Arylmethyl chlorides: New bifunctional reagents for palladium-catalyzed ortho -chlorination and acylation of 2-arylpyridines

Article abstract of DOI:10.1002/adsc.201400810

A chemoselective, palladium-catalyzed, ligand-directed ortho-C-H chlorination and acylation process has been developed, exhibiting high regioselectivity for 2-arylpyridines bearing a meta-substituent. Worthy of note is the fact that arylmethyl chlorides a

Full text of DOI:10.1002/adsc.201400810

FULL PAPERS
DOI: 10.1002/adsc.201400810
Arylmethyl Chlorides: New Bifunctional Reagents for Palladium-
Catalyzed ortho-Chlorination and Acylation of 2-Arylpyridines
Guodong Zhang,a Suyan Sun,a Fan Yang,a,* Qian Zhang,a Jianxun Kang,a
Yusheng Wu,a,* and Yangjie Wua,*
a
The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic
Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, 75 Daxue North Road,
Zhengzhou 450052, Peopleꢀs Republic of China
E-mail: yangf@zzu.edu.cn or yusheng.wu@tetranovglobal.com or wyj@zzu.edu.cn
Received: August 16, 2014; Revised: October 27, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400810.
Abstract: A chemoselective, palladium-catalyzed, reagents can selectively be utilized as chlorine or
À
ligand-directed ortho-C H chlorination and acyla- acyl sources.
tion process has been developed, exhibiting high re-
gioselectivity for 2-arylpyridines bearing a meta-sub-
stituent. Worthy of note is the fact that arylmethyl Keywords: acylation; C H activation; chemoselectiv-
chlorides as new, readily available, and inexpensive ity; chlorination; palladium
À
Introduction
À
Transition metal-catalyzed functionalization of C H
À
bonds has served as a robust and reliable tool in C C,
À
À
À
C O, C X and C N bond forming reactions during
recent years.[1] As part of this impressive research, sig-
nificant efforts have been devoted to establishing new
À
Scheme 1. Selective chlorination or acylation of 2-phenylpyr-
idine with benzyl chloride.
and efficient C H activation techniques with the help
of directing group such as pyridines, imines, esters, ke-
tones, oxazolines, amides and nitriles,[2] accompanied
by the appearance of diverse kinds of functionalizing
reagents. For instance, HCl, NCS, CuCl2 or LiCl can the same time, and may act as the chlorine or acyl
serve as specialized reagents for the ligand-directed source in the presence of an oxidant. As part of our
ortho-chlorination;[3] also aldehydes, a-oxocarboxylic continuing research program, we envisioned a new
acids, alcohols or toluene can be utilized for ortho- and facile protocol to fulfill the ligand-directed ortho-
acylation.[4] A new type of acylating reagent: aryl(me- chlorination and acylation using arylmethyl chloride
thyl)amine derivatives were also developed in our derivatives as potential bifunctional reagents, afford-
group.[5] Although these reagents could successfully ing chlorination or acylation products chemoselective-
be applied to one specific type of functionalization, ly under different conditions (Scheme 1).
the progress of developing versatile reagents suitable
for two or more reactions has lagged behind, and the
relative reports remain rare. Therefore, to develop Results and Discussion
such bifunctional or multifunctional reagents would
be fascinating and extremely desirable.
In our initial investigation, we performed the model
On the other hand, arylmethyl chloride derivatives reaction of 2-phenylpyridine 1a with benzyl chloride
constitute a family of important organic intermediates 2a in the presence of tert-butyl hydroperoxide
and can be further functionalized though substitution (TBHP) as the oxidant in chlorobenzene at 1008C
reactions, radical reactions and other reactions.[6] under an oxygen atmosphere, but the desired product
They possess a chlorine atom and a benzyl group at was not detected at all under these palladium-free
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Table 1. Optimization of reaction conditions.[a]
action under air or a nitrogen atmosphere, as well as
reducing the amount of benzyl chloride 2a to
1.5 equiv. or TBHP to 4 equiv. would lead to a de-
crease of the product yields to 33%–62% (Table 1, en-
tries 8–11). It should be noted that a large amount of
benzaldehyde as the oxidized product of benzyl chlo-
ride 2a was also obtained during the above chlorina-
tion process, which suggested that benzyl chloride 2a
may serve as a potential acyl source in the ligand-di-
rected ortho-acylation (Table 1, entries 1–11).[4] Cyclo-
palladated ferrocenylimine, which was discovered in
our research group, has successfully been applied to
a variety of catalytic reactions.[7] Interestingly, when
we took this palladacycle instead of PdCl2 as the cata-
lyst and changed the amounts of benzyl chloride 2a to
4.0 equiv. and TBHP to 8.0 equiv., the acylation prod-
uct could indeed be obtained in 47% yield without
the generation of the chlorinated product (Table 1,
entry 12). This acylation reaction under a nitrogen at-
Entry 2a
Oxidant
Additive
(0.5 equiv.)
Yield
[%][b]
3a 4a
(equiv.) (equiv.)
1[c,d]
2[d]
3[e]
4
5
6
2
2
2
2
2
2
2
2
2
1.5
2
4
4
4
4
4
4
4
5
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
DDQ (5)
K2S2O8 (5)
H2O2 (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (4)
TBHP (8)
TBHP (8)
TBHP (8)
TBHP (8)
TBHP (8)
TBHP (8)
TBHP (8)
TBHP (10)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
<5 <5
63 11
16 <5
82 <5
<5 <5 mosphere or air also afforded the products in similar
18 <5
<5 <5
45 <5
33 <5
62 <5
58 <5
<5 47
<5 42
<5 47
<5 33
<5 54
<5 59
<5 60
<5 75
yields (Table 1, entries 13 and 14). Some additives
(e.g., HOAc, KHCO3, KOAc and KF·2H2O) were
also checked, and KHCO3 could lead to a moderate
yield of 60% (Table 1, entries 15–18). In this transfor-
mation, benzyl chloride was fist oxidized to benzalde-
hyde by TBHP which also released a molecule of hy-
drogen chloride. The major part of the hydrogen chlo-
ride gas could volatilize to the air, and the remainder
in the reaction would be neutralized by KHCO3. Fi-
nally, increasing the amounts of benzyl chloride 2a
and oxidant could give the acylated product in a high
yield of up to 75% (Table 1, entry 19).
7
8[f]
9[g]
10
11
12[h]
13[g]
14
15
16
17
18
19
HOAc
KOAc
KF·2H2O
KHCO3
KHCO3
With the optimized reaction conditions in hand, the
scope of 2-arylpyridines in chlorination and acylation
was first explored. As summarized in Table 2 and
Table 3, various substituents (e.g., Me, MeO, t-Bu,
Ac, COOEt, Br and Cl) on the different positions of
the phenyl or pyridyl ring, regardless of their elec-
tronic nature, were well tolerated. Especially, the sub-
strates bearing moderate electron-withdrawing groups
in the phenyl ring could generate the desired products
in excellent yields, for example, 3l and 4j in yields of
up to 83% and 81%, respectively. Notably, both the
chlorination and the acylation showed high regiose-
lectivity for substrates containing a meta-substituent
in the phenyl ring. The reaction could take place at
À
[a]
Conditions A for entries 1–11: 1a (0.3 mmol), 2a, PdCl2
(5 mol%), and oxidant in DMSO (1.0 mL) at 1008C for
24 h under an oxygen atmosphere. Conditions B for en-
tries 12–19: 1a (0.3 mmol), 2a, palladacycle (4 mol%),
and TBHP in chlorobenzene (1.0 mL) at 1408C for 12 h
under air.
Isolated yield based on 1a.
Without palladium catalyst.
Chlorobenzene as the solvent.
Toluene as the solvent.
[b]
[c]
[d]
[e]
[f]
Under air.
Under a nitrogen atmosphere.
Under an oxygen atmosphere.
[g]
[h]
conditions (Table 1, entry 1). To our delight, the addi- the less sterically hindered ortho-C H bond, which
tion of PdCl2 (5 mol%) resulted in the chlorinated produced the monochlorinated products 3c, 3g–i, 3l
product 3a and acylated product 4a in the yields of and 3p and acylated products 4d, 4f, 4j–l and 4p in
63% and 11%, respectively (Table 1, entry 2). Other moderate to good yields. Moreover, the reaction sub-
solvents such as toluene and DMSO were then strates could also be extended to heterocycles such as
screened, and gratifyingly, DMSO could deliver the benzo[h]quinoline and 2-thienylpyridine, which pro-
chlorinated product as the sole product in up to 82% vided the monochlorinated products 3q and 3r and
isolated yield (Table 1, entries 3 and 4). Some others the acylated products 4q and 4r in satisfying yields.
oxidants such as DDQ, K2S2O8 and H2O2 were also However, the steric effect at the ortho-position in
explored, but the products were generated in only phenyl ring was decisive, which held back the cyclo-
low yields (Table 1, entries 5–7). Carrying out the re- palladation step of 2-arylpyridines, and would remark-
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Arylmethyl Chlorides: New Bifunctional Reagents
Table 2. Scope of 2-arylpyridines in chlorination.[a,b]
[a]
[b]
Conditions: 2-arylpyridine (0.3 mmol), 2a (2.0 equiv.), PdCl2 (5 mol%), and TBHP
(5.0 equiv.) in DMSO (1.0 mL) at 1008C for 24 h under an oxygen atmosphere.
Isolated yields.
ably prevent the catalytic process from proceeding. dine 1-oxyl (TEMPO) as a radical scavenger [Eqs. (1)
For example, the chlorination of a substrate possess- and (2)]. The formation of 3a and 4a was completely
ing an ortho-substituent at the phenyl ring afforded inhibited in these experiments, demonstrating that
the products 3b in a lower yield of 43%, and the acy- a radical process may be involved in these two reac-
lated product 4b was not observed at all. The molecu- tions.
lar structure of the acylated product (4c) was unam-
biguously determined by the single crystal X-ray dif-
fraction study.[8]
To further establish the substrate scope in these re-
actions, the acylations of various substituted arylmeth-
yl chlorides were then investigated (Table 4). It was
revealed that the reaction was independent of the
electronic properties of the substrate. Various func-
tional groups including Me, OMe, F, Cl, Br and
COOMe were well tolerated and the desired products
4s–z and 5 were formed in moderate yields.
In order to understand the mechanism of the trans-
formations, the chlorination and acylation of 2-phe-
nylpyridine 1a with benzyl chloride 2a were per-
formed in the presence of 2,2,6,6-tetramethylpiperi-
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Table 3. Scope of 2-arylpyridines in acylation.[a,b]
[a]
Conditions: 2-arylpyridine (0.3 mmol), 2a (5.0 equiv.), KHCO3 (0.5 equiv.), palladacycle (4 mol%), and TBHP
(10.0 equiv) in chlorobenzene (1.0 mL) at 1408C for 12 h under air.
Isolated yield.
[b]
Finally, some control experiments were preformed
[Eqs. (3) and (4)]. t-BuOCl was used instead of the
arylmethyl chloride and TBHP under the optimized
conditions, and only trace amounts of the chlorinated
product was detected. After 1.0 equiv. of TBHP had
been added to the above reaction, the product could
be obtained in 65% yield. The results indicate that t-
BuOCl may be an intermediate and can be taken in-
stead of the arylmethyl chloride. TBHP may act as
a free radical initiator in this transformation.
Although the mechanism is not completely clear
yet, on the basis of the previous reports[3–5] and the
above results, a plausible mechanism for the two
transformations is depicted in Scheme 2. For the
chlorination pathway, under an oxygen atmosphere,
benzyl chloride 2a is initially slowly oxidized to t-
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Arylmethyl Chlorides: New Bifunctional Reagents
Table 4. Scope of arylmethyl chlorides in acylation.[a,b]
[a]
[b]
Conditions: 1a (0.3 mmol), arylmethyl chloride (5.0 equiv.), KHCO3 (0.5 equiv.), palladacycle (4 mol%),
and TBHP (10.0 equiv.) in chlorobenzene (1.0 mL) at 1408C for 12 h under air.
Isolated yield.
BuOCl and benzaldehyde by TBHP. Cyclopalladation methyl chlorides – can be utilized as the chlorine and
À
of 2-phenylpyridine 1a with PdCl2 via C H activation acyl sources. This reaction can be controlled to only
takes place to form intermediate A. The insertion of generate monochlorinated product, which is unusual
À
t-BuOCl to the C Pd bond in intermediate A further to achieve in other conversions. In addition, arylmeth-
generates complex B via a free radical process. Disso- yl chlorides are also cheaper acyl sources, compared
ciation of complex B in the palladium center affords to aldehydes, a-oxocarboxylic acids, alcohols and ar-
the chlorinated product 3a and regenerates PdCl2. yl(methyl)amine derivatives. TBHP in 70% aqueous
Likewise, for the acylation pathway, the oxidative re- solution in our protocol is less expensive and easy to
action of the palladacycle catalyst with 2-phenylpyri- handle than that in decane solution, although toluene
dine 1a generates Pd species C. Ferrocenylimine as derivatives are used as acyl sources. Furthermore, the
a ligand of the Pd source possesses a bulky and steri- two transformations exhibit high regioselectivity for
cally hindered ferrocenyl moiety. The steric effect of the substrates containing a meta-substituent in the
intermediate C makes attack of the sterically hin- phenyl ring.
dered t-BuOCl to the Pd center difficult. On the con-
trary, the acyl radical, formed in situ from benzyl
chloride 2a and TBHP, reacts with intermediate C to
afford intermediate D due to its plane structure.[4,5] Fi-
nally, the reductive elimination of intermediate D
Experimental Section
leads to the acylated product 4a and the palladacycle
catalyst to fulfill the catalytic cycle.
General Procedure for the Chlorination of 2-
Arylpyridines
To
a solution of 2-arylpyridine (0.3 mmol) in DMSO
(1.0 mL), arylmethyl chloride (0.6 mmol), PdCl2 (5 mol%)
and TBHP (1.5 mmol) were added. The resulting mixture
was heated at 1008C under an oxygen atmosphere for 24 h.
After the reaction was complete and cooled to room tem-
perature, the mixture was added into H2O (25 mL) and ex-
tracted with ethyl acetate (10 mL) three times. The com-
bined organic layer was dried over anhydrous Na2SO4 and
filtered. After removal of the solvent under vacuum, the res-
idue was purified by column chromatography (ethyl acetate/
hexane) to afford the pure product. Examples of the new
Conclusions
In summary, we have developed new and efficient
protocols for selective ortho-C H chlorination or acy-
À
lation of 2-arylpyridines with arylmethyl chlorides,
and the chlorinated or acylated products can be selec-
tively generated in the presence of the simple palladi-
um salt under an oxygen atmosphere and the pallada-
cycle under air, respectively. Note that this new type
of cheap and effective bifunctional reagent – aryl- products are listed below.
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22.1, 125.6, 130.3, 131.1, 131.4, 133.2, 133.4, 137.7, 138.2,
140.0, 151.2, 155.5; HR-MS (ESI): m/z=218.0729, calcd. for
C13H13ClN [M+H]+: 218.0731.
2-(2-Chloro4-phenylphenyl)pyridine (3j): yield: 56 mg
(70%); light yellow oil; 1H NMR (400 MHz, CDCl3): d=
7.29 (t, J=6.0 Hz, 1H), 7.36–7.40 (m, 1H), 7.44–7.46 (m,
2H), 7.58–7.62 (m, 3H), 7.68–7.71 (m, 3H), 7.74–7.78 (m,
1H), 8.73 (d, J=4.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=122.4, 124.9, 125.7, 127.1, 128.1, 128.6, 129.0, 132.0, 132.5,
135.9, 137.8, 139.3, 142.8, 149.6, 156.5; HR-MS (ESI): m/z=
266.0731, calcd. for C17H13ClN [M+H]+: 266.0731.
Ethyl 3-chloro-4-(pyridin-2-yl)benzoate (3k): yield: 63 mg
(80%); light yellow oil; 1H NMR (400 MHz, CDCl3): d=
1.37 (t, J=7.0 Hz, 3H), 4.37 (q, J=7.2 Hz, 2H), 7.30–7.33
(m, 1H), 7.55 (d, J=8.4 Hz, 1H), 7.63 (d, J=7.8 Hz, 1H),
7.76–7.80 (m, 1H), 8.00 (dd, J=2.0, 8.4 Hz, 1H), 8.24 (d, J=
2.0 Hz, 1H), 8.74 (d, J=4.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=15.6, 62.6, 124.1, 126.1, 130.8, 131.6, 131.8, 134.0,
137.4, 138.3, 140.6, 151.0, 157.4, 166.9; HR-MS (ESI): m/z=
262.0636, calcd. for C14H13ClNO2 [M+H]+: 262.0629.
1-[3-Chloro-4-(pyridin-2-yl)phenyl]ethanone (3m): yield:
46 mg (66%); light yellow solid, mp 42–448C; 1H NMR
(400 MHz, CDCl3): d=2.61 (s, 3H), 7.30–7.33 (m, 1H),
7.65–7.70 (m, 2H), 7.77 (t, J=7.6 Hz, 1H), 7.90 (d, J=
8.0 Hz, 1H), 8.03 (s, 1H), 8.73 (d, J=4.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=26.8, 123.0, 124.9, 126.7, 130.1, 131.9,
132.8, 136.1, 137.9, 143.1, 149.7, 155.7, 196.6; HR-MS (ESI):
m/z=232.0531, calcd. for C13H11ClNO [M+H]+: 232.0524.
2-(4-Bromo-2-chlorophenyl)pyridine (3n): yield: 44 mg
(55%); white solid, mp 76–788C; 1H NMR (400 MHz,
CDCl3): d=7.29–7.33 (m, 1H), 7.42–7.66 (m, 4H), 7.75–7.79
(m, 1H), 8.72 (d, J=4.5 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=124.0, 126.1, 131.6, 134.0, 134.0, 134.4, 136.9,
137.3, 139.4, 151.0, 157.1; HR-MS (ESI): m/z=267.9525,
calcd. for C11H8BrClN [M+H]+: 267.9523.
2-(2,5-Dichlorophenyl)pyridine (3p): yield: 37 mg (56%);
1
white solid, mp 90–928C; H NMR (400 MHz, CDCl3): d=
7.30–7.33 (m, 2H), 7.41 (d, J=2.5 Hz, 1H), 7.62 (d, J=
2.6 Hz, 1H), 7.66 (dd, J=0.8, 7.8 Hz, 1H), 7.76–7.80 (m,
1H), 8.73 (d, J=4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=124.0, 126.1, 128.7, 131.2, 133.8, 134.2, 136.1, 137.3, 139.0,
151.0, 157.1; HR-MS (ESI): m/z=224.0027, calcd. for
C11H8Cl2N [M+H]+: 224.0028.
2-(3-Chlorothiophen-2-yl)pyridine (3r): yield: 33 mg
(57%); light yellow oil; 1H NMR (400 MHz, CDCl3): d=
6.99 (d, J=5.3 Hz, 1H), 7.18–7.21 (m, 1H), 7.34 (d, J=
5.3 Hz, 1H), 7.72–7.76 (m, 1H), 8.22 (d, J=8.1 Hz, 1H),
8.60 (d, J=4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
122.0, 123.4, 123.7, 127.8, 131.3, 137.9, 138.4, 150.8, 152.3;
HR-MS (ESI): m/z=195.9984, calcd. for C9H7ClNS [M+
H]+: 195.9982.
Scheme 2. Plausible mechanism.
2-(4-tert-Butyl-2-chlorophenyl)pyridine (3e): yield: 44 mg
(59%); light yellow oil; 1H NMR (400 MHz, CDCl3): d=
1.37 (s, 9H), 7.28 (t, J=5.5 Hz, 1H), 7.41 (dd, J=1.1,
8.2 Hz, 1H), 7.49 (d, J=1.3 Hz, 1H), 7.56 (d, J=8.1 Hz,
1H), 7.68 (d, J=7.8 Hz, 1H), 7.74–7.78 (m, 1H), 8.74 (d, J=
4.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=32.4, 36.1,
123.5, 125.6, 126.1, 128.4, 132.5, 133.0, 137.1, 137.5, 150.8,
154.6, 158.2; HR-MS (ESI): m/z=246.1044, calcd. for
C15H17ClN [M+H]+: 246.1044.
2-(2-Chloro-5-methylphenyl)-4-methylpyridine (3h): yield:
1
37 mg (57%); light yellow oil; H NMR (400 MHz, CDCl3):
d=2.34 (s, 3H), 2.39 (s, 3H), 7.08–7.12 (m, 2H), 7.32 (d, J=
8.1 Hz, 1H), 7.37 (d, J=1.7 Hz, 1H), 7.43 (s, 1H), 8.55 (d,
J=5.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=22.1, 22.5,
124.6, 127.0, 130.3, 131.1, 131.5, 133.4, 138.1, 140.2, 148.2,
150.5, 158.1; HR-MS (ESI): m/z=218.0729, calcd. for
C13H13ClN [M+H]+: 218.0731.
General Procedure for the Acylation of 2-Aryl-
pyridines
To a solution of 2-arylpyridine (0.3 mmol) in chlorobenzene
(1.0 mL), arylmethyl chloride (1.5 mmol), palladacycle
(4 mol%), TBHP (3.0 mmol) and KHCO3 (0.15 mmol) were
added. The resulting mixture was heated at 1408C under air
for 12 h. After the reaction was complete and cooled to
room temperature, the mixture was added into H2O
(25 mL) and extracted with ethyl acetate (10 mL) three
2-(2-Chloro-5-methylphenyl)-5-methylpyridine (3i): yield:
1
44 mg (68%); light yellow oil; H NMR (400 MHz, CDCl3):
d=2.34 (s, 3H), 2.37 (s, 3H), 7.10 (dd, J=1.7, 8.1 Hz, 1H),
7.32 (d, J=8.1 Hz, 1H), 7.39 (d, J=1.1 Hz, 1H), 7.54 (s,
2H), 8.52 (m, 1H); 13C NMR (100 MHz, CDCl3): d=19.6,
6
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Arylmethyl Chlorides: New Bifunctional Reagents
times. The combined organic layer was dried over anhydrous
Na2SO4 and filtered. After removal of the solvent under
vacuum, the residue was purified by column chromatogra-
phy (ethyl acetate/hexane) to afford the pure product. Ex-
amples of the new products examples are listed below.
Ethyl 4-benzoyl-3-(4-methylpyridin-2-yl)benzoate (4k):
yield: 54 mg (52%); light yellow solid, mp 78–808C;
1H NMR (400 MHz, CDCl3): d=1.45 (t, J=7.1 Hz, 3H),
2.31 (s, 3H), 4.45 (q, J=7.1 Hz, 2H), 6.86 (d, J=5.1 Hz,
1H), 7.26–7.30 (m, 2H), 7.39–7.44 (m, 2H), 7.58 (d, J=
8.0 Hz, 1H), 7.68 (d, J=7.4 Hz, 2H), 8.16–8.19 (m, 2H),
8.45 (d, J=1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
15.7, 22.4, 62.8, 124.7, 129.4, 130.3, 130.6, 130.6, 130.9, 133.2,
133.8, 138.8, 141.1, 144.9, 149.0, 150.0, 156.8, 167.2, 198.8;
HR-MS (ESI): m/z=346.1430, calcd. for C22H20NO3 [M+
H]+: 346.1438.
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Methyl 4-(2-(pyridin-2-yl)benzoyl)benzoate (4z): yield:
51 mg (54%); light yellow solid, mp 100–1018C; 1H NMR
(400 MHz, CDCl3): d=3.89 (s, 3H), 6.97–7.00 (m, 1H),
7.53–7.65 (m, 5H), 7.71 (d, J=8.3 Hz, 2H), 7.78 (d, J=
7.6 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 8.28 (d, J=4.9 Hz,
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127.6, 128.0, 128.1, 128.4, 129.7, 132.0, 135.7, 138.2, 138.6,
140.8, 148.0, 155.3, 165.5, 170.3, 196.6; HR-MS (ESI): m/z=
318.1132, calcd. for C20H16NO3 [M+H]+: 318.1125.
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Acknowledgements
We are grateful to the National Natural Science Foundation
of China (No. 21102134, 21172200) for financial support to
this research.
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Arylmethyl Chlorides: New Bifunctional Reagents for
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