Room-temperature hydrodehalogenation of halogenated heteropentalenes with one or two heteroatoms

Article abstract of DOI:10.1021/jo3019335

The pair NaBH₄-TMEDA as a hydride source and catalytic PdCl ₂(dppf) in THF prove to be an efficient system for the hydrodehalogenation of bromo(chloro)-heteropentalenes with one or two heteroatoms, while Pd(OAc)₂/PPh₃ is able to reduce reactive haloheteropentalenes, and PdCl₂(tbpf) allows the removal of the 2-chlorine from a thiophene ring. The reaction conditions tolerate various functional groups, allowing highly chemoselective reactions in the presence of halide, ester, alkyne, alkene, and nitrile substituents and also showing good efficiency in the regioselective hydrodehalogenation of a variety of polyhalogenated substrates.

Full text of DOI:10.1021/jo3019335

Note
pubs.acs.org/joc
Room-Temperature Hydrodehalogenation of Halogenated
Heteropentalenes with One or Two Heteroatoms
Giorgio Chelucci,* Salvatore Baldino, and Andrea Ruiu
̀
Dipartimento di Agraria, Universita di Sassari, Viale Italia 39, I-07100 Sassari, Italy
S
* Supporting Information
ABSTRACT: The pair NaBH4−TMEDA as a hydride source and catalytic
PdCl2(dppf) in THF prove to be an efficient system for the hydro-
dehalogenation of bromo(chloro)-heteropentalenes with one or two heter-
oatoms, while Pd(OAc)2/PPh3 is able to reduce reactive haloheteropentalenes,
and PdCl2(tbpf) allows the removal of the 2-chlorine from a thiophene ring. The
reaction conditions tolerate various functional groups, allowing highly chemoselective reactions in the presence of halide, ester,
alkyne, alkene, and nitrile substituents and also showing good efficiency in the regioselective hydrodehalogenation of a variety of
polyhalogenated substrates.
Recently, in a preliminary study we have found that the
he substitution of halogens from aromatic rings by
Thydrogen is an important chemical transformation in system formed by the pair NaBH4 and TMEDA (N,N,N′,N′-
tetramethylethylenediamine) as a hydride source in combina-
tion with a palladium catalyst is an efficient system for the
hydrodehalogenation of halopyridine derivatives.14 The good
results obtained in that work prompted us to verify the
potential of this system for the removal of halogens in less
reactive heterocycles. In this paper we wish to report that this
system is able to hydrodehalogenate efficiently and selectively a
variety of halogenated heteropentalenes with one or two
heteroatoms at room temperature.
Starting our investigation to optimize the reaction con-
ditions, the hydrodehalogenations were carried out with 2-
bromo-5-phenylthiophene 1 as a model substrate. Initial
experiments were performed at room temperature with
Pd(OAc)2 (5 mol %) and PPh3 (20 mol %) as the catalytic
system, and an excess of the couple NaBH4−TMEDA (1.7
equiv) in THF (Method A). Under these reaction conditions
the substitution of the bromine with hydrogen was incomplete
after 24 h (Table 1, entry 1). However, by doubling the amount
of NaBH4−TMEDA (3.4 equiv) (Method B) complete
conversion was achieved after 2 h and the product, 2-
phenylthiophene 2 was isolated in 94% yield (entry 2). Also
when PdCl2(dppf) [dppf = 1,1′-bis(diphenylphosphino)-
ferrocene] (5 mol %) was used as the catalyst in combination
with 1.7 equiv of the reducing system (Method C) incomplete
conversion occurred after 24 h (entry 3), but by using 3.4 equiv
of NaBH4−TMEDA (Method D) the reaction was complete in
1 h and 2 was formed in 92% yield (entry 4).
organic synthesis, and a wide variety of hydrodehalogenating
systems have been developed over the years for this purpose.1
Reduction is usually mediated by a transition-metal catalyst (Ni,
Pd, Rh, Pt) and is performed with molecular hydrogen, metal
hydrides, or hydrogen sources such as formic acid and its salts,
hydrazine, alkoxides possessing a β-hydrogen, etc.1 However,
the application of these systems to halogenated heterocycles is
rather sporadic, most often accomplished by catalytic hydro-
genation on a metal catalyst, Pd−C2 or Raney Nickel,3 and a
halogen−metal exchange reaction.4 These processes are often
troublesome to execute since the former ignites easily and the
latter requires anhydrous conditions and low reaction temper-
atures. For safety and simplicity of operation, a liquid-phase
process without using molecular hydrogen is more advanta-
geous.
Interestingly, some alternative methods have been recently
described, such as (i) hydrogenolysis of aryl halides with
catalytic Pd/C in the presence of hydrazine hydrochloride;5 (ii)
indium-mediated dehalogenation of haloheteroaromatics in
water;6 (iii) reduction of chloroarenes by Pd(OAc)2 in
combination with polymethylhydrosiloxane and aqueous KF,7
(iv) dehalogenation of activated and unactivated aryl halides by
catalytic Pd-complexes under transfer reaction conditions,8,9
(vi) deiodination10 and dechlorination11 with sodium formate
and catalytic palladium catalysts, (vii) Fe(acac)3 catalyzed
hydrodehalogenation of aryl halides with t-BuMgCl as a
reductant,12 and (viii) hydrodehalogenation with sodium
borohydride (NaBH4).13,14 However, most of these methods
appear limited to halopyridines, since they have only occasion-
ally been applied to other halogenated heterocycles, in
particular to brominated thiophenes5,9,12,13a,b and just in one
case to a different heteropentalene, namely to 5-iodopyrr-
roles.10 Thus, the development of a facile and general method
for the dehalogenation of heteroaromatic halides, besides
pyridines, is still of great value.
These findings appeared to indicate that both Pd(OAc)2/
PPh3 and PdCl2(dppf) in combination with a large excess of
NaBH4−TMEDA form efficient reducing systems for the rapid
and high yielding debromination of 1. This trend was
confirmed for the removal of the 2-bromine of the
Received: September 11, 2012
Published: October 17, 2012
© 2012 American Chemical Society
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Note
bromo derivatives of benzothiophene 6, 1-methylindole 7, and
benzofuran 9 was performed efficiently with method D
affording high yields (85−93%) of the parent heterocycles,
with the exception of 9 that gave benzofuran in a lower isolated
yield (64%) (entry 14).
Table 1. Hydrodehalogenation of Halogenated
Heteropentalenes
a
In the series of the heteropentalenes with two heteroatoms,
2-bromo-4-phenylthiazole was hydrodehalogenated efficiently
by method B (entry 16). Methods B and D were also successful
in the reduction of the low reactive 2-chlorine in the thiazole 13
(entries 16 and 18), but failed to remove the 5-chlorine from
the thiazole 14. On the other hand, this goal was efficiently
achieved by the complex PdCl2(tbpf) [tbpf = 1,1′-bis(di-tert-
butylphosphino)ferrocene] that required in any case heating at
65 °C to afford complete conversion (entry 21, Method E).
Finally, the removal of the bromine from 1-benzyl-2-
bromoimidazole was efficiently obtained with method B
(entry 22).
The removal of the chlorine from a thiophene ring was then
addressed, since this goal had been achieved only in some well-
defined cases.15 After several experiments with different
catalytic systems we found that the hydrodehalogenation of
2-chloro-5-phenylthiophene was more efficiently obtained by
using 5 mol % PdCl2(tbpf) at 65 °C for 8 h (96% yield) (entry
5, Table 2).
Table 2. Hydrodechlorination of 2-Chloro-5-
phenylthiophene
b
c
temp
(°C)
time
(h)
conv.
yield
(%)
a
entry
catalyst (mol %)
(P/S)
1
2
3
4
5
6
7
8
PdCl2(dppf) (5)
PdCl2(dppf) (5)
PdCl2(dppf)(10)
PdCl2(tbpf) (5)
PdCl2(tbpf) (5)
rt
48
48
24
48
8
30/70
35/65
100/0
32/68
100/0
100/0
12/88
62/38
nd
nd
85
nd
96
78
nd
nd
65
65
rt
65
65
rt
Pd2(dba)3/tbpf (2.5/5)
(A.caPhos)PdCl2 (5)
24
48
48
d
Pd2(dba)3/DavePhos
rt
e
(2.5/5)
9
Pd2(dba)3/P(t-Bu)3
(2.5/10)
rt
48
56/44
nd
a
Reaction conditions: heterocycle (0.66 mmol), catalyst, NaBH4 (3.4
b
1
equiv), TMEDA (3.4 equiv), THF (13.2 mL). Determined by H
c
NMR as product/starting compound ratio. Isolated yields.
d
(A.caPhos)PdCl2: bis[(dicyclohexyl)(4-dimethylaminophenyl)-
e
phosphine] palladium(II) chloride. DavePhos: 2-dicyclohexylphos-
a
Reaction conditions: heterocycle (0.66 mmol), catalyst, NaBH4/
phino-2′-(N,N-dimethylamino)biphenyl.
TMEDA, THF (13.2 mL). Method = A: Pd(OAc)2/PPh3 (5/20 mol
%), NaBH4−TMEDA (1.7/1.7 equiv); B: Pd(OAc)2/PPh3 (5/20 mol
%), NaBH4−TMEDA (3.4/3.4 equiv); C: PdCl2(dppf)] (5 mol %),
NaBH4−TMEDA (1.7/1.7 equiv); D: PdCl2(dppf)] (5 mol %),
NaBH4−TMEDA (3.4/3.4 equiv); E: PdCl2(tbpf) (5 mol %),
Next, the chemoselective reduction of some haloheteropen-
talenes was investigated (Table 3). The reducing system
showed high chemoselectivity (Br vs Cl) and functional group
tolerance, e.g., ester, alkyne, alkene, and nitrile substituents.
On the basis of the above results, the regioselective
hydrodehalogenation of some polyhalogenated substrates was
examined (Table 4). The simple catalyst Pd(OAc)2/PPh3 was
reactive enough to promote the selective removal with high
yields of the 2-bromo substituent in thiophenes 27 and 29,
benzothiophene 30, and 1-methylindole 31, leaving the
bromine unchanged in the other positions. Regioselective
hydrodehalogenation of 2,6-dichlorobenzo[d]thiazole was also
possible, and only the 2-chlorine was reduced. The hydro-
b
NaBH4−TMEDA (1.7/1.7 equiv). Determined by 1H NMR as
c
d
product/starting compound ratio. Isolated yields. Reaction carried
out at 65 °C.
benzothiophene ring 3 (entry 5 vs 7). Therefore, the
hydrodehalogenation of other haloheteropentalenes was
evaluated by employing these catalytic systems.
The known lower reactivity of the β-bromine in thiophene
was evident since PdCl2(dppf) (Method D) was necessary to
remove this halide (entry 9). Similarly, the reduction of the 3-
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Note
Table 3. Chemoselective Hydrodehalogenation of
Halogenated Heteropentalenes
Table 4. Regioselective Hydrodehalogenation of
Halogenated Heteropentalenes
a
a
a
Reaction conditions: heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol
%), PPh3 (20.0 mol %), NaBH4 (3.4 equiv), TMEDA (3.4 equiv),
b
c
THF (13.2 mL) at rt. Isolated yields. Reaction carried out with
PdCl2(dppf) (5.0 mol %) at 65 °C.
dehalogenation of 2,5-dibromo-4-phenylthiazole was less
satisfactory. With method B a mixture of 5-bromo-4-phenyl-
thiazole 35 and 4-phenylthiazole 12 in a 90/10 ratio was
obtained. When the reaction was carried out at 0 °C the 35/12
ratio was increased up to 93/7. Several attempts to improve the
selectivity by using different catalytic systems failed. Thus, for
instance, the use of both Pd2(dba)3 (2.5 mol %) and Pd(OAc)2
(5 mol %) in combination with XantPhos (5 mol %) at 0 °C
gave a mixture of 35 and 12 in high yield, but with a ratio of
only 86/14. Finally, the hydrodehalogenation of the more
demanding 1-benzyl-2,4,5-tribromoimidazole was examined.
Method B at room temperature gave a mixture of 1-benzyl-
4,5-dibromoimidazole 37 and 1-benzyl-4-bromoimidazole 38 in
a 63/17 ratio, containing also traces (<5%) of 1-benzylimida-
zole. Reducing the number of equivalents of the reductant from
3.4 to 2.5 increased only slightly the selectivity (37/38 = 76/
24), while a further decrease to 1.7 equiv gave only partial
conversion of the starting material after 72 h. After a series of
optimization experiments, the combination of Pd2(dba)3 (2.5
mol %) and XantPhos (5 mol %) at 0 °C was found to produce
with good yield 37 and 38 in an 87/13 ratio.
a
Reaction conditions: heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol
%), PPh3(20.0 mol %), NaBH4 (3.4 equiv), TMEDA (3.4 equiv), THF
b
c
(13.2 mL) at rt. Isolated yields. Reaction carried out at 0 °C.
d
e
1
Isolated yields of 35 (84%) and 12 (6%). Determined by H NMR
f
of the crude reaction mixture. Reaction carried out with Pd2(dba)3/
XantPhos (2.5/5 mol %) at 0 °C. Isolated yields of 37 (72%) and 38
(11%).
g
considerably enhances the performance of NaBH4.13d On the
basis of the generally accepted mechanism that includes
oxidative addition, hydride transfer (transmetalation), and
reductive elimination, the effect of TMEDA can be threefold:
(a) weak coordination to the electronically and coordinatively
unsaturated intermediate in the form of [Pd(ligand)-
(TMEDA)] thereby stabilizing the catalyst and minimizing
catalyst decomposition (the weak donor ability of TMEDA
ensures its cleavage upon entry of the substrate); (b) capture of
−
BH3 from BH4 provides an extra drive for hydride transfer to
the Pd center (ArBr + NaBH4 + 1/2TMEDA → ArH + NaBr +
1/2TMEDA•2BH3), with the resultant TMEDA•2BH3 adduct
possibly serving as an additional hydride source;16 (c)
alternative debromination pathway through the elimination of
HBr.
Since in the examined haloheteropentalenes the reactivity of
C-halogen bonds varies significantly from one substrate to
another, the rates and yields of the dehalogenation depend
critically on the choice of the catalyst, amount of the pair
NaBH4 and TMEDA, temperature, and reaction time. The
dehalogenation efficiency of NaBH4−TMEDA arises from the
fact that the addition of a nitrogen-base, especially TMEDA,
In conclusion, the pair NaBH4−TMEDA as a hydride source
and catalytic PdCl2(dppf) in THF prove to be an efficient
system for the hydrodehalogenation of bromo(chloro)-
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Note
Procedure Using Preformed Catalysts PdCl2(dppf), PdCl2(tbpf),
and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66
mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon
for a few minutes. Then, PdCl2(dppf)·CH2Cl2 (27.0 mg, 0.033 mmol,
5.0 mol %), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv), and finally
NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence.
The mixture was stirred at room temperature under argon for the
proper time and then worked up as described above.
heteropentalenes with one or two heteroatoms, while the
simple and inexpensive catalyst Pd(OAc)2/PPh3 is able to
reduce reactive haloheteropentalenes. In addition, PdCl2(tbpf)
has allowed the highly efficient removal of the 2-chlorine from a
thiophene ring, which is rather sluggish with other reagents.
The reaction conditions tolerate various functional groups,
allowing highly chemoselective reactions in the presence of
halide, ester, alkyne, alkene, and nitrile substituents and also
showing good efficiency in the regioselective hydrodehaloge-
nation of a variety of polyhalogenated substrates. The practical
and selective methodology offers a very powerful, low-cost, and
safe approach for the hydrodehalogenation of halogenated
heteroaromatics and may constitute a key step in the synthesis
of complex molecules.
5-Chloro-4-phenylthiazole (14). The title compound was
prepared according to the general procedure, as described above
(Table 3), and purified by flash chromatography using petroleum
ether/AcOEt = 95/5 to give compound 14 as an oil (0.102 mg, 79%):
1H NMR: δ 8.66 (s, 1H), 7.99−7.93 (m, 2H), 7.49−7.34 (m, 3H). 13
C
NMR: δ 150.2, 149.7, 132.5, 128.5, 128.3, 128.2, 121.2. Anal. Calcd for
C9H6ClNS: C, 55.24; H, 3.09; N, 7.16. Found: C, 55.12; H, 3.13; N,
7.12.
2-(4-Vinylphenyl)benzo[b]thiophene (24). The title compound
was prepared according to the general procedure, as described above
(Table 3), and purified by flash chromatography using petroleum ether
to give compound 24 as a a white solid (0.141 g, 91%): mp 195−196
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out under
nitrogen in oven-dried glassware with magnetic stirring. Unless
otherwise noted, all materials were obtained from commercial
suppliers and were used without further purification. All solvents
were reagent grade. THF was distilled from sodium-benzophenone
ketyl and degassed thoroughly with dry nitrogen directly before use.
Unless otherwise noted, organic extracts were dried with Na2SO4,
filtered through a fritted glass funnel, and concentrated with a rotary
evaporator (20−30 mmHg). Flash chromatography was performed
with silica gel (200−300 mesh) using the mobile phase indicated.
Melting points are uncorrected. The NMR spectra were measured on a
1
°C; H NMR: δ 7.82 (d, 1H, J = 7.5 Hz), 7.77 (d, 1H, J = 7.5 Hz),
7.68 (d, 2H, J = 8.2 Hz), 7.55 (s, 1H), 7.47 (d, 2H, J = 8.2 Hz), 7.37−
7.29 (m, 2H), 6.75 (dd, 1H, J = 17.1, 10.9 Hz), 5.81 (dd, 1H, J = 17.1,
0.8 Hz), 5.30 (dd, 1H, J = 10.9, 0.8 Hz). 13C NMR: δ 143.9, 140.7,
139.5, 137.5, 136.2, 133.7, 126.8, 126.6, 124.6, 124.4, 123.6, 122.3,
119.4, 114.4. Anal. Calcd for C16H12S: C, 81.31; H, 5.12. Found: C,
81.51; H, 5.16
2-(3-Cyanophenyl)benzo[b]thiophene (26). The title com-
pound was prepared according to the general procedure, as described
above (Table 3), and purified by flash chromatography using
petroleum ether/AcOEt = 8/2 to give compound 26 as a white
1
spectrometer at 300 MHz for H and 75.4 MHz for 13C in CDCl3
1
solution with TMS as an internal standard. Chemical shifts (δ) are
given in parts per million, and coupling constants (J), in hertz.
3-Bromobenzo[b]thiophene 6, 2-bromo-4-phenylthiazole 11, 2-
chloro-4-phenylthiazole 13, 2,3-dibromobenzo[b]thiophene 30, and
2,6-dichlorobenzo[d]thiazole 32 were commercial starting materials.
2-Bromo-5-phenylthiophene 1,17 2-bromobenzo[b]thiophene 3,18
4-bromo-2-phenylthiophene 5,19 3-bromo-1-methyl-1H-indole 7,20 3-
bromobenzofuran 9,21 2-chlorobenzo[d]thiazole 13,22 1-benzyl-2-
bromo-1H-imidazole 15,23 2-chloro-5-phenylthiophene 17,24 methyl
5-bromothiophene-2-carboxylate 19,25 3,5-dibromo-2-phenylthio-
phene 29,19 2,3-dibromo-1-methyl-1H-indole 31,26 2,5-dibromo-4-
phenylthiazole 34,27 and 1-benzyl-2,4,5-tribromo-1H-imidazole 3628
were prepared according to reported procedures.
Analytical and spectra data of the products 2-phenylthiophene 2,
benzo[b]thiophene 4, and benzofuran 10 were identical to those
obtained from commercial starting materials. Analytical and spectra
data of the products 4-bromo-2-phenylthiophene 5,19 1-methyl-1H-
indole 8,29 4-phenylthiazole 12,30 1-benzyl-1H-imidazole 16,31 methyl
thiophene-2-carboxylate 20,32 3-bromo-2-(phenylethynyl)benzo[b]-
thiophene 21,33 2-(phenylethynyl)benzo[b]thiophene 22,34 3-bromo-
2-phenylthiophene 28,35 6-chlorobenzo[d]thiazole 33,36 1-benzyl-4,5-
dibromo-1H-imidazole 37,37 and 1-benzyl-4-bromo-1H-imidazole 3828
were identical to those reported in the literature.
General Procedure for the Hydrodehalogenation of Halo-
genated Heterocycles. Procedure Using in Situ Formed Catalysts
Pd(OAc)2/PPh3, Pd2(dba)3/tbpf, Pd2(dba)3/DavePhos, Pd2(dba)3/P(t-
Bu)3, and Pd2(dba)3/XantPhos. Anhydrous THF (13.2 mL) was
degassed by bubbling argon for a few minutes, then Pd(OAc)2 (7.2
mg, 0.033 mmol, 5 mol %) and PPh3 (17.7 mg, 1.132 mmol, 20 mol
%) were added, and the resulting mixture was stirred at room
temperature for 30 min. The halogenated heterocycle (0.66 mmol),
TMEDA (0.130 g, 1.12 mmol, 1.7 equiv), and finally NaBH4 (42.4 mg,
1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was
stirred at room temperature or heated at 65 °C under argon for the
proper time. The residue was taken up in brine and extracted with
ethyl acetate. The organic phase was separated and dried, the solvent
was evaporated, and the residue was purified by flash chromatography
(mixtures of petroleum ether and ethyl acetate) to give pure
hydrodehalogenated heterocycles.
solid (0.147 g, 95%): mp 142−143 °C; H NMR: δ 7.95−7.94 (m,
1H), 7.87 (ddd, 1H, J = 7.9, 1.9, 1.2 Hz), 7.84−7.77 (m, 2H), 7.58 (td,
1H, J = 7.7, 1.3 Hz), 7.56 (d, 1H, J = 0.6 Hz), 7.50 (dt, 1H, J = 7.7, 0.6
Hz), 7.39−7.34 (m, 2H). 13C NMR: δ 141.2, 140.2, 139.6, 135.5,
131.2, 130.4, 129.7, 129.6, 125.1, 124.9, 124.0, 122.3, 121.0, 118.4,
113.2. Anal. Calcd for C15H9NS: C, 76.57; H, 3.86; N, 5.95. Found: C,
76.71; H, 3.82; N, 5.91.
5-Bromo-4-phenylthiazole (35). The title compound was
prepared according to the general procedure, as described above
(Table 4), and purified by flash chromatography using petroleum
ether/AcOEt = 95/5 to give compound 35 as an oil (0.133 g, 84%):
1H NMR: δ 8.77 (s, 1H), 7.96−7.90 (m, 2H), 7.50−7.34 (m, 3H). 13
C
NMR: δ 152.8, 133.0, 128.5, 128.4, 128.2, 126.3, 104.2. Anal. Calcd for
C9H6BrNS: C, 45.02; H, 2.52; N, 5.83. Found: C, 45.14; H, 2.55; N,
5.79.
2-Bromo-5-chloro-4-phenylthiazole (18). A mixture of 2-
bromo-4-phenylthiazole (1.0 g, 4.2 mmol) and N-chlorosuccinimide
(0.78 g, 5.8 mmol) in CH3CN (8 mL) was stirred at rt for 30 h and
then heated under reflux temperature for 1 h. The solvent was
removed by evaporation under reduced pressure, and the residue was
taken up in petroleum ether. The formed solid was filtered, triturated,
and washed with petroleum ether. The combined organic phase was
evaporated, and the residue was purified by flash chromatography
1
(petroleum ether/EtOAc = 95/5) to give 18: 1.1 g (96%); oil; H
NMR: δ 7.92−7.86 (m, 2H), 7.46−7.33 (m, 3H). 13C NMR: δ 150.1,
131.7, 131.5, 128.8, 128.3, 128.1, 121.9. Anal. Calcd for C9H5BrClNS:
C, 39.37; H, 1.84; N, 5.10. Found: C, 39.29; H, 1.85; N, 5.14.
3-Bromo-2-(4-vinylphenyl)benzo[b]thiophene (23). 2,3-
Dibromobenzo[b]thiophene (2.13 g, 7.34 mmol, 1 equiv), 4-
vinylphenylboronic acid MIDA ester (1.13 g, 7.71 mmol, 1.05
equiv), and Pd(PPh3)4 (424 mg, 367 μmol, 5 mol %) were dissolved
in 1,4-dioxane (75 mL), and degassed 2 M Na2CO3 (15 mL) was
added. The resulting mixture was refluxed for 16 h, after which the
solvent was removed under reduced pressure. The residue was taken
up in CH2Cl2 and washed with brine. The organic layer was dried over
anhydrous Na2SO4 and filtered, and the solvent was removed under
reduced pressure. The residue was purified by flash chromatography
by using petroleum ether as the eluent: 1.56 g (67%); white solid: mp
60−61 °C; 1H NMR: δ 7.83 (d, 1H, J = 8.4 Hz), 7.76−7.67 (m, 3H),
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Note
7.49−7.31 (m, 4H), 6.72 (dd, 1H, J = 17.4, 10.8 Hz), 5.80 (d, 1H, J =
17.4 Hz), 5.30 (d, 1H, J = 10.8 Hz). 13C NMR: δ 139.2, 137.9, 137.9,
137.6, 136.1, 132.3, 129.7, 126.3, 125.4, 125.2, 123.6, 122.1, 114.9,
104.9. Anal. Calcd for C16H11BrS: C, 60.96; H, 3.52. Found: C, 60.85;
H, 3.56.
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3-Bromo-2-(3-cyanophenyl)benzo[b]thiophene (25). 2,3-
Dibromobenzo[b]thiophene (2.31 g, 7.34 mmol, 1 equiv), 3-
cyanophenylboronic acid MIDA ester (1.98 g, 7.71 mmol, 1.05
equiv), and Pd(PPh3)4 (424 mg, 367 μmol, 5 mol %) were dissolved in
1,4-dioxane (100 mL), and degassed 3 M K3PO4 (20 mL) was added.
The resulting mixture was refluxed for 16 h, after which the solvent
was removed under reduced pressure. The residue was taken up in
CH2Cl2 and washed with brine. The organic layer was dried over
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1
white solid: mp 103−104 °C; H NMR: δ 8.06 (dt, 1H, J = 1.2, 0.4
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Hz), 7.98 (ddd, 1H, J = 7.8, 1.8, 1.4 Hz), 7.89 (ddd, 1H, J = 7.8, 1.4,
0.4 Hz), 7.84 (ddd, 1H, J = 7.8, 1.1, 0.6 Hz), 7.71 (ddd, 1H, J = 7.8,
1.6, 1.2 Hz), 7.60 (dt, 1H, J = 7.8, 0.6 Hz), 7.54−7.44 (m, 2H). 13C
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125.6, 124.0, 122.3, 118.3, 113.0, 106.5. Anal. Calcd for C15H8BrNS:
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ASSOCIATED CONTENT
■
(24) Bollige, J. L.; Frech, C. M. Chem.Eur. J. 2010, 16, 4075−4081.
(25) Suzuki, T.; Ota, Y.; Kasuya, Y.; Tsumoto, H.; Nakagawa, H.;
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S
* Supporting Information
1
Copies of H, 13C NMR spectra for all new products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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2010, 20, 5879−5882.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: chelucci@uniss.it.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the University of Sassari and the Regione
Autonoma della Sardegna for financial support.
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