Visible-Light-Induced Alkynylation of α-C–H Bonds of Ethers with Alkynyl Bromides without External Photocatalyst

Article abstract of DOI:10.1002/ejoc.201900872

A direct alkynylation of C(sp³)–H bonds adjacent to an oxygen atom of ethers under visible light irradiation was developed in the absence of an external photocatalyst. The reaction of ethers and alkynyl bromides underwent smoothly to generate the corresponding products in good yields with excellent functional-group tolerance. Initial mechanistic experimental results indicated that the reaction may involve a free radical pathway.

Full text of DOI:10.1002/ejoc.201900872

A Journal of
Accepted Article
Title: Visible-Light-Induced Alkynylation of α-C–H Bonds of Ethers with
Alkynyl Bromides without External Photocatalyst
Authors: Xiao Fei Xie, Jie Liu, Lei Wang, and Min Wang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900872
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900872
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10.1002/ejoc.201900872
European Journal of Organic Chemistry
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Visible-Light-Induced Alkynylation of α-C–H Bonds of Ethers with
Alkynyl Bromides without External Photocatalyst
Xiaofei Xie,[a] Jie Liu,*[a] Lei Wang,[a,b] and Min Wang*[a]
Abstract: A direct alkynylation of C(sp3)–H bonds adjacent to an
at the same time reported the functionalization of the C(sp3)–H
oxygen atom of ethers under visible light irradiation was developed
in the absence of an external photocatalyst. The reaction of ethers
and alkynyl bromides underwent smoothly to generate the
corresponding products in good yields with excellent functional-
group tolerance. Initial mechanistic experimental results indicated
that the reaction may involve a free radical pathway.
bond adjacent to an oxygen atom of ethers with various alkynyl
bromides (Scheme 2c).[6] However, harsh reaction conditions,
the use of metal, overstoichiometric amounts of oxidants or high
reaction temperature are required in the most cases. It is
desirable to achieve alkynylation of ethers under mild reaction
conditions.
Introduction
α-Substituted ethers are not only useful building blocks in
organic synthesis but also one of the most common structural
motifs spread across synthetic pharmaceuticals (Scheme 1),[1]
more than 20% of the top 200 small-molecule pharmaceuticals
containing at least one α-substituted ether moiety.[1a] Traditional
methods for the functionalization of ethers require multi-steps.[2]
Selective and direct C(sp3)–H functionalization of ethers, which
can eliminate the pre-functionalization step, has attracted
tremendous interest since the pioneering studies by Li,[3] and
provided a straightforward approach to access multiple α-
substituted ether analogues, such as α-arylated ethers,[4] α-
tetrahydrofuranyl ethers,[5] α-alkynyl ethers,[6] and so on. In
particular, direct C(sp3)–H alkynylation of ethers receives
considerable attention, as α-alkynyl ethers are potential
structural motifs of bioactive molecules.[1c] In 2014, Liu
developed a synthetic strategy to produce diverse α-alkynyl
ethers using readily available trityl ion (Scheme 2a).[7] Yu
developed an efficient direct alkynylation of ethers with
ethynylbenziodoxolones (Scheme 2b).[8] Wang and Liang almost
Scheme 2 Direct α-C(sp3)–H alkynylation of ethers.
Visible-light-mediated reaction, which is associated with
mild conditions, has been extensively studied and has become a
powerful tool in organic synthesis, especially since MacMillan
and coworker’s an elegant work had been reported.[9] All
achievements in photoreactions demonstrated the combined
effectiveness of employing visible light to facilitate organic
reactions. Recently, visible-light-induced C−H functionalization
has emerged as one of the most active research topics in
sustainable organic synthesis.[10] These processes are
associated with low energy consumption, concise route and mild
conditions. Along this line, C–H fluorinations,[11] arylations,[12]
and allylations[13] have been reported recently. Some
photoreactions require photosensitizers,[14] such as organic dyes
or metal complexes while others can proceed without additional
photosensitizers.[15] Being inspired by these work and with our
Scheme 1 Representative bioactive molecules with α-functionalized ethers.
previous
experience
of
visible-light-induced
organic
transformations in the absence of an external photosensitizer,[16]
we herein report a visible-light-induced α-position C–H activation
and alkynylation of ethers with alkynyl bromides to generate the
corresponding α-alkynyl ethers in good yields at room
temperature with broad substrate scope in the absence of any
external photocatalyst (Scheme 2d).
[a]
[b]
X. Xie, Dr. J. Liu, Prof. M. Wang, Prof. Dr. L. Wang
Department of Chemistry, Huaibei Normal University
Huaibei, Anhui 235000, P. R. China
E-mail: jieliu_1024@163.com, wangmin204@chnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
Shanghai 200032, P. R. China
Supporting information for this article is given via a link at the end of
the document.
Results and Discussion
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10.1002/ejoc.201900872
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Our investigations were started with a model reaction of
tetrahydrofuran (1a) and phenylethynyl bromide (2a), and the
results were summarized in Table 1. When the model reaction
was initially performed with 1.0 equivalent of LiOtBu under the
irradiation of 3 W blue LED (420–425 nm) in air atmosphere at
room temperature for 12
photoredox catalyst,
h
the
without the addition of any
desired product 2-
(phenylethynyl)tetrahydrofuran (3a) was obtained in 25% yield
(Table 1, entry 1). In the presence of KOtBu, only trace amount
3a was observed (Table 1, entry 2). Subsequently, a number of
other bases were screened and presented in entries 3–10 of
Table 1. Gratifyingly, the use of KF offered the target product 3a
in 83% yield (Table 1, entry 8), making it the most effective base
which was utilized for further investigation.
Table 1.Optimization of the reaction conditions[a]
Entry
1
Base
LiOtBu
KOtBu
K3PO4
NaOAc
KOAc
KPF6
NaF
Light source
Yield (%)[b]
25
420
420
420
420
420
420
420
420
420
420
380
395
410
410
450
420
420
420
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
425 nm
425 nm
425 nm
425 nm
425 nm
425 nm
425 nm
425 nm
425 nm
425 nm
385 nm
405 nm
415 nm
420 nm
455 nm
425 nm
425 nm
2
Trace
63
3
4
48
5
67
6
62
7
73
8
KF
83
9
K2CO3
KHCO3
KF
45
10
11
12
13
14
15
16
17
18
19
56
51
KF
52
KF
70
Scheme 3 The scope of substrates [reaction conditions: alkynyl bromide
(2, 0.20 mmol), ether (1, 2.0 mL), KF (1.0 equiv), blue LED (420–425
nm, 3 W) at room temperature for 12 h under air atmosphere;
isolated yield of the product after column chromatography].
KF
73
KF
NR
70[c]
KF
d]
81[
KF
was observed under blue LED irradiation with the wavelength of
450–455 nm (Table 1, entry 15). Extensive screening other
parameters revealed that the reaction time affected the reaction,
and the product yield was decreased for either 8 h or 16 h
(Table 1, entries 16 and 17). Finally, control experiments
conducted under the absence of either a base or LED (entries
18 and 19) pointed to complete inhibition of the reactivity.
_
425 nm
0
_
KF
0
[a] Reaction conditions: phenylethynyl bromide (2a
,
0.20 mmol),
tetrahydrofuran (1a, 2.0 mL, as well as solvent), base (1.0 equiv.),
under the LED irradiation at room temperature for 12 h. [b] Isolated
yield. [c] For 8 h. [d] For 16 h. NR = no reaction.
After establishment of the optimal reaction condition, the
generality and limitation of this method were examined, as
shown in Scheme 3. In the beginning, reactions of
tetrahydrofuran (1a) with various alkynyl bromides 2 were
investigated. Different electron-donating groups and electron-
withdrawing groups on the para-position of the phenyl rings in
alkynyl bromides 2 were well tolerated, and the corresponding
products (α-alkynyl ethers, 3b–3g) were obtained in 57–68%
yields. It should be noted that substrate 2h with a stronger
Encouraged by the results, the reactions were examined
with respect to the wavelength of the light source (Table 1,
entries 11–15). It was found that the desired product 3a was
obtained in comparable yields with the irradiation of LED at 380–
385 and 395–405 nm (Table 1, entries 11 and 12). Other light
sources including blue LED 410–415 nm and 410–420 nm was
also examined, the desired product 3a were obtained with
slightly less efficiency (Table 1, entries 13 and 14). No product
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10.1002/ejoc.201900872
European Journal of Organic Chemistry
FULL PAPER
electron-donating substituent (MeO), and substrates 2i and 2g
with a stronger electron-withdrawing substituent (CF3 and CN)
on the phenyl rings, proved to be suitable substrates for the
present reactions, generating the corresponding products in
55%, 64%, and 71% yield, respectively. Halogens including F, Cl,
and Br attached on the substrates 2 reacted well with THF,
giving the anticipated products (3k–3m) in 75–78% yields. The
substrates 2n and 2o with a substituted group (Me and Cl) on
the meta-position of the phenyl rings underwent the reactions
with THF smoothly to afford the corresponding products 3n and
3o in 65% and 74% yields, respectively. No significant steric
effect was observed during the reaction between 2p–2r with a
group on the ortho-position of the phenyl rings and THF, and the
alkynylated products 3p–3r were isolated in 62%, 72% and 55%
yields, respectively. However, the reactions of 2-
(bromoethynyl)pyridine and 2-(bromoethynyl)thiophene with THF
failed under the standard reaction conditions.
light (blue LED, 420−425 nm) irradiation to generate alkynyl
radical (I) and Br radical, which was further confirmed by the
formation of a by-product 4-(2,2-dibromovinyl)benzonitrile (5)
from the intermediate (III), which was derived from the addition
reaction of Br radical to 2j. Subsequently, the formed Br radical
reacted with tetrahydrofuran (1a) via a -position C(sp3)−H bond
cleavage of 1a to generate the tetrahydrofuran radical (II), which
underwent a cross-coupling with alkynyl radical (I) to afford the
final product 3j along with the generation of HBr, which reacted
with KF to generate a week acid HF (Path a). On the other hand,
tetrahydrofuran radical (II) reacted with 2j to form a radical (IV),
followed by Br radical elimination to produce the final product 3j
(Path b). However, the exact reaction mechanism remained
unclearuntil now, and further effort on the reaction mechanism is
underway in our laboratory.
We next turned our attention to investigate the scope of
ethers. Various ethers, including 1,3-dioxolane, tetrahydro-2H- Conclusions
pyran and 1,4-dioxane, participated in the alkynylation with a
An efficient and eco-friendly methodology for the synthesis of α-
slightly less activity as compared with the reaction of THF. It
should be noted that 2-methyltetrahydrofuran was an excellent
candidate, delivering the expected products (3w and 3x) in high
yields (89%, and 91% yields, respectively). An open-chain
aliphatic ether 1,2-dimethoxyethane reacted with phenylethynyl
bromide to furnish the desired product 3y in 48% yield.
alkynyl ethers was developed in moderate to good yields under
photo-induced alkynylation of α-C–H bonds of ethers with
alkynyl bromides without external photocatalyst. The value of
this strategy has been highlighted via the ability to perform the
reaction at room temperature by visible light irradiation protocol.
More detailed investigation of the reaction mechanism and
application of this kind of strategy are underway in our laboratory.
Experimental Section
General methods: All 1H NMR and 13C NMR spectra were recorded on a
400 MHz Bruker FT-NMR spectrometer (400 MHz or 100 MHz,
respectively). All chemical shifts are given as δ value (ppm) with
reference to tetramethylsilane (TMS) as an internal standard. The peak
patterns are indicated as follows: s, singlet; d, doublet; t, triplet; m,
multiplet; q, quartet. The coupling constants, J, are reported in Hertz (Hz).
High resolution mass spectroscopy data of the products were collected
on an Agilent Technologies 6540 UHD Accurate-Mass Q-TOF LC/MS
(ESI). All reactions were set up in air. All chemicals were purchased
commercially and used without further purification. Products were purified
by flash chromatography on 200–300 mesh silica gels, SiO2.
Scheme 4 Plausible mechanism for the reaction.
To investigate the reaction mechanism, the control
experiments were conducted. Under the optimal conditions,
when a radical-trapping reagent TEMPO (2,2,6,6-tetramethyl-1-
oxylpiperidine) was added to the reaction, no desired product
was detected, along with the formation of TEMPO−THF adduct
(4), which was detected by HRMS (high resolution mass
spectroscopy, SI for detail). This result suggested that the
reaction may proceed by a free radical pathway and a carbon-
centred radical of THF is probably involved. Based on the above
experimental results and the previous reports,[17] a plausible
reaction pathway was proposed with tetrahydrofuran (1a) and 4-
(bromoethynyl)benzonitrile (2j), as shown in Scheme 4. First, a
homolytic cleavage of alkynyl bromide was triggered by visible-
Typical procedure for the visible-light-induced alkynylation of α-C–
H
bonds of ethers with alkynyl bromides without external
photocatalyst: A 5 mL oven-dried reaction vessel equipped with a
magnetic stirrer bar was charged with tetrahydrofuran (THF, 1a, 2.0 mL)
and phenylethynyl bromide (2a). The reaction vessel was exposed to
blue LED (420−425 nm, 3 W) irradiation at room temperature in air with
stirring for 12 h. After completion of the reaction, the mixture was
concentrated to yield the crude product, which was further purified by
flash chromatography (silica gel, petroleum ether/ethyl acetate = 100:1)
to give the desired product 3a.
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10.1002/ejoc.201900872
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2-(Phenylethynyl)tetrahydrofuran (3a):[6a] Light yellow oil. 1H
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, 25.4.
NMR (400 MHz, CDCl3) δ: 7.44
4.82 4.78 (m, 1H), 4.03 3.97 (m, 1H), 3.87
2.17 (m, 1H), 2.13 2.02 (m, 2H), 1.97
1.88 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 131.6, 128.12, 128.09, 122.7, 89.0, 84.4, 68.5, 67.8, yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.36 (d, J = 8.8 Hz, 2H),
33.3, 25.4. 6.82 (d, J = 8.8 Hz, 2H), 4.81 4.78 (m, 1H), 4.03 3.98 (m,1H),
3.87 3.82 (m, 1H), 3.79 (s, 3H), 2.25 2.18 (m, 1H), 2.14 2.02 (m,
2H), 1.98
1.88 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 159.6, 133.1,
–7.41 (m, 2H), 7.29–7.27 (m, 3H),
–
–
–
3.81 (m, 1H), 2.24
–
–
–
2-((4-Methoxyphenyl)ethynyl)tetrahydrofuran
(3h):[6a]
Light
–
–
–
–
–
2-(p-Tolylethynyl)tetrahydrofuran (3b) [6a]
NMR (400 MHz, CDCl3) δ: 7.32 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0
Hz, 2H), 4.81 4.78 (m, 1H), 4.03 3.98 (m, 1H), 3.87 3.82 (m, 1H),
2.33 (s, 3H), 2.24 2.18 (m, 1H), 2.14 2.02 (m, 2H), 1.97 1.88 (m,
:
Light yellow oil. 1H
–
115.0, 113.8, 87.6, 84.4, 68.7, 67.8, 55.2, 33.4, 25.5.
–
–
–
–
–
–
2-((4-(Trifluoromethyl)phenyl)ethynyl)tetrahydrofuran
(3i):[6a]
7.51 (m, 4H),
3.85 (m, 1H), 2.29
–
1.92 (m, 1H); 13C NMR (100
1H); 13C NMR (100 MHz, CDCl3) δ: 138.3, 131.6, 128.9, 119.7, 88.3, Light yellow oil. H NMR (400 MHz, CDCl3) δ: 7.57
–
1
84.6, 68.6, 67.8, 33.4, 25.4, 21.4.
4.84
–
4.80 (m, 1H), 4.04
–
3.99 (m, 1H), 3.90
–
–
2.21 (m, 1H), 2.14
–
2.06 (m, 2H), 2.00
2-((4-Ethylphenyl)ethynyl)tetrahydrofuran (3c)
1H NMR (400 MHz, CDCl3) δ: 7.35 (d, J = 8.4 Hz, 2H), 7.12 (d, J =
8.0 Hz, 2H), 4.82-4.78 (m, 1H), 4.03 3.98 (m, 1H), 3.87 3.82 (m,
1H), 2.62 (q, J = 7.6 Hz, 2H), 2.25 2.17 (m, 1H), 2.13 2.02 (m, 2H),
1.97
1.89 (m, 1H), 1.21 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
:
Light yellow oil.
MHz, CDCl3) δ: 131.9, 130.0 (q, JCF = 32.4 Hz), 126.6, 125.1 (q, JCF
= 3.7 Hz), 123.9 (q, JCF = 270.3 Hz), 91.6, 83.1, 68.4, 68.0, 33.3,
25.5.
–
–
–
–
–
4-((Tetrahydrofuran-2-yl)ethynyl)benzonitrile (3j): Light yellow oil.
1H NMR (400 MHz, CDCl3) δ: 7.59 (d, J = 8.4 Hz, 2H), 7.50 (d, J =
CDCl3) δ: 144.5, 131.6, 127.7, 119.9, 88.2, 84.5, 68.6, 67.81, 33.4,
28.7, 25.4, 15.2. IR (KBr): 2966, 2874, 2200, 1414, 1112, 1052, 835 cm-
1; HRMS (ESI) [M + H]+ Calcd. for [C14H17O]+: 201.1274, found: 201.1274.
8.4 Hz, 2H), 4.84–4.80 (m, 1H), 4.03–3.98 (m, 1H), 3.90–3.85 (m,
1H), 2.29 2.22 (m, 1H), 2.15
–
–
2.04 (m, 2H), 2.01–
1.92 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 132.1, 131.8, 127.7, 118.3, 111.6, 93.7,
82.8, 68.3, 68.0, 33.2, 25.4. IR (KBr): 2954, 2343, 1677, 1407, 1054,
846, 669 cm-1; HRMS (ESI) [M + H]+ Calcd. for [C13H12NO]+: 198.0913,
found: 198.0914.
2-((4-Propylphenyl)ethynyl)tetrahydrofuran (3d):[6a] Light yellow
oil. 1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 8.0 Hz, 2H), 7.10 (d, J
= 8.4 Hz, 2H), 4.82
1H), 2.57 (t, J = 7.6 Hz, 2H), 2.25
1.98 1.89 (m, 1H), 1.62 (q, J = 7.6 Hz, 2H), 0.92 (t, J = 7.6 Hz, 3H);
–4.79 (m, 1H), 4.04–3.98 (m, 1H), 3.88-3.83 (m,
–
2.18 (m, 1H), 2.14-2.03 (m, 2H),
–
2-((4-Fluorophenyl)ethynyl)tetrahydrofuran (3k):[6a] Light yellow
13C NMR (100 MHz, CDCl3) δ: 143.1, 131.6, 128.4, 120.0, 88.3,
oil. 1H NMR (400 MHz, CDCl3) δ: 7.41
2H), 4.80 4.77 (m, 1H), 4.02 3.96 (m, 1H), 3.86
2.23 2.17 (m, 1H), 2.12 2.01 (m,2H), 1.96
1.87 (m, 1H); 13C NMR
–
7.38 (m, 2H), 7.00
–6.95 (m,
84.6, 68.7, 67.9, 37.9, 33.5, 25.5, 24.3, 13.7.
–
–
–
3.81 (m, 1H),
–
–
–
2-((4-(tert-Butyl)phenyl)ethynyl)tetrahydrofuran (3e):[6a] Light
(100 MHz, CDCl3) δ: 162.3 (d, JCF = 247.8 Hz), 133.4 (d, JCF = 8.4
Hz), 118.8 (d, JCF = 3.6 Hz), 115.3 (d, JCF = 21.9 Hz), 88. 7, 83.2,
68.3, 67.7, 33.2, 25.3.
1
yellow oil. H NMR (400 MHz, CDCl3) δ: 7.36 (d, J = 8.4 Hz, 2H),
7.31 (d, J = 8.4 Hz, 2H), 4.82
–4.79 (m, 1H), 4.03
–3.98 (m, 1H),
3.87 3.82 (m, 1H), 2.24 2.18 (m, 1H), 2.14
–
–
–2.03 (m, 2H), 1.97–
1.88 (m, 1H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 151.4,
2-((4-Chlorophenyl)ethynyl)tetrahydrofuran (3l):[6a] Light yellow
oil. 1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 8.4 Hz, 2H), 7.25 (d, J
131.4, 125.1, 119.8, 88.3, 84.5, 68.6, 67.8, 34.7, 33.4, 31.1, 25.4.
= 8.4 Hz, 2H), 4.80
–4.76 (m, 1H), 4.01–3.96 (m, 1H), 3.86–3.81 (m,
2-((4-Butylphenyl)ethynyl)tetrahydrofuran (3f): Light yellow oil.
1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 8.0 Hz, 2H), 7.10 (d, J =
1H), 2.23 2.17 (m, 1H), 2.11
–
–
2.01 (m, 2H), 1.96–
1.87 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 134.1, 132.7, 128.4, 121.2, 90.0, 83.1,
68.3, 67.8, 33.2, 25.3.
8.0 Hz, 2H), 4.82
1H), 2.58 (t, J = 8.0 Hz, 2H), 2.25
1.98 1.91 (m, 1H), 1.61 1.53 (m, 2H), 1.38
–
4.79 (m, 1H), 4.03
2.18 (m, 1H), 2.14
1.28 (m, 2H), 0.91 (t, J
–
3.98 (m, 1H), 3.88
–3.82 (m,
–
–2.03 (m, 2H),
–
–
–
2-((4-Bromophenyl)ethynyl)tetrahydrofuran (3m):[6a] Light yellow
oil. 1H NMR (400 MHz, CDCl3) δ: 7.42 (d, J = 8.8 Hz, 2H), 7.28 (d, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:143.3, 131.6, 128.3,
119.9, 88.3, 84.6, 68.6, 67.8, 35.5, 33.4, 33.3, 25.4, 22.2, 13.9. IR
(KBr): 2931, 2360, 2191, 1549, 1052, 845 cm-1; HRMS (ESI) [M + H]+
Calcd. for [C16H21O]+: 229.1587, found: 229.1585.
= 8.8 Hz, 2H), 4.80
–4.77 (m, 1H), 4.03
–3.97 (m, 1H), 3.88
–3.83 (m,
1H), 2.26 2.19 (m, 1H), 2.14
–
–
2.02 (m, 2H), 1.99–
1.90 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 133.1, 131.4, 122.5, 121.8, 90.3, 83.4,
68.5, 67.9, 33.3, 25.5.
2-([1,1'-Biphenyl]-4-ylethynyl)tetrahydrofuran
(3g):[6b]
7.55 (m, 2H), 7.53
7.31 (m, 1H), 4.84 4.81 (m,
2.19 (m, 1H),
Light
1
yellow oil H NMR (400 MHz, CDCl3) δ: 7.57
–
–
2-(m-Tolylethynyl)tetrahydrofuran (3n):[6a] Light yellow oil. 1H
7.48 (m, 4H), 7.43
1H), 4.04 3.99 (m, 1H), 3.88
2.14 2.02 (m, 2H), 1.97
–
7.39 (m, 2H), 7.35
–
–
NMR (400 MHz, CDCl3) δ: 7.25
7.09 7.08 (m, 1H), 4.80 4.77 (m, 1H), 4.02
3.80 (m, 1H), 2.29 (s, 3H), 2.22 2.16 (m, 1H), 2.12–
–
7.22 (m, 2H), 7.18
3.96 (m, 1H), 3.86
2.01 (m, 2H),
–7.14 (m, 1H),
–
–3.83 (m, 1H), 2.25
–
–
–
–
–
–
–
1.89 (m, 1H); 13C NMR (100 MHz, CDCl3)
–
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10.1002/ejoc.201900872
European Journal of Organic Chemistry
FULL PAPER
1.95
–
1.86 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 137.7, 132.1,
2-((4-(tert-Butyl)phenyl)ethynyl)-1,4-dioxane (3v):[6a] Light yellow
oil. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J
128.9, 128.6, 127.9, 122.5, 88.6, 84.4, 68.4, 67.7, 33.3, 25.3, 21.0.
= 8.4 Hz, 2H), 4.56 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H), 3.95
–3.90 (m,
2-((3-Chlorophenyl)ethynyl)tetrahydrofuran (3o): Light yellow oil.
2H), 3.77
–
3.65 (m, 4H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:
1H NMR (400 MHz, CDCl3) δ: 7.42
4.81 4.78 (m, 1H), 4.03 3.97 (m, 1H), 3.89
2.19 (m, 1H), 2.14 2.03 (m, 2H), 2.00
1.90 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 134.0, 131.5, 129.8, 129.4, 128.5, 124.5, 90.4, 83.0, 2-Methyl-2-(phenylethynyl)tetrahydrofuran (3w):[6a] Light yellow
–7.41 (m, 1H), 7.32
–7.22 (m, 3H), 152.0, 131.6, 125.2, 119.0, 86.7, 83.6, 70.5, 66.5, 66.3, 65.8, 34.7,
–
–
–
3.83 (m, 1H), 2.26
–
31.1.
–
–
68.4, 68.0, 33.3, 25.4. IR (KBr): 2959, 2343, 1433, 1131, 810, 757 cm-1;
HRMS (ESI) [M + H]+ Calcd. for [C12H12ClO]+: 207.0571, found: 207.0574.
oil. 1H NMR (400 MHz, CDCl3) δ: 7.43
3H), 4.05 3.94 (m, 2H), 2.33 2.27 (m, 1H), 2.21
2.04 1.95 (m, 1H), 1.89
1.82 (m, 1H), 1.63 (s, 3H); 13C NMR (100
–
7.40 (m, 2H), 7.29
–7.27 (m,
–
–
–
2.10 (m, 1H),
–
–
2-(o-Tolylethynyl)tetrahydrofuran (3p):[6a] Light yellow oil. 1H
MHz, CDCl3) δ: 131.6, 128.1, 128.0, 123.0, 92.3, 82.7, 76.4, 67.6,
40.1, 27.7, 25.7.
NMR (400 MHz, CDCl3) δ: 7.32 (d, J = 7.6 Hz, 2H), 7.12
2H), 7.05 7.01 (m, 1H), 4.80 4.77 (m, 1H), 3.97 3.92 (m, 1H),
3.82 3.77 (m, 1H), 2.34 (s, 3H), 2.19 2.12 (m, 1H), 2.08 1.97 (m,
2H), 1.92
–7.09 (m,
–
–
–
–
–
–
2-((4-Chlorophenyl)ethynyl)-2-methyltetrahydrofuran
(3x):[6a]
1
–
1.82 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 140.2, 132.0, Light yellow oil. H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 8.4 Hz,
129.3, 128.2, 125.4, 122.6, 93.1, 83.3, 68.7, 67.8, 33.6, 25.4, 20.6.
2H), 7.26 (d, J = 8.4 Hz, 2H), 4.03
–
3.93 (m, 2H), 2.31
–2.25 (m, 1H),
2.19 2.09 (m, 1H), 2.04 1.95 (m, 1H), 1.89–
–
–
1.82 (m, 1H), 1.62 (s,
2-((2-Chlorophenyl)ethynyl)tetrahydrofuran (3q): Light yellow oil.
3H); 13C NMR (100 MHz, CDCl3) δ: 134.1, 132.9, 128.5, 121.5, 93.4,
1H NMR (400 MHz, CDCl3) δ: 7.46
7.23 7.15 (m, 2H), 4.87 4.84 (m, 1H), 4.04
3.83 (m, 1H), 2.26 2.18 (m, 1H), 2.16 2.07 (m, 2H), 1.98
1H); 13C NMR (100 MHz, CDCl3) δ: 135.8, 133.2, 129.1, 129.0,
126.2, 122.5, 94.4, 81.0, 68.4, 67.7, 33.2, 25.2. IR (KBr): 2960, 2360, 4.42
–
7.44 (m, 1H), 7.37
3.99 (m, 1H), 3.89
1.89 (m,
–7.35 (m, 1H), 81.6, 76.3, 67.7, 40.1, 27.6, 25.7.
–
–
–
–
1
–
–
–
(3,4-Dimethoxybut-1-yn-1-yl)benzene (3y) [6a]
NMR (400 MHz, CDCl3) δ: 7.46 7.44 (m, 2H), 7.33
4.39 (m, 1H), 3.69 3.62 (m, 2H), 3.53 (s, 3H), 3.45 (s, 3H);
:
Light yellow oil. H
–
–7.30 (m, 3H),
–
–
1709, 1473, 1190, 1051, 754 cm-1; HRMS (ESI) [M + H]+ Calcd. for
[C12H12ClO]+: 207.0571, found: 207.0573.
13C NMR (100 MHz, CDCl3) δ: 131.8, 128.5, 128.2, 122.3, 86.8,
84.9, 74.9, 71.0, 59.3, 56.8.
2-(Naphthalen-1-ylethynyl)tetrahydrofuran (3r):[6b]
1H NMR (400 MHz, CDCl3) δ: 8.30 (d, J = 8.4 Hz, 1H), 7.80 (t, J =
9.2 Hz, 2H), 7.67 7.65 (m, 1H), 7.57 7.47 (m, 2H), 7.41 7.37 (m,
1H), 4.98 4.95 (m, 1H), 4.12 4.05 (m, 1H), 3.93 3.88 (m, 1H),
2.34 2.25 (m, 1H), 2.23 2.11 (m, 2H), 2.03
1.92 (m, 1H); 13C NMR
Light yellow oil.
Conflict of Interest
There are no conflicts to declare.
–
–
–
–
–
–
–
–
–
Acknowledgements
(100 MHz, CDCl3) δ: 133.3, 133.1, 130.5, 128.7, 128.2, 126.7,
126.3, 126.1, 125.1, 120.4, 94.1, 82.5, 68.8, 67.9, 33.6, 25.5.
We gratefully acknowledge the National Natural Science
Foundation of China (21772062, 21602072) and Excellent Youth
Talents Fund Program of Higer Education Institutions of Anhui
Province, China (gxyq2019167) for financial support of this work.
1
2-(Phenylethynyl)-1,3-dioxolane (3s):[6a] Light yellow oil. H NMR
(400 MHz, CDCl3) δ: 7.48
1H), 4.15 4.11 (m, 2H), 3.99
CDCl3) δ: 131.9, 128.9, 128.2, 121.6, 93.4, 85.2, 84.5, 64.5.
–7.45 (m, 2H), 7.34–7.30 (m, 3H), 5.89 (s,
–
–
3.96 (m, 2H); 13C NMR (100 MHz,
Keywords: Alkynylation• C–H Functionalization • Visible-light
2-(Phenylethynyl)tetrahydro-2H-pyran (3t):[6a] Light yellow oil. H
NMR (400 MHz, CDCl3) δ: 7.46 7.44 (m, 2H), 7.31 7.29 (m, 3H),
4.51 (dd, J1 = 2.8 Hz, J2 = 7.6 Hz, 1H), 4.08 4.03 (m, 1H), 3.62
3.56 (m, 1H), 1.96 1.88 (m, 2H), 1.83 1.75 (m, 1H), 1.66 1.56 (m,
1
irradiation • Alkynyl bromides • Ethers
–
–
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Table of Contents
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Alkynylation via Alkynyl Bromides
Xiaofei Xie, Jie Liu,* Lei Wang and Min
Wang*
Page No. – Page No.
Visible-Light-Induced Alkynylation of
α-C–H Bonds of Ethers with Alkynyl
A direct alkynylation of -C(sp3)–H of ethers with alkynyl bromides under visible-
light irradiation at room temperature without external photocatalyst was developed.
Bromides
without
External
Photocatalyst
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