Palladium-catalyzed intermolecular oxyvinylcyclization of alkenes with alkynes: An approach to 3-methylene γ-lactones and tetrahydrofurans

Article abstract of DOI:10.1021/jo501606c

A novel chloropalladation-initiated intermolecular oxyvinylcyclization of alkenes with alkynoic acids or alkynols is developed. This protocol provides a series of 3-methylene γ-lactone and tetrahydrofuran derivatives in moderate to excellent yields with high stereoselectivities in the presence of PdCl₂ and CuCl₂ or CuCl₂·2H₂O. Besides a broad substrate scope, this method has the advantages of mild reaction conditions and easily accessible starting materials. Furthermore, the construction of C-Cl, C(sp²)-C(sp³), and C-O bonds in one step was also achieved in this transformation.

Full text of DOI:10.1021/jo501606c

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Palladium-Catalyzed Intermolecular Oxyvinylcyclization of Alkenes
with Alkynes: An Approach to 3‑Methylene γ‑Lactones and
Tetrahydrofurans
Zhenming Zhang, Lu Ouyang, Wanqing Wu,* Jianxiao Li, Zhicai Zhang, and Huanfeng Jiang*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, P. R. China
S
* Supporting Information
ABSTRACT: A novel chloropalladation-initiated intermolecular oxy-
vinylcyclization of alkenes with alkynoic acids or alkynols is developed.
This protocol provides a series of 3-methylene γ-lactone and
tetrahydrofuran derivatives in moderate to excellent yields with high
stereoselectivities in the presence of PdCl2 and CuCl2 or CuCl2·2H2O.
Besides a broad substrate scope, this method has the advantages of mild
reaction conditions and easily accessible starting materials. Furthermore, the construction of C−Cl, C(sp2)−C(sp3), and C−O
bonds in one step was also achieved in this transformation.
nucleopalladation of alkyne-initiated reactions could provide
efficient and convenient access to both carbon−carbon and
carbon−heteroatom bonds in an atom-economical way.18
Our group has continuous interest in developing new
transformations based on vinlypalladium species, which can
be easily obtained from nucleopalladation of alkynes.18,19 In
2012, we reported a palladium-catalyzed intermolecular oxy-
vinylcyclization reaction of alkenes with alkynoates or
alkynamides, which provided different substituted α-methylene
γ-lactones in good yields.20 However, either a complex
substrate or high temperature was required in this reaction
under O2 atmosphere. Considering that a hydrolysis process of
amides or esters and reductive elimination of palladium−
oxygen bond would occur during this cyclization reaction of
alkenes with alkynoates or alkynamides, we envisioned that the
substrates containing a hydroxyl group such as alkynoic acids
and alkynols could be employed directly in such reactions.
Herein, we report an efficient palladium-catalyzed intermolec-
ular oxyvinylcyclization of alkenes with alkynoic acids or
alkynols at room temperature under air to afford diverse α-
methylene γ-lactones or 3-methylene tetrahydrofuran deriva-
tives (Scheme 1, eq 3).
INTRODUCTION
■
Oxygen-containing five-membered heterocycles, particularly γ-
lactones and tetrahydrofurans, are commonly found in many
biologically active natural products and pharmaceutical
compounds.1 Accordingly, much effort has been devoted to
construct these heterocyclic frameworks,2 among which,
palladium-catalyzed cyclization reaction of alkenes and C-
(sp2)-PdII intermediates is one of the powerful tools.3
Significant progress has been achieved in palladium-catalyzed
intramolecular or intermolecular cyclization reactions of alkenes
with aryl or vinyl halides via oxidative addition by Pd0 (Scheme
1, eqs 1 and 2).4−10 However, hydrogen halide is always formed
during the reaction process with oxidative addition of halides,
and a strong base is necessary. Compared to oxidative addition
of halides by Pd0, nucleopalladation by PdII-initiated cyclization
of alkenes showed high reactivity and functional group
tolerance under mild conditions.11−17 On the other hand,
Scheme 1. Pd-Catalyzed Oxyvinylcyclization of Alkenes with
Halides vs Alkynes
RESULTS AND DISCUSSION
■
We began our investigation with 3-phenylpropiolic acid (1a)
and styrene (2a) as the model reaction (Table 1). Initial
screening found that product 3aa was obtained in 43% GC
yield with high stereoselectivity (Z/E = 85/15) when using
PdCl2 (5 mol %) as the catalyst and CuCl2 or CuCl2·2H2O (2
equiv) as the additive in DMF at room temperature under air
(entry 1). Other solvents such as THF, DCE, and MeCN were
also tested (entries 2−4). Notably, MeCN was identified as the
Received: July 17, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

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a
Table 1. Optimization of Reaction Conditions
b
c
entry
[Pd] (mol %)
additive (equiv)
solvent
time (h)
yield (%)
Z/E
1
PdCl2 (5)
CuCl2 (2)
CuCl2 (2)
CuCl2 (2)
CuCl2 (2)
CuCl2 (2)
CuCl2 (2)
CuCl2 (2)
LiCl (4)
DMF
7
5
43
56
85/15
92/8
90/10
93/7
90/10
91/9
nd
2
PdCl2 (5)
DCE
3
PdCl2 (5)
THF
5
70
4
5
PdCl2 (5)
Pd(OAc)2 (5)
Pd(dba)2 (5)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
5
93 (89)
88
5
6
5
60
7
5
n.d.
trace
45
8
PdCl2 (5)
PdCl2 (5)
PdCl2 (2.5)
PdCl2 (5)
12
7
nd
9
CuCl2 (1)
CuCl2 (2)
CuCl2 (2)
86/14
91/9
65/35
10
7
89
d
11
1
84
a
The reaction was carried out with 1 (0.20 mmol), 2 (0.24 mmol), Pd catalyst, and additive in solvent (0.5 mL) at room temperature. nd = not
b
c
d
detected. GC yield, isolated yield in parentheses. Determined by GC. The reaction was performed at 80 °C.
optimal solvent for the formation of 3aa (entry 4). Slightly
lower yield was observed with Pd(OAc)2 or Pd(dba)2 as the
catalyst (entries 5 and 6). However, no reaction occurred in the
absence of palladium catalyst or replacement of CuCl2 by LiCl
(entries 7 and 8). These results suggested that both PdCl2 and
CuCl2 are crucial for the successful of this transformation. The
loading of PdCl2 had a slight effect on the yield and
stereoselectivity of the product, but the additive had an obvious
one (entries 9 and 10). However, a significant decrease of
stereoselectivity was observed when the reaction was performed
at reflux (entry 11). Thus, the optimal reaction conditions were
PdCl2 (5 mol %) and CuCl2 or CuCl2·2H2O (2 equiv) in
CH3CN at room temperature under air (Table 1, entry 4).
Under the optimized reaction conditions, we then inves-
tigated the substrate scope of this intermolecular Pd-catalyzed
oxyvinylcyclization of 3-phenylpropiolic acid (1a) and aryl
alkenes (2) (Table 2). It was found that good to excellent yields
and stereoselectivities were achieved regardless of the electronic
properties and substitution pattern of the aryl alkenes. Both
electron-withdrawing substituents, such as fluoro and bromo
groups, and electron-donating substituents such as methoxy
group could be tolerated in this reaction system, providing the
corresponding products 3ab−am in good yields (80−91%) and
stereoselectivities (entries 2−10, 11−13). The structure of
product was further confirmed by X-ray crystallography and
NOE NMR (see the Supporting Information for details).21
However, multisubstituted styrenes (2n and 2o) showed
slightly lower yields than monosubstituted ones, which was
probably caused by the steric effects (entries 14 and 15). Good
yield and stereoselectivity could be also obtained when using 2-
vinylnaphthalene (2p) and 2-vinylthiophene (2q) as the
substrates (entries 16 and 17). Furthermore, 2-vinylpyridine
could transfer to the corresponding product 3ar in 50% yield
with excellent Z/E ratio equaling to 96/4 under the optimized
conditions (entry 18). In addition, when α-methylstyrene (2s)
was employed, better results could be achieved (82% yield and
Z/E = 92/8) (entry 19).
Table 2. Substrate Scope of Pd-Catalyzed Intermolecular
Oxyvinylcyclization of Arylalkenes with 1a
a
time
(h)
yield
(%)
b
entry
Ar
product
Z/E
1
Ph (2a)
3aa
3ab
3ac
3ad
3ae
3af
5
8
5
5
5
6
8
8
7
7
5
7
6
8
8
5
8
8
5
89
78
89
88
91
90
84
87
85
79
86
80
85
68
71
89
75
50
82
93/7
91/9
96/4
97/3
92/8
95/5
95/5
97/3
92/8
96/4
98/2
91/9
97/3
94/6
90/10
93/7
92/8
96/4
92/8
2
2-ClC6H4 (2b)
3
3-ClC6H4 (2c)
4
4-FC6H4 (2d)
5
4-ClC6H4 (2e)
6
4-BrC6H4 (2f)
7
4-CNC6H4 (2g)
4-COOMeC6H4 (2h)
4-NO2C6H4 (2i)
4-CF3C6H4 (2j)
4-MeC6H4 (2k)
4-t-BuC6H4 (2l)
4-MeOC6H4 (2m)
2,4,6-trimethyl-C6H2 (2n)
perfluorophenyl (2o)
2-naphthyl (2p)
2-thiophene-yl (2q)
2-pyridyl (2r)
3ag
3ah
3ai
8
9
10
11
12
13
14
15
16
17
18
19
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
3ar
3as
α-methylstyrene (2s)
a
Reaction conditions: unless otherwise noted, all reactions were
performed with 1a (0.5 mmol), 2 (0.6 mmol), CuCl2 (1.0 mmol), and
PdCl2 (5 mol %) in 1.0 mL of acetonitrile at room temperature for 5−
b
8 h. Determined by GC.
acrylamide derivatives (entries 4 and 5), and vinyl ketone
(entry 6) could be used in the reaction to afford the desired
products 5aa−af in good yields and stereoselectivities.
Unfortunately, only moderate yield (49%) could be obtained
when acrylonitrile (4g) was employed in this reaction (entry 7)
for 8 h. Notably, linear alkenes 4h and 4i were also suitable for
this reaction to give the corresponding products in good yields
and stereoselectivities (entries 8 and 9).
After the success of palladium-catalyzed intermolecular
oxyvinylcyclization of 3-phenylpropiolic acid with arylalkenes,
the reactions of alkylalkenes were also investigated (Table 3).
Various alkylalkenes including acrylic esters (entries 1−3),
B
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electron-withdrawing (1b-1g) or electron-donating substituents
(3h and 3i) could be transferred to the desired products 3ba−
la in good yields (78−91%) and stereoselectivities (Z/E up to
98/2) (entries 1−6, 7 and 8). To our delight, this method was
successfully applied to 3-alkylpropiolic acids, and these
substrates were smoothly converted to the cyclization products
(3ja and 3ka) in high yields with excellent stereoselectivities
(88% with Z/E ratio = 98/2 and 90% with Z/E ratio = 99/1)
(entries 9 and 10). Unfortunately, a lower stereoselectivity was
observed in the reaction of 3-cyclopropylpropiolic acid (1l) and
styrene (entry 11).
Table 3. Substrate Scope of Pd-Catalyzed Intermolecular
Oxyvinylcyclization of Alkenes 4 with 1a
a
Encouraged by the results of palladium-catalyzed intermo-
lecular oxyvinylcyclization of alkenes and alkynoic acids, we
envisioned that alkynols could also undergo a nucleopalladation
process to give the corresponding tetrahydrofuran products. To
our delight, it was found that under the above optimized
conditions, the reaction of 2-methyl-4-phenylbut-3-yn-2-ol (6a)
and styrene (2a) afforded the corresponding product 7aa in
73% yield with moderate stereoselectivity (Z/E = 82/18) for 12
h. After simple optimization of the reaction conditions, 7aa
could be obtained in 74% yield with 93/7 Z/E ratio at room
temperature for 12 h when the loading of additive CuCl2 was
increased (Table 5, entry 1). Other substituted phenyl alkenes
Table 5. Substrate Scope of Pd-Catalyzed Intermolecular
a
Oxyvinylcyclization of Alkenes with Alkynols
a
Reaction conditions: unless otherwise noted, all reactions were
6
performed with 1a (0.5 mmol), 4 (0.6 mmol), CuCl2 (1.0 mmol), and
PdCl2 (5 mol %) in 1.0 mL of acetonitrile at room temperature for 5−
2,
time
(h)
yield
(%)
b
entry
R1
R2
Ar product
Z/E
b
8 h. Determined by GC.
c
1
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
H
6a
6a
6a
6a
6b
6c
6d
6e
6f
2a
2d
2f
7aa
7ad
7af
12
14
12
12
12
16
14
12
12
24
74
78
71
68
76
52
72
71
73
nd
93/7
94/6
93/7
94/6
95/5
92/8
96/4
95/5
96/4
2
Next, the reactions of styrene with a variety of alkynoic acids
were also examined (Table 4). The alkynoic acids with either
3
4
2t
7at
7ba
7ca
7da
7ea
7fa
5
2a
2a
2a
2a
2a
2a
Table 4. Substrate Scope of Pd-Catalyzed Intermolecular
6
2-F-Ph
Me
a
Oxyvinylcyclization of Styrene with Alkynoic Acids 1
7
3-Me-Ph Me
4-Me-Ph Me
8
9
4-Cl-Ph
Me
Me
10
2-
6g
7ga
pyridyl
a
Reaction conditions: all reactions were performed with 1 (0.5 mmol),
2a (0.6 mmol), CuCl2 (1.5 mmol), and PdCl2 (5 mol %) in 1.0 mL of
b
entry
R
product time (h) yield (%)
Z/E
acetonitrile at room temperature for 12−24 h. nd = not detected.
b
c
1
2-ClC6H4 (1b)
3-ClC6H4 (1c)
4-ClC6H4 (1d)
4-FC6H4 (1e)
4-BrC6H4 (1f)
4-NO2C6H4 (1g)
4-MeOC6H4 (1h)
4-MeC6H4 (1i)
methyl (1j)
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
7
5
5
7
5
7
5
5
5
5
5
82
85
91
88
90
78
85
89
90
88
90
90/10
97/3
95/9
91/9
95/5
98/2
90/10
93/7
98/2
99/1
70/30
Determined by GC. Under the optimized conditions, the
2
corresponding product was obtained in 73% yield and Z/E = 85/15.
3
4
such as 4-fluorostyrene (2d), 4-bromrostyrene (2f), and 3-
methylstyrene (2t) could be also converted to the desired
products in good yields with excellent stereoselectivities
(entries 2−4). In addition, different substituted alkynols
could also be used to construct the 3-methylenetetrahydrofuran
derivatives 7ba−fa in moderate to good yields (52−76%) with
excellent stereoselectivities (entries 5−9). Disappointingly, no
desired product was observed when pyridine-substituted
alkynol was employed in the reaction (entry 10).
5
6
7
8
9
3ja
10
11
pentyl (1k)
3ka
3la
cyclopropyl (1l)
a
Reaction conditions: unless otherwise noted, all reactions were
performed with 1 (0.5 mmol), 2a (0.6 mmol), CuCl2 (1.0 mmol), and
PdCl2 (5 mol %) in 1.0 mL of acetonitrile at room temperature for 5−
On the basis of the above observations and literatures,11a,19,20
we propose a plausible mechanism as depicted in Scheme 2.
First, vinylpalladium intermediate I was generated by trans-
b
7 h. Determined by GC.
C
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

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(Z)-3-(Chloro(phenyl)methylene)-5-(2-chlorophenyl)-
Scheme 2. Plausible Mechanism
dihydrofuran-2(3H)-one (3ab): yield 78% (124.0 mg); white solid;
1
mp 112−114 °C; TLC Rf = 0.48 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.51−7.49 (m, 3H), 7.45−7.44 (m, 3H), 7.37−7.28
(m, 3H), 5.75 (t, J = 7.2 Hz, 1H), 3.65 (dd, J = 16.8 Hz, J = 7.6 Hz,
1H), 3.05 (dd, J = 17.2 Hz, J = 6.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 167.2, 140.8, 137.5, 137.4, 131.2, 130.4, 129.7, 129.6, 128.6,
128.2, 127.4, 126.0, 121.6, 74.0, 38.5 ppm; IR νmax (KBr)/cm−1 3745,
3363, 2919, 1699, 1515, 954, 457; MS (EI) m/z 77, 89, 115, 150, 178,
202, 318; HRMS-ESI (m/z) calcd for C17H13Cl2O2 [M + H]+
319.0287, found 319.0287.
(Z)-3-(Chloro(phenyl)methylene)-5-(3-chlorophenyl)-
dihydrofuran-2(3H)-one (3ac): yield 89% (141.5 mg); white solid;
mp 129−131 °C; TLC Rf = 0.25 (PE/EA = 10:1, v/v); 1H NMR (400
MHz, CDCl3) δ 7.50−7.47 (m, 2H), 7.44−7.42 (m, 3H), 7.31−7.30
(m, 3H), 7.20−7.18 (m, 1H), 5.46 (t, J = 7.6 Hz, 1H), 3.45 (dd, J =
16.4 Hz, J = 7.2 Hz, 1H), 3.02 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 166.9, 141.3, 140.7, 137.6, 134.9, 130.4,
130.2, 128.8, 128.6, 128.1, 125.5, 123.4, 121.8, 75.9, 39.7 ppm; IR νmax
(KBr)/cm−1 3746, 2362, 1761, 1638, 1200, 1089, 695; MS (EI) m/z
77, 89, 115, 150, 178, 202, 281, 318; HRMS-ESI (m/z) calcd for
C17H13Cl2O2 [M + H]+ 319.0287, found 319.0287.
chloropalladation of the alkyne moiety. Then, syn-insertion of
alkene with intermediate I occurred to generate alkylpalladium
II. Simultaneously, the alkylpalladium species II coordinated to
the oxygen atom of the OH group and generated the
intermediate III. Subsequently, C−O bond formation by
reductive elimination and regeneration of the active Pd(II)
species by oxidation took place in the presence of CuCl2, and
the catalytic cycle was completed.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-fluorophenyl)-
dihydrofuran-2(3H)-one (3ad): yield 88% (132.9 mg); white solid;
1
mp 121−122 °C; TLC Rf = 0.37 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.52−7.50 (m, 2H), 7.45 (d, J = 3.2 Hz, 3H), 7.32−
7.29 (m, 2H), 7.07 (t, J = 8.4 Hz, 2H), 5.39 (t, J = 7.2 Hz, 1H), 3.45
(dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.04 (dd, J = 16.4 Hz, J = 7.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 167.1, 164.0 (J = 246.1 Hz),
140.3, 137.6, 135.0 (J = 3.2 Hz), 130.4, 128.6, 128.2, 127.4 (J = 8.3
Hz), 122.3, 115.9 (J = 21.6 Hz), 76.3, 39.9 ppm; 19F NMR (376 MHz,
CDCl3) δ −112.86 ppm; IR νmax (KBr)/cm−1 3747, 2924, 1756, 1509,
1195, 1091, 833; MS (EI) m/z 75, 95, 115, 150, 178, 202, 221, 302.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-chlorophenyl)-
dihydrofuran-2(3H)-one (3ae): yield 91% (144.7 mg); white solid;
CONCLUSION
■
In summary, we have developed a new palladium-catalyzed
intermolecular oxyvinylcyclization of alkenes with alkynoic
acids or alkynols under mild conditions. This transformation
provides a convenient and efficient method for the synthesis of
α-methylene γ-lactones and tetrahydrofuran derivatives in
moderate to excellent yields with high regio- and stereo-
selectivities. Moreover, this oxyvinylcyclization process also
provides a new tool for the construction of C−Cl, C(sp2)−
C(sp3), and C−O bonds in a single step. The readily available
starting materials and mild reaction conditions are some of the
additional features of this protocol.
1
mp 95−96 °C; TLC Rf = 0.44 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.51−7.50 (m, 2H), 7.45−7.43 (m, 3H), 7.36 (d, J =
8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 5.38 (t, J = 7.2 Hz, 1H), 3.45
(dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.02 (dd, J = 16.4 Hz, J = 7.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 167.1, 140.4, 137.8, 137.5,
134.5, 130.5, 129.1, 128.6, 128.2, 126.8, 122.1, 76.1, 39.8 ppm; IR νmax
(KBr)/cm−1 3491, 2921, 2363, 1760, 1629, 1198, 1089, 756; MS (EI)
m/z 75, 89, 115, 150, 178, 202, 318.
(Z)-5-(4-Bromophenyl)-3-(chloro(phenyl)methylene)-
EXPERIMENTAL SECTION
dihydrofuran-2(3H)-one (3af): yield 90% (163.8 mg); white solid; mp
■
1
118−119 °C; TLC Rf = 0.51 (PE/EA = 4:1, v/v); H NMR (400
General Methods. Unless otherwise noted, all purchased
chemicals were used without further purification. H and 13C NMR
1
MHz, CDCl3) δ 7.51 (d, J = 6.8 Hz, 4H), 7.44 (s, 3H), 7.21 (d, J = 7.6
Hz, 2H), 5.37 (t, J = 7.2 Hz, 1H), 3.46 (dd, J = 16.4 Hz, J = 7.2 Hz,
1H), 3.02 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 167.1, 140.5, 138.3, 137.5, 132.0, 130.5, 128.6, 128.2, 127.1,
122.6, 122.0, 76.2, 39.8 ppm; IR νmax (KBr)/cm−1 3362, 2921, 2362,
1759, 1628, 1196, 1090, 756; MS (EI) m/z 77, 115, 150, 178, 281,
364.
spectra were measured on a 400 MHz NMR spectrometer. IR spectra
were measured with an infrared spectrometer on potassium bromide
pellets. GC−MS data were obtained using electron ionization. HRMS
was obtained with a LCMS−IT-TOF mass spectrometer. TLC was
performed using commercially available 100−400 mesh silica gel plates
(GF254). The alkynoic acids 1b−l22 and alkynols 6a−g23 were
prepared according to the literature.
General Procedure. A mixture of propiolic acid 1 or alkynol 6
(0.5 mmol), alkene 2 or 4 (0.60 mmol), PdCl2 (5 mol %), CuCl2 or
CuCl2·2H2O (1.0 or 1.5 mmol), and MeCN (1 mL) was placed in a
test tube (10 mL) equipped with a magnetic stirring bar. The mixture
was stirred at room temperature under air. After the reaction was
completed, purification of the mixture on a preparative TLC afforded
the desired products.
(Z)-3-(Chloro(phenyl)methylene)-5-phenyldihydrofuran-2(3H)-
one (3aa): yield 89% (126.4 mg); white solid; mp 65−67 °C; TLC Rf
= 0.35 (PE/EA = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.50−7.49
(m, 2H), 7.43−7.30 (m, 8H), 5.40 (t, J = 8.0 Hz, 1H), 3.43 (dd, J =
16.4 Hz, J = 7.2 Hz, 1H), 3.05 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 167.2, 140.1, 139.3, 137.7, 130.3, 128.9,
128.7, 128.6, 128.2, 125.3, 122.4, 76.9, 40.0 ppm; IR νmax (KBr)/cm−1
3743, 2922, 2335, 1754, 1644, 1200, 757, 698; MS (EI) m/z 77, 115,
150, 178, 202, 284.
(Z)-4-(4-(Chloro(phenyl)methylene)-5-oxotetrahydrofuran-2-yl)-
benzonitrile (3ag): yield 84% (129.8 mg); white solid; mp 53−55 °C;
1
TLC Rf = 0.15 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
7.67 (d, J = 8.0 Hz, 2H), 7.52−7.44 (m, 7H), 5.48 (t, J = 7.6 Hz, 1H),
3.53 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H), 3.02 (dd, J = 16.4 Hz, J = 7.2
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.80, 144.5, 141.1, 137.4,
132.7, 130.6, 128.7, 128.1, 126.1, 121.4, 118.4, 112.4, 75.7, 39.5 ppm;
IR νmax (KBr)/cm−1 2923, 2228, 1763, 1629, 1198, 1092, 757; MS
(EI) m/z 73, 96, 115, 150, 178, 281, 309; HRMS-ESI (m/z) calcd for
C18H12ClNNaO2 [M + Na]+ 332.0449, found 332.0452.
(Z)-Methyl 4-(4-(chloro(phenyl)methylene)-5-oxotetrahydrofur-
an-2-yl)benzoate (3ah): yield 87% (148.8 mg); white solid; mp
1
131−132 °C; TLC Rf = 0.33 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 8.06 (d, J = 7.6 Hz, 2H), 7.49 (s, 2H), 7.40−7.39 (m,
5H), 5.47 (t, J = 7.6 Hz, 1H), 3.93 (s, 3H), 3.49 (dd, J = 16.4 Hz, J =
7.6 Hz, 1H), 3.04 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 167.0, 166.5, 144.2, 140.7, 137.5, 130.5, 130.4, 130.2,
D
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
128.6, 128.1, 125.2, 121.8, 76.1, 52.3, 39.7 ppm; IR νmax (KBr)/cm−1
3061, 2951, 1762, 1750, 1621, 1281, 1195, 1103, 702; MS (EI) m/z
89, 101, 115, 150, 178, 202, 281, 311, 342; HRMS-ESI (m/z) calcd for
C19H16ClO4 [M + H]+ 343.0732, found 343.0736.
7.2 Hz, 1H), 3.50 (dd, J = 17.2 Hz, J = 8.8 Hz, 1H), 3.26 (dd, J = 16.8
Hz, J = 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 165.9, 145.5
(dm, J = 249 Hz), 141.6, 139.8 (dm, J = 138 Hz), 137.6, 130.5, 129.1,
128.7, 128.0, 120.7, 112.4, 67.0, 36.5 ppm; 19F NMR (376 MHz,
CDCl3) δ −142.44 (dd, J = 21.4 Hz, J = 6.4 Hz), −151.66 (t, J = 20.7
Hz), −160.61 (td, J = 37.6 Hz, J = 21.1 Hz, J = 7.1 Hz) ppm; IR νmax
(KBr)/cm−1 3744, 2919, 2364, 1767, 1628, 1506, 1200, 957; MS (EI)
m/z 77, 89, 115, 150, 178, 274, 374; HRMS-ESI (m/z) calcd for
C17H8ClF5NaO2 [M + Na]+ 397.0025, found 397.0028.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-nitrophenyl)dihydrofuran-
2(3H)-one (3ai): yield 85% (139.8 mg); yellow solid; mp 143−144 °C;
1
TLC Rf = 0.30 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
8.24 (d, J = 8.4 Hz, 2H), 7.53−7.47 (m, 4H), 7.45−7.43 (m, 3H), 5.53
(t, J = 7.2 Hz, 1H), 3.55 (dd, J = 16.8 Hz, J = 8.0 Hz, 1H), 3.02 (dd, J
= 16.8 Hz, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.6,
147.9, 146.4, 141.4, 137.4, 130.6, 128.7, 128.1, 126.2, 124.2, 121.2,
75.4, 39.5 ppm; IR νmax (KBr)/cm−1 3061, 2921, 1762, 1627, 1438,
1196, 1087, 1026, 753; HRMS-ESI (m/z) calcd for C17H12ClNNaO4
[M + H]+ 352.0347, found 352.0346.
(Z)-3-(Chloro(phenyl)methylene)-5-(naphthalen-2-yl)-
dihydrofuran-2(3H)-one (3ap): yield 89% (148.6 mg); white solid;
1
mp 134−135 °C; TLC Rf = 0.53 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.86−7.81 (m, 3H), 7.78 (s, 1H), 7.51−7.48 (m, 4H),
7.41−7.40 (m, 3H), 7.36 (dd, J = 8.8 Hz, J = 1.6 Hz, 1H), 5.55 (t, J =
7.2 Hz, 1H), 3.49 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H), 3.11 (dd, J = 16.4
Hz, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.4, 140.3,
137.7, 136.5, 133.2, 133.1, 130.3, 129.0, 128.6, 128.2, 128.1, 127.8,
126.7, 126.6, 124.6, 122.7, 122.4, 100.0, 76.9, 39.9 ppm; IR νmax
(KBr)/cm−1 3057, 2923, 1758, 1628, 1318, 1199, 1059, 754; MS (EI)
m/z 77, 127, 149, 177, 184, 202, 334.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-(trifluoromethyl)phenyl)-
dihydrofuran-2(3H)-one (3aj): yield 79% (139.0 mg); white solid; mp
1
113−114 °C; TLC Rf = 0.45 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 2H), 7.51−7.46 (m, 9H), 5.49 (t,
J = 7.2 Hz, 1H), 3.53 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H), 3.05 (dd, J =
16.4 Hz, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.9,
143.3, 140.9, 137.5, 130.8 (J = 32.3 Hz), 130.5, 128.7, 128.1, 125.2,
125.9 (q, J = 3.7 Hz), 125.6, 121.6, 75.9, 39.7 ppm; 19F NMR (376
MHz, CDCl3) δ −62.85 ppm; IR νmax (KBr)/cm−1 3741, 3062, 2922,
1763, 1626, 1324, 1120, 699; MS (EI) m/z 89, 115, 150, 178, 202,
333, 318, 352; HRMS-ESI (m/z) calcd for C18H12ClF3NaO2 [M +
Na]+ 375.0370, found 375.0371.
(Z)-3-(Chloro(phenyl)methylene)-5-(thiophene-2-yl)-
dihydrofuran-2(3H)-one (3aq): yield 75% (108.7 mg); brown oil;
1
TLC Rf = 0.35 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
7.51−7.49 (m, 2H), 7.43−7.42 (m, 3H), 7.31 (d, J = 5.2 Hz, 1H), 7.04
(d, J = 3.2 Hz, 1H), 6.96 (t, J = 3.2 Hz, 1H), 5.61 (t, J = 7.2 Hz, 1H),
3.45 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.20 (dd, J = 16.4 Hz, J = 6.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.6, 141.6, 140.5, 137.6,
130.4, 128.7, 128.2, 127.1, 126.5, 126.2, 122.1, 73.1, 39.8 ppm; IR νmax
(KBr)/cm−1 3106, 2924, 1760, 1630, 1439, 1204, 1093, 700; MS (EI)
m/z 73, 89, 115, 150, 178, 202, 290; HRMS-ESI (m/z) calcd for
C15H12ClO2S [M + H]+ 291.0241, found 291.0239.
(Z)-3-(Chloro(phenyl)methylene)-5-p-tolyldihydrofuran-2(3H)-
one (3ak): yield 86% (128.1 mg); white solid; mp 96−97 °C; TLC Rf
1
= 0.60 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.51 (s,
2H), 7.45 (s, 3H), 7.24−7.20 (m, 4H), 5.39 (t, J = 7.2 Hz, 1H), 3.45
(dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.07 (dd, J = 16.4 Hz, J = 6.8 Hz,
1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4, 139.9,
138.6, 137.7, 136.2, 130.3, 129.5, 128.6, 128.2, 125.4, 122.6, 77.0, 40.0,
21.2 ppm; IR νmax (KBr)/cm−1 3500, 3027, 2922, 2364, 1758, 1628,
1440, 1198, 1093, 696; MS (EI) m/z 77, 89, 115, 150, 178, 202, 281,
298.
(Z)-3-(Chloro(phenyl)methylene)-5-(pyridin-2-yl)dihydrofuran-
2(3H)-one (3ar): yield 50% (71.2 mg); brown oil; TLC Rf = 0.63 (PE/
1
EA = 1:1, v/v); H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.8 Hz,
1H), 7.76 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 3H), 7.42−7.41 (m,
3H), 7.26 (s, 2H), 5.52 (t, J = 7.2 Hz, 1H), 3.55 (dd, J = 17.2 Hz, J =
8.4 Hz, 1H), 3.31 (dd, J = 16.8 Hz, J = 6.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 167.1, 158.1, 149.3, 140.6, 137.7, 137.4, 130.3, 128.6,
128.2, 123.4, 121.7, 120.5, 76.3, 37.4 ppm; IR νmax (KBr)/cm−1 2850,
2362, 1759, 1628, 1401, 1198, 1038, 752; MS (EI) m/z 78, 115, 150,
194, 206, 222, 250, 268, 285; HRMS-ESI (m/z) calcd for
C16H13ClNO2 [M + H]+ 286.0629, found 286.0627.
(Z)-5-(4-tert-Butylphenyl)-3-(chloro(phenyl)methylene)-
dihydrofuran-2(3H)-one (3al): yield 80% (136.0 mg); white solid; mp
1
96−98 °C; TLC Rf = 0.64 (PE/EA = 4:1, v/v); H NMR (400 MHz,
CDCl3) δ 7.54−7.53 (m, 2H), 7.45−7.42 (m, 5H), 7.30 (d, J = 8.0 Hz,
2H), 5.41 (t, J = 7.2 Hz, 1H), 3.46 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H),
3.10 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 1.35 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 167.4, 151.8, 139.8, 137.7, 136.2, 130.3, 128.6, 128.2,
125.8, 125.3, 122.8, 76.9, 39.9, 34.7, 31.3 ppm; IR νmax (KBr)/cm−1
3059, 2961, 1761, 1634, 1199, 1100, 1029, 697; MS (EI) m/z 91, 115,
150, 163, 178, 325, 340.
(Z)-3-(Chloro(phenyl)methylene)-5-methyl-5-phenyldihydrofur-
an-2(3H)-one (3as): yield 82% (122.2 mg); yellow oil; TLC Rf = 0.31
1
(PE/EA = 6:1, v/v); H NMR (400 MHz, CDCl3) δ 7.44−7.41 (m,
5H), 7.35 (d, J = 8.0 Hz, 4H), 7.31−7.27 (m, 1H), 3.25 (q, J = 28.0
Hz, J = 16.4 Hz, 2H), 1.68 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
166.8, 144.2, 140.1, 137.7, 130.3, 128.7, 128.6, 128.2, 127.8, 124.1,
123.1, 82.5, 45.5, 29.8 ppm; IR νmax (KBr)/cm−1 3063, 2927, 2363,
1758, 1629, 1444, 1226, 1054, 938, 698; MS (EI) m/z 77, 89, 105,
115, 121, 150, 178, 202, 219, 283, 298.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-methoxyphenyl)-
dihydrofuran-2(3H)-one (3am): yield 85% (133.5 mg); white solid;
1
mp 110−112 °C; TLC Rf = 0.30 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.53−7.51 (m, 2H), 7.45−7.44 (m, 3H), 7.27 (d, J =
8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 5.36 (t, J = 7.2 Hz, 1H), 3.82 (s,
3H), 3.41 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.08 (dd, J = 16.4 Hz, J =
7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.4, 159.9, 139.8,
137.7, 131.0, 130.3, 128.6, 128.2, 127.0, 122.8, 114.2, 77.0, 55.4, 40.0
ppm; IR νmax (KBr)/cm−1 3626, 2918, 2370, 1754, 1616, 1512, 1246,
1176, 1029, 696; MS (EI) m/z 77, 89, 115, 137, 150, 178, 314.
(Z)-3-(Chloro(phenyl)methylene)-5-mesityldihydrofuran-2(3H)-
one (3an): yield 68% (110.8 mg); yellow oil; TLC Rf = 0.68 (PE/EA =
(Z)-3-(Chloro(2-chlorophenyl)methylene)-5-phenyldihydrofuran-
2(3H)-one (3ba): yield 82% (130.4 mg); colorless oil; TLC Rf = 0.52
1
(PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.51−7.29 (m,
9H), 5.52−5.44 (m, 1H), 3.28−3.07 (m, 1H), 2.91−2.68 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 166.5, 139.3, 136.7, 131.6, 131.0, 130.3,
129.3, 129.0, 128.9, 128.7, 127.6, 125.5, 125.3, 77.0, 38.3 ppm; IR νmax
(KBr)/cm−1 3064, 2925, 1763, 1653 1433, 1322, 1207, 1103, 756; MS
(EI) m/z 77, 114, 149, 177, 202, 247, 283, 318; HRMS-ESI (m/z)
calcd for C17H13Cl2O2 [M + H]+ 319.0287, found 319.0290.
1
4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.56−7.54 (m, 2H), 7.46−
7.44 (m, 3H), 6.88 (s, 2H), 5.79 (t, J = 8.0 Hz, 1H), 3.25 (dd, J = 7.6
Hz, J = 4.8 Hz, 2H), 2.35 (s, 6H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.5, 140.0, 138.2, 137.8, 136.0, 130.9, 130.5, 130.3, 128.6,
128.2, 123.1, 74.7, 37.4, 20.8, 20.6 ppm; IR νmax (KBr)/cm−1 2966,
2362, 1757, 1622, 1448, 1326, 1199, 1101, 758; MS (EI) m/z 75, 102,
129, 136, 180, 198, 214, 326; HRMS-ESI (m/z) calcd for C20H20ClO2
[M + H]+ 327.1146, found 327.1149.
(Z)-3-(Chloro(3-chlorophenyl)methylene)-5-phenyldihydrofuran-
2(3H)-one (3ca): yield 85% (135.2 mg); colorless oil; TLC Rf = 0.50
1
(PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H),
7.42−7.37 (m, 6H), 4.33 (d, J = 7.6 Hz, 1H), 5.44 (t, J = 7.2 Hz, 1H),
3.45 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.05 (dd, J = 16.8 Hz, J = 6.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.9, 139.3, 139.0, 138.2,
134.7, 130.4, 129.9, 128.9, 128.8, 128.2, 126.3, 125.4, 123.5, 76.9, 39.8
ppm; IR νmax (KBr)/cm−1 3066, 2925, 2362, 1760, 1633, 1201, 1102,
695; MS (EI) m/z 77, 149, 177, 184, 202, 212, 318.
(Z)-3-(Chloro(phenyl)methylene)-5-(perfluorophenyl)-
dihydrofuran-2(3H)-one (3ao): yield 71% (132.8 mg); white solid;
1
mp 90−92 °C; TLC Rf = 0.45 (PE/EA = 4:1, v/v); H NMR (400
MHz, CDCl3) δ 7.53−7.52 (m, 2H), 7.47−7.45 (m, 3H), 5.75 (t, J =
E
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
(Z)-3-(Chloro(4-chlorophenyl)methylene)-5-phenyldihydrofuran-
37.5, 26.5 ppm; IR νmax (KBr)/cm−1 3745, 2917, 1753, 1650, 1226,
1142, 1019, 696; MS (EI) m/z 53, 77, 88, 105, 116, 143, 187, 222.
(Z)-3-(1-Chlorohexylidene)-5-phenyldihydrofuran-2(3H)-one
(3ka): yield 88% (122.3 mg); colorless oil; TLC Rf = 0.55 (PE/EA =
4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.41−7.31 (m, 5H), 5.43 (t,
J = 7.2 Hz, 1H), 3.44 (dd, J = 16.4 Hz, J = 8.4 Hz, 1H), 2.91 (dd, J =
16.4 Hz, J = 7.2 Hz, 1H), 2.44 (t, J = 7.2 Hz, 2H), 1.69−1.64 (m, 2H),
1.33−1.24 (m, 4H), 0.88 (t J = 6.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 166.9, 145.3, 139.8, 128.9, 128.6, 125.3, 120.4, 76.3, 39.3,
37.5, 30.9, 26.5, 22.4, 13.9 ppm; IR νmax (KBr)/cm−1 3064, 2930,
2361, 1760, 1646, 1227, 1140, 1033, 697; MS (EI) m/z 77, 88, 116,
137, 172, 202, 278.
2(3H)-one (3da): yield 91% (144.7 mg); white solid; mp 124−126 °C;
1
TLC Rf = 0.56 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
7.46 (d, J = 7.6 Hz, 2H), 7.42−7.35 (m, 5H), 7.32 (d, J = 7.2 Hz, 2H),
5.43 (t, J = 7.2 Hz, 1H), 3.45 (dd, J = 16.8 Hz, J = 7.6 Hz, 1H), 3.06
(dd, J = 16.4 Hz, J = 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
167.5, 134.0, 137.7, 130.3, 128.6, 128.1, 122.6, 74.0, 58.8, 38.4, 37.2
ppm; IR νmax (KBr)/cm−1 3035, 2919, 1758, 1628, 1488, 1198, 1092,
828; MS (EI) m/z 63, 77, 105, 114, 149, 177, 184, 212, 318; HRMS-
ESI (m/z) calcd for C17H13Cl2O2 [M + H]+ 319.0287, found
319.0288.
(Z)-3-(Chloro(4-fluorophenyl)methylene)-5-phenyldihydrofuran-
2(3H)-one (3ea): yield 88% (132.9 mg); white solid; mp 96−97 °C;
(Z)-3-(chloro(cyclopropyl)methylene)-5-phenyldihydrofuran-
1
TLC Rf = 0.50 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
2(3H)-one (3la): yield 90% (111.6 mg); yellow oil; TLC Rf = 0.38
1
7.50 (q, J = 8.0 Hz, J = 5.6 Hz, 2H), 7.39−7.29 (m, 5H), 7.10 (t, J =
8.4 Hz, 2H), 5.41 (t, J = 7.2 Hz, 1H), 3.42 (dd, J = 16.4 Hz, J = 7.2 Hz,
1H), 3.03 (dd, J = 16.8 Hz, J = 7.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 167.1, 164.7 (J = 250.8 Hz), 139.2, 138.9, 133.7 (J = 3.4
Hz), 130.5 (J = 9.7 Hz), 128.9, 128.7, 125.4, 122.6, 115.9 (J = 21.9
Hz), 76.8, 39.9 ppm; 19F NMR (376 MHz, CDCl3) δ −108.73 ppm;
IR νmax (KBr)/cm−1 3745, 3067, 2922, 1759, 1629, 1504, 1234, 838,
696; MS (EI) m/z 77, 107, 133, 168, 196, 220, 302.
(PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.43−7.35 (m,
5H), 5.51 (t, J = 7.6 Hz, 1H), 3.60 (dd, J = 16.4 Hz, J = 8.4 Hz, 1H),
3.06 (dd, J = 16.4 Hz, J = 6.4 Hz, 1H), 1.80−1.73 (m, 1H), 1.20−1.14
(m, 2H), 1.01−0.92 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 166.7,
146.7, 140.1, 128.7, 128.5, 125.4, 118.8, 76.3, 37.4, 18.0, 8.0, 8.0 ppm;
IR νmax (KBr)/cm−1 3068, 2925, 1747, 1639, 1236, 1168, 995, 698;
MS (EI) m/z 77, 79, 91, 107, 114, 129, 153, 167, 191, 220, 248;
HRMS-ESI (m/z) calcd for C14H14ClO2 [M + H]+ 249.0677, found
249.0674.
(Z)-3-((4-Bromophenyl)chloromethylene)-5-phenyldihydrofuran-
2(3H)-one (3fa): yield 90% (162.9 mg); white solid; mp 131−132 °C;
(Z)-Ethyl 4-(chloro(phenyl)methylene)-5-oxotetrahydrofuran-2-
1
TLC Rf = 0.55 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
carboxylate (5aa): yield 89% (124.6 mg); colorless oil; TLC Rf =
1
7.58 (d, J = 8.4 Hz, 2H), 7.42−7.36 (m, 5H), 7.33 (d, J = 8.8 Hz, 2H),
5.43 (t, J = 7.6 Hz, 1H), 3.44 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 3.05
(dd, J = 16.8 Hz, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
167.0, 139.1, 138.8, 136.5, 131.9, 129.8, 128.9, 128.7, 125.3, 124.8,
123.0, 76.8, 39.9 ppm; IR νmax (KBr)/cm−1 3746, 3364, 2919, 1758,
1637, 1199, 1029, 701; MS (EI) m/z 77, 114, 149, 177, 193, 202, 230,
258, 362; HRMS-ESI (m/z) calcd for C17H13BrClO2 [M + H]+
362.9782, found 362.9784.
0.27 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.50−7.45
(m, 5H), 4.86 (dd, J = 9.6 Hz, J = 5.2 Hz, 1 H), 4.30−4.19 (m, 2H),
3.40 (q, J = 17.2 Hz, J = 9.2 Hz, 1H), 3.10 (q, J = 17.2 Hz, J = 4.8 Hz,
1H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.2,
166.2, 141.4, 137.5, 130.5, 128.7, 128.0, 119.9, 71.8, 62.2, 34.5, 14.0
ppm; IR νmax (KBr)/cm−1 3743, 2984, 2361, 1769, 1760, 1628, 1195,
1068, 696; MS (EI) m/z 77, 89, 115, 144, 171, 179, 217, 245, 280.
(Z)-Cyclohexyl 4-(chloro(phenyl)methylene)-5-oxotetrahydrofur-
an-2-carboxylate (5ab): yield 85% (141.9 mg); colorless oil; TLC Rf
= 0.50 (PE/EA = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.48−7.43
(m, 5H), 4.85−4.79 (m, 2H), 3.39 (dd, J = 16.8 Hz, J = 8.8 Hz, 1H),
3.06 (dd, J = 16.8 Hz, J = 4.4 Hz, 1H), 1.80−1.78 (m, 2H), 1.68−1.66
(m, 2H), 1.51−1.23 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 168.7,
166.4, 141.4, 137.5, 130.5, 128.7, 128.1, 128.0, 120.1, 74.8, 72.1, 34.6,
31.2, 25.1, 23.3 ppm; IR νmax (KBr)/cm−1 3061, 2937, 1772, 1765,
1631, 1446, 1195, 1067, 696; MS (EI) m/z 55, 83, 115, 144, 179, 217,
252, 281, 334; HRMS-ESI (m/z) calcd for C18H20ClO4 [M + H]+
335.1045, found 335.1042.
(Z)-3-(Chloro(4-nitrophenyl)methylene)-5-phenyldihydrofuran-
2(3H)-one (3ga): yield 78% (128.3 mg); yellow solid, mp 112−116
°C; TLC Rf = 0.52 (PE/EA = 3:1, v/v); 1H NMR (400 MHz, CDCl3)
δ 8.32 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.43−7.38 (m,
3H), 7.32 (d, J = 7.2 Hz, 2H), 5.48 (t, J = 7.6 Hz, 1H), 3.44 (dd, J =
16.8 Hz, J = 7.6 Hz, 1H), 3.07 (dd, J = 16.4 Hz, J = 6.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 166.5, 148.4, 143.5, 138.8, 137.0, 129.3,
129.0, 128.9, 125.2, 125.0, 123.9, 76.9, 39.7 ppm; IR νmax (KBr)/cm−1
3744, 3360, 2918, 2362, 1754, 1645, 1517, 1346, 699; HRMS-ESI (m/
z) calcd for C17H12ClNNaO4 [M + Na]+ 352.0347, found 352.0344.
(Z)-3-(Chloro(4-methoxyphenyl)methylene)-5-phenyldihydrofur-
an-2(3H)-one (3ha): yield 85% (133.5 mg); colorless oil; TLC Rf =
0.45 (PE/EA = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J =
8.0 Hz, 2H), 7.42−7.33 (m, 5H), 6.95 (d, J = 8.0 Hz, 2H), 5.41 (t, J =
7.2 Hz, 1H), 3.86 (s, 3H), 3.49 (dd, J = 16.0 Hz, J = 7.2 Hz, 1H), 3.09
(dd, J = 16.4 Hz, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
167.6, 161.1, 140.1, 139.4, 130.1, 129.8, 128.9, 128.6, 125.4, 120.9,
113.8, 76.8, 55.5, 40.3 ppm; IR νmax (KBr)/cm−1 2840, 2335, 1757,
1602, 1508, 1401, 1303, 1249, 1178, 698; MS (EI) m/z 73, 91, 105,
145, 180, 207, 281, 314; HRMS-ESI (m/z) calcd for C18H16ClO3 [M +
H]+ 315.0782, found 315.0781.
(Z)-2,2,2-Trifluoroethyl 4-(chloro(phenyl)methylene)-5-oxotetra-
hydrofuran-2-carboxylate (5ac): yield 83% (138.6 mg); colorless
oil; TLC Rf = 0.35 (PE/EA = 4:1, v/v); 1H NMR (400 MHz, CDCl3)
δ 7.49 (s, 5H), 5.00 (dd, J = 9.2 Hz, J = 4.8 Hz, 1H), 4.58 (q, J = 15.6
Hz, J = 7.6 Hz, 2H), 3.46 (dd, J = 17.2 Hz, J = 9.2 Hz, 1H), 3.13 (dd, J
= 17.2 Hz, J = 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.8,
165.6, 142.6, 137.3, 132.5, 130.7, 128.8, 128.5 (q, J = 236 Hz), 118.8,
71.1, 61.1 (q, J = 36.9 Hz), 34.3 ppm; 19F NMR (376 MHz, CDCl3) δ
−77.08 (t, J = 8.6 Hz); IR νmax (KBr)/cm−1 2929, 2363, 1767, 1760,
1628, 1201, 1070, 696; HRMS-ESI (m/z) calcd for C14H11ClF3O4 [M
+ H]+ 335.0292, found 335.0285.
(Z)-3-(Chloro(p-tolyl)methylene)-5-phenyldihydrofuran-2(3H)-
one (3ia): yield 89% (132.6 mg); colorless oil; TLC Rf = 0.49 (PE/EA
= 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.44−7.33 (m, 7H), 7.27
(d, J = 8.0 Hz, 2H), 5.41 (t, J = 7.2 Hz, 1H), 3.48 (dd, J = 16.4 Hz, J =
7.2 Hz, 1H), 3.08 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 2.41 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.5, 140.9, 140.3, 139.4, 134.8, 129.2,
128.9, 128.6, 128.2, 125.4, 121.8, 76.8, 40.1, 21.4 ppm; IR νmax (KBr)/
cm−1 3033, 2922, 2335, 1759, 1627, 1453, 1198, 1032, 697; MS (EI)
m/z 77, 105, 129, 164, 192, 298; HRMS-ESI (m/z) calcd for
C18H16ClO2 [M + H]+ 299.0833, found 299.0834.
(Z)-4-(Chloro(phenyl)methylene)-5-oxotetrahydrofuran-2-car-
boxamide (5ad): yield 65% (81.6 mg); white solid; mp 153−155 °C;
TLC Rf = 0.45 (PE/EA = 0:1, v/v); 1H NMR (400 MHz, CD3OD) δ
7.65−7.63 (m, 2H), 7.55−7.52 (m, 3H), 7.23 (br, 1H), 6.87 (br, 1H),
4.90 (dd, J = 8.8 Hz, J = 5.2 Hz, 1H), 3.45 (dd, J = 17.2 Hz, J = 8.8 Hz,
1H), 3.18 (dd, J = 16.8 Hz, J = 5.2 Hz, 1H); 13C NMR (100 MHz,
CD3OD) δ 171.1, 165.8, 138.6, 137.8, 130.3, 128.7, 128.2, 122.2, 72.9,
34.4 ppm; IR νmax (KBr)/cm−1 3440, 2924, 2363, 1764, 1682, 1628,
1438, 1203, 1057, 697; MS (EI) m/z 89, 115, 144, 179, 216, 251. 5ad
is known.
(Z)-3-(1-Chloroethylidene)-5-phenyldihydrofuran-2(3H)-one
(Z)-4-(Chloro(phenyl)methylene)-N,N-dimethyl-5-oxotetrahydro-
(3ja): yield 90% (99.9 mg); white solid; mp 92−93 °C; TLC Rf = 0.40
furan-2-carboxamide (5ae): yield 78% (108.8 mg); white solid; mp
1
1
(PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.39−7.29 (m,
110−113 °C; TLC Rf = 0.46 (PE/EA = 0:1, v/v); H NMR (400
5H), 5.44 (d, J = 7.6 Hz, 1H), 3.43 (dd, J = 16.8 Hz, J = 8.4 Hz, 1H),
2.89 (dd, J = 16.4 Hz, J = 6.4 Hz, 1H), 2.27 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 166.7, 140.3, 139.8, 128.9, 128.6, 125.3, 120.8, 76.2,
MHz, CDCl3) δ 7.54−7.53 (m, 2H), 7.44−7.43 (m, 3H), 5.09 (dd, J =
7.6 Hz, J = 6.4 Hz, 1H), 3.58 (dd, J = 16.8 Hz, J = 5.2 Hz, 1H), 3.15
(dd, J = 26.4 Hz, J = 17.2 Hz, 1H), 3.12 (s, 3H), 2.97 (s, 3H); 13C
F
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
NMR (100 MHz, CDCl3) δ 166.8, 166.4, 140.6, 137.7, 130.3, 128.6,
128.2, 121.1, 71.0, 37.0, 36.1, 33.0 ppm; IR νmax (KBr)/cm−1 2935,
1764, 1657, 1496, 1207, 1060, 696; MS (EI) m/z 89, 115, 144, 179,
216, 279.
MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2H), 7.44−7.32 (m, 7H), 4.94
(dd, J = 10.4 Hz, J = 2.4 Hz, 1H), 2.74 (dd, J = 16.8 Hz, J = 10.8 Hz,
1H), 2.62 (dd, J = 16.8 Hz, J = 2.8 Hz, 1H), 1.65 (s, 3H), 1.64 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 140.7, 139.7, 133.5, 131.6, 131.6,
(Z)-3-(Chloro(phenyl)methylene)-5-propionyldihydrofuran-
128.3, 128.1, 127.8, 127.5, 121.5, 77.5, 69.7, 40.8, 28.5, 24.3 ppm; IR
νmax (KBr)/cm−1 3747, 3363, 2923, 2363, 2648, 1487, 1367, 1078,
697; MS (EI) m/z 77, 115, 142, 157, 177, 192, 361, 377; HRMS-ESI
(m/z) calcd for C19H18BrClNaO [M + Na]+ 399.0122, found
399.0119.
(Z)-3-(Chloro(phenyl)methylene)-2,2-dimethyl-5-m-tolyltetrahy-
drofuran (7at): yield 68% (106.1 mg); colorless oil; TLC Rf = 0.52
(PE/DCM = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.43−7.27 (m,
8H), 7.14 (d, J = 6.8 Hz, 1H), 4.96 (dd, J = 14.4 Hz, J = 2.4 Hz, 1H),
2.81 (dd, J = 16.8 Hz, J = 10.8 Hz, 1H), 2.62 (dd, J = 16.8 Hz, J = 2.8
Hz, 1H), 2.41 (s, 3H), 1.66 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
141.5, 134.0, 138.1, 133.5, 131.9, 128.5, 128.4, 128.2, 128.1, 127.4,
126.7, 123.2, 77.4, 70.4, 40.9, 28.6, 24.3, 21.5 ppm; IR νmax (KBr)/
cm−1 3054, 2981, 2361, 1606, 1449, 1369, 1174, 1029, 698; MS (EI)
m/z 77, 91, 105, 142, 157, 177, 192, 297, 312; HRMS-ESI (m/z) calcd
for C20H22ClO [M + H]+ 313.1354, found 313.1349.
(Z)-4-(Chloro(phenyl)methylene)-2-phenyltetrahydrofuran (7ba):
yield 76% (102.6 mg); colorless oil; TLC Rf = 0.68 (PE/DCM = 4:1,
v/v); 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.42−
7.32 (m, 8H), 5.03 (dd, J = 9.2 Hz, J = 6.0 Hz, 1H), 4.91 (d, J = 15.2
Hz, 1H), 4.71 (d, J = 14.8 Hz, 1H), 3.08 (dd, J = 16.0 Hz, J = 5.2 Hz,
1H), 2.78 (dd, J = 15.6 Hz, J = 9.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 140.7, 138.3, 137.8, 128.5, 128.4, 128.2, 128.0, 127.9, 125.8,
121.9, 82.3, 72.4, 41.6 ppm; IR νmax (KBr)/cm−1 3734, 3062, 2924,
2360, 1763, 1686, 1449, 1028, 697; MS (EI) m/z 77, 104, 129, 164,
202, 235, 270; HRMS-ESI (m/z) calcd for C17H15ClNaO [M + Na]+
293.0704, found 293.0716.
2(3H)-one (5af): yield 86% (113.5 mg); yellow oil; TLC Rf = 0.30
1
(PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.50−7.46 (m,
5H), 4.74 (q, J = 8.4 Hz, J = 6.0 Hz, 1H), 3.29 (dd, J = 17.2 Hz, J = 8.8
Hz, 1H), 3.14 (dd, J = 17.2 Hz, J = 6.0 Hz, 1H), 2.70 (q, J = 14.4 Hz, J
= 7.2 Hz, 2H), 1.10 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 208.0, 166.3, 141.8, 137.4, 130.6, 128.7, 128.1, 120.1, 77.5, 33.2, 32.5,
6.9 ppm; IR νmax (KBr)/cm−1 3744, 2927, 2360, 1763, 1719, 1626,
1200, 1066, 696; MS (EI) m/z 77, 89, 144, 179, 217, 264.
(Z)-4-(Chloro(phenyl)methylene)-5-oxotetrahydrofuran-2-car-
bonitrile (5ag): yield 49% (57.1 mg); yellow oil; TLC Rf = 0.45 (PE/
EA = 1:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.49 (s, 5H), 5.09 (dd,
J = 8.8 Hz, J = 4.8 Hz, 1H), 3.49 (dd, J = 16.8 Hz, J = 8.8 Hz, 1H),
3.35 (dd, J = 16.8 Hz, J = 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 164.3, 144.6, 136.9, 131.1, 128.9, 128.0, 117.0, 116.1, 61.0, 35.5 ppm;
IR νmax (KBr)/cm−1 3363, 3062, 2366, 1776, 1628, 1440, 1200, 1044,
699; MS (EI) m/z 77, 89, 115, 127, 158, 177, 216, 233.
(Z)-3-(Chloro(phenyl)methylene)-5-hexyldihydrofuran-2(3H)-one
(5ah): yield 81% (118.3 mg); colorless oil; TLC Rf = 0.54 (PE/EA =
1
4:1, v/v); H NMR (400 MHz, CDCl3) δ 7.51−7.49 (m, 2H), 7.60−
7.32 (m, 3H), 4.38 (t, J = 6.4 Hz, 1H), 3.11 (dd, J = 16.0 Hz, J = 7.2
Hz, 1H), 2.70 (dd, J = 16.8 Hz, J = 6.8 Hz, 1H), 1.74−1.68 (m, 1H),
1.62−1.53 (m, 1H), 1.32−1.28 (m, 8H), 0.94−0.82 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.5, 139.3, 137.8, 130.1, 128.5, 128.1,
123.1, 76.3, 37.1, 35.9, 31.6, 28.9, 24.8, 22.5, 14.0 ppm; IR νmax (KBr)/
cm−1 3061, 2929, 2860, 2362, 1758, 1630, 1447, 1204, 1093, 696; MS
(EI) m/z 89, 95, 115, 150, 179, 256, 292; HRMS-ESI (m/z) calcd for
C17H22ClO2 [M + H]+ 293.1303, found 293.1305.
(Z)-3-(Chloro(2-fluorophenyl)methylene)-2,2-dimethyl-5-phenyl-
(Z)-3-(Chloro(phenyl)methylene)-5-(2-hydroxyethyl)-
tetrahydrofuran (7ca): yield 52% (82.2 mg); white solid; mp 65−67
1
dihydrofuran-2(3H)-one (5ai): yield 88% (110.9 mg); colorless oil;
°C; TLC Rf = 0.45 (PE/DCM = 4:1, v/v); H NMR (400 MHz,
1
TLC Rf = 0.28 (PE/EA = 4:1, v/v); H NMR (400 MHz, CDCl3) δ
CDCl3) δ 7.47 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.33−7.28
(m, 3H), 7.20−7.01 (m, 2H), 5.00 (dd, J = 10.4 Hz, J = 1.2 Hz, 1H),
2.77 (dd, J = 16.8 Hz, J = 10.4 Hz, 1H), 2.58 (dd, J = 16.8 Hz, J = 1.6
Hz, 1H), 1.65 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 160.6 (J =
245.3 Hz), 141.5, 135.9, 130.5 (J = 3.8 Hz), 129.4, 129.4, 128.5, 127.7,
127.3, 126.1, 124.0 (J = 3.5 Hz), 115.9 (J = 21.8 Hz), 77.4, 70.2, 40.0,
28.5, 24.3 ppm; 19F NMR (376 MHz, CDCl3) δ −114.94 ppm; IR νmax
(KBr)/cm−1 3745, 2924, 1698, 1540, 1459, 1019, 753; MS (EI) m/z
77, 91, 105, 133, 160, 175, 195, 210, 301, 316; HRMS-ESI (m/z) calcd
for C19H18ClFNaO [M + Na]+ 339.0922, found 339.0924.
(Z)-3-(Chloro(m-tolyl)methylene)-2,2-dimethyl-5-phenyltetrahy-
drofuran (7da): yield 72% (112.3 mg); colorless oil; TLC Rf = 0.53
(PE/DCM = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.6
Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.35−7.29 (m, 2H), 7.17−7.14 (m,
3H), 4.98 (dd, J = 10.4 Hz, J = 1.6 Hz, 1H), 2.80 (dd, J = 16.8 Hz, J =
10.8 Hz, 1H), 2.62 (dd, J = 16.8 Hz, J = 2.0 Hz, 1H), 2.41 (s, 3H),
1.65 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 141.7, 139.9, 137.8,
133.3, 132.0, 128.7, 128.5, 128.2, 128.1, 127.7, 126.1, 125.2, 77.4, 70.3,
41.0, 28.6, 24.3, 21.5 ppm; IR νmax (KBr)/cm−1 3031, 2981, 2363,
1603, 1490, 1454, 1368, 1169, 1071, 699; MS (EI) m/z 77, 91, 105,
141, 156, 171, 191, 206, 297, 312; HRMS-ESI (m/z) calcd for
C20H22ClO [M + H]+ 313.1354, found 313.1350.
(Z)-3-(Chloro(p-tolyl)methylene)-2,2-dimethyl-5-phenyltetrahy-
drofuran (7ea): yield 71% (110.7 mg); colorless oil; TLC Rf = 0.55
(PE/DCM = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.6
Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.32 (d, J = 8.8 Hz, 1H), 7.23 (q, J =
17.2 Hz, J = 8.0 Hz, 4H), 4.96 (dd, J = 10.8 Hz, J = 2.4 Hz, 1H), 2,77
(dd, J = 16.8 Hz, J = 10.8 Hz, 1H), 2.60 (dd, J = 16.8 Hz, J = 2.8 Hz,
1H), 2.39 (s, 3H), 1.63 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
141.7, 137.2, 136.9, 133.2, 131.7, 128.9, 128.5, 128.0, 127.6, 126.0,
77.2, 70.3, 40.9, 28.5, 24.2, 21.2 ppm; νmax (KBr)/cm−1 3029, 2928,
2362, 1646, 1510, 1454, 1175, 1023, 698; MS (EI) m/z 77, 91, 105,
141, 156, 171, 191, 206, 297, 312; HRMS-ESI (m/z) calcd for
C20H21ClNaO [M + Na]+ 335.1173, found 335.1172.
7.51−7.50 (m, 2H), 7.49−7.45 (m, 3H), 4.67−4.60 (m, 1H), 3.87−
3.77 (m, 2H), 3.18 (dd, J = 16.4 Hz, J = 7.2 Hz, 1H), 2.82 (dd, J = 16.4
Hz, J = 6.8 Hz, 1H), 2.06 (br, 1H), 2.00−1.84 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 167.5, 140.0, 137.7, 130.3, 128.6, 128.1, 122.6,
74.0, 58.8, 38.4, 37.2 ppm; IR νmax (KBr)/cm−1 3469(br), 3061, 2924,
2363, 1750, 1630, 1206, 1054, 697; MS (EI) m/z 77, 89, 115, 150,
178, 202, 252; HRMS-ESI (m/z) calcd for C13H13ClNaO3 [M + Na]+
275.0445, found 275.0444.
(Z)-3-(Chloro(phenyl)methylene)-2,2-dimethyl-5-phenyltetrahy-
drofuran (7aa): yield 74% (110.3 mg); colorless oil; TLC Rf = 0.65
(PE/DCM = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.6
Hz, 2H), 7.43−7.31 (m, 8H), 5.99 (dd, J = 10.8 Hz, J = 2.8 Hz, 1H),
2.81 (dd, J = 16.8 Hz, J = 10.4 Hz, 1H), 2.64 (dd, J = 16.8 Hz, J = 2.8
Hz, 1H), 1.66 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 141.6, 139.9,
133.5, 131.9, 128.5, 128.2, 128.1, 127.7, 127.4, 126.1, 77.4, 70.3, 40.9,
28.5, 24.3 ppm; IR νmax (KBr)/cm−1 3060, 2930, 2363, 1450, 1369,
1023, 697; MS (EI) m/z 77, 91, 105, 115, 129, 142, 157, 177, 192, 283,
298; HRMS-ESI (m/z) calcd for C19H19ClNaO [M + Na]+ 321.1017,
found 321.1013.
(Z)-3-(Chloro(phenyl)methylene)-5-(4-fluorophenyl)-2,2-dime-
thyltetrahydrofuran (7ad): yield 78% (123.2 mg); colorless oil; TLC
Rf = 0.69 (PE/DCM = 4:1, v/v); 1H NMR (400 MHz, CDCl3) δ 7.43
(q, J = 15.6 Hz, J = 8.0 Hz, 4H), 7.37−7.32 (m, 3H), 7.09 (t, J = 8.0
Hz, 2H), 4.96 (dd, J = 10.4 Hz, J = 2.0 Hz, 1H), 2.77 (dd, J = 16.8 Hz,
J = 10.8 Hz, 1H), 2.61 (dd, J = 16.8 Hz, J = 2.4 Hz, 1H), 1.64 (s, 6H);
13C NMR (100 MHz, CDCl3) δ 163.5 (J = 244.1 Hz), 139.8, 137.5 (J
= 3.1 Hz), 133.5, 131.7, 128.3, 128.1, 127.8 (J = 8.1 Hz), 127.5, 115.4
(J = 21.2 Hz), 77.5, 69.7, 41.0, 28.5, 24.3 ppm; 19F NMR (376 MHz,
CDCl3) δ −114.84 ppm; IR νmax (KBr)/cm−1 3058, 2982, 2363, 1605,
1511, 1226, 1082, 965, 698; MS (EI) m/z 77, 109, 123, 142, 157, 177,
192, 266, 301, 316; HRMS-ESI (m/z) calcd for C19H18ClFNaO [M +
Na]+ 339.0922, found 339.0918.
(Z)-5-(4-Bromophenyl)-3-(chloro(phenyl)methylene)-2,2-dime-
thyltetrahydrofuran (7af): yield 71% (133.8 mg); white solid; mp
(Z)-3-(Chloro(4-chlorophenyl)methylene)-2,2-dimethyl-5-phenyl-
tetrahydrofuran (7fa): yield 73% (121.2 mg); white solid; mp 85−87
1
81−83 °C; TLC Rf = 0.61 (PE/DCM = 4:1, v/v); H NMR (400
G
dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
1
°C; TLC Rf = 0.56 (PE/DCM = 4:1, v/v); H NMR (400 MHz,
CDCl3) δ 7.49 (d, J = 7.6 Hz, 2H), 7.45−7.29 (m, 7H), 4.99 (d, J =
10.8 Hz, 1H), 2.80 (dd, J = 16.8 Hz, J = 10.4 Hz, 1H), 2.60 (dd, J =
16.4 Hz, J = 2.0 Hz, 1H), 1.67 (s, 6H); 13C NMR (100 MHz, CDCl3)
δ 141.5, 138.2, 134.2, 133.3, 130.8, 129.6, 128.5, 128.5, 127.8, 126.1,
77.4, 70.3, 40.8, 28.5, 24.3 ppm; IR νmax (KBr)/cm−1 3745, 3360,
2923, 2362, 1646, 1488, 1018, 696; MS (EI) m/z 77, 91, 105, 141,
156, 176, 191, 211, 226, 317, 332; HRMS-ESI (m/z) calcd for
C19H18Cl2NaO [M + Na]+ 355.0627, found 355.0626.
(6) (a) Pinho, P.; Minnaard, A. J.; Feringa, B. L. Org. Lett. 2003, 5,
259−261. (b) Rossiter, L. M.; Slater, M. L.; Giessert, R. E.; Sakwa, S.
A.; Herr, R. J. J. Org. Chem. 2009, 74, 9554−9557.
(7) Khanna, A.; Premachandra, I. D.; Sung, P. D.; Vranken, D. L. Org.
Lett. 2013, 15, 3694−3697.
(8) For selected examples, see: (a) Ney, J. E.; Wolfe, J. P. J. Am.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Spectra data for all products and the crystallographic data of 3ai
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org
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2009, 48, 7224−7226. (b) Hayashi, S.; Yorimitsu, H.; Oshima, K. J.
Am. Chem. Soc. 2009, 131, 2052−2053.
AUTHOR INFORMATION
■
Corresponding Authors
*Fax: (+86) 20-8711-2906. E-mail: cewuwq@scut.edu.cn.
*Fax: (+86) 20-8711-2906. E-mail: jianghf@scut.edu.cn.
Notes
The authors declare no competing financial interest.
(11) Selected recent examples: (a) Xie, X.; Lu, X.; Liu, Y.; Xu, W. J.
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ACKNOWLEDGMENTS
■
We thank the National Basic Research Program of China (973
Program) (2011CB808600), the National Natural Science
Foundation of China (21172076 and 21202046), Guangdong
Natural Science Foundation (10351064101000000 and
S2012040007088), and the Fundamental Research Funds for
the Central Universities (2014ZP0004 and 2014ZZ0046) for
financial support.
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dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX

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(21) The CCDC no. of compound 3ai is 1006530. For more details,
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dx.doi.org/10.1021/jo501606c | J. Org. Chem. XXXX, XXX, XXX−XXX