15, 1990.
9. For several reviews, see: (a) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg.
Chem. 2003, 3513; (b) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev.
2011, 40, 5049; (c) Kim, J.; Kim, H. J.; Chang, S. Angew. Chem. 2012, 124, 12114
Angew. Chem., Int. Ed. 2012, 51, 11948.
17. Tsoi, Y.; Zhou, Z.; Yu, W.-Y. Org. Lett. 2011, 13, 5370.
18. Han, W.; Liu, C.; Jin, Z. Adv. Synth. Catal. 2008, 350, 501.
19. Suzuki, Y.; Yoshino, T.; Moriyama, K.; Togo, H. Tetrahedron 2011, 67, 3809.
20. Zhou, W.; Xu, J.; Zhang, L.; Jiao, N. Org. Lett. 2010, 12, 2888.
21. Portela-Cubillo, F.; Surgenor, B. A.; Aitken, R. A.; Walton, J. C. J. Org. Chem. 2008,
73, 8124.
22. Cristau, H.-J.; Ouali, A.; Spindler, J.-F.; Taillefer, M. Chem.dEur. J 2005, 11, 2483.
23. Ushijima, S.; Moriyama, K.; Togo, H. Tetrahedron 2011, 67, 958.
24. Chen, C.-T.; Kuo, J.-H.; Pawar, V. D.; Munot, Y. S.; Weng, S.-S.; Ku, C.-H.; Liu, C.-Y.
J. Org. Chem. 2005, 70, 1188.
10. Zhang, Z.; Liebeskind, L. S. Org. Lett. 2006, 8, 4331.
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