Gallium-catalyzed reductive chlorination of carboxylic acids with copper(II) chloride

Article abstract of DOI:10.1021/jo501912v

Described herein is the direct chlorination of carboxylic acids using copper(II) chloride via a gallium(III)-catalyzed reduction in the presence of a hydrosiloxane. During this reductive chlorination, the counteranions of CuCl₂ functioned as a chloride source.

Full text of DOI:10.1021/jo501912v

Note
pubs.acs.org/joc
Gallium-Catalyzed Reductive Chlorination of Carboxylic Acids with
Copper(II) Chloride
Norio Sakai,* Takumi Nakajima, Shinichiro Yoneda, Takeo Konakahara, and Yohei Ogiwara
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (RIKADAI), Noda,
Chiba 278-8510, Japan
*
S Supporting Information
ABSTRACT: Described herein is the direct chlorination of
carboxylic acids using copper(II) chloride via a gallium(III)-
catalyzed reduction in the presence of a hydrosiloxane. During
this reductive chlorination, the counteranions of CuCl2
functioned as a chloride source.
8,9
lkyl chlorides constitute useful and versatile intermediates
using a combination of In(OH) and Me SiHCl (route D).
3 2
A
that can be readily transformed into other valuable
compounds, such as amines, ethers, and nitriles. A number of
However, as far as we could ascertain, the direct reductive
conversion of carboxylic acids to alkyl chlorides without
decarboxylation has not been achieved (route E). This is
probably because of the lower nucleophilicity of a chloride ion,
compared with that of a bromide or an iodide ion, and also
because of the tolerance of a carboxylic acid for typical reducing
conditions.
1
approaches toward a practical synthesis of alkyl chlorides have
1
been attempted (Scheme 1). As a representative example, the
Scheme 1. Divergent Approaches to Alkyl Chlorides
During research on the transformation of carboxylic acids by
10
indium(III)-catalyzed reduction, we succeeded in the one-pot
chlorination of a carboxylic acid via a substitution of the alkyl
10a
iodide intermediate.
However, we encountered a serious
problem where the indium(III) compound, which showed a
relatively mild Lewis acidity, would not undergo direct
chlorination of carboxylic acids when typical chloride sources
were used. After a number of examinations for a solution to this
problem, we found that gallium(III) chloride exhibited the best
catalytic activity for the reductive chlorination of carboxylic acids
1
1,12
using copper(II) chloride and a hydrosiloxane.
Herein we
describe a new synthetic approach to an alkyl chloride (route E).
Initially, we sought an optimal chlorine source for the
chlorination of alcohols has been reported (route A) using a
chlorination of o-tolylacetic acid (1a) with InBr and 1,1,3,3-
1
2a,b
3
number of chlorination agents: HCl, Ph P−CCl (CBrCl ),
3
4
3
tetramethyldisiloxane (TMDS) in chloroform at 60 °C (Table
2
c
2d
1
2e
PCl −DMF, POCl −DMF, SOCl , HCl−ZnCl , BiCl −
3
3
2
2
3
1
). The use of chlorotrimethylsilane (Me SiCl) and hydrogen
2
f
2g
3
3
TMSCl, InCl −Ph MeSiCl, and others. As unique examples
3
2
chloride gave reduced alcohol 1b as a major product along with
the undesired bromination product 1c as a minor product,
instead of the expected alkyl chloride 1a (entries 1 and 2). These
results showed that the nucleophilicity of the chloride ion was
using organometallic compounds, a reaction of alkylmercuric
halides with sulfuryl chloride through a radical coupling that
4
a
produced alkyl chlorides has been reported, and Molander et al.
have reported under metal catalyst-free conditions the coupling
of alkyltrifluoroborates with trichloroisocyanuric acid (route
B). A Hunsdiecker-type reaction from carboxylic acids and
chlorination sources along with decarboxylation has also been
developed in which lead(IV) acetate and a silver(I) compound
rather low, which meant that the bromide ion of InBr functioned
3
4
b
as a halogen source. Therefore, we attempted to use a counterion
of a metal chloride. After several examinations using AlCl3,
ZnCl , FeCl , and CuCl (entries 3−6), we found that CuCl was
2
3
2
5
,6
the most effective chlorine source, although solubility of the
chloride compound was rather low (entry 7). Unfortunately, the
reaction system shown in entry 7 produced a mixture of alkyl
chloride and bromide, the formation of which made the isolation
promoted a radical decarboxylative chlorination. The reaction
of a carboxylic acid ester derived from N-hydroxypyridine-2-
thione with CCl also afforded alkyl chlorides after decarbox-
4
7
ylation (route C). Thus far, a direct conversion using reducible
reagents from carbonyl compounds to alkyl chlorides has not
been studied extensively. Baba and co-workers, however, have
developed a reductive chlorination of aldehydes and ketones
Received: August 18, 2014
Published: October 8, 2014
©
2014 American Chemical Society
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The Journal of Organic Chemistry
Note
Table 1. Examination of Reaction Conditions for
Chlorination
Scheme 2. One-Pot Synthesis of Alkyl Chlorides from
Aliphatic Carboxylic Acids
a
a
b
yield (%)
chloride
source
temp
entry
catalyst
InBr3
solvent
(°C)
1a
1b
1c
1
2
3
4
5
6
7
8
9
TMSCl
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
DCE
60
60
60
60
60
60
60
60
60
60
80
rt
ND
ND
67
80
8
c
InBr3
InBr3
InBr3
InBr3
InBr3
InBr3
InCl3
GaCl3
GaCl3
GaCl3
GaCl3
GaCl3
GaCl3
HCl
10
AlCl3
CM
65
ZnCl2
FeCl3
CuCl
ND
17
13
8
20
18
51
10
9
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
85
ND
42
ND
54
19
10
11
12
13
14
15
76
ND
ND
ND
ND
ND
ND
DCE
ND
91
DCE
d
d
d
DCE
rt
(87)
80
,
,
e
f
DCE
rt
GaCl3/
AgOTf
DCE
rt
72
d
d
1
1
6
7
CuCl2
CuCl2
DCE
DCE
rt
rt
NR
NR
,
g
GaCl3
a
Reaction conditions: o-tolylacetic acid (0.6 mmol), catalyst (0.03
mmol), TMDS (1.8 mmol), chloride source (0.6 mmol), solvent (0.6
b
c
d
mL), 3 h. GC (isolated) yield. 4 mol/L in dioxane. TMDS (Si−H:
e
f
4
equiv). CuCl (0.5 equiv). GaCl (0.03 mmol) and AgOTf (0.09
2 3
g
mmol) were used. Without TMDS.
a
of alkyl chloride 1a quite troublesome. Thus, to restrain the
formation of the byproduct 1c, a counteranion of the indium
Carboxylic acid (0.6 mmol), GaCl
(0.6 mmol), ClCH CH
(0.03 mmol), TMDS (1.2 mmol),
3
b
CuCl
Cl (0.6 mL), rt. TMDS (Si−H: 5
2
2
2
c
d
equiv), 40 °C. TMDS (Si−H: 6 equiv), 80 °C. GaCl (10 mol %),
catalyst was then changed. However, InCl was ineffective for this
3
3
e
TMDS (Si−H: 12 equiv), CuCl (2 equiv), 60 °C. TMDS (6 equiv),
2
chlorination (entry 8). We were pleased to find that GaCl3
promoted the chlorination series to produce the expected alkyl
chloride 1a (entry 9) in a satisfactory yield. When the reaction
was carried out in 1,2-dichloroethane (DCE), the product yield
was slightly increased (entry 10). Contrary to our expectations,
further increase of the reaction temperature led to the formation
of a complex mixture (entry 11). In contrast, the chlorination
successfully proceeded at room temperature to give the
corresponding alkyl chloride 1a in a good yield (entry 12).
Also, the conditions with 2 equiv of TMDS (Si−H: 4 equiv) were
determined to be the best conditions in the present chlorination
6
0 °C.
but the substrate had a nitro group at the para position that led to
a complex mixture. The functional groups, such as a methoxy and
a halogen group, showed no reducing effect. Chlorination of 3-
phenylpropanoic acid also gave a satisfactory yield of product 7a.
Unlike our previous results from the bromination of 4-
phenylbutyric acid, chlorination resulted in the formation of
tetralin 8a′ via intramolecular cyclization of the product 8a. This
may have been due to the fact that a stronger Lewis acid, GaCl ,
3
(
entry13). Interestingly, the use of 0.5 equiv of CuCl gave 80%
promoted the intramolecular Friedel−Crafts alkylation of 8a.
When 2-phenylisobutyric acid was used, which has a branched
carbon adjacent to a carboxylic moiety, the desired alkyl chloride
9a was obtained in a good yield. When 3 equiv of TMDS (Si−H:
6 equiv) was used at 80 °C, the linear fatty acids with either a
terminal or an internal alkene were converted to the
corresponding alkyl chlorides 10a and 11a in modest yields.
During the chlorination series, both the alkene moiety and the
cis-configuration of the double bond on oleic acid remained. Also,
chlorination of the substrates with a dicarboxylic acid was
2
of the corresponding alkyl chloride 1a, which showed that both
counteranions of CuCl functioned as a chloride source (entry
2
1
4). When a similar chlorination was carried out in the hope of in
situ generation of the active cation species, such as GaCl (OTf)
2
13
and GaCl(OTf) , the yield was slightly decreased (entry 15).
Without either the gallium catalyst or the hydrosiloxane, no
chlorination proceeded (entries 16 and 17).
With the optimal reaction conditions in hand, the scope and
limitations for the chlorination of carboxylic acids were next
investigated, and the results are shown in Scheme 2. With no
reference to the type of substituent group on the benzene ring, a
series of phenylacetic acids were converted to the corresponding
phenethyl chloride derivatives 2a−5a in good to excellent yields,
2
achieved by excess amounts of TMDS and CuCl to produce
2
alkyl chlorides 12a and 13a in relatively good yields. When the
reaction was conducted using the carboxylic acid with a fluorenyl
moiety, alkyl chloride 14a was obtained in a 72% yield with the
1
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The Journal of Organic Chemistry
Note
14
ring-expanding product, phenanthrene. Chlorination of 1-
naphthaleneacetic acid also yielded a good result. When a
carboxylic acid containing a thioether moiety was treated under
the optimal conditions, the corresponding alkyl chloride 16a was
obtained in a 65% yield. Unfortunately, the substrate with a
thiophene ring did not undertake the desired chlorination.
Moreover, unlike the use of 9a and 14a, relatively bulky
carboxylic acids, such as cyclohexanecarboxylic acid and pivalic
acid, produced the alcohol derivatives in 68 and 46% yields rather
than the expected alkyl chlorides. We have no clear reasons for
these results at this stage. To further expand the substrate scope,
the chlorination was applied to several substrates, such as
cinnamic acid, propiolic acid, and an aliphatic carboxylic acid
having a ketone moiety. However, all examples did not include
chlorination, which led to the formation of a complex mixture.
Chlorination using gallium chloride showed behavior similar
to that of an aromatic carboxylic acid as well as examples of a
reductive iodination/bromination of a carboxylic acid using an
Scheme 4. Control Experiments for the Reductive
Chlorination
a
1
0
InBr −TMDS system. In short, only benzoic acids bearing a
3
strong electron-withdrawing group, such as a p-CF and p-NO ,
3
2
a
managed to undertake the expected chlorination to produce alkyl
NMR yield.
chlorides 20a and 21a in low yields (Scheme 3). These results
promotion of a substitution by the chloride ion. In this context,
when the reaction with o-tolylacetic acid was conducted with our
optimal conditions (rt, 3 h) in a large-scale reaction (3 mmol),
the remarkable decrease of chlorinated product 1a (56%) and the
formation of reduced alcohol 1b (12%) was observed. On the
basis of these results, a plausible mechanism for this chlorination
is shown in Scheme 5. We assumed that a route from a carboxylic
a
Scheme 3. Chlorination of Aromatic Carboxylic Acids
Scheme 5. Plausible Mechanism for GaCl -Catalyzed
3
a
Chlorination of a Carboxylic Acid
Isolated yield.
indicated that the electronic effect of an electron-donating
substituent decreased the electrophilicity of the carbonyl group
on the aromatic carboxylic acid, which led to the deactivation of
the initial hydrosilylation by the hydrosiloxane.
When a mixture of 3-phenylpropionic acid (δ = 179.3 ppm)
and a stoichiometric amount of GaCl in a CDCl solution was
3
3
13
measured with C NMR, a remarkably lower magnetic field (δ =
87.1 ppm) was observed. This result shows that there was an
1
interaction with GaCl and the carboxylic moiety. We then
3
examined several control experiments, and the results are listed in
1
5
Scheme 4. Based on the results obtained by an indium-
catalyzed bromination/iodination of carboxylic acids, we
anticipated that the reaction intermediate of the chlorination
series would be a silyl ether. Initially, when the silyl ether 22,
16
which was prepared from o-tolylethanol and triethylsilane, was
treated either with CuCl alone or with the GaCl −CuCl system
2
3
2
in the absence of the hydrosiloxane, both reactions would not
undergo the desired chlorination (eqs 1 and 2). Also, without
acid to a silyl ether would pass through the same steps as that
described in our reductive bromination or iodination of a
GaCl , silyl ether 22 was quantitatively converted to the
3
10
desilylated alcohol 1b (eq 3). These results indicated that a
carboxylic acid. Although an explanation for the final step that
involves transformation of the silyl ether to the alkyl chloride is
unclear at this point, we supposed that a substitution via the
intermediate of the chlorocopper species coordinated gallium
combination of GaCl with TMDS was indispensable for the
3
promotion of a substitution of the silyl ether with the chloride
ion. Strangely, when the silyl ether was used under our optimal
conditions at room temperature, the desired chlorination would
not occur at all. Under slight heating conditions (40 °C), a
smooth conversion to alkyl chloride 1a was observed (eq 4).
During the preparatory step, and after the final addition of
TMDS, quite an exothermic phenomenon with an emission of
hydrogen gas was observed, the heat of which led to the
1
7,18
complex occurred, finally producing the alkyl chloride.
In conclusion, we have demonstrated the direct chlorination of
aliphatic and aromatic carboxylic acids through a GaCl -catalyzed
3
reduction using CuCl as a chloride source. In addition, we found
2
that the gallium compound positively activated the carbonyl
moiety of a carboxylic acid and disclosed that both counteranions
1
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The Journal of Organic Chemistry
Note
of CuCl functioned as a chloride source. This reducing system
NMR (125 MHz, CDCl
3
) δ 43.4, 43.7, 100.3, 128.4, 128.8, 130.5, 139.7,
2
+
+
1
40.6; MS (EI) m/z 266 (M , 100), 268 (M + 2, 33).
showed a tolerance toward functional groups, such as an alkyl
group, a methoxy group, a halogen substituent, an alkene moiety,
and a nitro group. This procedure provided a novel example of
the one-pot direct chlorination of carboxylic acids with the
chloride ion of a metal compound.
23
1
3
-Phenylpropyl chloride (7a): colorless oil (75.2 mg, 81%); H
NMR (500 MHz, CDCl ) δ 2.05−2.10 (m, 2H), 2.77 (t, J = 7.5 Hz, 2H),
3
13
3
.51 (t, J = 6.5 Hz, 2H), 7.18−7.21 (m, 3H), 7.27−7.30 (m, 2H);
C
NMR (125 MHz, CDCl ) δ 32.7, 34.0, 44.2, 126.1, 128.5, 128.5, 140.7;
MS (EI) m/z 154 (M , 100), 156 (M + 2, 33).
3
+
+
24
1
,2,3,4-Tetrahydronaphthalene (8a′): colorless oil (40.5 mg,
1
5
(
1%); H NMR (300 MHz, CDCl ) δ 1.48−1.81 (m, 4H), 2.74−2.76
EXPERIMENTAL SECTION
3
■
13
m, 4H), 7.03−7.10 (m, 4H); C NMR (75 MHz, CDCl ) δ 23.2, 29.4,
3
General Methods. All reactions were carried out under a N2
atmosphere, unless otherwise noted. 1,2-Dichloroethane (DCE) and
chloroform were freshly distilled from K CO after the removal of H O
+
125.4, 129.1, 137.1; MS (EI) m/z 132 (M , 100).
25
1
1
-Chloro-2-phenylbutane (9a): colorless oil (81.0 mg, 80%); H
2
3
2
NMR (500 MHz, CDCl ) δ 1.06 (t, J = 7.5 Hz, 2H), 1.64−1.73 (m, 1H),
3
by P O prior to use. All metal compounds, chloride sources, and
2
5
1.81−1.89 (m, 1H), 3.04 (d, J = 6.5 Hz, 2H), 4.02−4.08 (m, 1H), 7.21−
1
3
carboxylic acids were commercially available and were used without
further purification. Hydrosilanes were also used without further
purification. Silyl ether 22 shown in Scheme 3 was prepared by a
7
.22 (m, 2H), 7.25−7.26 (m, 1H), 7.30−7.33 (m, 2H); C NMR (125
MHz, CDCl ) δ 10.9, 30.6, 44.6, 65.6, 126.7, 128.4, 129.3, 138.1; MS
(EI) m/z 168 (M , 100), 170 (M + 2, 33).
3
+
+
16
26
1
previously established method. Reactions were monitored by TLC
analysis of reaction aliquots. Thin-layer chromatography (TLC) was
performed on silica gel 60 F254, and the components were located by
observation under UV light. Column chromatography was also
11-Chloro-1-undecene (10a): colorless oil (63.4 mg, 56%); H
NMR (500 MHz, CDCl ) δ 1.29−1.43 (m, 13H), 1.76 (quint, J = 7.0
3
Hz, 2H), 2.02−2.06 (m, 2H), 3.52 (t, J = 7.0 Hz, 2H), 4.92−4.94 (m,
13
1H), 4.97−5.01 (m, 1H), 5.77−5.85 (m, 1H); C NMR (125 MHz,
1
performed using silica gel. H NMR spectra were measured at 500 or
CDCl ) δ 26.9, 28.9, 28.9, 29.1, 29.4, 29.4, 32.6, 33.8, 45.1, 114.1, 139.1;
3
+
+
3
00 MHz using tetramethylsilane as an internal standard (0.00 ppm).
C NMR spectra were measured at 125 or 75 MHz using the center
MS (EI) m/z 188 (M , 100), 190 (M + 2, 34).
1
3
27
1-Chlorooctadecane-9-ene (11a): colorless oil (94.7 mg, 55%);
1
peak of chloroform (77.0 ppm).
General Procedure for the Gallium-Catalyzed Reductive
Chlorination of a Carboxylic Acid. To a freshly distilled DCE
H NMR (500 MHz, CDCl ) δ 0.88 (t, J = 7.0 Hz, 3H), 1.26−1.30 (m,
3
22H), 1.76 (quint, J = 7.0 Hz, 2H), 2.01−2.03 (m, 2H), 3.52 (t, J = 7.0
13
Hz, 2H), 5.33−5.36 (m, 2H); C NMR (125 MHz, CDCl ) δ 14.1,
3
solution (0.6 mL) in a screw-capped vial under an N atmosphere were
22.7, 26.9, 27.2, 28.9, 29.2, 29.3, 29.4, 29.5, 29.6, 29.7, 29.8, 31.9, 32.6,
2
+
+
successively added a magnetic stirrer bar, GaCl (0.030 mmol, 5.3 mg),
45.1, 129.7, 130.0; MS (EI) m/z 286 (M , 100), 288 (M + 2, 33).
3
CuCl (0.600 mmol, 80.9 mg), a carboxylic acid (0.60 mmol), and
TMDS (1.2 mmol, 2.2 × 10 μL). The vial was sealed with a cap that
1,2-Bis(2-chloroethyl)benzene (12a): colorless oil (78.0 mg, 64%);
2
2
1
H NMR (300 MHz, CDCl ) δ 3.10 (t, J = 7.5 Hz, 4H), 3.68 (t, J = 7.5
3
13
contained a PTFE septum. After the final addition of TMDS, the color of
the reaction mixture was changed from yellowish brown to black with an
exothermic phenomenon and an emission of hydrogen gas. If necessary,
an appropriate release of the gas is required. During the stirring of the
reaction mixture under the conditions noted in the text, the reaction was
monitored by TLC until consumption of the silyl ether intermediate
that, in practice, was observed as the desilylated alcohol. The resultant
Hz, 4H), 7.20−7.21 (m, 4H); C NMR (75 MHz, CDCl ) δ 35.7, 44.3,
3
+
127.3, 129.8, 136.2; HRMS (EI-Quadrupole) calcd for C H Cl (M )
1
0
12
2
202.0316, found 202.0325.
1,10-Dichlorodecane (13a): colorless oil (90.0 mg, 71%); H
NMR (500 MHz, CDCl ) δ 1.30 (m, 8H), 1.41−1.44 (m, 4H), 1.77
(quint, J = 7.0 Hz, 4H), 3.53 (t, J = 7.0 Hz, 4H); C NMR (125 MHz,
28
1
3
13
+
CDCl
100), 93 (M − C H12Cl + 2, 33).
6
2
) δ 26.8, 28.8, 29.3, 32.6, 45.1; MS (EI) m/z 91 (M − C
H
12Cl,
3
6
+
mixture was filtered using a Celite pad to remove the black solid. H O (6
2
9
1
9
-(Chloromethyl)fluorene (14a): colorless oil (92.7 mg, 72%); H
mL) was poured into the filtrate, and the aqueous layer was extracted
three times with EtOAc (6 mL). The combined organic phase was dried
over anhydrous Na SO , filtered, and then evaporated under reduced
NMR (500 MHz, CDCl ) δ 3.89 (d, J = 6.5 Hz, 2H), 4.23 (t, J = 6.5 Hz,
3
1
7
1
2
H), 7.31−7.34 (m, 2H), 7.39−7.42 (m, 2H), 7.67 (d, J = 7.5 Hz, 2H),
2
4
.74 (d, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl ) δ 46.9, 49.3,
pressure. The crude product was purified by column chromatography
silica gel, 99/1 = hexane/EtOAc) to give the corresponding alkyl
3
+
20.0, 124.9, 127.2, 128.0, 141.1, 144.0; MS (EI) m/z 214 (M , 100),
(
+
16 (M + 2, 37).
chloride. The spectral data of the produced chlorides were determined
30
1
Phenanthrene (14a′): colorless oil (11.8 mg, 11%); H NMR (500
after further purification by gel permeation chromatography.
o-Methylphenethyl chloride (1a): colorless oil (80.7 mg, 87%); H
1
9
1
MHz, CDCl ) δ 7.56−7.59 (m, 2H), 7.61−7.65 (m, 2H), 7.72 (s, 2H),
3
13
7
.85−7.88 (m, 2H), 8.66 (d, J = 8.0 Hz, 2H); C NMR (125 MHz,
NMR (500 MHz, CDCl ) δ 2.33 (s, 3H), 3.08 (t, J = 8.0 Hz, 2H), 3.67
3
13
CDCl ) δ 122.6 (2C), 126.5 (4C), 126.9 (2C), 128.5 (2C), 130.3 (2C),
3
(
3
1
t, J = 8.0 Hz, 2H), 7.16 (m, 4H); C NMR (125 MHz, CDCl ) δ 19.3,
6.6, 43.8, 126.2, 127.0, 129.4, 130.5, 136.2; MS (EI) m/z 154 (M ,
3
+
+
132.0 (2C); MS (EI) m/z 178 (M , 100).
31
+
1-(2-Chloroethyl)naphthalene (15a): colorless oil (91.5 mg,
00), 156 (M + 2, 31).
1
2
0
80%); H NMR (300 MHz, CDCl ) δ 3.55 (t, J = 7.5 Hz, 2H), 3.83
3
p-Methoxyphenethyl chloride (2a): colorless oil (89.1 mg, 87%);
H NMR (500 MHz, CDCl ) δ 3.00 (t, J = 7.0 Hz, 2H), 3.66 (t, J = 7.0
1
(t, J = 7.5 Hz, 2H), 7.37−7.57 (m, 4H), 7.77 (d, J = 7.8 Hz, 1H), 7.87 (d,
3
13
J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H); C NMR (125.8 MHz,
Hz, 2H), 3.78 (s, 3H), 6.85 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.5 Hz, 2H);
CDCl ) δ 36.5, 44.1, 123.1, 125.5, 125.7, 126.3, 127.2, 127.8, 129.0,
1
3
3
C NMR (125 MHz, CDCl ) δ 38.3, 45.3, 55.2, 113.9, 129.8, 130.1,
+
+
3
+
1
31.7, 133.9, 133.9; MS (EI) m/z 190 (M , 100), 192 (M + 2, 38).
32
+
1
58.5; MS (EI) m/z 170 (M , 100), 172 (M + 2, 34).
1
Phenylthioethyl chloride (16a): colorless oil (67.3 mg, 65%); H
2
0
1
p-Chlorophenethyl chloride (3a): colorless oil (78.8 mg, 75%); H
NMR (500 MHz, CDCl ) δ 3.01 (t, J = 7.5 Hz, 2H), 3.67 (t, J = 7.5 Hz,
2
NMR (500 MHz, CDCl ) δ 3.21−3.24 (m, 2H), 3.60−3.63 (m, 2H),
3
13
3
7.23−7.26 (m, 1H), 7.30−7.33 (m, 2H), 7.39−7.40 (m, 2H); C NMR
13
H), 7.13 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H); C NMR (125
(
125 MHz, CDCl ) δ 36.1, 42.3, 127.1, 129.2, 130.5, 134.2; MS (EI) m/
3
MHz, CDCl ) δ 38.2, 44.7, 128.6, 130.1, 132.6, 136.4; MS (EI) m/z 174
+
+
3
z 172 (M , 100), 174 (M + 2, 38).
+
+
33
(
M , 100), 176 (M + 2, 66).
p-Bromophenethyl chloride (4a): colorless oil (118.5 mg, 90%);
p-(Trifluoromethyl)benzyl chloride (20a): colorless oil (38.5 mg,
3%); H NMR (500 MHz, CDCl ) δ 4.59 (s, 2H), 7.49 (d, J = 8.0 Hz,
2H), 7.61 (d, J = 8.0 Hz, 2H); C NMR (125 MHz, CDCl ) δ 45.0,
2
1
1
3
3
1
13
H NMR (500 MHz, CDCl ) δ 3.01 (t, J = 7.0 Hz, 2H), 3.69 (t, J = 7.0
3
3
13
Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H); C NMR
125 MHz, CDCl ) δ 38.4, 44.6, 120.8, 130.5, 131.6, 137.0; MS (EI) m/
123.9 (q, JC−F = 271.7 Hz), 125.7 (q, JC−F = 3.8 Hz), 128.8, 130.5 (q, J
C−F
+
+
(
= 32.7 Hz), 141.3; MS (EI) m/z 286 (M , 100), 288 (M + 2, 32).
3
+
+
+
34
1
z 220 (M + 2, 100), 218 (M , 81), 222 (M + 4, 28).
p-Nitrobenzyl chloride (21a): yellow oil (23.7 mg, 23%); H NMR
2
2
1
o-Iodophenethyl chloride (5a): colorless oil (147.1 mg, 92%); H
(500 MHz, CDCl ) δ 4.65 (s, 2H), 7.58 (d, J = 8.5 Hz, 2H), 8.23 (d, J =
3
8.5 Hz, 2H); 13C NMR (125 MHz, CDCl ) δ 44.5, 123.9, 129.3, 144.3,
NMR (500 MHz, CDCl ) δ 3.19 (t, J = 7.5 Hz, 2H), 3.71 (t, J = 7.5 Hz,
3
3
13
+
+
2
H), 6.93−6.97 (m, 1H), 7.26−7.32 (m, 2H), 7.83−7.84 (m, 1H);
C
147.7; MS (EI) m/z 171 (M , 100), 173 (M + 2, 31).
1
0622
dx.doi.org/10.1021/jo501912v | J. Org. Chem. 2014, 79, 10619−10623

The Journal of Organic Chemistry
Note
1
o-Methylphenethyl triethylsilyl ether (22): colorless oil; H NMR
(12) For selected recent papers of a GaCl -catalyzed reaction, see:
3
(
500 MHz, CDCl ) δ 0.58 (q, J = 8.0 Hz, 6H), 0.94 (t, J = 8.0 Hz, 9H),
(a) Kiyokawa, K.; Yasuda, M.; Baba, A. Org. Lett. 2010, 12, 1520−1523.
(b) Li, H.-J.; Guillot, R.; Gandon, V. J. Org. Chem. 2010, 75, 8435−8449.
(c) Hirashita, T.; Kawai, D.; Araki, S. Tetrahedron Lett. 2007, 48, 5421−
5424. (d) Ikeshita, K.-i.; Kihara, N.; Sonoda, M.; Ogawa, A. Tetrahedron
Lett. 2007, 48, 3025−3028. (e) Simmons, E. M.; Sarpong, R. Org. Lett.
3
2
.33 (s, 3H), 2.87 (t, J = 7.5 Hz, 2H), 3.76 (t, J = 7.5 Hz, 2H), 7.09−7.15
13
(
m, 4H); C NMR (125 MHz, CDCl ) δ 4.3, 6.7, 19.4, 36.9, 63.2, 125.9,
3
1
26.3, 129.7, 130.1, 136.3, 136.9; HRMS (ESI-TOF) calcd for
+
C H OSi (M + Na) 273.1651, found 273.1662.
15
26
2
006, 8, 2883−2886. (f) Mantri, K.; Nakamura, R.; Komura, K.; Sugi, Y.
ASSOCIATED CONTENT
Chem. Lett. 2005, 34, 1502−1503. (g) Yonehara, F.; Kido, Y.; Sugimoto,
H.; Morita, S.; Yamaguchi, M. J. Org. Chem. 2003, 68, 6752−6759.
■
*
S
Supporting Information
(
2
7
h) Arisawa, M.; Amemiya, R.; Yamaguchi, M. Org. Lett. 2002, 4, 2209−
Copies of the H and 13C NMR spectra of the chlorinated
products produced by this method. This material is available free
of charge via the Internet at http://pubs.acs.org.
1
211. (i) Arisawa, M.; Akamatsu, K.; Yamaguchi, M. Org. Lett. 2001, 3,
89−790.
(13) For a combination of gallium(III) chloride and silver salt, such as
AgClO , AgSbF , and AgOTf, promoted Friedel−Crafts acylation, see:
4
6
AUTHOR INFORMATION
Corresponding Author
E-mail: sakachem@rs.noda.tus.ac.jp.
(a) Suzuki, K.; Kitagawa, H.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1993,
6, 3729−3734. (b) Mukaiyama, T.; Ohno, T.; Nishimura, T.; Suda, S.;
Kobayashi, S. Chem. Lett. 1991, 20, 1059−1062.
14) For a report of rearrangement from 9-fluorenyl derivatives to 9-
■
*
6
(
Notes
phenanthorols in the presence of a Grignard reagent and nickel(II)
The authors declare no competing financial interest.
acetylacetonate, see: Tantivanich, A.; Supatimusro, D. Tetrahedron Lett.
1
986, 27, 5301−5302.
15) In the control experiment using the corresponding phenethyl
alcohol derivative at 60 °C for 3 h, only a small amount of chlorination
<10%) was observed.
16) Sridhar, M.; Raveendra, J.; China Ramanaiah, B.; Narsaiah, C.
(
ACKNOWLEDGMENTS
■
This work was partially supported by a Grant-in-Aid for Scientific
Research (C) (No. 25410120) supported by the Ministry of
Education, Culture, Sports, Science and Technology (MEXT).
We deeply thank Shin-Etsu Chemical Co., Ltd., for the gift of
hydrosilanes.
(
(
Tetrahedron Lett. 2011, 52, 5980−5982.
(17) Formation of a Ga−Cl−Cu complex is already reported; see:
Joost, M.; Mallet-Ladeira, S.; Miqueu, K.; Amgoune, A.; Bourissou, D.
Organometallics 2013, 32, 898−902.
(18) During chlorination series, we had no observation of aldehydes or
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