Nucleopalladation-initiated oxyalkenylation of alkenes: A strategy to construct functionalized oxygenated heterocycles

Article abstract of DOI:10.1021/jo501317v

A convenient and efficient approach to construct functionalized oxygen heterocycles, i.e., tetrahydrofurans, tetrahydropyrans, and γ-lactones, has been reported. This process successfully provides a route to construct derivatives of naturally occurring biologically active tetrahydrofurans, especially ones with spirocyclic structure. Highly regio- and stereoselective nucleopalladation of alkynes initiates the cross-coupling between alkynamides and alkenes to give the olefin oxyalkenylation products in good to excellent yields. The hydroxyl group in the olefins cooperates with the amide in alkynamides to promote the cyclization by suppressing the β-H elimination.

Full text of DOI:10.1021/jo501317v

Note
pubs.acs.org/joc
Nucleopalladation-Initiated Oxyalkenylation of Alkenes: A Strategy
To Construct Functionalized Oxygenated Heterocycles
Liangbin Huang,† Qian Wang,† Wanqing Wu, and Huanfeng Jiang*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
S
* Supporting Information
ABSTRACT: A convenient and efficient approach to
construct functionalized oxygen heterocycles, i.e., tetrahydro-
furans, tetrahydropyrans, and γ-lactones, has been reported.
This process successfully provides a route to construct
derivatives of naturally occurring biologically active tetrahy-
drofurans, especially ones with spirocyclic structure. Highly
regio- and stereoselective nucleopalladation of alkynes initiates the cross-coupling between alkynamides and alkenes to give the
olefin oxyalkenylation products in good to excellent yields. The hydroxyl group in the olefins cooperates with the amide in
alkynamides to promote the cyclization by suppressing the β-H elimination.
alladium-catalyzed cross-coupling reaction to construct C−
remote hydroxyl group could cooperate with the amide to
suppress the β-H elimination of alkyl-Pd intermediate (Scheme
2, path c).8 On the basis of our previous work and inspired by
Wolfe-type carbooxygenation of alkenes with aromatic electro-
philes,9 herein we disclose a Pd-catalyzed intermolecular
oxyalkenylation of terminal alkenes (Scheme 2, path d).
Various functionalized oxygenated heterocycles, such as
tetrahydrofurans, tetrahydropyrans, and γ-lactones, were
smoothly constructed in high yields. It also provides a route
to construct derivatives of naturally occurring biologically active
tetrahydrofurans, especially the spirocyclic compounds.
P
C bonds is of great importance in organic synthesis.1 The
palladium catalyst, as a Lewis-acidic transition metal, could also
promote the C−C multiple bonds to undergo nucleophilic
addition. Nucleopalladation of alkynes and alkenes, which
affords the alkyl-Pd and vinyl-Pd species, respectively, (Scheme
1) has been proven to be a highly important route to generate
Scheme 1. Nucleopalladation of Alkenes and Alkynes
Our initial investigation concentrated on Pd-catalyzed
coupling of 3-phenylpropiolamide (1a) with pent-4-en-1-ol
(2a) in the presence of PdCl2 (5 mol %), CuCl2·2H2O (2
equiv) in CH3CN at room temperature for 12 h, which
efficiently gave the desired product in 83% GC yield. Further
exploration of catalyst revealed that 3aa could be obtained in
90% yield (Table 1, entry 3) when using Pd(OAc)2 instead of
PdCl2. However, with the use of other oxidants, such as
Cu(OAc)2, O2, BQ, and Ag2CO3, the yield of the desired
product plummeted to less than 15%; no product could be
observed when LiCl acted as the chloride source (Table 1,
entries 4−7). Unfortunately, only trace target product was
detected by GC−MS when the amount of CuCl2·2H2O was
dropped to 10 mol %, and O2 played a co-oxidant role in this
reaction (Table 1, entry 8). Two other solvents, DMF and
toluene, had a slight effect on this reaction (Table 1, entries 9
and 10). By contrast, the blank experiment illustrated that no
reaction occurred in the absence of palladium catalyst (Table 1,
entry 11).
C−X (X  O, N, halogen) bonds.2,3 In comparison to the
obvious tendency to undergo β-H elimination in alkyl-Pd
species, the vinyl-Pd intermediate could be captured by a
variety of electrophiles. Also, the vinyl-Pd intermediate could
undergo the oxidative cross-coupling reaction with nucleophi-
les.1b,4
In the traditional Heck and oxidative Heck processes, the
aryl-Pd species was easily captured by activated olefins.5
Similarly, the in situ formed vinyl-Pd intermediate coupled
with a variety of activated olefins to give the conjugated diene
derivatives via rapid β-H elimination (Scheme 2, path a).6 Later
we found that the nucleopalladation of alkyne triggered
oxidative coupling between alkynoates and allylic alcohols
affording the γ,σ-unsaturated carbonyl compounds via selective
β-H elimination (Scheme 2, path b).7 Very recently, a
potentially bioactive α-methylene-γ-lactone skeleton was
successfully constructed via palladium-catalyzed coupling
between alkynamides and homoallylic alcohols, in which the
With the optimized conditions established, the scope of the
terminal alkenes was first examined. Initially, 2-methylhex-5-en-
2-ol and 5-butylnon-1-en-5-ol could be transformed to the
Received: June 12, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 2. Pd-Catalyzed Cross-Coupling Reactions of Alkynes and Alkenes
a
a
Table 1. Optimization of Reaction Conditions
Table 2. Substrate Scope of Alkenes
b
entry
Pd catalyst
additive/oxidant
solvent
yield (%)
1
2
3
PdCl2
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
LiCl/Cu(OAc)2
LiCl/1 atm O2
LiCl/Ag2CO3
LiCl/BQ
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
83
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
86
92 (90)
15
c
4
c
5
<5
c
6
nd
c
7
nd
d
8
LiCl/CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
<5
9
83
10
11
toluene
CH3CN
80
nr
a
Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), Pd catalyst (5
mol %), oxidant (1.0 mmol) in CH3CN (0.5 mL) at room temperature
b
for 12 h. Yield was determined by GC analysis using dodecane as the
c
internal standard. Isolated yield product in parentheses. LiCl (4
a
Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), Pd(OAc)2 (5 mol
%), CuCl2·2H2O (1.0 mmol) in CH3CN (0.5 mL) at room
temperature for 12 h.
d
mmol), oxidant (1.0 mmol). CuCl2·2H2O (10 mol %) at 1 atm O2
for 12 h.
desired products 3ab in 83% yield and 3ac in 80% yield,
respectively (Table 2). Then, we explored whether four kinds
of α-substituted cyclic olefinic alcohols were suitable for the
reaction. To our delight, all of them generated the
corresponding spirocyclic compounds (3ad−3ag) successfully,
while 3ae and 3af could reach excellent yields. It is worth
noting that increasing tension of the substituted rings led to a
dramatic decline in yield (3ad). Subsequently, with the carbon
chain of terminal olefins extended, the tetrahydro-2H-pyran
derivatives 3ah and 3ai were successfully obtained in moderate
yields.
With the positive results above, we next explored the scope
of carboetherification of N-substituted alkynamides with olefins,
which showed high tolerance to the reactions. N-Substituted
alkynamides with a series of alkyl groups, such as methyl, n-
propyl, isopropyl, and n-butyl, could convert to the
corresponding products (3da−3ga) in moderate yields (Table
3). Afterward, 3ia−3la could be transformed efficiently, in
which the substituted groups on benzene rings slightly affected
the yields of products. Moreover, the halide functional groups,
such as -F, -Cl, and -Br, could be tolerated in this
transformation and gave good yields (3ma−3oa). Notably,
thiophene- and furan-substituted alkynamides could still
perform well under the standard reaction conditions (3pa−
3qa). Then, but-2-ynamide and oct-2-ynamide were converted
to the tetrahydrofuran derivatives 3ba, and 3cb in 80% and 82%
yields, respectively.
The feasibility of conversion of 1a provided us a possible
route to the synthesis of γ-lactones. Under the standard
conditions, it afforded γ-lactones (4aa) in 79% yield with the
formation of C−O bond (Scheme 3). Notably, γ-lactones exist
widely in a large number of natural products and drugs as an
active moiety.10
On the basis of the above results, a plausible mechanism was
proposed for Pd-catalyzed carboetherification of alkenes with
alkynamides (Scheme 4). The process was initiated by the
trans-halopalladation to triple bond, which resulted in vinyl-
palladium intermediate I. Afterward, the insertion of a double
bond experienced a Heck addition to produce the intermediate
B
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
bond formation, and PdII active species was regenerated via
oxidation by CuII.
Table 3. Substrate Scope of Alkynamides
In conclusion, we have developed a simple and efficient
method for the synthesis of oxygenated heterocycles through
Pd-catalyzed chelation-assisted carboetherification of alkyna-
mides with olefins. With broad functional group tolerance,
those oxygenated heterocycles that contain a halogen and
amide group were easily modified. Moreover, this method
provides a new route to suppress the β-H elimination and
potentially synthesize biologically active compounds conven-
iently.
EXPERIMENTAL SECTION
■
1
General Methods. H and 13C NMR spectra were recorded on a
400 MHz spectrometer using CDCl3 as solvent and TMS as an
internal standard. High resolution mass spectra were obtained with Q-
TOF analyzer equipment.
General Procedure for Synthesis of Tetrahydrofuran
Derivatives. A mixture of alkynamides (0.5 mmol), Pd(OAc)2 (5.6
mg, 0.025 mmol,), olefin (0.6 mmol), and CuCl2·2H2O (207 mg, 1.0
mmol) in CH3CN (0.5 mL) was stirred at room temperature for 12 h.
The mixture was extracted with ethyl acetate (3 × 10 mL), and organic
layer was dried by anhydrous MgSO4 and concentrated in vacuum.
The resulting residue was purified by flash silica gel chromatography to
give the desired products.
(Z)-3-Chloro-3-phenyl-2-((tetrahydrofuran-2-yl)methyl)-
acrylamide (3aa). White solid (119.0 mg, 90%), mp 142−144 °C. 1H
NMR (400 MHz, CDCl3): δ 7.34−7.44 (m, 5H), 6.57 (s, 1H), 6.15 (s,
1H), 3.98−4.01 (m, 1H), 3.70−3.39 (m, 2H), 2.56 (dd, J = 14.2, 3.7
Hz, 1H), 2.40 (dd, J = 14.2, 9.8 Hz, 1H), 1.93 (dt, J = 13.1, 6.6 Hz,
1H), 1.77−1.84 (m, 2H), 1.37 (ddd, J = 15.0, 12.2, 7.5 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 170.5, 137.3, 133.7, 130.6,
128.9, 128.9, 128.4, 77.0, 67.8, 37.8, 31.4, 25.6. HRMS (ESI) m/z:
calcd for C14H16ClNNaO2 [M + Na]+, 288.0762; found, 288.0763. IR
(KBr pellet): 3183, 2990, 1764, 1664, 1378, 1243, 1056, 926, 850, 758,
700 cm−1.
a
Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), Pd(OAc)2 (5 mol
%), CuCl2·2H2O (2 equiv) in CH3CN (0.5 mL) at room temperature
for 12 h.
(Z)-3-Chloro-2-((5,5-dimethyltetrahydrofuran-2-yl)methyl)-
Scheme 3. Synthesis of γ-Lactones
1
3-phenylacrylamide (3ab). Pale yellow liquid (122.0 mg, 83%). H
NMR (400 MHz, CDCl3): δ 7.47 (dd, J = 7.5, 1.5 Hz, 2H), 7.30−7.38
(m, 3H), 6.85 (s, 1H), 6.57 (s, 1H), 4.09 (dd, J = 7.5, 5.3 Hz, 1H),
2.56 (dd, J = 14.1, 3.8 Hz, 1H), 2.42 (dd, J = 14.1, 9.5 Hz, 1H), 1.96
(dt, J = 12.5, 6.3 Hz, 1H), 1.66 (dd, J = 10.9, 5.0 Hz, 2H), 1.45−1.52
(m, 1H), 1.19 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ 170.9,
137.3, 133.9, 130.2, 129.0, 128.8, 128.2, 81.5, 76.4, 38.7, 38.3, 32.0,
29.0, 28.0. HRMS (ESI) m/z: calcd for C16H20ClNNaO2 [M + Na]+,
316.1075; found, 316.1069. IR (KBr pellet): 3298, 2990, 2877, 1764,
1663, 1376, 1243, 1056, 928, 849, 702 cm−1.
Scheme 4. Plausible Reaction Mechanism
(Z)-3-Chloro-2-((5,5-dibutyltetrahydrofuran-2-yl)methyl)-3-
phenylacrylamide (3ac). Pale yellow solid (151.0 mg, 80%), mp
1
93−95 °C. H NMR (400 MHz, CDCl3): δ 7.27−7.46 (m, 5H), 6.70
(s, 1H), 6.33 (s, 1H), 3.97−3.98 (m, 1H), 2.58 (d, J = 14.1 Hz, 1H),
2.40 (dd, J = 13.9, 9.7 Hz, 1H), 1.84−1.88 (m, 1H), 1.62−1.66 (m,
2H), 1.33−1.46 (m, 5H), 1.26−1.29 (m, 8H), 0.89−0.91 (m, 6H)
13C{1H} NMR (100 MHz, CDCl3): δ 170.9, 137.3, 134.0, 130.3,
129.0, 128.8, 128.3, 86.0, 76.3, 39.3, 38.7, 38.1, 35.0, 32.3, 26.6, 26.5,
23.3, 23.3, 14.2, 14.1. HRMS (ESI) m/z: calcd for C22H32ClNNaO2
[M + Na]+, 400.2014; found, 400.2002. IR (KBr pellet): 2991, 2876,
1764, 1669, 1376, 1243, 1056, 928, 849 cm−1.
(Z)-2-(5-Oxaspiro[3.4]octan-6-ylmethyl)-3-chloro-3-phenyla-
1
crylamide (3ad). Pale yellow liquid (90.0 mg, 59%). H NMR (400
MHz, CDCl3): δ 7.42−7.47 (m, 2H), 7.31−7.38 (m, 3H), 6.80 (s,
1H), 6.73 (s, 1H), 4.05−4.08 (m, 1H), 2.58−2.47 (m, 1H), 2.33−2.40
(m, 1H), 2.15 (dd, J = 22.7, 10.6 Hz, 2H), 1.82−1.94 (m, 5H), 1.63
(dd, J = 13.8, 6.7 Hz, 1H), 1.43 (ddd, J = 15.3, 14.3, 7.8 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 171.0, 137.2, 133.7, 130.5,
128.9, 128.9, 128.3, 83.6, 76.7, 38.8, 36.2, 36.0, 36.0, 30.7, 12.7. HRMS
(ESI) m/z: calcd for C17H20ClNNaO2 [M + Na]+, 328.1075; found,
II, and then Pd was captured by the hydroxyl group in the
olefin, which could easily give access to form six- or seven-
membered palladacycle intermediate III. Finally, the reductive
elimination generated the corresponding product IV with C−O
C
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
328.1074. IR (KBr pellet): 2990, 1764, 1666, 1377, 1243, 1056, 929,
757, 699 cm−1.
(Z)-3-Chloro-3-phenyl-N-propyl-2-((tetrahydrofuran-2-yl)-
methyl)acrylamide (3ea). White solid (120.0 mg, 78%), mp 72−74
1
°C. H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 7.3 Hz, 2H), 7.33−
(Z)-2-(1-Oxaspiro[4.4]nonan-2-ylmethyl)-3-chloro-3-phenyl-
1
7.38 (m, 3H), 6.57 (t, J = 5.0 Hz, 1H), 3.94 (td, J = 6.5, 3.2 Hz, 1H),
3.76 (dd, J = 14.5, 7.3 Hz, 1H), 3.69 (dd, J = 14.7, 7.3 Hz, 1H), 3.36
(qd, J = 13.3, 6.5 Hz, 2H), 2.54 (dd, J = 14.2, 3.9 Hz, 1H), 2.38 (dd, J
= 14.2, 9.7 Hz, 1H), 1.91 (dt, J = 12.9, 6.6 Hz, 1H), 1.76−1.80 (m,
2H), 1.63 (dd, J = 14.5, 7.3 Hz, 2H), 1.34 (dd, J = 12.1, 7.5 Hz, 1H),
0.99 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.2,
137.3, 134.6, 129.8, 128.9, 128.8, 128.3, 76.8, 67.7, 41.3, 37.9, 31.3,
25.5, 22.6, 11.5. HRMS (ESI) m/z: calcd for C17H22ClNNaO2 [M +
Na]+, 330.1231; found, 330.1238. IR (KBr pellet): 3298, 2976, 2874,
1764, 1643, 1540, 1376, 1243, 1057, 850, 764, 703 cm−1.
(Z)-3-Chloro-N-isopropyl-3-phenyl-2-((tetrahydrofuran-2-
yl)methyl)acrylamide (3fa). Pale yellow solid (132.0 mg, 86%), mp
89−91 °C. 1H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 7.3 Hz, 2H),
7.31−7.38 (m, 3H), 6.25 (d, J = 7.9 Hz, 1H), 4.23 (dd, J = 13.8, 6.9
Hz, 1H), 3.90−3.93 (m, 1H), 3.77 (dd, J = 14.5, 7.2 Hz, 1H), 3.68
(dd, J = 14.8, 7.3 Hz, 1H), 2.53 (dd, J = 14.2, 3.9 Hz, 1H), 2.37 (dd, J
= 14.1, 9.7 Hz, 1H), 1.92 (dt, J = 13.0, 6.6 Hz, 1H), 1.75−1.80 (m,
2H), 1.35 (dd, J = 12.1, 7.5 Hz, 1H), 1.22−1.26 (m, 6H). 13C{1H}
NMR (100 MHz, CDCl3): δ 167.2, 137.3, 134.7, 129.8, 128.9, 128.8,
128.3, 76.8, 67.6, 41.5, 37.8, 31.3, 25.5, 22.6, 22.4. HRMS (ESI) m/z:
calcd for C17H22ClNNaO2 [M + Na]+, 330.1231; found, 330.1238. IR
(KBr pellet): 3297, 3060, 2979, 1764, 1638, 1538, 1376, 1242, 1057,
764, 703 cm−1.
acrylamide (3ae). Pale yellow liquid (136.0 mg, 85%). H NMR
(400 MHz, CDCl3): δ 7.45−7.47 (m, 2H), 7.32−7.39 (m, 3H), 6.91
(s, 1H), 6.13 (s, 1H), 3.48 (t, J = 10.4 Hz, 1H), 2.52 (dd, J = 14.3, 3.2
Hz, 1H), 2.28 (dd, J = 14.3, 9.7 Hz, 1H), 1.71 (dd, J = 14.5, 7.4 Hz,
1H), 1.52 (dd, J = 7.4, 6.0 Hz, 2H), 1.37−1.46 (m, 4H), 1.28 (dd, J =
12.4, 5.8 Hz, 2H), 0.89−0.98 (m, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 171.0, 137.6, 133.8, 131.2, 128.8, 128.8, 128.4, 76.6, 68.8,
38.6, 32.1, 31.6, 22.5, 19.1, 7.5, 7.3. HRMS (ESI) m/z: calcd for
C18H22ClNNaO2 [M + Na]+, 342.1231; found, 342.1223. IR (KBr
pellet): 3298, 2988, 1764, 1669, 1376, 1243, 1056, 928, 849, 700 cm−1.
(Z)-2-(1-Oxaspiro[4.5]decan-2-ylmethyl)-3-chloro-3-phenyl-
acrylamide (3af). Pale yellow liquid (152.0 mg, 91%). 1H NMR (400
MHz, CDCl3): δ 7.47 (dd, J = 7.7, 1.6 Hz, 2H), 7.31−7.39 (m, 3H),
6.80 (s, 1H), 6.42 (s, 1H), 4.01−4.06 (m, 1H), 2.56 (dd, J = 14.1, 3.7
Hz, 1H), 2.40 (dd, J = 14.1, 9.6 Hz, 1H), 1.87−1.96 (m, 2H), 1.61−
1.65 (m, 3H), 1.46−1.50 (m, 3H), 1.37−1.44 (m, 6H). 13C{1H} NMR
(100 MHz, CDCl3): δ 170.9, 137.3, 134.0, 130.3, 129.0, 128.8, 128.3,
83.4, 75.9, 38.5, 38.4, 37.3, 35.9, 31.6, 25.6, 24.1, 23.7. HRMS (ESI)
m/z: calcd for C19H24ClNNaO2 [M + Na]+, 356.1338; found,
356.1379. IR (KBr pellet): 3331, 3187, 2932, 2857, 1764, 1668,
1377, 1242, 1057, 757, 699 cm−1.
(Z)-2-(1-Oxaspiro[4.7]dodecan-2-ylmethyl)-3-chloro-3-phe-
nylacrylamide (3ag). Pale yellow solid (128.0 mg, 71%), mp 92−94
1
(Z)-N-Butyl-3-chloro-3-phenyl-2-((tetrahydrofuran-2-yl)-
°C. H NMR (400 MHz, CDCl3): δ 7.45−7.48 (m, 2H), 7.35−7.38
1
methyl)acrylamide (3ga). Pale yellow liquid (128.0 mg, 80%). H
(m, 3H), 6.73 (s, 1H), 6.28 (s, 1H), 3.97−4.00 (m, 1H), 2.56 (dd, J =
14.1, 3.6 Hz, 1H), 2.39 (dd, J = 14.1, 9.7 Hz, 1H), 1.86−1.89 (m, 1H),
1.69−1.78 (m, 2H), 1.43−1.78 (m, 15H). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.9, 137.3, 134.0, 130.3, 129.0, 128.8, 128.3, 86.8, 75.8,
38.3, 37.0, 36.9, 35.4, 31.8, 28.2, 28.2, 24.5, 22.9, 22.6. HRMS (ESI)
m/z: calcd for C21H28ClNNaO2 [M + Na]+, 384.1701; found,
384.1694. IR (KBr pellet): 3298, 2990, 1764, 1665, 1376, 1242,
1056, 927, 759, 699 cm−1.
NMR (400 MHz, CDCl3): δ 7.41−7.44 (m, 2H), 7.35−7.39 (m, 3H),
6.38 (s, 1H), 3.91−3.95 (m, 1H), 3.77 (dd, J = 14.4, 7.3 Hz, 1H), 3.69
(dd, J = 14.7, 7.4 Hz, 1H), 3.34−3.44 (m, 2H), 2.55 (dd, J = 14.2, 3.8
Hz, 1H), 2.36 (dd, J = 14.2, 9.9 Hz, 1H), 1.93 (dt, J = 18.7, 6.6 Hz,
1H), 1.76−1.82 (m, 2H), 1.60 (dd, J = 14.6, 7.4 Hz, 2H), 1.33−1.45
(m, 3H), 0.96 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 168.2, 137.4, 134.7, 129.9, 128.9, 128.8, 128.3, 76.9, 67.8, 39.3, 37.9,
31.4, 31.3, 25.6, 20.1, 13.8. HRMS (ESI) m/z: calcd for
C18H24ClNNaO2 [M + Na]+, 344.1388; found, 344.1389. IR (KBr
pellet): 3298, 2990, 1764, 1645, 1376, 1242, 1057, 927, 850, 765, 703
cm−1.
(Z)-3-Chloro-3-phenyl-2-((tetrahydro-2H-pyran-2-yl)-
methyl)acrylamide (3ah). Pale yellow solid (100.0 mg, 72%), mp
1
163−165 °C. H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 6.6 Hz,
2H), 7.34−7.41 (m, 3H), 6.48 (s, 1H), 6.17 (s, 1H), 3.96−3.98 (m,
1H), 3.32−3.42 (m, 2H), 2.43−2.46 (m, 2H), 1.76 (d, J = 11.0 Hz,
1H), 1.40−1.54 (m, 4H), 1.13 (dt, J = 12.1, 10.5 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.7, 137.2, 133.6, 130.3, 129.0, 128.9,
128.4, 75.8, 68.5, 38.4, 31.8, 25.7, 23.3. HRMS (ESI) m/z: calcd for
C15H18ClNNaO2 [M + Na]+, 302.0918; found,302.0913. IR (KBr
pellet): 2991, 2896, 1764, 1376, 1243, 1056, 930, 850 cm−1.
(Z)-3-Chloro-2-((6,6-diethyltetrahydro-2H-pyran-2-yl)-
methyl)-3-phenylacrylamide (3ai). Pale yellow liquid (137.0 mg,
77%). 1H NMR (400 MHz, CDCl3): δ 7.45−7.47 (m, 2H), 7.34−7.40
(m, 3H), 6.92 (s, 1H), 6.37 (s, 1H), 3.48 (dd, J = 14.9, 5.9 Hz, 1H),
2.52 (dd, J = 14.3, 3.2 Hz, 1H), 2.29 (dd, J = 14.3, 9.6 Hz, 1H), 1.66−
1.74 (m, 1H), 1.50−1.53 (m, 2H), 1.39−1.46 (m, 4H), 1.25−1.30 (m,
2H), 0.91−1.01 (m, 1H), 0.81−0.86 (m, 6H). 13C{1H} NMR (100
MHz, CDCl3): δ 171.2, 137.6, 133.7, 131.2, 128.8, 128.7, 128.4, 76.6,
68.8, 38.6, 32.1, 31.7, 31.6, 22.5, 19.1, 7.5, 7.3. HRMS (ESI) m/z: calcd
for C19H26ClNNaO2 [M + Na]+, 358.1544; found, 358.1540. IR (KBr
pellet): 3297, 2990, 2890, 1764, 1653, 1376, 1243, 1056, 927, 848, 703
cm−1.
(Z)-N-Benzyl-3-chloro-3-phenyl-2-((tetrahydrofuran-2-yl)-
1
methyl)acrylamide (3ha). Pale yellow liquid (149.0 mg, 84%). H
NMR (400 MHz, CDCl3): δ 7.33−7.42 (m, 9H), 7.29 (d, J = 7.0 Hz,
1H), 6.70 (s, 1H), 4.64 (dd, J = 14.8, 5.9 Hz, 1H), 4.55 (dd, J = 14.8,
5.6 Hz, 1H), 3.90 (ddd, J = 9.7, 6.5, 2.9 Hz, 1H), 3.70 (dd, J = 14.8, 6.9
Hz, 1H), 3.60 (dd, J = 15.0, 7.1 Hz, 1H), 2.57 (dd, J = 14.2, 3.7 Hz,
1H), 2.38 (dd, J = 14.2, 9.9 Hz, 1H), 1.89 (dd, J = 12.2, 6.6 Hz, 1H),
1.73−1.80 (m, 2H), 1.31−1.37 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 168.3, 138.0, 137.3, 134.4, 130.4, 128.9, 128.9, 128.7, 128.4,
128.0, 127.5, 76.9, 67.7, 43.7, 37.9, 31.4, 25.5. HRMS (ESI) m/z: calcd
for C21H22ClNNaO2 [M + Na]+, 378.1231; found, 378.1233. IR (KBr
pellet): 3298, 2990, 2876, 1760, 1650, 1373, 1243, 1056, 928, 848,
761, 700 cm−1.
(Z)-3-Chloro-N-(4-methoxybenzyl)-3-phenyl-2-((tetrahydro-
furan-2-yl)methyl)acrylamide (3ia). White solid (154.0 mg, 80%),
mp 114−116 °C. 1H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 7.3 Hz,
2H), 7.28−7.36 (m, 5H), 6.86 (d, J = 8.4 Hz, 2H), 6.80 (t, J = 5.3 Hz,
1H), 4.51 (ddd, J = 34.0, 14.6, 5.7 Hz, 2H), 3.88−3.91 (m, 1H), 3.76
(s, 3H), 3.68 (dd, J = 14.5, 7.2 Hz, 1H), 3.59 (dd, J = 14.4, J = 7.3 Hz,
1H), 2.54 (dd, J = 14.2, 3.9 Hz, 1H), 2.38 (dd, J = 14.1, 9.6 Hz, 1H),
1.87 (dt, J = 12.9, 6.6 Hz, 1H), 1.70−1.77 (m, 2H), 1.26−1.33 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.1, 159.0, 137.3, 134.4,
130.2, 130.1, 129.3, 128.9, 128.9, 128.4, 114.0, 76.9, 67.7, 55.3, 43.1,
37.9, 31.3, 25.5. HRMS (ESI) m/z: calcd for C22H24ClNNaO3 [M +
Na]+, 408.1337; found, 408.1337. IR (KBr pellet): 3299, 2991, 2878,
1764, 1649, 1513, 1377, 1243, 1056, 843, 763, 702 cm−1.
(Z)-3-Chloro-N-methyl-3-phenyl-2-((tetrahydrofuran-2-yl)-
1
methyl)acrylamide (3da). Pale yellow liquid (85.0 mg, 61%). H
NMR (400 MHz, CDCl3): δ 7.41−7.43 (m, 2H), 7.33−7.33 (m, 3H),
6.60 (d, J = 4.2 Hz, 1H), 3.94 (ddd, J = 10.6, 6.5, 3.3 Hz, 1H), 3.67−
3.78 (m, 2H), 2.94 (d, J = 4.9 Hz, 3H), 2.53 (dd, J = 14.2, 4.0 Hz, 1H),
2.39 (dd, J = 14.2, 9.6 Hz, 1H), 1.93 (dt, J = 19.0, 6.6 Hz, 1H)., 1.73−
1.84 (m, 2H), 1.35 (tt, J = 14.9, 7.4 Hz, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ 169.0, 137.3, 134.5, 130.1, 128.9, 128.8, 128.3, 76.8,
67.8, 37.9, 31.3, 26.2, 25.5. HRMS (ESI) m/z: calcd for
C15H18ClNNaO2 [M + Na]+, 302.0918; found, 302.0926. IR (KBr
pellet): 3298, 3060, 2987, 1764, 1648, 1543, 1376, 1243, 1058, 852,
764, 704 cm−1.
(Z)-3-Chloro-N-(4-methylbenzyl)-3-phenyl-2-((tetrahydro-
furan-2-yl)methyl)acrylamide (3ja). Pale yellow liquid (151.0 mg,
82%). 1H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 7.3 Hz, 2H), 7.30−
7.37 (m, 3H), 7.26 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 6.79
(t, J = 5.0 Hz, 1H), 4.53 (qd, J = 14.7, 5.7 Hz, 2H), 3.88−3.92 (m,
D
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1H), 3.68 (dd, J = 14.4, 7.2 Hz, 1H), 3.59 (dd, J = 14.4, J = 7.3 Hz,
1H), 3.64 (dq, J = 37.3, 7.5 Hz, 2H), 2.55 (dd, J = 14.2, 3.9 Hz, 1H),
2.44−2.37 (m, 1H), 2.32 (s, 3H), 1.87 (dt, J = 13.1, 6.6 Hz, 1H),
1.71−1.78 (m, 2H), 1.28−1.34 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 168.2, 137.4, 137.1, 135.0, 134.4, 130.3, 129.3, 128.9, 128.9,
128.4, 128.0, 76.9, 67.7, 43.5, 37.9, 31.3, 25.5, 21.1. HRMS (ESI) m/z:
calcd for C22H24ClNNaO2 [M + Na]+, 392.1388; found, 392.1391. IR
(KBr pellet): 3298, 2989, 1764, 1647, 1520, 1376, 1242, 1057, 848,
762, 702 cm−1.
(Z)-3-Chloro-N-(2-methoxybenzyl)-3-phenyl-2-((tetrahydro-
furan-2-yl)methyl)acrylamide (3ka). Pale yellow liquid (152.0 mg,
79%). 1H NMR (400 MHz, CDCl3): δ 7.40 (t, J = 8.7 Hz, 3H), 7.31−
7.34 (m, 3H), 7.26 (t, J = 7.8 Hz, 1H), 6.83−6.94 (m, 3H), 4.60 (d, J =
5.9 Hz, 2H), 3.85−3.89 (m, 1H), 3.83 (s, 3H), 3.69 (dd, J = 14.5, 7.2
Hz, 1H), 3.58 (dd, J = 14.8, 7.2 Hz, 1H), 2.54 (dd, J = 14.2, 4.0 Hz,
1H), 2.39 (dd, J = 14.1, 9.5 Hz, 1H), 1.86 (td, J = 13.1, 6.6 Hz, 1H),
1.69−1.76 (m, 2H), 1.23−1.34 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 168.1, 157.5, 137.4, 134.5, 130.0, 129.7, 128.9, 128.9, 128.8,
128.3, 126.0, 120.6, 110.2, 76.8, 67.6, 55.3, 39.3, 37.9, 31.3, 25.5.
HRMS (ESI) m/z: calcd for C22H24ClNNaO3 [M + Na]+, 408.1337;
found,408.1334. IR (KBr pellet): 3297, 2990, 2879, 1764, 1653, 1375,
1243, 1056, 757, 702 cm−1.
Na]+, 456.0336; found, 456.0341. IR (KBr pellet): 3282, 3059, 2975,
2870, 1764, 1649, 1525, 1369, 1243, 1056, 900, 761, 702 cm−1.
(Z)-3-Chloro-3-phenyl-2-((tetrahydrofuran-2-yl)methyl)-N-
(thiophen-2-ylmethyl)acrylamide (3pa). White solid (148.0 mg,
1
82%), mp 126−128 °C. H NMR (400 MHz, CDCl3): δ 7.41−7.32
(m, 5H), 7.22 (d, J = 5.1 Hz, 1H), 7.04 (s, 1H), 6.95 (t, J = 3.9 Hz,
1H), 6.89 (s, 1H), 4.75 (d, J = 5.7 Hz, 2H), 3.93−3.86 (m, 1H), 3.69
(q, J = 7.2 Hz, 1H), 3.61 (q, J = 7.3 Hz, 1H), 2.57−2.53 (m, 1H),
2.40−2.34 (m, 1H), 1.92−1.79 (m, 1H), 1.75 (td, J = 13.0, 6.7 Hz,
2H), 1.36−1.26 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 167.9,
140.3, 137.1, 133.9, 130.5, 128.7, 128.2, 126.7, 126.1, 125.1, 76.7, 67.6,
38.2, 37.7, 31.2, 25.4. HRMS (ESI) m/z: calcd for C19H21ClNO2S [M
+ H]+, 362.0976; found, 362.0977. IR (KBr pellet): 3289, 3061, 2966,
2868, 1650, 1649, 1520, 1441, 1295, 897, 762, 700 cm−1.
(Z)-3-Chloro-N-(furan-2-ylmethyl)-3-phenyl-2-((tetrahydro-
furan-2-yl)methyl)acrylamide (3qa). Pale yellow liquid (134.0 mg,
1
78%). H NMR (400 MHz, CDCl3): δ 7.42−7.32 (m, 6H), 6.94 (s,
1H), 6.31 (d, J = 5.2 Hz, 2H), 4.57 (d, J = 5.6 Hz, 2H), 3.91−3.85 (m,
1H), 3.71 (q, J = 7.2 Hz, 1H), 3.62 (q, J = 7.3 Hz, 1H), 2.56−2.52 (m,
1H), 2.40−2.34 (m,1H), 1.94−1.82 (m, 1H), 1.75 (td, J = 13.0, 6.7
Hz, 2H), 1.36−1.27 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
168.0, 151.0, 141.9, 137.1, 133.9, 130.3, 128.7, 128.2, 76.7, 67.5, 37.6,
36.4, 31.1, 25.3. HRMS (ESI) m/z: calcd for C19H20ClNNaO3 [M +
Na]+, 368.1024; found, 368.1028. IR (KBr pellet): 3291, 3060, 2973,
2871, 1764, 1653, 1370, 1242, 1057, 920, 741, 702 cm−1.
(Z)-3-Chloro-N-(2-chlorobenzyl)-3-phenyl-2-((tetrahydrofur-
an-2-yl)methyl)acrylamide (3la). White solid (159.0 mg, 82%), mp
1
125−127 °C. H NMR (400 MHz, CDCl3): δ 7.53−7.56 (m, 1H),
(Z)-3-Chloro-2-((tetrahydrofuran-2-yl)methyl)oct-2-enamide
(3ba). Pale yellow liquid (75.0 mg, 80%). 1H NMR (400 MHz,
CDCl3): δ 6.48 (s, 1H), 6.23 (s, 1H), 4.02−3.95 (m, 1H), 3.85 (dd, J
= 14.5, 7.3 Hz, 1H), 3.73 (dd, J = 14.7, 7.4 Hz, 1H), 2.61−2.56 (m,
1H), 2.49−2.45 (m, 1H), 2.41 (dd, J = 14.2, 6.8 Hz, 2H), 2.09−2.01
(m, 1H), 1.95−1.85 (m, 2H), 1.65−1.50 (m, 3H), 1.32 (s, 4H), 0.90
(t, J = 6.4 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 170.9, 134.8,
131.1, 77.7, 67.7, 36.7, 35.3, 31.4, 31.0, 27.0, 25.5, 22.4, 13.8. HRMS
(ESI) m/z: calcd for C13H22ClNNaO2 [M + Na]+, 282.1231; found,
282.1235. IR (KBr pellet): 3289, 3060, 2966, 2868, 1747, 1650, 1520,
1440, 1295, 1056, 897, 762, 702 cm−1.
7.41 (d, J = 7.1 Hz, 2H), 7.32−7.37 (m, 4H), 7.21−7.26 (m, 2H), 6.93
(t, J = 5.6 Hz, 1H), 4.67 (d, J = 6.0 Hz, 2H), 3.85 (dt, J = 9.5, 3.2 Hz,
1H), 3.71 (dd, J = 14.7, 7.0 Hz, 1H), 3.61 (dd, J = 14.9, 7.2 Hz, 1H),
2.55 (dd, J = 14.2, 3.8 Hz, 1H), 2.37 (dd, J = 14.2, 9.8 Hz, 1H), 1.86
(td, J = 12.9, 6.5 Hz, 1H), 1.71−1.78 (m, 2H), 1.26−1.33 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 168.4, 137.3, 135.5, 134.2,
133.6, 130.6, 130.3, 129.4, 128.9, 128.9, 128.4, 127.1, 77.0, 67.7, 41.5,
37.9, 31.4, 25.5. HRMS (ESI) m/z: calcd for C21H21Cl2NNaO2 [M +
Na]+, 412.0842; found, 412.0837. IR (KBr pellet): 2991, 2882, 1764,
1376, 1243, 1056, 928, 850, 756 cm−1.
(Z)-3-Chloro-N-(4-fluorobenzyl)-3-phenyl-2-((tetrahydrofur-
(Z)-3-Chloro-2-((5,5-dimethyltetrahydrofuran-2-yl)methyl)-
an-2-yl)methyl)acrylamide (3ma). White solid (158 mg, 85%), mp
1
but-2-enamide (3cb). Pale yellow liquid (95.0 mg, 82%). H NMR
1
133−135 °C. H NMR (400 MHz, CDCl3): δ 7.41−7.34 (m, 7H),
(400 MHz, CDCl3): δ 6.75 (s, 1H), 6.24 (s, 1H), 4.01−4.08 (m, 1H),
2.51 (dd, J = 14.3, 4.0 Hz, 1H), 2.37 (dd, J = 14.3, 8.8 Hz, 1H), 2.08
(s, 3H), 2.01 (dd, J = 12.1, 6.5 Hz, 1H), 1.66−1.71 (m, 2H), 1.56−
1.63 (m, 1H), 1.20 (s, 3H), 1.14 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 171.1, 131.4, 130.2, 81.6, 76.8, 38.2, 38.0, 31.9, 29.1, 28.0,
22.9. HRMS (ESI) m/z: calcd for C11H19ClNO2 [M + H]+, 232.1098;
found, 232.1102. IR (KBr pellet): 3290, 3060, 2965, 2870, 1750, 1653,
1520, 1368, 1293, 1054, 900, 761, 700 cm−1.
7.01 (t, J = 8.5 Hz, 2H), 6.88−6.85 (m, 1H), 4.54 (ddd, J = 38.0, 14.8,
5.9 Hz, 2H), 3.92−3.84 (m, 1H), 3.69 (dd, J = 14.5, 7.2 Hz, 1H), 3.60
(dd, J = 14.5, 7.2 Hz, 1H), 2.57−2.53 (m, 1H), 2.41−2.35 (m, 1H),
1.92−1.84 (m, 1H), 1.75 (td, J = 13.0, 6.6 Hz, 2H), 1.36−1.30 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.1, 162.0 (d, J = 245.4
Hz), 137.1, 134.1, 133.7 (d, J = 3.2 Hz), 130.3, 129.5 (d, J = 8.1 Hz),
128.8, 128.7, 128.2, 115.2 (d, J = 21.4 Hz), 76.8, 67.6, 42.7, 37.8, 31.2,
25.4. HRMS (ESI) m/z: calcd for C21H22ClFNO2 [M + H]+,
374.1318; found, 374.1319. IR (KBr pellet): 3292, 2978, 1764, 1647,
1439, 1376, 1241, 1058, 915, 826, 751, 701 cm−1.
(Z)-3-Chloro-2-((5-oxotetrahydrofuran-2-yl)methyl)-3-phe-
1
nylacrylamide (4aa). Pale yellow liquid (110.0 mg, 79%). H NMR
(400 MHz, CDCl3): δ 7.35−7.43 (m, 5H), 6.47 (s, 2H), 4.63−4.70
(m, 1H), 2.73 (dd, J = 14.6, 4.0 Hz, 1H), 2.57 (dd, J = 14.6, 9.6 Hz,
1H), 2.38−2.50 (m, 2H), 2.28−2.30 (m, 1H), 1.70−1.79 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 176.7, 169.5, 136.8, 132.3,
131.3, 129.3, 128.7, 128.6, 78.1, 37.8, 28.4, 27.6. HRMS (ESI) m/z:
calcd for C14H14ClNNaO3 [M + Na]+, 302.0554; found, 302.0549. IR
(KBr pellet): 2988, 1770, 1726, 1373, 1242, 1054, 902, 765, 703 cm−1.
(Z)-3-Chloro-N-(4-chlorobenzyl)-3-phenyl-2-((tetrahydrofur-
an-2-yl)methyl)acrylamide (3na). White solid (169.0 mg, 87%),
mp 118−120 °C. 1H NMR (400 MHz, CDCl3): δ 7.40−7.27 (m, 9H),
6.95 (t, J = 5.4 Hz, 1H), 4.54 (ddd, J = 38.0, 15.0, 5.9 Hz, 2H), 3.92−
3.92 (m,1H), 3.70 (dd, J = 14.4, J = 7.2 Hz, 1H), 3.61 (dd, J = 14.4, J =
7.3 Hz, 1H), 2.57−2.52 (m, 1H), 2.41−2.35 (m, 1H), 1.92−1.84 (m,
1H), 1.75 (td, J = 13.0, 6.7 Hz, 2H), 1.36−1.27 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 168.2, 137.0, 136.5, 134.1, 133.0, 130.3,
129.1, 128.7, 128.7, 128.5, 128.2, 76.8, 67.6, 42.7, 37.7, 31.2, 25.3.
HRMS (ESI) m/z: calcd for C21H21Cl2NNaO2 [M + Na]+, 412.0842;
found, 412.0849. IR (KBr pellet): 3289, 3060, 2973, 1763, 1647, 1528,
1443, 1243, 1054, 899, 762, 702 cm−1.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of all synthesized compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(Z)-N-(4-Bromobenzyl)-3-chloro-3-phenyl-2-((tetrahydrofur-
an-2-yl)methyl)acrylamide (3oa). White solid (191.0 mg, 88%),
1
mp 126−128 °C. H NMR (400 MHz, CDCl3): δ = 7.45−7.34 (m,
7H), 7.28−7.24 (m, 2H), 6.96 (t, J = 5.2 Hz, 1H), 4.52 (ddd, J = 37.5,
15.0, 5.9 Hz, 2H), 3.91−3.85 (m, 1H), 3.69 (dd, J = 14.5, 7.3 Hz, 1H),
3.61 (dd, J = 14.4, 7.2 Hz, 1H), 2.56−2.52 (m, 1H), 2.41−2.35 (m,
1H), 1.94−1.82 (m, 1H), 1.75 (td, J = 13.0, 6.7 Hz, 2H), 1.36−1.27
(m,1H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.2, 137.0, 134.0,
131.4, 130.3, 129.4, 128.7, 128.7, 128.2, 121.1, 76.8, 67.6, 42.8, 37.7,
31.2, 25.3. HRMS (ESI) m/z: calcd for C21H21BrClNNaO2 [M +
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jianghf@scut.edu.cn.
Author Contributions
†These authors contributed equally to this work.
E
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(e) Hanley, P. S.; Hartwig, J. F. Angew. Chem., Int. Ed. 2013, 52, 8510−
8525.
(10) (a) Montgomery, T. P.; Hassan, A.; Park, B. Y.; Krische, M. J. J.
Am. Chem. Soc. 2012, 134, 11100−11103. (b) Reynolds, A. J.; Scott, A.
J.; Turner, C. I.; Sherburn, M. S. J. Am. Chem. Soc. 2003, 125, 12108−
12109.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21172076 and 21202046), the National Basic Research
Program of China (973 Program) (2011CB808600), the
G u a n g d o n g N a t u r a l S c i e n c e F o u n d a t i o n
(10351064101000000 and S2012040007088), and the Funda-
mental Research Funds for the Central Universities
(2014ZP0004 and 2014ZZ0046).
REFERENCES
■
(1) (a) Zhang, Q.; Lu, X. J. Am. Chem. Soc. 2000, 122, 7604−7605.
(b) Zhao, L.; Lu, X. Angew. Chem., Int. Ed. 2002, 41, 4343−4345.
(c) Welbes, L. L.; Lyons, T. W.; Cychosz, K. A.; Sanford, M. S. J. Am.
Chem. Soc. 2007, 129, 5836−5837. (d) Tong, X.; Beller, M.; Tse, M. K.
J. Am. Chem. Soc. 2007, 129, 4906−4907. (e) Huang, J.; Zhou, L.;
Jiang, H. Angew. Chem., Int. Ed. 2006, 45, 1945−1949. (f) Gagnier, S.
V.; Larock, R. C. J. Org. Chem. 2000, 65, 1525−1529. (g) Xie, X.; Lu,
X.; Liu, Y.; Xu, W. J. Org. Chem. 2001, 66, 6545−6550. (h) Aubert, C.;
Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813−834.
(2) (a) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644−4680.
(b) Patil, N. P.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395−3442.
(c) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111, 215−283. (d) Yin, G.;
Liu, G. Angew. Chem., Int. Ed. 2008, 47, 5442−5445. (e) Liu, R.;
Zhang, J. Chem.Eur. J. 2009, 15, 9303−9306. (f) Li, W.; Zhang, J.
Chem. Commun. 2010, 46, 8839−8841. (g) Zhang, X.; Lu, Z.; Fu, C.;
Ma, S. J. Org. Chem. 2010, 75, 2589−2598.
(3) (a) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111,
2981−3019. (b) Ma, S.; Lu, X. J. Org. Chem. 1991, 56, 5120−5125.
(c) Huang, L.; Wang, Q.; Liu, X.; Jiang, H. Angew. Chem., Int. Ed.
2012, 51, 5696−5700. (d) Feng, C.; Loh, T.-P. J. Am. Chem. Soc. 2010,
132, 17710−17712. (e) Jiang, H.; Qiao, C.; Liu, W. Chem.Eur. J.
2010, 16, 10968−10970. (f) Chen, D.; Cao, Y.; Yuan, Z.; Cai, H.;
Zheng, R.; Kong, L.; Zhu, G. J. Org. Chem. 2011, 76, 4071−4074.
(4) (a) Jia, X.; Petrone, D. A.; Lautens, M. Angew. Chem., Int. Ed.
2012, 51, 9870−9872. (b) Jiang, H.; Liu, X.; Zhou, L. Chem.Eur. J.
2008, 14, 11305−11309. (c) Zhou, P.; Zheng, M.; Jiang, H.; Li, X.; Qi,
C. J. Org. Chem. 2011, 76, 4759−4763. (d) Gabriele, B.; Salerno, G.;
Pascali, F.; Costa, M.; Chiusoli, G. P. J. Org. Chem. 1999, 64, 7693−
7699. (e) Kato, K.; Motodate, S.; Mochida, T.; Kobayashi, T.; Akita,
H. Angew. Chem., Int. Ed. 2009, 48, 3326−3328. (f) Gabriele, B.; Veltri,
L.; Mancuso, R.; Salerno, G.; Maggi, S.; Maria Aresta, B. J. Org. Chem.
2012, 77, 4005−4016.
(5) (a) Bras, J. L.; Muzart, J. Chem. Rev. 2011, 111, 1170−1214.
(b) Su, Y.; Jiao, N. Org. Lett. 2009, 11, 2980−2983. (c) Yoo, K. S.;
Park, C. P.; Yoon, C. H.; Sakaguchi, S.; O’Neill, J.; Jung, K. W. Org.
Lett. 2007, 9, 3933−3935. (d) Xiong, D.; Zhang, L.; Ye, X. Org. Lett.
2009, 11, 1709−1712. (e) Thirunavukkarasu, V. S.; Parthasarathy, K.;
Cheng, C. Angew. Chem., Int. Ed. 2008, 47, 9462−9465. (f) Yoo, K. S.;
Yoon, C. H.; Jung, K. W. J. Am. Chem. Soc. 2006, 128, 16384−16393.
(6) (a) Huang, J.; Dong, Y.; Wang, X.; Luo, H. Chem. Commun.
2010, 46, 1035−1037. (b) Zhou, P.; Jiang, H.; Huang, L.; Li, X. Chem.
Commun. 2011, 47, 1003−1005. (c) Zhou, P.; Huang, L.; Jiang, H.;
Wang, A.; Li, X. J. Org. Chem. 2010, 75, 8279−8282. (d) Silva, F.;
Reiter, M.; Mills-Webb, R.; Sawicki, M.; Klar, D.; Bensel, N.; Wagner,
̈
A.; Gouverneur, V. J. Org. Chem. 2006, 71, 8390−8394.
(7) Wen, Y.; Huang, L.; Jiang, H.; Chen, H. J. Org. Chem. 2012, 77,
2029−2034.
(8) Huang, L.; Wang, Q.; Wu, W.; Jiang, H. ChemCatChem. 2014, 6,
561−566.
(9) (a) Zhu, C.; Falck, J. R. Angew. Chem., Int. Ed. 2011, 50, 6626−
6629. (b) Wolfe, J. P.; Rossi, M. A. J. Am. Chem. Soc. 2004, 126, 1620−
1621. (c) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi,
J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369−4378.
(d) Ward, A. F.; Wolfe, J. P. Org. Lett. 2010, 12, 1268−1271.
F
dx.doi.org/10.1021/jo501317v | J. Org. Chem. XXXX, XXX, XXX−XXX