Palladium-catalyzed cyanation of aryl perfluorooctylsulfonates

Article abstract of DOI:10.1071/CH08095

Cyanation of aryl perfluorooctylsulfonates with potassium hexacyanoferrate(ii) catalyzed by an efficient catalyst system comprising Pd(OAc)₂, CuI and PPh₃ or 1,1′- bis(diphenylphosphino)ferrocene (dppf) is described. CSIRO 2008.

Full text of DOI:10.1071/CH08095

Corrigendum
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Aust. J. Chem. 2010, 63, 1311
Palladium-Catalyzed Cyanation of Aryl
Perfluorooctylsulfonates
Yi-Zhong Zhu and Chun Cai
(Vol. 61, no. 8, pp. 581–584)
The publisher wishes to apologize for the error that appeared in
reference 8m for the above article.
The correct reference should have read:
[8] (m) A. W. Franz, L. N. Popa, T. J. J. Müller, Tetrahedron Lett.
2008, 49, 3300. doi:10.1016/J.TETLET.2008.03.071
© CSIRO 2010
10.1071/CH08095_CO
0004-9425/10/081311

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CSIRO PUBLISHING
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Aust. J. Chem. 2008, 61, 581–584
Palladium-Catalyzed Cyanation of Aryl
Perfluorooctylsulfonates
Yi-Zhong ZhuA and Chun CaiA,B
AChemical Engineering College, Nanjing University of Science and Technology,
Nanjing 210094, China.
BCorresponding author. Email: c.cai@mail.njust.edu.cn
Cyanation of aryl perfluorooctylsulfonates with potassium hexacyanoferrate(ii) catalyzed by an efficient catalyst system
comprising Pd(OAc)2, CuI and PPh3 or 1,1ꢀ-bis(diphenylphosphino)ferrocene (dppf) is described.
Manuscript received: 5 March 2008.
Final version: 11 June 2008.
Aryl nitriles are important compounds not only for their interest-
ingbiologicalproperties, butalsobecauseoftheiruseasversatile
starting materials for many important aromatic compounds,
including acids, ketones, oximes, and amines.[1,2] Various meth-
ods for the synthesis of aryl nitriles have been reported. In
general, the most direct and versatile method is based on the
transition metal-mediated displacement of aromatic halides and
triflates by the cyanide ion. Since the discovery of transi-
tion metal-catalyzed cross-coupling reactions, much interest has
been shown in the development of a practical version of this
transformation. Until now, several successful palladium-[3,4] and
nickel-catalyzed[5,6] displacements of aryl halides and triflates
with the cyanide ion to afford the corresponding aryl nitriles
have been reported. However, most of the work concentrated on
the inconvenient traditional cyanide sources, which have some
severe drawbacks. To avoid these problems, potassium hexa-
cyanoferrate(ii) was rediscovered as a non-toxic cyanide source
by Beller in 2004.[7] This procedure provided, for the first time,
a generally applicable and relatively non-toxic approach for the
synthesis of various aryl nitriles. Since then, several publica-
tions have reported the development of new catalytic systems for
cyanation using potassium hexacyanoferrate(ii) as the cyanide
source.[8]
Aryl perfluoroalkanesulfonates are well-known aryl halide
equivalents for palladium-catalyzed coupling reactions owing
to the diversity of available phenols and the simple conversion
of phenols to aryl perfluoroalkanesulfonates,[9] making it clear
that the cyanation of aryl perfluoroalkanesulfonates as an alter-
native route to aryl nitriles will have significant synthetic value.
However, most accounts of cyanations focussed on the use of
aryl triflate rather than other aryl perfluoroalkanesulfonates.[4,6]
In a close look at the literature, the only other report
that deals with the cyanation of 3-(methoxycarbonyl)-1,2,3,4-
tetrahydro-1-oxonaphthalen-6-yltrifluoromethanesulfonatecat-
alyzed by Pd(OAc)2 using potassium hexacyanoferrate(ii) as
the cyanide source was shown by Torrado and coworkers.[10]
However, the yield of the corresponding product was moderate
(43%). Aryl perfluorooctylsulfonates are an attractive alter-
native to triflates because of the following reasons: (1) aryl
perfluorooctylsulfonates can easily be prepared from commer-
cially available phenols and are stable to chromatography and
storage at room temperature;[11] (2) aryl perfluorooctylsul-
fonateshavebeenshowntohavereactivitysimilartoaryltriflates
in cross-coupling reactions such as Suzuki,[11b] amination,[11e]
and reduction,[11c] and are more stable toward hydrolysis; and
(3) it is also noteworthy that perfluorooctylsulfonates contain-
ing a light C8F17 chain can be used as a fluorous tag for
the fluorous solid-phase extraction (F-SPE) separation to sim-
plify reaction mixture purifications in multistep synthesis.[11]
However, no detailed study of palladium-catalyzed cyanation
of aryl perfluorooctylsulfonates has been reported. Following
our interest in the cyanation,[12] herein we present our stud-
ies toward the conversion of phenols via their corresponding
aryl perfluorooctylsulfonates[13] to aryl nitriles using potassium
hexacyanoferrate(ii) as the cyanide source.
Our goal was to find an efficient approach to synthesize
aryl nitriles from phenols via their corresponding aryl per-
fluorooctylsulfonates using potassium hexacyanoferrate(ii). As
indicated in Table 1, we chose the reaction of phenyl perfluoro-
octylsulfonate with K4[Fe(CN)6], which was ground to a fine
powder and dried under a high vacuum at 80◦C overnight, as a
model for exploring optimized reaction conditions. Because the
perfluoroalkanesulfonate group is an excellent leaving group,[9]
conversion of phenyl perfluorooctylsulfonate into benzonitrile
was initially tried using standard conditions for the cyanation of
aromatic halides (Pd(OAc)2 only),[8a,8b] but the yield of our tar-
get product, benzonitrile, was low, with recovery of significant
amounts of unreacted phenyl perfluorooctylsulfonate (entry 1).
Increasing the amount of Pd(OAc)2 and adding PPh3 as ligand
only led to a slight increase in product yields (entries 2, 3). After
switching from PPh3 to 1,1ꢀ-bis(diphenylphosphino)ferrocene
(dppf), the yield was enhanced to 73% (entry 4). Cyana-
tion of phenyl perfluorooctylsulfonate under the catalysis of
Pd(dppf)Cl2, a good catalyst in some cross-coupling reactions
using aryl perfluorooctylsulfonates as substrates,[11a–11d] pro-
vided the corresponding product in 76% yield (entry 5). As
addition of copper salts has recently been shown to increase reac-
tion rates in palladium-catalyzed cyanation,[8k,14] we attempted
© CSIRO 2008
10.1071/CH08095
0004-9425/08/080581

582
Y.-Z. Zhu and C. Cai
Table 1. Evaluation of various reaction conditions
Table 2. Pd-catalyzed cyanation of various aryl perfluorooctylsul-
fonates
Reaction conditions: 1 mmol aryl perfluorooctylsulfonate, 20 mol-%
dry K4[Fe(CN)6], 2 mol-% Pd(OAc)2, 4 mol-% PPh3, 3 mL DMF,
100 mol-%Na2CO3, 10 mol-% CuI, 140◦C, N2 atmosphere, 5 h
Reaction conditions: 1 mmol phenyl perfluorooctylsulfonate, 2 mol-%
Pd(OAc)2, 20 mol-% dry K4[Fe(CN)6], 3 mL DMF, 100 mol-% Na2CO3,
10 mol-% additive, 140◦C, N2 atmosphere
LigandA
Additive
[10 mol-%]
Time
[h]
Yield
[%]B
Pd(OAc)2/CuI/PPh3 (or dppf)
R
R
Entry
CN
OPf
K4[Fe(CN)6]
1
2
3
4
5
6
7
8
9
–
–
–
–
–
24
24
24
24
24
5
5
5
5
5
33C
38
46D
73D
76E
95
Pf ϭ ϪSO2(CF2)7CF3
2
1
PPh3
PPh3
dppf
–
PPh3
PPh3
PPh3
PPh3
PPh3
Entry
1
Aryl perfluorooctylsulfonate
Aryl nitriles
Yield [%]A
91 (82)
–
CuI
Cu(OAc)2
CuI
CuI
OPf
2a
2b
12
0F
54G
11H
OPf
OPf
10
CuI
2
90 (81)
ALigand:Pd = 2/1.
BYields were determined by gas chromatography with 1,3-dimethoxy-
benzene as the internal standard.
C0.1 mol-% Pd(OAc)2 was used.
D5 mol-% Pd(OAc)2 was used.
E5 mol-% Pd(dppf)Cl2 was used.
FNo Pd(OAc)2.
3
4
2c
89 (82)
87 (80)
Ph
OPf
2d
MeO
GSolvent: DMAc.
HSolvent: NMP.
OPf
5
6
2e
2f
93 (85)
92 (83)
F3C
OPf
to add simple copper salts to improve the yield.As we expected, a
higher yield and shorter time were obtained by adding 10 mol-%
CuI (entry 6). In contrast to what has been previously
observed,[8k] the reaction afforded benzonitrile only in a poor
yield of 12% when adding Cu(OAc)2 (entry 7). A blank test
using CuI without Pd(OAc)2 gave no corresponding product
(entry 8). The beneficial effect of CuI as an additive prompted
us to examine other copper salts and iodine salts in the cyana-
tion of phenyl perfluorooctylsulfonate. In agreement with our
previous results on the cyanation of aryl triflates, other salts
such as CuBr, CuCl, CuCl2, CuBr2, CuO, AgI, KI, and ZnI2
were far less effective than CuI. In addition, a switch in the sol-
venttoN,N-dimethylacetamide(DMAc)orN-methylpyrolidone
(NMP) gave inferior results (entries 9, 10). This is opposite to
that noticed in the cyanation of aryl triflates, in which DMAc as
a solvent gives the best result.
F
OPf
7
8
2g
2h
91 (84)
Cl
OPf
93 (87)B
OPf
9
2i
2j
91 (84)B
OMe
OPf
10, 11
14 (6)C
76 (68)D
After optimized reaction conditions were obtained, the reac-
tion scope was explored with various aryl perfluorooctylsul-
fonates. The results are summarized in Table 2. It was found
that meta-substituted and para-substituted aryl perfluorooctyl-
sulfonates were suitable for the reaction conditions, giving the
desired products in good to excellent yields (entries 1–7). When
4-chlorophenyl perfluorooctylsulfonate was used as the sub-
strate, only the product reacted at the C–O bond was isolated
in 84% yield (entry 7), which implies that there existed great
selectivity between aryl perfluorooctylsulfonates and aryl chlo-
rides under the present reaction conditions. Also, extension to
synthetic access to naphthyl derivatives was also achieved in
good yields with lower catalyst loading (entries 8, 9). Con-
version of ortho-substituted aryl perfluorooctylsulfonate was
affected by the steric environment around the reaction site,
as 2-methoxyphenyl perfluorooctylsulfonate, an electron-rich
aryl perfluorooctylsulfonate, gave a considerably lower yield in
comparison with that of less hindered 4-methoxyphenyl perfluo-
rooctylsulfonate, even adding more catalyst and prolonging the
AYields were determined by gas chromatography with 1,3-
dimethoxybenzene as the internal standard. Numbers in parentheses
show isolated yields.
B1 mol-% Pd(OAc)2 and 2 mol-% PPh3 were used.
C4 mol-% Pd(OAc)2 and 8 mol-% PPh3 were used with a reaction time of
24 h.
Ddppf used instead of PPh3.
reaction time (compare entries 4 and 10). In this case, using
dppf as the ligand instead of PPh3 gave the product in 68% yield
(entry 11).
To conclude, we have developed an efficient catalyst sys-
tem for the cyanation of aryl perfluorooctylsulfonates with
K4[Fe(CN)6] by using Pd(OAc)2/CuI as catalyst and PPh3 or
dppf as ligand. An important value of the protocol we describe
lies in the use of a readily available and cheap catalyst sys-
tem based on Pd(OAc)2, CuI and PPh3 or dppf. Furthermore,
the diversity of available phenols and the simple conversion

Palladium-Catalyzed Cyanation of Aryl Perfluorooctylsulfonates
583
of phenols to aryl perfluorooctylsulfonates and the non-toxic
cyanide source make this catalytic reaction attractive as a syn-
thetic method for aryl nitriles. Application of a fluorous tag for
multistep synthesis is currently under investigation in our group.
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General Procedure for the Cyanation of Aryl
Perfluorooctylsulfonates
After standard cycles of evacuation and filling with dry and
pure nitrogen, an oven-dried tube was charged with 1 mmol
aryl perfluorooctylsulfonate, 20 mol-% K4[Fe(CN)6], 2 mol-%
Pd (OAc)2, 4 mol-% PPh3, 10 mol-% CuI, 1 mmol Na2CO3, and
3 mL of DMF. The tube was evacuated and filled with nitro-
gen. Then the tube was sealed, and the mixture was stirred at
140◦C for 5 h. After cooling to room temperature, the mix-
ture was diluted with ethyl acetate (30 mL) and filtered. Then
1,3-dimethoxybenzene (130 µL) was added as the internal stan-
dard. The filtrate was washed with water (3 × 10 mL) and
analyzed by gas chromatography (GC). The GC yields were
determined by obtaining correction factors using authentic sam-
ples of the expected products. For isolating the products: after
the reaction was completed, the mixture was diluted with ethyl
acetate (30 mL) and filtered. The filtrate was washed with water
(3 × 10 mL).The organic phase was dried over Na2SO4, filtered,
and concentrated under vacuum. Finally, the product was iso-
lated by flash chromatography on silica gel with EtOAc/light
petroleum as the eluent. All prepared aryl nitriles are known
compounds and identified by GC–mass spectrometry.
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