Palladium-catalyzed/norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction: An approach to the synthesis of ortho-aminated vinylarenes

Article abstract of DOI:10.1021/jo501125b

ortho-Aminated vinylarene derivatives were obtained via a reaction of aryl iodides, N-benzoyloxyamines, and N-tosylhydrazones. This approach involves a palladium-catalyzed, norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction. In this transformation, one C-N bond and one C-C bond are formed and an amine group is introduced at the ortho position successfully.

Full text of DOI:10.1021/jo501125b

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Article
Palladium-Catalyzed/Norbornene-Mediated ortho-
amination/N-Tosylhydrazone Insertion Reaction: An
Approach to the Synthesis of ortho-amination Vinylarenes
Ping-Xin Zhou, Yu-Ying Ye, Jun-Wei Ma, Lan Zheng, Qian Tang, Yi-
Feng Qiu, Bo Song, Zi-Hang Qiu, Peng-Fei Xu, and Yong-Min Liang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo501125b • Publication Date (Web): 02 Jul 2014
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Palladium-Catalyzed/Norbornene-Mediated
ortho-amination/N-Tosylhydrazone Insertion Reaction: An Approach to the
Synthesis of ortho-amination Vinylarenes
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Ping-Xin Zhou, Yu-Ying Ye, Jun-Wei Ma, Lan Zheng, Qian Tang, Yi-Feng Qiu, Bo
Song, Zi-Hang Qiu, Peng-Fei Xu* and Yong-Min Liang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000 (China)
E-mail: xupf@lzu.edu.cn and liangym@lzu.edu.cn
ABSTRACT: Ortho-amination vinylarene derivatives are obtained via a
reaction of aryl iodides, N-benzoyloxyamines and N-tosylhydrazones. This
approach involves
a
palladium-catalyzed, norbornene-mediated
ortho-amination/N-tosylhydrazone insertion reaction. In this transformation,
one C-N bond and one C-C bond are formed and an amine group is
introduced at the ortho-position successfully.
INTRODUCTION
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Palladium catalyzed cross-coupling reactions, which represent one of the
most reliable and powerful tools for the organic synthesis and natural product total
synthesis, have attracted the interest of several groups.1 More recently,
considerable attention has been focused on the utility of N-tosylhydrazones as the
new cross-coupling partners in palladium catalyzed transformations, which was
initially reported by Barluenga in 2007 (eq 1)2 and further developed by Wang,
Van Vranken, our group and others.3 Despite the variety of possibilities offered by
this transformation, it still needs to develop new chemical transformations based
on this unique coupling to further increase its effectiveness and usefulness.
Combining multistep process into a one-step protocol is an important goal of
transition-metal-catalyzed reactions. A remarkable type of this reaction was firstly
reported by Catellani and further modified by Lautens. This strategy provided a
way to synthesize highly substituted aromatic compounds and fused aromatic
rings from easily accessible starting materials in an efficient, atom economic way
by the palladium-catalyzed norbornene mediated ortho C-H functionalization,
followed by terminal cross-coupling processes. The scope of this reaction has
been broadened considerably since its discovery.4 For example, Lautens reported
a palladium-catalyzed intramolecular alkylation/intermolecular cyanation reaction
to afford polycyclic benzonitriles (eq 2).5 We successfully modified this sequence
by using N-tosylhydrazones as a terminal reagent to give polycyclic vinylarenes
via intramolecular alkylation/N-tosylhydrazones insertion reaction (eq 3).6
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Recently, Dong and co-worker developed the first example of forming C-N bonds
at the ortho position of aryl iodides via Catellani-Lautens type C-H activation (eq
4).7 Inspired by Dong’s work and in connection with our interest in using
N-tosylhydrazones as a new coupling partner in Catellani-Lautens reaction6, 8 and
our interest in palladium-catalyzed insertion of N-tosylhydrazones 3m, 3n, 3o, 9, we
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wish
to
report
a
palladium-catalyzed,
norbornene-mediated
ortho-amination/N-tosylhydrazone insertion reaction to obtain the ortho-amination
vinylarenes (eq 5).
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RESULTS AND DISCUSSION
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Initially, we employed the 1-iodo-2-methylbenzene 1a, N-benzoyloxyamine
2a and N-tosylhydrazone 3a as the substrates. To our delight, the product 4-1 was
afforded in 17% yield when the reaction were catalyzed by Pd(OAc)2 (10
mol%)/TFP (20 mol%)/norbornene (1.0 equiv) in the presence of Cs2CO3 in
CH3CN (Table 1, entry 1). A further investigation of the solvent revealed that the
reaction proceeded more efficiently in nonpolar solvents than in polar solvents
(Table 1, entries 2-6).
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Table 1. Optimization of reaction conditionsa
Entry
1
Catalyst
ligand
TFP
Solvent
CH3CN
dioxan
Yield
17
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
2
TFP
23
e
3
TFP
DME
18
4
TFP
DMF
<10%
trace
47
5
TFP
DCE
6
TFP
toluene
toluene
toluene
toluene
toluene
toluene
toluene
7
Xphos
trace
16
8
dppe
dppb
9
35
10
11
12
PPh3
L1
62
50
L2
49
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PdCl2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
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61
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32
50b
0
Pd(CH3CN)2Cl2
Pd(PPh3)4
.
Pd2(dba)3 CHCl3
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Pd2(dba)3
Pd(OAc)2
none
Pd(OAc)2
0c
a.1a (0.3 mmol, 1.0 equiv), 2a (0.33 mmol, 1.1 equiv), 3a (0.75 mmol, 2.5 equiv),
Pd (10 mol %), ligand (20 mol %), norbornene (0.3 mmol, 1.0 equiv), Cs2CO3 (1.5
b
mmol, 5.0 equiv), solvent (4.5 mL), 100 °C, 20 h. . 5 mol % of Pd(OAc)2 and 10
c
mol% PPh3 were employed. .The reaction was carried out in the absence of
norbornene.
The yield was slightly improved when the solvent was replaced by dioxane (Table
1, entry 2). However, DCE and DMF were found to be less effective for this
reaction (Table 1, entries 4-5). Using nonpolar toluene gave a better yield (Table 1,
entry 6). According to previous reports, it may be due to that the more polar
solvents increased the decomposition of N-benzoyloxyamine 2a.7, 10 A series of
mono- and bidentate phosphine ligands were envisioned. Only a trace amount of
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product was detected when Xphos was used and a lower yield was obtained with
dppe (Table 1, entries 7-8). Switching the ligand to dppb could not further improve
the yield (Table 1, entry 9). PPh3 gave a better result compared with L1 and L2
(Table 1, entries 10-12). Different palladium catalysts, including Pd(II) and Pd(0)
were surveyed, and it was found that Pd(OAc)2 could catalyzed this reaction more
effectively (Table 1, entries 13-17). Lowering the catalyst loading to 5 mol %
diminished the product yield (Table 1, entry 18). Further inspection of the reaction
conditions indicated that norbornene was essential for this reaction (Table 1, entry
20). Decreasing the amount of norbornene relative to 1a led to a decreased yield
(data not shown in Table 1). In previous studies, Wang has indicated that using
triethylamine as co-base was beneficial for the palladium-catalyzed insertion of
N-tosylhydrazone.3p, 11 Addition of 2.0 equivalents of NEt3, however, led to a slight
reduction in yield (data not shown in Table 1). Glorius has demonstrated that more
electron-deficient electrophilic amination reagent was found to be effective in
Rh-catalyzed C-H amination reaction.12 Nevertheless, an attempt to further
improve the yield by employing electron-deficient 2a’ in this reaction was not
successful (data not shown in Table 1). Finally, none of the desired product was
detected without palladium catalyst or norbornene in the control experiment (Table
1, entries 19 and 20).
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With the optimal conditions, we turned out to explore the scope of this
reaction with a variety of substituted aryl iodides and N-benzoyloxyamines. The
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results are summarized in Table 2. Both electron-donating and
electron-withdrawing groups on the aromatic ring could be compatible with the
reaction. Highly sterically hindered 1-iodo-2-isopropylbenzene could also lead to
the coupling product 4-3 in 48% yields. 2-Iodonaphthalene also worked, providing
the amination vinylarene in moderate yield (Table 2, 4-5). It was noteworthy that
chloro substituted product could be achieved successfully, which allowed further
metal-catalyzed coupling reaction (Table 2, 4-4). Furthermore, the reactions
demonstrated high functional group tolerance. For instance, TBS ether and nitro
Table 2. Scope of aryl iodides 1 and N-benzoyloxyamines 2 a
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a.Reaction conditions as in Table 1. b. NMR yield. c. TFP was used as ligand. d. 2.5
equiv of 2a, 2.0 equiv of norbornene and 6.0 equiv of Cs2CO3 were employed.
groups were all compatible (Table 2, 4-6, 4-9). Next, we studied the scope of the
electrophilic amine partners. Pyrrolidine gave the desired product in a low yield
(Table 2, 4-11). N-benzoyloxyamines containing the ester or Boc protecting group
were also compatible and afforded the corresponding amination products in
moderate yields (Table 2, 4-12, 4-13). Finally, we were pleased to find that the 1,
3-diamination product could be afforded in 36% yield by a double C-H activation
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of two ortho positions of aryl iodide (Table 2, 4-14). The low yield of 4-14 may be
attributed to the steric hindrance of two morpholine groups.
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The scope of this reaction was subsequently explored with various
N-tosylhydrazones 3. Ortho-, para-, and meta-substituted N-tosylhydrazones
were all good coupling partners in this reaction, resulting in the corresponding
products in moderate to good yields (Table 3). Cyclic N-tosylhydrazones led to a
good yield of 4-29 and 4-30. The naphthyl N-tosylhydrazone also worked
efficiently (Table 3, 4-31).
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Table 3. Scope of N-tosylhydrazones 3a
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a. Reaction conditions as in Table 1. b. NMR yield.
To further demonstrate the generality of this reaction, α-diazocarbonyl
compound 5a was employed as substrate under slightly modified conditions. To
our delight, the desired product 6a was given in moderate yield.
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To further demonstrate the practical utility of this protocol, we carried this
reaction on a gram scale. Gratifyingly, the desired product 4-1 could also be
afforded in moderate yield.
Gram scale
According to previous reports, 3, 4, 7, 13 we envisioned a possible catalytic
cycle for this palladium-catalyzed transformation. A oxidative addition of
substrate 1 to Pd(0) would occur to produce the intermediated A. Then, the
norbornene insertion into the intermediated A would proceed to finish
intermediate B. An electrophilic metalation at the ortho position occurs and
further elimination of HI delivers C. A further oxidative addition of
N-benzoyloxyamine 2 to species C result in the formation of cyclic Pd(IV)
complex D, followed by reductive elimination to produce the Pd(II) complex E.
Alternatively, direct electrophilic amination of the intermediate C to give the Pd(II)
complex E. Intermediated F, resulting from norbornene release, undergoes
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palladium carbene formation and migratory insertion, followed by β-H elimination
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to yield the 4.
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CONCLUSION
In
conclusion,
we
have
developed
a
palladium-catalyzed
norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction to
synthesize ortho-amination vinylarenes. In this approach, it afforded a C-N bond
and a C-C bond by using the electron-deficient N-benzoyloxyamines as an
efficient electrophilic nitrogen source and with N-tosylhydrazones as nucleophilic
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coupling partners in the termination steps. This transformation is complementary
to the Catellani-Lautens reaction, Dong’s work and Barluenga’s work. Importantly,
this reaction further demonstrates the possibility of utility N-tosylhydrazones as a
coupling partner in Catellani-Lautens reaction and the possibility of incorporation
of C-H activation in the palladium-catalyzed insertion of N-tosylhydrazone, which
opens a new avenue for the development of more novel Pd-catalyzed insertion of
N-tosylhydrazone.
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EXPERIMENTAL SECTION
General procedure for the preparation of the products 4. An dried
Schlenk tube under argon atmosphere was charged with aryl iodide 1 (0.3 mmol,
1.0 equiv), N-benzoyloxyamines 2 (0.33 mmol, 1.1 equiv), N-tosylhydrazones 3
(0.75 mmol, 2.5 equiv), Pd(OAc)2 (6.7mg, 0.03mmol, 10 mol %), PPh3 (15.7mg,
0.06mmol, 20 mol %), norbornene (28mg, 0.3 mmol, 1.0 equiv), Cs2CO3 (487mg,
1.5 mmol, 5.0 equiv) and toluene (4.5 mL). The mixture was stirred at room
temperature for 15 minutes and then stirred at 100°C for 20 h. The resulting
mixture was cooled to room temperature and filtered through celite with EtOAc as
eluents. The solvents were evaporated under reduced pressure and the residue
was purified by flash chromatography on silica gel using petroleum ether/ethyl
acetate to afford 4 in over 90% purity.
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General procedure for the preparation of the products 6a. An dried
Schlenk tube under argon atmosphere was charged with aryl iodide 1a (65.4mg,
0.3 mmol, 1.0 equiv), N-benzoyloxyamines 2a (124mg, 0.45 mmol, 1.5 equiv),
α-diazocarbonyl compounds 5a (73.4mg, 0.36 mmol, 1.2 equiv), Pd(OAc)2 (6.7mg,
0.03mmol, 10 mol%), TFP (14mg, 0.06mg, 20 mol%), norbornene (56mg, 0.60
mmol, 2.0 equiv), Cs2CO3 (215mg, 0.66 mmol, 2.2 equiv) and DCE (3.0 mL). The
mixture was stirred at room temperature for 15 minutes and then stirred at 60°C
for 30 h. The resulting mixture was cooled to room temperature and filtered
through celite with EtOAc as eluents. The solvents were evaporated under
reduced pressure and the residue was purified by flash chromatography on silica
gel using petroleum ether/ethyl acetate to afford pure 6a.
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4-(3-methyl-2-(1-phenylvinyl)phenyl)morpholine (4-1): Flash chromatography
on silica using petroleum ether/ethyl acetate (4% ethyl acetate in
petroleum ether) as eluent to affored 4-1 (52 mg, 62% yield); coreless oil,
slowly solidifying to a white solid; 1H NMR (400MHz, CDCl3) δ ppm: 7.26-7.21(m,
6H), 7.04(d, J = 7.2Hz, 1H), 6.94(d, J = 8.0Hz, 1H), 5.94(d, J = 1.2Hz, 1H), 5.16(d,
J = 1.2Hz, 1H), 3.50(s, 2H), 3.34(s, 2H), 3.01(s, 2H), 2.58(s, 2H), 2.25(s, 3H);
13C{H} NMR (100MHz, CDCl3) δ ppm: 151.1, 146.4, 141.2, 137.8, 137.6, 128.0,
127.9, 127.1, 125.8, 125.7, 117.9, 115.5, 67.1, 52.3, 20.7; HRMS (ESI) m/z: calcd
for C19H21NO: M+H=280.1696; found: 280.1699.
4-(3-methoxy-2-(1-phenylvinyl)phenyl)morpholine(4-2):Flash chromatography
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on silica using petroleum ether/ethyl acetate (4% ethyl acetate in
petroleum ether) as eluent to affored 4-2 (65 mg, 73% yield); yellow solid; 1H
NMR (400MHz, CDCl3) δ ppm: 7.30-7.19(m, 6H), 6.75-6.70(m, 2H), 5.95(d, J =
1.2Hz, 1H), 5.31(d, J = 1.2Hz, 1H), 3.71(s, 3H), 3.43(t, J = 4.4Hz, 4H), 2.83(s, 4H);
13C{H} NMR (100MHz, CDCl3) δ ppm:158.1, 152.2, 142.9, 141.3, 128.8, 127.9,
127.0, 125.8, 125.7, 116.6, 112.5, 106.7, 67.1, 56.0, 51.8; HRMS (ESI) m/z: calcd
for C19H21NO2: M+H=296.1645; found: 296.1648.
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4-(3-isopropyl-2-(1-phenylvinyl)phenyl)morpholine
(4-3):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-3 (44 mg, 48% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.35-7.31(m, 1H), 7.24-7.15(m,
6H), 6.96 (d, J =7.6Hz, 1H), 5.95(d, J = 1.2Hz, 1H), 5.11(d, J = 1.2Hz, 1H),
3.53-3.48(m, 2H), 3.33-3.27(m, 2H), 3.25-3.20(m, 1H), 3.02-2.97(m, 2H),
2.54-2.50(m, 2H), 1.22(d, J = 6.8Hz, 3H), 1.11(d, J = 6.8Hz, 3H); 13C{H} NMR
(100MHz, CDCl3) δ ppm: 150.8, 148.7, 146.1, 141.6, 137.1, 130.4, 127.9, 127.1,
125.8, 121.6, 118.3, 114.9, 67.2, 52.5, 29.8, 25.0, 24.1; HRMS (ESI) m/z: calcd for
C21H25NO: M+H=308.2009; found: 308.2011.
4-(3-chloro-2-(1-phenylvinyl)phenyl)morpholine (4-4): Flash chromatography
on silica using petroleum ether/ethyl acetate (4% ethyl acetate in
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petroleum ether) as eluent to affored 4-4 (44% yield) as colorless liquid; H
NMR (400MHz, CDCl3) δ ppm: 7.22(d, J = 9.2Hz, 7H), 6.96(dd, J = 6.8 Hz, 2.0Hz,
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1H), 6.02(s, 1H), 5.32(s, 1H), 3.50(s, 2H), 3.36(s, 2H), 3.01(s, 2H), 2.63(s, 2H);
13C{H} NMR (100MHz, CDCl3) δ ppm: 152.6, 144.3, 140.1, 136.1, 134.7, 128.9,
128.1, 127.3, 125.7, 124.7, 118.6, 117.4, 66.9, 51.9; HRMS (ESI) m/z: calcd for
C18H18ClNO: M+H=300.1150; found: 300.1151.
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4-(1-(1-phenylvinyl)naphthalen-2-yl)morpholine (4-5): Flash chromatography
on silica using petroleum ether/ethyl acetate (4% ethyl acetate in
petroleum ether) as eluent to affored 4-5 (62% yield) as white liquid; 1H NMR
(400MHz, CDCl3) δ ppm: 8.08-8.06(m, 1H), 7.87-7.82(m, 2H), 7.41-7.37(m, 3H),
7.25-7.20(m, 5H), 6.14(d, J =1.2 Hz, 1H), 5.29(d, J =1.2 Hz, 1H), 3.59-3.54(m,
2H), 3.40-3.36(m, 2H), 3.13-3.08(m, 2H), 2.69-2.65(m, 2H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 147.3, 145.4, 141.7, 133.8, 133.5, 131.0, 128.9, 128.0, 127.8,
127.2, 126.2, 126.1, 125.8, 124.7, 120.3, 116.9, 67.2, 52.1; HRMS (ESI) m/z:
calcd for C22H21NO: M+H=316.1696; found: 316.1699.
4-(3-(((tert-butyldimethylsilyl)oxy)methyl)-2-(1-phenylvinyl)phenyl)morpholi
ne (4-6): Flash chromatography on silica using petroleum ether/ethyl acetate
(4% ethyl acetate in petroleum ether) as eluent to affored 4-6 (75 mg, 61%
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yield); colorless liquid; H NMR (400MHz, CDCl3) δ ppm: 7.49-7.38(m, 2H),
7.25-7.24(m, 5H), 7.07(d, J = 7.2Hz, 1H), 5.96(d, J = 1.6Hz, 1H), 5.22(d, J =
1.2Hz, 1H), 4.83(d, J = 13.6Hz, 1H), 4.64(d, J = 13.6Hz, 1H), 3.57-3.53(m, 2H),
3.35(s, 2H), 3.09(d, J = 8.8Hz, 2H), 2.62-2.58(m, 2H), 0.97(s, 9H), 0.09(s, 3H),
0.07(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 150.5, 145.4, 141.0, 140.8,
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135.6, 128.3, 128.0, 127.2, 125.8, 122.5, 119.1, 115.7, 67.1, 63.1, 52.3, 26.0, 18.4,
-5.4; HRMS (ESI) m/z: calcd for C25H35NO2Si: M+H=410.2510; found: 410.2513;
EA: calcd for C: 73.30%, H: 8.61%, N:3.42%; found: C: 73.10%, H: 8.42%, N:
2.95%.
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4-(3,5-dimethyl-2-(1-phenylvinyl)phenyl)morpholine
(4-7):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-7 (53 mg, 60% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.20(d, J = 11.2Hz, 5H), 6.87(s,
1H), 6.74(s, 1H), 5.92(d, J = 1.2Hz, 1H), 5.14(d, J = 0.8Hz, 1H), 3.49(s, 2H),
3.33(s, 2H), 3.00(s, 2H), 2.57(s, 2H), 2.34(s, 3H), 2.21(s, 3H); 13C{H} NMR
(100MHz, CDCl3) δ ppm: 151.0, 146.4, 141.4, 137.6, 137.5, 134.6, 128.0, 127.1,
126.4, 125.8, 118.6, 115.6, 67.1, 52.3, 21.3, 20.6; HRMS (ESI) m/z: calcd for
C20H23NO: M+H=294.1852; found: 294.1854.
4-(5-chloro-3-methyl-2-(1-phenylvinyl)phenyl)morpholine
(4-8):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-8 (43 mg, 46% yield); white
liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.26-7.19(m,5H), 7.02(d, J = 1.6Hz, 1H),
6.88(d, J = 1.6Hz, 1H), 5.96(s, 1H), 5.16(s, 1H), 3.49(s, 2H), 3.33(s, 2H), 3.00(s,
2H), 2.59(s, 2H), 2.21(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 152.2, 145.5,
140.5, 139.4, 135.6, 133.2, 128.1, 127.4, 125.7, 125.3, 118.2, 116.2, 66.9, 52.0,
20.7; HRMS (ESI) m/z: calcd for C19H20ClNO: M+H=314.1306; found: 314.1307;
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EA: calcd for C: 72.72%, H: 6.42%, N:4.46%; found: C: 72.58%, H: 6.58%, N:
4.00%.
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4-(3-methyl-5-nitro-2-(1-phenylvinyl)phenyl)morpholine
(4-9):
Flash
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chromatography on silica using petroleum ether/ethyl acetate (5% ethyl
acetate in petroleum ether) as eluent to affored 4-9 (35 mg, 36% yield);
yellow liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.89(d, J = 2.0Hz, 1H), 7.75(d, J =
2.0Hz, 1H), 7.29-7.26(m, 3H), 7.20-7.18(m, 2H), 6.05(s, 1H), 5.24(s, 1H), 3.53(s,
2H), 3.39(s, 2H), 3.08(s, 2H), 2.69(s, 2H), 2.32(s, 3H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 152.1, 147.6, 144.9, 143.7, 139.5, 139.4, 128.4, 127.9, 125.5,
120.0, 116.6, 112.7, 66.8, 51.9, 21.0; HRMS (ESI) m/z: calcd for C19H20N2O3:
M+H=325.1547; found: 325.1550.
4-(4,5-dimethoxy-3-methyl-2-(1-phenylvinyl)phenyl)morpholine (4-10): Flash
chromatography on silica using petroleum ether/ethyl acetate (5% ethyl
acetate in petroleum ether) as eluent to affored 4-10 (45 mg, 44% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.26-7.20(m, 5H), 6.56(s, 1H),
5.91(d, J = 1.6Hz, 1H), 5.10(d, J = 1.6Hz, 1H), 3.88(s, 3H), 3.81(s, 3H), 3.50(d, J
=8.0Hz, 2H), 3.32(s, 2H), 2.95(s, 2H), 2.54(s, 2H), 2.19(s, 3H); 13C{H} NMR
(100MHz, CDCl3) δ ppm: 152.1, 147.0, 146.2, 143.9, 141.7, 131.7, 131.3, 127.9,
127.1, 125.8, 115.7, 102.9, 67.1, 60.3, 55.7, 52.5, 13.6; HRMS (ESI) m/z: calcd for
C21H25NO3: M+H=340.1907; found: 340.1912.
1-(3-methyl-2-(1-phenylvinyl)phenyl)pyrrolidine (4-11): Flash chromatography
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on silica using petroleum ether/ethyl acetate (1% ethyl acetate in
petroleum ether) as eluent to affored 4-11 (16% yield) as colorless liquid; 1H
NMR (400MHz, CDCl3) δ ppm: 7.38-7.36(m, 2H), 7.29-7.22(m, 3H), 7.15-7.11(m,
1H), 6.70(dd, J =7.2 Hz, 15.6 Hz, 2H), 6.01(d, J =0.8 Hz, 1H), 5.20(d, J =0.8 Hz,
1H), 3,21(s, 2H), 3.11(s, 2H), 2.06(s, 3H), 1.71(t, J =6.4 Hz, 4H); 13C{H} NMR
(100MHz, CDCl3) δ ppm: 148.5, 147.0, 140.7, 137.9, 128.2, 127.6, 127.2, 126.0,
125.6, 120.2, 115.5, 112.9, 50.6, 25.3, 21.0; HRMS (ESI) m/z: calcd for C19H21N:
M+H=264.1747; found: 264.1750.
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Tert-butyl
4-(3-methyl-2-(1-phenylvinyl)phenyl)piperazine-1-carboxylate
(4-12): Flash chromatography on silica using petroleum ether/ethyl acetate
(4% ethyl acetate in petroleum ether) as eluent to affored 4-12 (64 mg, 56%
yield); colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.23-7.19(m, 6H), 7.05(d,
J = 7.6 Hz, 1H), 6.91(d, J = 8.0 Hz,1H), 5.94(s, 1H), 5.14(s, 1H), 3.26-3.22(m, 2H),
3.02-2.94(m, 4H), 2.50(s, 2H), 2.27(s, 3H), 1.42(s, 9H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 154.7, 151.1, 146.3, 141.1, 137.9, 137.8, 128.0, 127.9, 127.1,
125.9, 125.6, 118.1, 115.4, 79.4, 51.9, 28.4, 20.7; HRMS (ESI) m/z: calcd for
C24H30N2O2: M+H=379.2380; found: 379.2383.
Ethyl 1-(3-methyl-2-(1-phenylvinyl)phenyl)piperidine-4-carboxylate (4-13):
Flash chromatography on silica using petroleum ether/ethyl acetate (4%
ethyl acetate in petroleum ether) as eluent to affored 4-13 (55 mg, 53% yield);
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colorless liquid; H NMR (400MHz, CDCl3) δ ppm: 7.22-7.17(m, 6H), 7.01(d, J =
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7.2 Hz, 1H), 6.92(d, J = 8.0Hz, 1H), 5.93(d, J = 1.2Hz, 1H), 5.13(d, J = 1.2Hz, 1H),
4.09(q, J = 7.2 Hz, 2H), 3.28(d, J = 10.4Hz, 1H), 2.74-2.66(m, 2H), 2.49-2.39(m,
1H), 2.23 (s, 3H), 2.21-2.15(m, 1H), 1.67(d, J = 17.6Hz, 4H), 1.23-1.20(m, 3H);
13C{H} NMR (100MHz, CDCl3) δ ppm: 175.2, 152.0, 146.4, 141.1, 137.9, 137.5,
127.9, 127.7, 127.0, 125.7, 125.4, 118.1, 115.1, 60.0, 53.0, 50.9, 41.0, 28.5, 20.7,
14.2; HRMS (ESI) m/z: calcd for C23H27NO2: M+H=350.2115; found: 350.2118.
EA: calcd for C: 79.05%, H: 7.79%, N: 4.01%; found: C: 79.03%, H: 7.86%, N:
3.70%.
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4,4'-(2-(1-phenylvinyl)-1,3-phenylene)dimorpholine
(4-14):
Flash
chromatography on silica using petroleum ether/ethyl acetate (5% ethyl
acetate in petroleum ether) as eluent to affored 4-14 (38 mg, 36% yield);
white solid; 1H NMR (400MHz, CDCl3) δ ppm: 7.30-7.21(m, 6H), 6.84(d, J = 8.0Hz,
2H), 5.94(s, 1H), 5.51(s, 1H), 3.46(s, 8H), 2.84(s, 8H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 152.2, 144.1, 142,1, 131.7, 128.8, 127.9, 126.9, 125.5, 116.2,
115.4, 67.0, 51.8; HRMS (ESI) m/z: calcd for C22H26N2O2: M+H=351.2067; found:
351.2072.
4-(2-(1-(4-fluorophenyl)vinyl)-3-methylphenyl)morpholine
(4-15):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-15 (59 mg, 67% yield;
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white solid); H NMR (400MHz, CDCl3) δ ppm: 7.25-7.16(m, 3H), 7.04(d, J =
7.6Hz, 1H), 6.96-6.91(m, 3H), 5.88(d, J =0.4Hz, 1H), 5.13(s, 1H), 3.51(s, 2H),
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3.35(s, 2H), 3.03(s, 2H), 2.56(s, 2H), 2.25(s, 3H); 13C{H} NMR (100MHz, CDCl3)
δ ppm: 163.4, 161.0, 151.0, 145.4, 137.7, 137.4, 137.3, 137.2, 128.1, 127.3,
127.2, 125.8, 118.0, 115.3, 114.9, 114.7, 67.1, 52.3, 20.6; HRMS (ESI) m/z: calcd
for C19H20FNO: M+H=298.1602; found: 298.1601. EA: calcd for C: 76.74%, H:
6.78%, N:4.71%; found: C: 76.61%, H: 7.05%, N: 4.28%.
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4-(2-(1-(4-chlorophenyl)vinyl)-3-methylphenyl)morpholine
(4-16):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-16 (64 mg, 68% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.25-7.20(m, 3H), 7.15-7.13(m,
2H), 7.04(d, J = 7.6Hz, 1H), 6.94(d, J = 7.6Hz, 1H), 5.93(s, 1H), 5.17(s, 1H),
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3.51(s, 2H), 3.35(s, 2H), 3.02(d, J = 8.8Hz, 2H), 2.56(s, 2H), 2.24(s, 3H); C{H}
NMR (100MHz, CDCl3) δ ppm: 151.0, 145.3, 139.7, 137.7, 137.1, 132.8, 128.2,
128.1, 127.0, 125.9, 118.0, 116.0, 67.1, 52.3, 20.6; HRMS (ESI) m/z: calcd for
C19H20ClNO: M+H=314.1306; found: 314.1308. EA: calcd for C: 72.72%, H:
6.42%, N:4.46%; found: C: 72.59%, H: 6.25%, N: 4.07%.
4-(2-(1-(4-chlorophenyl)vinyl)-3-methoxyphenyl)morpholine (4-17): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-17 (72% yield) as
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.29(d, J =8.4 Hz, 1H), 7.26(s,
4H), 6.74-6.70(m, 2H), 5.93(s, 1H), 5.33(s, 1H), 3.72(s, 3H), 3.46-3.44(m, 4H),
2.83(s, 4H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 158.1, 152.1, 141.8, 139.9,
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132.6, 129.0, 128.0, 127.0, 125.0, 117.1, 112.5, 106.7, 67.0, 56.0, 51.9; HRMS
(ESI) m/z: calcd for C19H20ClNO2: M+H=330.1255; found: 330.1258.
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chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-18 (62% yield) as white
liquid; HRMS (ESI) m/z: calcd for C19H20BrNO2: M+H=374.0750; found: 374.0752.
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4-(3-methyl-2-(1-(p-tolyl)vinyl)phenyl)morpholine
(4-19):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-19 (57 mg, 65% yield);
white solid; 1H NMR (400MHz, CDCl3) δ ppm: 7.24-7.20(m, 1H), 7.12(d, J = 8.4Hz,
2H), 7.05-7.01(m, 3H), 6.93(d, J = 7.6Hz, 1H), 5.90(d, J = 1.2Hz, 1H), 5.10(d, J =
1.2Hz, 1H), 3.54-3.50(m, 2H), 3.37(s, 2H), 3.02(d, J = 8.8 Hz, 2H), 2.63-2.59(m,
2H), 2.32(s, 3H), 2.22(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 151.1, 146.1,
138.1, 137.8, 137.6, 136.9, 128.7, 127.8, 125.6, 125.5, 117.7, 114.6, 67.2, 52.3,
21.1, 20.6; HRMS (ESI) m/z: calcd for C20H23NO: M+H=294.1852; found:
294.1855.
4-(3-methoxy-2-(1-(4-methoxyphenyl)vinyl)phenyl)morpholine (4-20): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-20 (67 mg, 69% yield);
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white solid; H NMR (400MHz, CDCl3) δ ppm: 7.28-7.24(m, 1H), 7.21(d, J = 9.2
Hz, 2H), 6.77(d, J = 9.2Hz, 2H), 6.73-6.69(m, 2H), 5.86(d, J = 1.6Hz, 1H), 5.20(d,
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J = 1.2Hz, 1H), 3.78(s, 3H), 3.70(s, 3H), 3.48-3.46(m, 4H), 2.85(s, 4H); 13C{H}
NMR (100MHz, CDCl3) δ ppm: 158.8, 158.1, 152.1, 142.2, 133.7, 128.6, 126.9,
125.7, 114.6, 113.2, 112.3, 106.6, 67.1, 56.0, 55.2, 51.8; HRMS (ESI) m/z: calcd
for C20H23NO3: M+H=326.1751; found: 326.1754. EA: calcd for C: 73.82%, H:
7.12%, N:4.30%; found: C: 73.45%, H: 7.02%, N: 3.88%.
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4-(2-(1-(3-fluorophenyl)vinyl)-3-methylphenyl)morpholine
(4-21):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-21 (55 mg, 62% yield);
white solid; 1H NMR (400MHz, CDCl3) δ ppm: 7.25-7.17(m, 2H), 7.05-7.01(m, 2H),
6.96-6.88(m, 3H), 5.95(d, J = 0.6 Hz, 1H), 5.20(s, 1H), 3.51(s, 2H), 3.34(s, 2H),
3.01(s, 2H), 2.56(s, 2H), 2.25(s, 3H), 13C{H} NMR (100MHz, CDCl3) δ ppm: 164.1,
161.7, 151.0, 145.5, 145.4, 143.8, 143.7, 137.7, 137.1, 129.4, 129.3, 128.2, 125.9,
121.4, 121.3, 118.0, 116.6, 114.0, 113.7, 112.6, 112.4, 67.1, 52.3, 20.6; HRMS
(ESI) m/z: calcd for C19H20FNO: M+H=298.1602; found: 298.1603. EA: calcd for C:
76.74%, H: 6.78%, N:4.71%; found: C: 77.15%, H: 6.82%, N: 4.32%.
4-(2-(1-(3-fluorophenyl)vinyl)-3-methoxyphenyl)morpholine (4-22): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-22 (76% yield) as white
solid; HRMS (ESI) m/z: calcd for C19H20FNO2: M+H=314.1551; found: 314.1553.
4-(2-(1-(3-chlorophenyl)vinyl)-3-methylphenyl)morpholine
(4-23):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
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acetate in petroleum ether) as eluent to affored 4-23 (50 mg, 54% yield);
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yellow solid; H NMR (400MHz, CDCl3) δ ppm: 7.26-7.15(m, 4H), 7.10-7.04(m,
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2H), 6.96(d, J = 15.6 Hz, 1H), 5.95(s, 1H), 5.20(s, 1H), 3.51(s, 2H), 3.35(s, 2H),
3.01(s, 2H), 2.56(s, 2H), 2.25(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 151.0,
145.3, 143.2, 137.7, 137.0, 134.0, 129.2, 128.2, 127.1, 126.0, 125.8, 123.9, 118.1,
116.8, 67.1, 52.3, 20.7; HRMS (ESI) m/z: calcd for C19H20ClNO: M+H=314.1306;
found: 314.1308.
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4-(3-methoxy-2-(1-(3-nitrophenyl)vinyl)phenyl)morpholine
(4-24):
Flash
chromatography on silica using petroleum ether/ethyl acetate (5% ethyl
acetate in petroleum ether) as eluent to affored 4-24 (58% yield) as yellow oil;
1H NMR (400MHz, CDCl3) δ ppm: 8.13-8.06(m, 2H), 7.58(d, J =15.6 Hz, 1H),
7.41(t, J =8.0 Hz, 1H), 7.34-7.30(m, 1H), 6.79-6.74(m, 2H), 6.08(s, 1H), 5.50(s,
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1H), 3.74(s, 3H), 3.41-3.39(m, 4H), 2.83(s, 4H); C{H} NMR (100MHz, CDCl3) δ
ppm: 157.9, 151.9, 148.2, 143.3, 140.8, 131.6, 129.5, 128.6, 123.9, 121.6, 120.6,
119.4, 112.6, 106.8, 66.8, 55.8, 51.8; HRMS (ESI) m/z: calcd for C19H20N2O4:
M+H=341.1496; found: 341.1499.
4-(3-methyl-2-(1-(m-tolyl)vinyl)phenyl)morpholine
(4-25):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-25 (46 mg, 52% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.24-7.20(m, 1H), 7.12(dd, J =
7.6Hz, 1H), 7.09(dd, J = 8.4Hz, 1H), 7.03(d, J = 7.6Hz, 2H), 6.99(d, J = 7.6Hz, 1H),
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6.94(d, J = 8.0Hz, 1H), 5.92(d, J = 1.2Hz, 1H), 5.14(d, J = 1.2Hz, 1H), 3.52(s, 2H),
3.36(s, 2H), 3.00(s, 2H), 2.60(s, 2H), 2.30(s, 3H), 2.24(s, 3H); 13C{H} NMR
(100MHz, CDCl3) δ ppm: 151.1, 146.4, 141.1, 137.8, 137.7, 137.4, 127.9, 127.8,
127.8, 126.4, 125.7, 123.1, 117.9, 115.4, 67.2, 52.3, 21.5, 20.7; HRMS (ESI) m/z:
calcd for C20H23NO: M+H=294.1852; found: 294.1851.
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4-(2-(1-(3-fluorophenyl)vinyl)-3-methoxyphenyl)morpholine (4-26): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-26 (70% yield) as solid; 1H
NMR (400MHz, CDCl3) δ ppm: 7.26(d, J =8.8Hz, 1H), 7.13-7.10(m, 2H),
7.04-7.01(m, 2H), 6.74-6.70(m, 2H), 5.94(s, 1H), 5.29(s, 1H), 3.71(s, 3H),
3.47-3.45(m, 4H), 2.84(s, 4H), 2.30(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm:
158.1, 152.1, 142.9, 141.2, 137.2, 128.7, 127.8, 126.4, 125.8, 123.1, 116.3, 112.4,
106.7, 67.1, 56.1, 51.8, 21.5; HRMS (ESI) m/z: calcd for C20H23NO2:
M+H=310.1802; found: 310.1804.
4-(2-(1-(3-methoxyphenyl)vinyl)-3-methylphenyl)morpholine (4-27): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-27 (46 mg, 50% yield);
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colorless liquid; H NMR (400MHz, CDCl3) δ ppm: 7.25-7.14(m, 2H), 7.02(d, J =
7.6 Hz, 1H), 6.93(d, J = 8.0 Hz, 1H), 6.83-6.76(m, 3H), 5.94(d, J =1.6 Hz, 1H),
5.16(d, J =1.2 Hz, 1H), 3.75(s, 3H), 3.55(d, J =15.2Hz, 2H), 3.38(s, 2H), 3.00(s,
2H), 2.61(s, 2H), 2.24(s, 3H); 13C{H} NMR (100MHz, CDCl3) δ ppm: 159.5, 151.1,
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146.2, 142.8, 137.8, 137.5, 128.9, 128.0, 125.7, 118.6, 117.9, 115.8, 112.2, 111.9,
67.2, 55.2, 52.3, 20.7; HRMS (ESI) m/z: calcd for C20H23NO2: M+H=310.1802;
found: 310.1805.
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4-(3-methoxy-2-(1-(o-tolyl)vinyl)phenyl)morpholine
(4-28):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-28 (50 mg, 54% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.27-7.23(m, 1H), 7.20-7.18(m,
1H), 7.08-7.07(m, 3H), 6.77-6.72(m, 2H), 5.64(d, J = 2.0Hz, 1H), 5.50(d, J = 2.0
Hz, 1H), 3.78(s, 3H), 3.45(t, J = 4.4 Hz, 4H), 2.73-2.71(m, 4H), 2.14(s, 3H); 13C{H}
NMR (100MHz, CDCl3) δ ppm: 157.8, 152.1, 142.5, 142.3, 134.7, 130.5, 129.1,
128.6, 128.1, 126.3, 125.1, 121.0, 113.1, 107.4, 66.8, 55.8, 52.3, 20.8; HRMS
(ESI) m/z: calcd for C20H23NO2: M+H=310.1802; found: 310.1805.
4-(2-(3,4-dihydronaphthalen-1-yl)-3-methoxyphenyl)morpholine (4-29): Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-29 (85 mg, 88% yield);
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white solid; H NMR (400MHz, CDCl3) δ ppm: 7.28-7.24(m, 1H), 7.13(d, J = 7.6
Hz, 1H), 7.09-7.05(m, 1H), 7.00-6.96(m, 1H), 6.71-6.68(m, 2H), 6.64(d, J = 7.6 Hz,
1H), 6.08-6.06(m, 1H), 3.66(s, 3H), 3.48-3.39(m, 4H), 2.99-2.94(m, 2H),
2.89-2.85(m, 2H), 2.78-2.74(m, 2H), 2.53-2.33(m,2H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 158.4, 152.4, 135.7, 135.6, 133.1, 129.2, 128.5, 127.1, 126.2,
125.9, 124.0, 123.4, 111.8, 106.4, 67.1, 56.0, 51.6, 28.1, 23.5; HRMS (ESI) m/z:
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calcd for C21H23NO2: M+H=322.1802; found: 322.1804. EA: calcd for C: 78.47%,
H: 7.21%, N:4.36%; found: C: 78.03%, H: 6.97%, N: 4.04%.
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4-(2-(2H-chromen-4-yl)-3-methoxyphenyl)morpholine
(4-30):
Flash
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chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-30 (69 mg, 71% yield);
colorless liquid; 1H NMR (400MHz, CDCl3) δ ppm: 7.30-7.26(m, 1H), 7.09-7.05(m,
1H), 6.85(dd, J = 1.2 Hz, J = 8.0 Hz, 1H), 6.75-6.67(m, 3H), 6.64-6.62(m, 1H),
5.83-5.81(m, 1H), 4.94-4.90(m, 1H), 4.86-4.81(m, 1H), 3.70(s, 3H), 3.48-3.46(m,
4H), 2.99-2.94(m, 2H), 2.82-2.77(m,2H); 13C{H} NMR (100MHz, CDCl3) δ ppm:
158.3, 154.6, 152.3, 130.8, 129.1, 128.4, 125.1, 124.0, 122.4, 120.8, 120.6, 115.7,
111.8, 106.1, 67.1, 65.3, 55.9, 51.7; HRMS (ESI) m/z: calcd for C20H21NO3:
M+H=324.1594; found: 324.1592.
4-(3-methyl-2-(1-(naphthalen-2-yl)vinyl)phenyl)morpholine
(4-31):
Flash
chromatography on silica using petroleum ether/ethyl acetate (4% ethyl
acetate in petroleum ether) as eluent to affored 4-31 (46 mg, 47% yield);
white solid; 1H NMR (400MHz, CDCl3) δ ppm: 7.79-7.73(m, 2H), 7.69-7.66(m, 1H),
7.54-7.50(m, 2H), 7.40-7.38(m, 2H), 7.28-7.24(m, 1H), 7.07(d, J = 7.6 Hz, 1H),
6.97(d, J = 7.6 Hz, 1H), 6.07(d, J = 1.2 Hz, 1H), 5.26(d, J = 1.2 Hz, 1H), 3.45(s,
2H), 3.29(s, 2H), 3.01(s, 2H), 2.60(s, 2H), 2.27(s, 3H); 13C{H} NMR (100MHz,
CDCl3) δ ppm: 151.2, 146.2, 138.4, 137.8, 137.5, 133.3, 132.8, 128.1, 128.0,
127.6, 127.5, 125.9, 125.8, 125.6, 124.4, 124.3, 118.0, 116.1, 67.1, 52.3, 20.7;
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HRMS (ESI) m/z: calcd for C23H23NO: M+H=330.1852; found: 330.1854. EA:
calcd for C: 83.85%, H: 7.04%, N:4.25%; found: C: 83.80%, H: 6.93%, N: 3.90%.
(E)-ethyl 2-(2-methyl-6-morpholinophenyl)-3-phenylacrylate (6a): Flash
chromatography on silica using petroleum ether/ethyl acetate (5% ethyl
acetate in petroleum ether) as eluent to affored 6a (60 mg, 57% yield);
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colorless solid; H NMR (400 MHz, CDCl3) δ: 7.74(s, 1H), 7.31-7.26(m, 1H),
7.23-7.16(m, 3H), 7.08(d, J = 7.2 Hz, 2H), 7.00-6.98(m, 2H), 4.26-4.18(m, 2H),
3.68-3.63(m, 2H), 3.60-3.55(m, 2H), 2.91-2.86(m, 2H), 2.74-2.68(m, 2H), 2.00(s,
3H), 1.25-1.21(m, 3H); 13C{H} NMR (100 MHz, CDCl3) δ: 168.8, 151.5, 138.9,
137.5, 135.4, 132.6, 130.8, 129.4, 129.1, 128.8, 128.5, 126.1, 117.7, 67.4, 60.8,
52.3, 19.7, 14.4; HRMS (ESI) m/z: calcd for C22H25NO3: M+H=352.1907; found:
352.1891.
ASSOCIATED CONTENT
ACKNOWLEDGMENTS
We thank the National Science Foundation (NSF 21072080 and 21272101) and
National Basic Research Program of China (973 Program) 2010CB833203 and
“111” program of MOE and PCSIRT: IRT1138 for financial support.
Supporting Information
1
The copies of H, 13C spectra for new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
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REFERENCES
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(1) (a) Negishi, E.-I.; Meijere, A. De, (Eds.). Hand book of Organopalladium
Chemistry for Organic Synthesis, Wiley-Interscience, New York, 2002. (b) Tsuji, J.
Palladium Reagents and Catalysts, Wiley, Chichester, 2004. (c) Tsuji, J. (Ed.),
Palladium in Organic Synthesis Springer, Berlin, 2005.
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(3) For reviews on using N-tosylhydrazones compound as coupling partner in
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Int. Ed. 2011, 50, 7486. (b) Franssen, N. M. G.; Walters, A. J. C.; Reek, J. N.
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Chem. Soc. Rev. 2012, 41, 560. (d) Zhang, Y.; Wang, J. Top. Curr. Chem.
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236. (f) Xia, Y.; Zhang, Y.; Wang, J. ACS Catal. 2013, 3, 2586. For rencently
work on palladium catalysed insertion N-tosylhydrazones see: (g) Khanna, A.;
Maung, C.; Johnson, K. R.; Luong, T. T.; Van Vranken, D. L. Org. Lett. 2012
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14, 3233. (h) Chen, H.; Huang, L.; Fu, W.; Liu, X.; Jiang, H. Chem. Eur. J.
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11884. (j) Roche, M.; Hamze, A.; Brion, J.-D.; Alami, M. Org. Lett. 2013, 15,
148. (k) Xia, Y.; Hu, F.; Liu, Z.; Qu, P.; Ge, R.; Ma, C.; Zhang, Y.; Wang, J.
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