Synthesis of 2-alkynyltetrahydrofuran derivatives from tetrahydrofuran and alkynyl bromides

Article abstract of DOI:10.1055/s-0033-1338534

An efficient and general method for the synthesis of 2- alkynyltetrahydrofuran was developed. The regioselective functionalization of the C(sp³)-H bond adjacent to an oxygen atom with various alkynyl bromides has been achieved under transition-

Full text of DOI:10.1055/s-0033-1338534

PAPER
▌3137
paper
Synthesis of 2-Alkynyltetrahydrofuran Derivatives from Tetrahydrofuran and
Alkynyl Bromides
Synthesis of 2-Alkynyltetrahydrofuran Derivatives
Yuan Yang,a Hui Huang,a Xiaoyun Zhang,a Weilan Zeng,a Yun Liang*a,b
a
National & Local Joint Engineering Laboratory for New Petro-chemical Materials and Fine Utilization of Resources, Key Laboratory of
Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Hunan Normal University, Changsha, Hunan 410081,
P. R. of China
Fax +86(731)88872533; E-mail: yliang@hunnu.edu.cn
b
Beijing National Laboratory for Molecular Sciences, Beijing 100871, P. R. of China
Received: 24.06.2013; Accepted after revision: 29.08.2013
mediated method for C(sp3)–C(sp) cross-coupling from
Abstract: An efficient and general method for the synthesis of 2-al-
ethynylbenziodoxolones with aliphatic carboxylic acids.9
kynyltetrahydrofuran was developed. The regioselective function-
alization of the C(sp3)–H bond adjacent to an oxygen atom with
various alkynyl bromides has been achieved under transition-metal-
Although these alkynylating agents are useful and inter-
esting, diverse alkynylating agents for the synthesis of al-
free reaction conditions. Sodium fluoride was found, for the first kynes are still in great demand. Herein, we report a
time, to promote the efficient functionalization process remarkably.
Moreover, 1,2-dibromostyrenes were also found to be effective in
this method forming 2-alkenyltetrahydrofurans.
sodium fluoride promoted synthesis of substituted al-
kynes from alkynyl bromides and tetrahydrofuran
(Scheme 1). To the best of our knowledge, this is the first
example of alkynyl bromides serving as radical acceptors.
Key words: 2-alkynyltetrahydrofuran, tetrahydrofuran, alkynyl
bromides, sodium fluoride, free radical
O
O
NaF (6 equiv)
N2, 120 °C
R
Br
+
R
Alkynes are useful building blocks in organic synthesis.1
Alkynes are also basic structural units in many natural
products and bioactive compounds.2 For these reasons,
much attention has been given to the development of effi-
cient and selective methods for the synthesis of various al-
kynes.3–9 Traditionally, alkynes are prepared by the
transition-metal-catalyzed Sonogashira reaction starting
from terminal alkynes, alkyl halides, or aryl halides.3,4
However, high catalyst loading is demanded in some tran-
sition-metal-catalyzed processes resulting in heavy metal
residues in the product, high catalyst cost, and a large
workload during purification. Consequently, the develop-
ment of transition-metal-free methods for the synthesis of
alkynes is significant from an atom-economical and envi-
ronmental point of view. Fuchs and co-workers reported
that the reaction of ethers with acetylenic triflones provid-
ed facile access to substituted alkynes.5 The reaction pro-
ceeds via radical C–H abstraction by strong electrophilic
trifluoromethyl radical and substitution (addition–elimi-
nation). In addition to acetylenic triflones as alkynylating
agent for radical alkynylation reactions, Russell and co-
workers reported radical alkynylation reactions of alkyl-
mercury halides with various alkynes (including alkynyl
sulfones, alkynyl sulfides, alkynyl iodides, and alkynyl
stannanes) for the first time;6 Renaud et al. developed the
radical-mediated alkynylation of alkynyl sulfones with β-
alkylcatecholboranes;7 Landais et al. extended this meth-
od to free-radical three-component carboalkynylation;8
and Li and co-workers successfully developed a radical-
Scheme 1 Synthesis of 2-alkynyltetrahydrofuran derivatives from
tetrahydrofuran and alkynyl bromides
As we have a continued interest in the reaction chemistry
of 1,2-dibromostyrenes,10 the reaction of 1,2-dibromosty-
rene with sulfonamide was tentatively conducted with
tetrahydrofuran as solvent. What is interesting is that
phenylethynyl bromide and 2-(phenylethynyl)tetrahydro-
furan were observed in the final product mixture. Inspired
by this result, the reaction of phenylethynyl bromide with
tetrahydrofuran was selected for optimization of the reac-
tion conditions, and the results are summarized in Table 1.
Firstly, the reaction of phenylethynyl bromide with tetra-
hydrofuran at 100 °C without an additive was conducted,
forming the desired product in 20% isolated yield (entry
1). This result encouraged us to develop an efficient meth-
od to synthesize various 2-alkynyltetrahydrofurans. We
found that the additive played an important role in this re-
action. Thus we screened a variety of additives, such as
cesium carbonate, sodium hydroxide, sodium tert-butox-
ide, and cesium fluoride (entries 2–5). Results indicated
that cesium fluoride is the best additive for the reaction af-
fording the highest yield.11 Sequentially, the catalytic ef-
ficiency of various fluorides such as lithium fluoride,
sodium fluoride, potassium fluoride, and tetrabutylammo-
nium fluoride were tried (entries 6–9), and the highest iso-
lated yield (74%) was obtained with sodium fluoride used
as the additive. When the concentration of substrate in-
creased, the yield of product decreased markedly (entry
10). This result displayed the characteristics of a radical
reaction mechanism. The trace amount of peroxide con-
tained in the solvent tetrahydrofuran might be the radical
SYNTHESIS 2013, 45, 3137–3146
Advanced online publication: 25.09.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338534; Art ID: SS-2013-H0432-OP
© Georg Thieme Verlag Stuttgart · New York

3138
Y. Yang et al.
PAPER
Table 1 Optimization of Reaction Conditionsa
initiator. To test the hypothesis, we used a radical initiator
such as 2,2′-azobis(isobutyronitrile) (AIBN) in the pres-
ence of sodium fluoride, and the 2-alkynyltetrahydrofuran
2a was obtained in 80% yield (entry 11). However, when
radical initiators such as AIBN and di-tert-butyl peroxide
(DTBP) were used in the absence of sodium fluoride, the
product was obtained in lower yields (entries 12 and 13).
These results showed the presence of sodium fluoride
could promote the generation of a radical species. When
2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO, a typical
radical scavenger) was added under the same conditions,
the desired product was not observed (entry 14). Thus,
this radical quenching study also suggested that a radical
intermediate is important in this transformation. Finally,
the amount of sodium fluoride and the reaction tempera-
ture were optimized (entries 15–18). Relatively low yields
were found when the reaction was carried out in room
temperature or 50 °C, and the highest yield of 2a was ob-
tained when six equivalents of sodium fluoride was used
at the temperature of 120 °C. Thus, the optimal reaction
conditions were as follows: 1a (0.3 mmol), THF (6 mL),
and NaF (1.8 mmol), at 120 °C.
O
O
additive (3 equiv)
N2, 100 °C
Br
+
2a
1a
Entry
Additive
Yieldb (%) of 2a
1
–
20
26
25
0
2
Cs2CO3
NaOH
t-BuONa
CsF
3
4
5
57
68
74
51
0
6
KF
7
NaF
8
LiF
9
TBAF
NaF
10c
11d
12
13
14e
15f
16g
17h
18i
52
80
68
53
0
NaF
Once the optimal reaction conditions between phenyl-
ethynyl bromide (1a) and tetrahydrofuran were achieved,
various alkynylating agents 1b–i were investigated as the
starting materials for the synthesis of 2-alkynyltetrahy-
drofurans, and the results are summarized in Scheme 2.
Under the standard reaction conditions, reactions of the
alkynylating agents phenylethynyl iodide (1b), phenyl-
ethynyl chloride (1c), phenylacetylene (1d), trimeth-
yl(phenylethynyl)silane (1e), phenylpropiolic acid (1f),
[(phenylethynyl)sulfonyl]benzene (1g), phenyl(phenyl-
ethynyl)iodonium triflate (1h), and (phenylethynyl)benz-
iodoxolone (1i) were performed in tetrahydrofuran. They
either gave none of the expected product 2a or they gave
2a in only trace amounts, with the exception of 1i which
afforded 2a in 54% yield. Compared with phenylethynyl
bromide (1a), compounds 1b–i were not good alkynylat-
ing agents with tetrahydrofuran under the standard reac-
tion conditions.
DTBP
AIBN
NaF
NaF
26
77
82
85
NaF
NaF
NaF
a Reaction conditions: 1a (0.3 mmol), additive (3 equiv), THF (6 mL),
100 °C, 24 h.
b Isolated yield.
c THF (1 mL).
d AIBN (20 mol%).
e TEMPO (1 equiv).
f 50 °C.
g 120 °C.
h NaF (6 equiv).
i NaF (6 equiv), 120 °C.
O
O
NaF (6 equiv)
X
+
N2, 120 °C, 24 h
2a
1
alkynylating reagent (yield of 2a)
Under the standard reaction conditions, the coupling reac-
tions of various alkynyl bromides with tetrahydrofuran
were then investigated, and the results are summarized in
Table 2. The reaction between alkynyl bromides and tet-
rahydrofuran demonstrated good functional group toler-
ance for substrates. Arylethynyl bromides bearing
electron-withdrawing groups such as F, Cl, Br, CN,
COMe, or electron-donating groups such as OMe, Me, Et,
Pr, pentyl afforded the corresponding 2-alkynyltetrahy-
drofuran in good yields. For example, alkynyl bromides
bearing 4-fluorophenyl or 4-methoxylphenyl groups af-
forded the corresponding products 2b and 2j in 79% and
80% yields, respectively. Similarly, 4-(bromoethynyl)bi-
phenyl and 1-(bromoethynyl)naphthalene efficiently re-
I
(trace)
Cl
(trace)
(0%)
1c
1b
(0%)
(0%)
TMS
1d
1f
1e
O
S
(trace)
COOH
O
1g
1i
O
O
I
(trace)
(54%)
I
TfO
1h
Scheme 2 Phenylethynylation of tetrahydrofuran
Synthesis 2013, 45, 3137–3146
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of 2-Alkynyltetrahydrofuran Derivatives
3139
acted with tetrahydrofuran to afford the corresponding found to be suitable substrates for functionalization of tet-
products in 2o and 2p in 79% and 70% yields, respective- rahydrofuran under the standard conditions. When ali-
ly. Furthermore, heterocyclic 2-(thiophen-2-ylethy- phatic alkynes bearing a hydroxy or ester group were
nyl)tetrahydrofuran (2q) was obtained in 67% yield. The employed as substrates, the reaction proceeded in moder-
results showed that the aryl substituent of ethynyl bro- ate to good yields. In addition, six-membered cyclic ethers
mides did not remarkably affect the reaction. Besides ar- such as tetrahydro-2H-pyran and 1,4-dioxane gave the de-
ylethynyl bromides, the alk-1-ynyl bromides were also sired products 2v,w in moderate yields.
Table 2 Formation of Various 2-Substituted Tetrahydrofurans, a Tetrahydro-2H-pyran and a 1,4-Dioxanea
O
O
NaF (6 equiv)
N2, 120 °C
R
Br
+
R
1
2
Entry
1
Substrate 1
Time (h)
35
Product 2
Yieldb (%)
79
O
2b
F
Br
F
O
Br
Br
Br
2
3
4
5
35
35
35
25
2c
2d
2e
2f
90
74
80
68
Br
Br
O
Br
O
O
Cl
Br
Br
Cl
Br
Br
Cl
Cl
NC
NC
O
6
7
35
24
2g
2h
77
75
Br
O
O
O
Br
Br
O
O
O
8
25
25
40
40
40
2i
75
80
80
76
85
MeO
MeO
MeO
MeO
O
Br
9
2j
O
Br
10
11
12
2k
2l
O
Pr
Br
Pr
O
C5H11
Br
C5H11
2m
Et
Et
O
O
13
14
24
36
2n
2o
71
79
Br
Br
O
Ph
Br
Ph
15
35
2p
70
© Georg Thieme Verlag Stuttgart · New York
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Y. Yang et al.
PAPER
Table 2 Formation of Various 2-Substituted Tetrahydrofurans, a Tetrahydro-2H-pyran and a 1,4-Dioxanea (continued)
O
O
NaF (6 equiv)
N2, 120 °C
R
Br
+
R
1
2
Entry
Substrate 1
Time (h)
Product 2
Yieldb (%)
67
S
16
39
2q
S
O
Br
O
C8H17
Br
C8H17
17
18
29
48
2r
2s
62
58
OH
OH
O
Br
O
Br
19
20
34
38
2t
42
51
HO
HO
O
O
O
Br
O
O
2u
O
O
Br
21
22
40
30
2vc
32
58
O
2wd
Br
a Compound 1 (0.3 mmol), NaF (1.8 mmol), THF (6 mL), 120 °C, N2.
b Isolated yields.
c THF was replaced by 1,4-dioxane.
d THF was replaced by tetrahydro-2H-pyran.
Importantly, as given in Table 3, the synthetic protocol zene was found not to be a suitable substrate and only 18%
could be also applied to the reaction of 1,2-dibromosty- of (Z)-2-styryltetrahydrofuran was obtained.
renes 3 with tetrahydrofuran. Products 4 could be ob-
tained in good yields under the optimal reaction
conditions as given in Table 1. In this case as the product
4 contains two isomers, the investigation of chemoselec-
The reaction has the characteristics of a radical process.
High purity tetrahydrofuran does not react with alkynyl
bromide 1a when heated under a nitrogen atmosphere. In
addition, the addition of TEMPO prevents the reaction
tivity and stereoselectivity of this reaction is necessary.
from occurring. Based on above experimental observa-
The selectivity between 1,2-dibromostyrenes and tetrahy-
tions, a possible mechanism is given in Scheme 3.12 First-
drofuran was evaluated with (Z)-1,2-dibromostyrene and
ly, small amounts of peroxide in tetrahydrofuran serve to
(E)-1,2-dibromostyrene
under
standard
reaction
initiate the process and generate the tetrahydrofuran radi-
cals. Then, a direct radical addition to the alkynyl bromide
forms a bromovinyl radical. Subsequent bromine radical
elimination occurred and generated the final product. The
bromine radical captures the hydrogen atom of tetrahy-
drofuran with the aid of the fluoro anion and the tetrahy-
drofuran radical is regenerated. To further understand this
radical mechanism, we conducted the competition reac-
tion between tetrahydrofuran (1 mL) and tetrahydrofuran-
d8 (1 mL) in Scheme 4. The observed high KH/KD value
(4.0) implies that the rate determining step contains C–H
bond cleavage. Thus, the elimination of the bromine radi-
cal from bromovinyl radical is faster than the abstraction
of the hydrogen atom from tetrahydrofuran.
conditions. When (E)-1,2-dibromostyrene reacted with
tetrahydrofuran, the product 2-(2-bromo-2-phenyl-
vinyl)tetrahydrofuran (4a/4a′ E/Z 2:1) was obtained in
63% isolated yield. When (Z)-1,2-dibromostyrene reacted
with tetrahydrofuran, the product 2-(2-bromo-2-phenylvi-
nyl)tetrahydrofuran (4a/4a′ E/Z 1:10) was obtained in the
same yield. These results showed the reaction between
1,2-dibromostyrene and tetrahydrofuran undergoes a rad-
ical addition–elimination mechanism. The scope and re-
activity of various (Z)-1,2-dibromostyrenes were also
examined under the optimized conditions. The benzene
ring of (Z)-1,2-dibromostyrene bearing either electron-
withdrawing groups such as Cl, Br or electron-donating
groups such as Me or Pr gave the corresponding products
in good isolated yields. However, (Z)-(2-bromovinyl)ben-
Synthesis 2013, 45, 3137–3146
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Synthesis of 2-Alkynyltetrahydrofuran Derivatives
3141
Table 3 Formation of Various 2-Substituted Tetrahydrofuransa
Br
Br
O
NaF (6 equiv)
O
Br
+
N2, 27 h, 120 °C
R
R
4
3
Entry
1
Substrate 3
3a′
Product 4
Yieldb (%)
Ratio
O
Br
O
63
4a/4a′ 2:1
Br
Br
Br
Br
4a
4a
4a'
4a'
O
O
Br
Br
2
3a
63
4a/4a′ 1:10
Br
O
Br
O
3
4
5
6
3b
3c
3d
3e
65
62
63
62
4b/4b′ 1:8
4c/4c′ 1:8
4d/4d′ 1:10
4e/4e′ 1:8
Br
Br
Br
4b
4b'
O
Br
Br
Br
O
Pr
Cl
Br
Pr
Cl
Br
Pr
Br
Br
Br
4c
4c'
O
O
Cl
Br
Br
Br
4d
4d'
4e'
O
O
Br
Br
Br
Br
4e
a Compound 3 (0.3 mmol), NaF (1.8 mmol), THF (6 mL), 120 °C, N2.
b Isolated yields.
R
H
H
H
H
H
O
O
H
O
R
Br
H
O
H
H
H
H
H
Br
NaF(6 equiv)
N2, 120 °C
H
H
D
O
Br
+
H
2a
D
D
D
D
D
O
D
Br
D
D
Br + HF
D
D
O
O
D
D
D
F
R
D
+
2a-d7
75%, 2a/2a-d7 = 4.0:1
Scheme 3 Possible mechanism for the reaction
Scheme 4 Competition reaction between tetrahydrofuran and tetra-
hydrofuran-d8
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3137–3146

3142
Y. Yang et al.
PAPER
(m, 1 H), 2.25–2.20 (m, 1 H), 2.12–2.05 (m, 2 H), 1.98–1.92 (m, 1
H).
13C NMR (125 MHz, CDCl3): δ = 162.4 (d, J = 248.0 Hz), 133.6 (d,
J = 8.25 Hz), 118.8 (d, J = 3.5 Hz), 115.4 (d, J = 22 Hz), 88.7, 83.4,
68.5, 67.9, 33.3, 25.5.
MS (EI): m/z = 191 [M + H]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H10FO: 189.0710; found:
In summary, we have developed a novel sodium fluoride
promoted alkynylation with various alkynyl bromides.
Moreover, this protocol could be extended to construct
C(sp2)–C(sp3) bonds by the reaction between 1,2-dibro-
mostyrenes and tetrahydrofuran. This reaction provides
the efficient synthesis of alkynylation or alkenylation
products, which represents a novel method for the con-
struction of C(sp)–C(sp3) and C(sp2)–C(sp3) bonds. In ad-
dition, fluoride was found, remarkably, to promote the
efficiency of this activation process; this is the first exam-
ple of such an activation by fluoride. This method pro-
vides an alternative method for the selective activation of
the C(sp3)–H bond and their synthetically useful applica-
tions can be expected.
189.0706.
2-[(4-Bromophenyl)ethynyl]tetrahydrofuran (2c)
Pale yellow oil; yield: 68.1 mg (90%).
IR (KBr): 2977, 2954, 2924, 2868, 2223, 1483, 1396, 1330, 1260,
1174, 1051, 1008, 818 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.42 (dd, J = 6.5, 1.5 Hz, 2 H),
7.28 (dd, J = 6.5, 1.5 Hz, 2 H), 4.80–4.77 (m, 1 H), 4.02–3.98 (m, 1
H), 3.87–3.83 (m, 1 H), 2.25–2.19 (m, 1 H), 2.08–2.04 (m, 2 H),
1.98–1.92 (m, 1 H).
1H and 13C NMR spectra were recorded on a standard spectrometer
13C NMR (125 MHz, CDCl3): δ = 133.1, 131.4, 122.4, 121.7, 90.2,
83.4, 68.5, 68.0, 33.3. 25.5.
1
operating at 500 MHz (500 MHz for H; 125 MHz for 13C) at r.t.,
1
respectively. H NMR spectra were recorded in CDCl3 with TMS
used as an internal standard. 13C NMR spectra were recorded in
CDCl3 and the central peak of the solvent was adjusted to δ = 77.00
and used as a reference. IR spectra were recorded on a Thermo
Nicolet Avatar 370 FT-IR spectrophotometer. Mass spectrometry
data were collected on an HRMS instrument or a LR-MS instrument
using ESI or EI ionization. Melting points were measured uncor-
rected. Reactions were monitored by TLC or GC-MS analysis. Col-
umn chromatography (petroleum ether–EtOAc) was performed on
silica gel (200–300 mesh). Unless otherwise noted, all reactions
were run under N2 atmosphere.
MS (EI): m/z = 250, 252 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H1079BrO: 248.9910;
found: 248.9906.
2-[(2-Bromophenyl)ethynyl]tetrahydrofuran (2d)
Pale yellow oil; yield: 55.9 mg (74%).
IR (KBr): 3060, 2977, 2951, 2924, 2868, 2227, 1469, 1430, 1333,
1177, 1051, 755 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.56 (dd, J = 8.0, 1.0 Hz, 1 H),
7.45 (dd, J = 7.5, 1.5 Hz, 1 H), 7.23 (td, J = 7.5, 1.5 Hz, 1 H), 7.14
(td, J = 7.8, 2.0 Hz, 1 H), 4.88–4.86 (m, 1 H), 4.06–4.01 (m, 1 H),
3.90–3.86 (m, 1 H), 2.27–2.21 (m, 1 H), 2.18–2.12 (m, 2 H), 1.98–
1.92 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 133.3, 132.3, 129.4, 126.9, 125.6,
124.9, 93.9, 83.0, 68.5, 67.9, 33.3, 25.3.
Aryl(tetrahydrofuran-2-yl)acetylenes 2; General Procedure
To a Schlenk tube were added alkynyl bromide (0.3 mmol), NaF
(1.8 mmol) and THF (6 mL). The tube was charged with N2 and the
mixture was stirred at 120 °C for the appropriate time. When the re-
action was complete, the mixture was filtered by a crude column
(EtOAc), and evaporated under vacuum. The residue was purified
by column chromatography (silica gel, petroleum ether–EtOAc,
40:1) to provide the desired product.
MS (EI): m/z = 250 and 252 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H1079BrO: 248.9910;
found: 248.9906.
1-Aryl-1-bromo-2-(tetrahydrofuran-2-yl)ethenes 4; General
Procedure
2-[(4-Chlorophenyl)ethynyl]tetrahydrofuran (2e)
To a Schlenk tube were added 1,2-dibromoalk-1-ene (0.3 mmol),
NaF (1.8 mmol) and THF (6 mL). The tube was charged with N2
and the mixture was stirred at 120 °C for the appropriate time.
When the reaction was complete, the mixture was filtered by a crude
column (EtOAc), and evaporated under vacuum. The residue was
purified by column chromatography (silica gel, petroleum ether–
EtOAc, 40:1) to provide the desired product.
Yellow oil; yield: 49.2 mg (80%).
IR (KBr): 2977, 2954, 2927, 2868, 2223, 1489, 1337, 1091, 1051,
828 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.35 (dd, J = 6.5, 2.0 Hz, 2 H),
7.26 (dd, J = 6.5, 2.0 Hz, 2 H), 4.80–4.78 (m, 1 H), 4.02–3.98 (m, 1
H), 3.87–3.83 (m, 1 H), 2.26–2.19 (m, 1 H), 2.11–2.04 (m, 2 H),
1.98–1.91 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 134.2, 132.9, 128.5, 121.2, 90.0,
83.3, 68.4, 67.9, 33.3, 25.5.
MS (EI): m/z = 206 and 208 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H1035ClO: 205.0415;
2-(Phenylethynyl)tetrahydrofuran (2a)5c
Pale yellow oil; yield: 44.3 mg (85%).
1H NMR (500 MHz, CDCl3): δ = 7.44–7.42 (m, 2 H), 7.29–7.28 (m,
3 H), 4.82–4.80 (m, 1 H), 4.03–3.99 (m, 1 H), 3.88–3.83 (m, 1 H),
2.25–2.19 (m, 1 H), 2.12–2.05 (m, 2 H), 1.97–1.91 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 131.6, 128.2, 128.1, 122.7, 89.0,
84.4, 68.5, 67.9, 33.4, 25.4.
found: 205.0411.
HRMS (ESI): m/z [M – H]+ calcd for C12H11O: 171.0804; found:
171.0802.
2-[(2-Bromo-4-chlorophenyl)ethynyl]tetrahydrofuran (2f)
Pale yellow oil; yield: 58.1 mg (68%).
IR (KBr): 3087, 2977, 2947, 2927, 2868, 2227, 1582, 1466, 1376,
1330, 1101, 1051, 818 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.58 (d, J = 2.0 Hz, 1 H), 7.37 (d,
J = 8.0 Hz, 1 H), 7.22 (dd, J = 8.5, 2.5 Hz, 1 H), 4.87–4.85 (m, 1 H),
4.05–4.00 (m, 1 H), 3.90–3.86 (m, 1 H), 2.26–2.21 (m, 1 H), 2.16–
2.11 (m, 2 H), 1.98–1.94 (m, 1 H).
2-[(4-Fluorophenyl)ethynyl]tetrahydrofuran (2b)
Pale yellow oil; yield: 45.4 mg (79%).
IR (KBr): 2980, 2947, 2871, 2227, 1599, 1506, 1237, 1157, 1051,
838 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.42–7.39 (m, 2 H), 6.99 (t,
J = 8.8 Hz, 2 H), 4.80–4.78 (m, 1 H), 4.03–3.98 (m, 1 H), 3.88–3.83
13C NMR (125 MHz, CDCl3): δ = 134.5, 133.9, 132.1, 127.4, 126.0,
123.5, 94.9, 82.0, 68.5, 67.9, 33.2, 25.3.
Synthesis 2013, 45, 3137–3146
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Synthesis of 2-Alkynyltetrahydrofuran Derivatives
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MS (EI): m/z = 284, 286, and 288 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H979Br35ClO: 282.9520;
IR (KBr): 3027, 2980, 2924, 2868, 2230, 1509, 1459, 1337, 1058,
818 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.32 (d, J = 8.0 Hz, 2 H), 7.09 (d,
J = 8.0 Hz, 2 H), 4.81–4.79 (m, 1 H), 4.03–3.99 (m, 1 H), 3.87–3.83
(m, 1 H), 2.33 (s, 3 H), 2.24–2.19 (m, 1 H), 2.10–2.05 (m, 2 H),
1.96–1.92 (m, 1 H).
found: 282.9521.
3-[(Tetrahydrofuran-2-yl)ethynyl]benzonitrile (2g)
Pale yellow oil; yield: 45.6 mg (77%).
13C NMR (125 MHz, CDCl3): δ = 138.3, 131.6, 128.9, 119.7, 88.3,
84.6, 68.6, 67.9, 33.4, 25.5, 21.4.
MS (EI): m/z = 186 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C13H13O: 185.0961; found:
IR (KBr): 3070, 2977, 2951, 2871, 2230, 1592, 1476, 1413, 1333,
1180, 1054, 898, 802, 686 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.70 (t, J = 1.3 Hz, 1 H), 7.64 (dt,
J = 8.0, 1.5 Hz, 1 H), 7.58 (dt, J = 8.0, 1.5 Hz, 1 H), 7.42 (t, J = 8.0
Hz, 1 H), 4.82–4.80 (m, 1 H), 4.03–3.98 (m, 1 H), 3.89–3.85 (m, 1
H), 2.28–2.23 (m, 1 H), 2.11–2.08 (m, 2 H), 1.98–1.95 (m, 1 H).
185.0956.
13C NMR (125 MHz, CDCl3): δ = 135.7, 134.9, 131.4, 129.1, 124.3,
117.9, 112.6, 91.7, 82.0, 68.2, 68.0, 33.2, 25.4.
2-[(4-Propylphenyl)ethynyl]tetrahydrofuran (2l)
Pale yellow oil; yield: 48.9 mg (76%).
MS (EI): m/z = 196 [M – H]+.
HRMS (ESI): m/z [M – H]+ calcd for C13H10NO: 196.0757; found:
IR (KBr): 3027, 2957, 2927, 2864, 2223, 1506, 1456, 1337, 1174,
1051, 838 cm–1.
196.0754.
1H NMR (500 MHz, CDCl3): δ = 7.34 (d, J = 8.0 Hz, 2 H), 7.09 (d,
J = 8.5 Hz, 2 H), 4.81–4.79 (m, 1 H), 4.01–3.98 (m, 1 H), 3.87–3.82
(m, 1 H), 2.56 (t, J = 7.8 Hz, 2 H), 2.22–2.19 (m, 1 H), 2.10–2.05
(m, 2 H), 1.94–1.91 (m, 1 H), 1.65–1.59 (m, 2 H), 0.91 (t, J = 7.3
Hz, 3 H).
1-{4-[(Tetrahydrofuran-2-yl)ethynyl]phenyl}ethanone (2h)
Pale yellow oil; yield: 48.4 mg (75%).
IR (KBr): 2977, 2951, 2924, 2871, 2220, 1682, 1602, 1406, 1360,
1263, 1177, 1058, 842 cm–1.
13C NMR (125 MHz, CDCl3): δ = 143.0, 131.5, 128.3, 119.9, 88.3,
1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.5 Hz, 2 H), 7.50 (d,
J = 8.5 Hz, 2 H), 4.84–4.81 (m, 1 H), 4.03–3.99 (m, 1 H), 3.89–3.85
(m, 1 H), 2.58 (s, 3 H), 2.27–2.23 (m, 1 H), 2.13–2.06 (m, 2 H),
1.99–1.94 (m, 1 H).
84.6, 68.6, 67.8, 37.8, 33.4, 25.4, 24.2, 13.7.
MS (EI): m/z = 214 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C15H17O: 213.1274; found:
213.1271.
13C NMR (125 MHz, CDCl3): δ = 197.2, 136.2, 131.7, 128.0, 127.6,
92.5, 83.6, 68.4, 68.0, 33.2, 26.5, 25.4.
MS (EI): m/z = 214 [M]+.
2-[(4-Pentylphenyl)ethynyl]tetrahydrofuran (2m)
Pale yellow oil; yield: 61.7 mg (85%).
IR (KBr): 2957, 2927, 2854, 2220, 1506, 1456, 1340, 1054, 835
cm–1.
HRMS (ESI): m/z [M – H]+ calcd for C14H13O2: 213.0910; found:
213.0907.
1H NMR (500 MHz, CDCl3): δ = 7.34 (d, J = 8.0 Hz, 2 H), 7.09 (d,
J = 8.0 Hz, 2 H), 4.81–4.79 (m, 1 H), 4.02–3.98 (m, 1 H), 3.86–3.82
(m, 1 H), 2.57 (t, J = 7.8 Hz, 2 H), 2.24–2.18 (m, 1 H), 2.11–2.04
(m, 2 H), 1.96–1.89 (m, 1 H), 1.61–1.55 (m, 2 H), 1.33–1.28 (m, 4
H), 0.88 (t, J = 7.0 Hz, 3 H).
Methyl 4-[(Tetrahydrofuran-2-yl)ethynyl]benzoate (2i)
Pale yellow solid; yield: 52.0 mg (75%); mp 44.7–45.8 °C.
IR (KBr): 2951, 2871, 2227, 1722, 1606, 1436, 1277, 1180, 1107,
1054, 862, 765, 699 cm–1.
13C NMR (125 MHz, CDCl3): δ = 143.3, 131.5, 128.2, 119.9, 88.3,
84.6, 68.6, 67.8, 35.8, 33.4, 31.4, 30.8, 25.4, 22.4, 13.9.
MS (EI): m/z = 242 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C17H21O: 241.1587; found:
1H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 8.5 Hz, 2 H), 7.48 (d,
J = 8.5 Hz, 2 H), 4.84–4.81 (m, 1 H), 4.03–3.99 (m, 1 H), 3.91 (s, 3
H), 3.89–3.85 (m, 1 H), 2.27–2.21 (m, 1 H), 2.12–2.07 (m, 2 H),
1.99–1.94 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 166.4, 131.6, 129.5, 129.3, 127.5,
92.2, 83.7, 68.4, 68.0, 52.1, 33.3, 25.5.
241.1584.
MS (EI): m/z = 230 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C14H13O3: 229.0859; found:
2-[(2-Ethylphenyl)ethynyl]tetrahydrofuran (2n)
Pale yellow oil; yield: 42.9 mg (71%).
IR (KBr): 3060, 2967, 2931, 2871, 2223, 1483, 1453, 1337, 1054,
755 cm–1.
229.0862.
1H NMR (500 MHz, CDCl3): δ = 7.40 (dd, J = 7.5, 1.0 Hz, 1 H),
7.23 (td, J = 7.5, 1.5 Hz, 1 H), 7.18 (dd, J = 7.5, 1.0 Hz, 1 H), 7.11
(td, J = 7.5, 1.5 Hz, 1 H), 4.87–4.85 (m, 1 H), 4.03–3.99 (m, 1 H),
3.89–3.85 (m, 1 H), 2.81–2.76 (m, 2 H), 2.24–2.19 (m, 1 H), 2.12–
2.07 (m, 2 H), 1.96–1.93 (m, 1 H), 1.24 (t, J = 7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 146.2, 132.3, 128.4, 127.8, 125.5,
121.8, 92.5, 83.1, 68.7, 67.7, 33.5, 27.6, 25.3, 14.7.
2-[(4-Methoxyphenyl)ethynyl]tetrahydrofuran (2j)
Pale yellow oil; yield: 48.7 mg (80%).
IR (KBr): 2954, 2931, 2871, 2838, 2220, 1606, 1506, 1290, 1250,
1174, 1051, 832 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.36 (d, J = 9.0 Hz, 2 H), 6.81 (d,
J = 8.5 Hz, 2 H), 4.80–4.78 (m, 1 H), 4.02–3.98 (m, 1 H), 3.86–3.82
(m, 1 H), 3.78 (s, 3 H), 2.23–2.18 (m, 1 H), 2.11–2.03 (m, 2 H),
1.96–1.91 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 159.5, 133.1, 114.8, 113.7, 87.5,
84.3, 68.6, 67.8, 55.1, 33.4, 25.4.
MS (EI): m/z = 202 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C13H13O2: 201.0910; found:
MS (EI): m/z = 200 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C14H15O: 199.1117; found:
199.1119.
2-(Biphenyl-4-ylethynyl)tetrahydrofuran (2o)
Pale yellow solid; yield: 59.1 mg (79%); mp 50.2–51.4 °C.
201.0914.
IR (KBr): 3057, 3030, 2927, 2871, 2220, 1486, 1333, 1170, 1051,
842, 762, 696 cm–1.
2-(p-Tolylethynyl)tetrahydrofuran (2k)
Pale yellow oil; yield: 45.1 mg (80%).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3137–3146

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Y. Yang et al.
PAPER
1H NMR (500 MHz, CDCl3): δ = 7.57 (d, J = 7.0 Hz, 2 H), 7.53–
7.48 (m, 4 H), 7.42 (t, J = 7.8 Hz, 2 H), 7.34 (t, J = 7.3 Hz, 1 H),
4.84–4.82 (m, 1 H), 4.04–4.00 (m, 1 H), 3.88–3.84 (m, 1 H), 2.26–
2.20 (m, 1 H), 2.12–2.07 (m, 2 H), 1.98–1.92 (m, 1 H).
MS (EI): m/z = 194 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C12H17O2: 193.1223; found:
193.1224.
13C NMR (125 MHz, CDCl3): δ = 140.9, 140.3, 132.1, 128.8, 127.5,
126.9, 126.8, 121.7, 89.7, 84.3, 68.6, 67.9, 33.4, 25.5.
4-(Tetrahydrofuran-2-yl)but-3-yn-2-ol (2t)
Pale yellow oil; yield: 17.7 mg (42%).
MS (EI): m/z = 248 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C18H15O: 247.1117; found:
IR (KBr): 3399, 2980, 2927, 2871, 2227, 1456, 1327, 1144, 1054
cm–1.
1H NMR (500 MHz, CDCl3): δ = 4.63–4.60 (m, 1 H), 4.58–4.54 (m,
1 H), 3.97–3.92 (m, 1 H), 3.83–3.79 (m, 1 H), 2.28 (s, 1 H), 2.19–
2.12 (m, 1 H), 2.06–1.89 (m, 3 H), 1.44 (d, J = 7.0 Hz, 3 H).
247.1118.
2-(Naphthalen-1-ylethynyl)tetrahydrofuran (2p)
Pale yellow oil; yield: 46.5 mg (70%).
13C NMR (125 MHz, CDCl3): δ = 86.5, 83.6, 68.0, 67.8, 58.2, 33.2,
IR (KBr): 3057, 2980, 2947, 2927, 2871, 2223, 1586, 1503, 1459,
1396, 1330, 1180, 1051, 802, 775 cm–1.
25.3, 24.2.
MS (EI): m/z = 139 [M – H]+.
HRMS (ESI): m/z [M – H]+ [M + Na]+ calcd for C8H12O2Na:
163.0730; found: 163.0729.
1H NMR (500 MHz, CDCl3): δ = 8.30 (d, J = 8.5 Hz, 1 H), 7.82–
7.78 (m, 2 H), 7.66 (dd, J = 7.0, 0.5 Hz, 1 H), 7.55 (td, J = 7.5, 1.0
Hz, 1 H), 7.49 (td, J = 7.5, 1.0 Hz, 1 H), 7.40–7.37 (m, 1 H), 4.97–
4.95 (m, 1 H), 4.09–4.05 (m, 1 H), 3.92–3.88 (m, 1 H), 2.30–2.27
(m, 1 H), 2.20–2.13 (m, 2 H), 1.97–1.95 (m, 1 H).
4-(Tetrahydrofuran-2-yl)but-3-yn-2-yl Benzoate (2u)
Pale yellow oil; yield: 37.6 mg (51%).
13C NMR (125 MHz, CDCl3): δ = 133.2, 133.0, 130.4, 128.7, 128.1,
126.6, 126.3, 126.1, 125.1, 120.4, 94.1, 82.5, 68.7, 67.9, 33.6, 25.5.
IR (KBr): 3063, 2987, 2934, 2874, 2246, 1718, 1599, 1453, 1313,
1267, 1111, 1048, 712, 686 cm–1.
MS (EI): m/z = 222 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C16H13O: 221.0961; found:
1H NMR (500 MHz, CDCl3): δ = 8.07–8.05 (m, 2 H), 7.58–7.54 (m,
1 H), 7.44 (t, J = 7.8 Hz, 2 H), 5.76–5.72 (m, 1 H), 4.63–4.61 (m, 1
H), 3.97–3.91 (m, 1 H), 3.82–3.77 (m, 1 H), 2.17–2.11 (m, 1 H),
1.99–1.95 (m, 2 H), 1.91–1.88 (m, 1 H), 1.61 (d, J = 7.0 Hz, 3 H).
221.0959.
13C NMR (125 MHz, CDCl3): δ = 165.3, 133.0, 129.9, 129.7, 128.3,
84.8, 82.8, 67.9, 67.8, 60.9, 33.1, 25.3, 21.4.
2-(Thiophen-2-ylethynyl)tetrahydrofuran (2q)
Red-brown oil; yield: 35.8 mg (67%).
IR (KBr): 3097, 2977, 2951, 2871, 2220, 1519, 1456, 1423, 1356,
1330, 1194, 1048, 915, 852, 832, 702 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.22 (dd, J = 5.0, 1.0 Hz, 1 H),
7.19 (dd, J = 3.5, 1.0 Hz, 1 H), 6.94 (t, J = 6.8 Hz, 1 H), 4.83–4.80
(m, 1 H), 4.01–3.97 (m, 1 H), 3.87–3.83 (m, 1 H), 2.24–2.19 (m, 1
H), 2.11–2.06 (m, 2 H), 1.97–1.91 (m, 1 H).
MS (EI): m/z = 244 [M]+.
HRMS (ESI): m/z [M – H]+ calcd for C15H15O3: 243.1016; found:
243.1018.
2-(Phenylethynyl)-1,4-dioxane (2v)5c
Pale yellow oil; yield: 18.1 mg (32%).
13C NMR (125 MHz, CDCl3): δ = 132.1, 127.0, 126.8, 122.7, 92.9,
77.7, 68.6, 67.9, 33.2, 25.4.
1H NMR (500 MHz, CDCl3): δ = 7.46–7.44 (m, 2 H), 7.34–7.29 (m,
3 H), 4.58–4.56 (m, 1 H), 3.95–3.92 (m, 2 H), 3.75–3.67 (m, 4 H).
MS (EI): m/z = 178 [M]+.
13C NMR (125 MHz, CDCl3): δ = 131.8, 128.7, 128.2, 122.0, 86.5,
HRMS (ESI): m/z [M – H]+ calcd for C10H9OS: 177.0369; found:
177.0364.
84.3, 70.4, 66.43, 66.36, 65.8.
HRMS (ESI): m/z [M – H]+ calcd for C12H11O2: 187.0754; found:
187.0751.
2-(Dec-1-ynyl)tetrahydrofuran (2r)
2-(Phenylethynyl)tetrahydro-2H-pyran (2w)5c
Pale yellow oil; yield: 32.6 mg (58%).
Pale yellow oil; yield: 38.8 mg (62%).
IR (KBr): 2927, 2851, 2230, 1456, 1330, 1184, 1051 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.39–7.37 (m, 2 H), 7.23–7.21 (m,
3 H), 4.45–4.42 (m, 1 H), 4.00–3.96 (m, 1 H), 3.54–3.49 (m, 1 H),
1.87–1.81 (m, 2 H), 1.75–1.69 (m, 1 H), 1.57–1.49 (m, 3 H).
1H NMR (500 MHz, CDCl3): δ = 4.57–4.54 (m, 1 H), 3.96–3.92 (m,
1 H), 3.80–3.76 (m, 1 H), 2.19 (t, J = 7.3 Hz, 2 H), 2.14–2.10 (m, 1
H), 2.04–1.99 (m, 1 H), 1.95–1.87 (m, 2 H), 1.52–1.47 (m, 2 H),
1.39–1.35 (m, 2 H), 1.30–1.26 (m, 8 H), 0.88 (t, J = 7.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 131.7, 128.24, 128.17, 122.7,
13C NMR (125 MHz, CDCl3): δ = 85.2, 79.9, 68.4, 67.6, 33.5, 31.8,
29.1, 29.0, 28.8, 28.6, 25.4, 22.6, 18.7, 14.0.
88.1, 85.2, 67.4, 66.6, 32.2, 25.7, 21.8.
HRMS (ESI): m/z [M – H]+ calcd for C13H13O: 185.0961; found:
MS (EI): m/z = 207 [M – H]+.
185.0957.
HRMS (ESI): m/z [M – H]+ calcd for C14H23O: 207.1743; found:
207.1747.
(E)-2-(2-Bromo-2-phenylvinyl)tetrahydrofuran (4a) and (Z)-2-
(2-Bromo-2-phenylvinyl)tetrahydrofuran (4a′) (2:1)
Pale yellow oil; yield: 48.1 mg (63%).
1H NMR (500 MHz, CDCl3): δ = 7.54 (dd, J = 8.5, 2.0 Hz, 1 H),
7.40 (dd, J = 8.5, 1.5 Hz, 2 H), 7.36–7.29 (m, 4.5 H), 6.34 (d, J = 7.0
Hz, 0.5 H), 6.21 (d, J = 9.5 Hz, 1 H), 4.82–4.78 (m, 0.5 H), 4.24–
4.19 (m, 1 H), 3.97–3.93 (m, 0.5 H), 3.91–3.87 (m, 1 H), 3.86–3.82
(m, 0.5 H), 3.73–3.69 (m, 1 H), 2.34–2.28 (m, 0.5 H), 2.03–1.93 (m,
3 H), 1.86–1.81 (m, 1 H), 1.72–1.66 (m, 1.5 H).
1-[(Tetrahydrofuran-2-yl)ethynyl]cyclohexanol (2s)
Pale yellow oil; yield: 33.7 mg (58%).
IR (KBr): 3372, 2931, 2858, 2233, 1449, 1340, 1184, 1054, 968
cm–1.
1H NMR (500 MHz, CDCl3): δ = 4.64–4.62 (m, 1 H), 3.97–3.92 (m,
1 H), 3.83–3.79 (m, 1 H), 2.27 (s, 1 H), 2.18–2.13 (m, 1 H), 2.06–
1.87 (m, 5 H), 1.69–1.67 (m, 2 H), 1.59–1.51 (m, 4 H), 1.26–1.23
(m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 139.1, 138.1, 134.7, 132.8, 129.0,
128.8, 128.7, 128.2, 128.1, 127.5, 125.4, 124.4, 79.3, 77.2, 68.3,
68.0, 32.3, 31.7, 26.1, 26.0.
13C NMR (125 MHz, CDCl3): δ = 88.2, 83.9, 68.4, 68.1, 67.6, 39.8,
33.4, 25.2, 25.1, 23.3.
Synthesis 2013, 45, 3137–3146
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Alkynyltetrahydrofuran Derivatives
3145
HRMS (ESI): m/z [M + H]+ calcd for C12H1479BrO: 253.0228;
found: 253.0223.
HRMS (ESI): m/z [M – H]+ calcd for C12H11O (2a): 171.0804;
found: 171.0802, m/z [M + H]+ calcd for C12H6D7O (2a-d7):
180.1400; found: 180.1404.
(E)-2-(2-Bromo-2-p-tolylvinyl)tetrahydrofuran (4b) and (Z)-2-
(2-Bromo-2-p-tolylvinyl)tetrahydrofuran (4b′) (1:8)
Pale yellow oil; yield: 52.1 mg (65%).
(Z)-2-Styryltetrahydrofuran12b
Pale yellow oil; yield: 18 mg (35%).
1H NMR (500 MHz, CDCl3): δ = 7.43 (d, J = 8.0 Hz, 2 H), 7.13 (d,
J = 8.0 Hz, 2 H), 6.29 (d, J = 7.0 Hz, 1 H), 6.18 (d, J = 9.5 Hz, 0.12
H) (4b), 4.81–4.77 (m, 1 H), 3.97–3.92 (m, 1 H), 3.86–3.81 (m, 1
H), 2.34 (s, 3 H), 2.32–2.27 (m, 1 H), 1.99–1.95 (m, 2 H), 1.71–1.66
(m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 138.7, 136.4, 131.9, 128.9, 127.4,
125.6, 79.4, 68.2, 31.7, 26.0, 21.0.
1H NMR (500 MHz, CDCl3): δ = 7.35–7.26 (m, 4 H), 7.25–7.23 (m,
1 H), 6.59 (d, J = 11.5 Hz, 1 H), 5.71 (dd, J = 12.0, 9.0 Hz, 1 H),
4.69–4.65 (m, 1 H), 3.98–3.93 (m, 1 H), 3.80–3.76 (m, 1 H), 2.14–
2.11 (m, 1 H), 2.02–1.91 (m, 2 H), 1.72–1.65 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 136.7, 132.9, 131.4, 128.8, 128.1,
127.1, 75.0, 68.0, 32.9, 26.4.
HRMS (ESI): m/z [M]+ calcd for C12H14O: 174.1045; found:
174.1037.
HRMS (ESI): m/z [M + H]+ calcd for C13H1679BrO: 267.0379;
found: 267.0381.
(E)-2-Styryltetrahydrofuran12b
Pale yellow oil; yield: 15 mg (29%).
1H NMR (500 MHz, CDCl3): δ = 7.39–7.37 (m, 2 H), 7.30 (t,
J = 7.5 Hz, 2 H), 7.24–7.21 (m, 1 H), 6.58 (d, J = 16.0 Hz, 1 H),
6.21 (dd, J = 16.0, 7.0 Hz, 1 H), 4.50–4.45 (m, 1 H), 3.99–3.95 (m,
1 H), 3.86–3.82 (m, 1 H), 2.16–2.10 (m, 1 H), 2.01–1.92 (m, 2 H),
1.75–1.68 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 136.8, 130.5, 130.4, 128.5, 127.5,
126.4, 79.6, 68.2, 32.4, 25.9.
HRMS (ESI): m/z [M]+ calcd for C12H14O: 174.1045; found:
(E)-2-[2-Bromo-2-(4-propylphenyl)vinyl]tetrahydrofuran (4c)
and (Z)-2-[2-Bromo-2-(4-propylphenyl)vinyl]tetrahydrofuran
(4c′) (1:8)
Pale yellow oil; yield: 55.1 mg (62%).
1H NMR (500 MHz, CDCl3): δ = 7.46 (d, J = 8.0 Hz, 2 H), 7.13 (d,
J = 8.0 Hz, 2 H), 6.31 (d, J = 7.0 Hz, 1 H), 6.18 (d, J = 9.5 Hz, 0.12
H) (4c), 4.82–4.77 (m, 1 H), 3.97–3.92 (m, 1 H), 3.85–3.81 (m, 1
H), 2.58 (t, J = 7.8 Hz, 2 H), 2.33–2.27 (m, 1 H), 1.99–1.95 (m, 2
H), 1.71–1.67 (m, 1 H), 1.65–1.60 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3
H).
13C NMR (125 MHz, CDCl3): δ = 143.5, 136.5, 131.9, 128.3, 127.4,
174.1037.
125.6, 79.4, 68.2, 37.6, 31.7, 26.0, 24.3, 13.7.
HRMS (ESI): m/z [M + H]+ calcd for C15H2079BrO: 295.0692;
found: 295.0697.
Acknowledgment
We thank the Natural Science Foundation of China (21072054),
New Teachers’ Fund for Doctor Stations, Ministry of Education of
China (20094306120003), Training Program Foundation for the
Young Talents by Hunan Normal University of China (ET21003),
Hunan Provincial Natural Science Foundation of China (12JJ2009),
Scientific Research Fund of Hunan Provincial Education Depart-
ment (12A095), and Aid Program for Science and Technology In-
novative Research Team in Higher Educational Institutions of
Hunan Province for financial support.
(E)-2-[2-Bromo-2-(4-chlorophenyl)vinyl]tetrahydrofuran (4d)
and (Z)-2-[2-Bromo-2-(4-chlorophenyl)vinyl]tetrahydrofuran
(4d′) (1:8)
Pale yellow oil; yield: 54.2 mg (63%).
1H NMR (500 MHz, CDCl3): δ = 7.47 (d, J = 8.5 Hz, 2 H), 7.09 (d,
J = 8.5 Hz, 2 H), 6.33 (d, J = 7.0 Hz, 1 H), 6.22 (d, J = 9.5 Hz, 0.13
H) (4d), 4.80–4.76 (m, 1 H), 3.97–3.93 (m, 1 H), 3.86–3.82 (m, 1
H), 2.34–2.28 (m, 1 H), 2.01–1.96 (m, 2 H), 1.72–1.66 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 137.6, 134.6, 133.4, 128.7, 128.3,
124.0, 79.3, 68.3, 31.6, 26.0.
HRMS (ESI): m/z [M + H]+ calcd for C12H1379Br35ClO: 286.9833;
found: 286.9837.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
(E)-2-[2-Bromo-2-(4-bromophenyl)vinyl]tetrahydrofuran (4e)
and (Z)-2-[2-Bromo-2-(4-bromophenyl)vinyl]tetrahydrofuran
(4e′) (1:10)
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