Efficient assembly of ynones via palladium-catalyzed sequential carbonylation/alkynylation

Article abstract of DOI:10.1039/C8OB02092B

Based on the intramolecular Heck-type reaction, a convenient and efficient strategy to construct functionalized ynones by a palladium-catalyzed cascade annulation reaction has been developed. This reaction possesses good functional group compatibility, a broad substrate scope, and high atom- and step-economy. Furthermore, this approach could also be extended to direct alkynylation that gave another route to synthesize dihydrobenzofurans.

Full text of DOI:10.1039/C8OB02092B

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Efficient Assembly of Ynones via Palladium-Catalyzed Sequential
Carbonylation/Alkynylation
Received 00th January 20xx,
Accepted 00th January 20xx
Miao Hu, Yang Gao, Wanqing Wu, Jianxiao Li, Chunsheng Li, Hao Zhang, and Huanfeng Jiang*
DOI: 10.1039/x0xx00000x
Based on intramolecular Heck-type reaction, a convenient and efficient strategy to construct functionalized ynones by
palladium-catalyzed cascade annulation reaction has been developed. This reaction possesses good functional group
compatibility, broad substrate scope, and high atom- and step-economy. Furthermore, this approach could also be
www.rsc.org/
extended
to
direct
alkynylation
that
gave
another
route
to
synthesize
dihydrobenzofurans.
Scheme 1 The transformations of C(sp3)-Pd species
Introduction
Ynones are privileged structural motifs which have been widely
utilized as valuable framework in organic synthesis, biological and
pharmaceutical research. Major advances in the construction of
heterocyclic derivatives such as acylindoles,1 thiophenes,2 furans,3
pyrroles4 etc. have been made with significant contribution by
Marinelli, Harrity, Maekawa and others through the annulation
reactions of ynones. Alternatively, owing to the prevalence of
ynones in natural products and bioactive molecules, the
development of new transition metal-catalyzed reactions for the
construction of ynones remains to be highly desirable.
The general strategies to synthesize ynones are the oxidation of
propargyl alcohols.5 However, low chemoselectivity was obtained
because of the over-oxidation process. Furthermore, a series of
efficient and novel methods have been designed and successfully
applied to the construction of a variety of ynones.6 Typically, Yao et.
al reported the synthesis of ynones by direct coupling of
acylchlorides and terminal alkyne in the presence of a reusable
copper nanoparticle catalyst.7 Huang group disclosed a direct
synthesis of various ynones from readily available aldehydes and
hypervalent alkynyl iodides by gold / amine synergistic catalysis.8
However, both reaction partners need to be preactivated in these
cases. Specifically, Bäckvall,9 Lee,10 Wu,11 and others successfully
synthesized a wide range of ynones by the employment of carbon
monoxide or formic acid as the CO source under palladium catalysis.
To the best of our knowledge, only one report has demonstrated
the palladium-catalyzed oxidative cascade reaction to construct
ynones via carbon monoxide insertion of C(sp3)-Pd species.9
Despite the remarkable progress achieved in this area, the
synthesis of functionalized ynones through the insertion of carbon
monoxide to C(sp3)-Pd species remains a challenging goal. In
continuation with our current research interest in the
transformation of C(sp3)-Pd species,12, 13 we showcase a novel Pd-
catalyzed cascade annulation reaction through the insertion of
carbon monoxide to C(sp3)-Pd species, which generated functional
ynones in good to excellent yields under mild reaction conditions.
Moreover, this protocol could also be used for direct alkynylation.
aKey Laboratory of Functional Molecular Engineering of Guangdong Province,
Guangdong Engineering Research Center for Green Fine Chemicals, School of
Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640 (P. R. China), E-mail: jianghf@scut.edu.cn
†Electronic Supplementary Information (ESI) available: General experimental
information, and NMR spectra. See DOI: 10.1039/x0xx00000x
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Results and discussion
Table 1 Optimization of the reaction conditions for the synthesis of ynones a
Entry
1
Ligand
PPh3
PPh3
PPh3
PPh3
-
Base
Cs2CO3
KOtBu
CsF
Solvent
toluene
T (oC)
80
Yieldb (%)
30
2
toluene
80
27
3
toluene
80
55
4
CsF
toluene
60
60
5
KOtBu
KOtBu
CsF
toluene
80
20
6c
-
toluene
80
<5
7
PPh3
L1d
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
60
68
8
CsF
60
70
9
PPh3
L2e
CsF
60
75
10
CsF
60
78 (74)
a Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), Pd(OAc)2 catalyst (5 mol %),
ligand (15 mol %), base (1 equiv), solvent (1.5 mL), under CO (1atm), 8 h. b Yield
was determined by NMR analysis using dibromomethane as the internal
c
standard. Isolated yield product in parentheses. PdCl2 was used to replace
d
Pd(OAc)2. L1 was N, N-dimethylglycine. L2 was tris(2,4-di-tert-butylphenyl)
e
phosphite.
The initial studies were conducted with 1-iodo-2-((2-
methylallyl)oxy)benzene (1a) and ethynylbenzene (2a) as the model
substrates in the presence of Pd(OAc)2 (5 mol %), Cs2CO3 (1 equiv),
PPh3 (15 mol %) in toluene at 80 °C for 8 h, but the yield of the
desired product 3a was obtained only in 30% yield (Table 1, Entry 1).
Under this condition, apart from the carbonylation product, the
direct coupling product was also obsered, and the ratio is about 3:4.
In subsequent base screening, CsF was found to be the best choice
(Table 1, Entries 2-3). In addition, the reaction temperature slightly
affected the reaction. We found the yield of 3a would decrease no
matter increase or decrease the temperature (Table 1, Entry 4).
Among the screening solvents, 1,4-dioxane was optimal for this
transformation (Table 1, Entry 7). To further improve the yield,
different kinds of ligands were investigated, and L2 (tris(2,4-di-tert-
butylphenyl) phosphite) was selected (Table 1, Entries 8-10).
Further control experiments showed that the reaction could not
proceed smoothly without the ligand (Table 1, Entries 5-6).
a Reaction condition: 1 (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (5 mol %), L2 (15 mol %),
b
CsF (1 equiv), 1,4-dioxane (1.5 mL), 60 oC, CO (1atm), 8 h. Yields of isolated products
were given. c L2 was tris(2,4-di-tert-butylphenyl) phosphite.
Under the optimal reaction conditions, the scope of
functionalized ynones was studied with a variety of ethynylbenzene
compounds 1 and 1-iodo-2-((2-methylallyl)oxy)benzene compounds
2. Likewise, we set out to explore the substrate scope of 1-iodo-2-
((2-methylallyl)oxy)benzene compounds 1. Electron-deficient
groups, such as -CF3, -COOMe, -F, -CI were well tolerated in our
reaction (3b-3e). To our delight, the electronic effects did not affect
the reaction significantly (3f-3p). Notably, many functional groups
on ethynylbenzene ring, including alkyl (3f-3i, 3o), ether (3j and 3n),
-F (3k), -Cl (3l), -Br (3p) and ester (3m) were tolerated. The
corresponding expected products were obtained in moderate
yields. It should be noted that linear alkyl substituted alkynes have
been tested in the carbonylative coupling reaction, and the results
indicated that they may be not suitable for this transformation (see
the Supporting Information for details). Moreover, some
naphthenic substituted alkynes could participate in the reaction (3q
Scheme 2 Substrate scope of functionalized ynones a,b,c
and
3r).
However,
when
using
1-bromo-2-((2-
methylallyl)oxy)benzene as substrate, no desired 3a was detected
under the carbonylation process.
Encouraged by these promising results, we further attempted to
apply our developed procedure to alkynylation reaction. We used 1-
iodo-2-((2-methylallyl)oxy)benzene (1a) and ethynylbenzene (2a) as
2 | J. Name., 2012, 00, 1-3
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the model substrates in the presence of Pd(OAc)2 (5 mol %), Cs2CO3
Using the optimized reaction condition, we investigated the
(1 equiv), PPh3 (15 mol %) in DMF at 80 °C for 8 h. However, the scope of this alkynylation reaction. Different types of 1-iodo-2-
desired product 4a was obtained only in 15% yield (Table 2, Entry 1). ((2methylallyl)oxy)benzene substrates 1 reacted smoothly with
Furthermore, other solvents such as DMSO, MeCN and toluene phenylacetylene (2a). Diverse functional groups at the meta- or
were investigated (Table 2, Entries 2-4). To our delight, the solvent para- on the benzene ring of 1-iodo-2-((2-methylallyl)oxy)benzene
had a significant impact on promoting the reaction efficiency, and were successfully transformed into the corresponding products (4a-
the expected product 4a could be detected in 85% yield when using 4h) in moderate to good yields. Moreover, a wide range of
toluene as solvent. Then the bases were examined (Table 2, Entries phenylacetylene compounds 2, with no matter electron-rich or
5-6), and Cs2CO3 was the most effective base in this reaction electron-deficient group on the para- positions of benzene ring,
compared with K2CO3 and Et3N. Moreover, different Pd catalysts converted into the desired products in moderate to good yields (4n-
were examined as well (Table 2, Entries 7-9), such as Pd(PPh3)2Cl2, 4v). Remarkably, the electronic effects had little influence on the
PdCl2 and Pd(PPh3)4, and Pd(OAc)2 still gave the excellent yield than efficiency of the reaction. Moreover, some heterocycles and fused
those of other catalysts. Experiments on ligand screening showed rings such as 3-ethynylpyridine (4w), 4-ethynyl-1,1'-biphenyl (1x)
that PPh3 was the best ligand (see the Supporting Information for and 6-ethynyl-1,9-dihydropyrene (1y) were also applicable (4w-4y).
details). Control experiments revealed that the reaction did not However, the yields of 4w and 4x were only 33% and 48% when 1w
occur in the absence of palladium catalyst (Table 2, Entry 12). and 1x were surveyed respectively. Notably, terminal acetylenic
Notably, both base and ligand were required for this transformation acid could be utilized for the construction of products with alkyl
(Table 2, Entries 13-14). Interestingly, product 4a could be also groups as well (4i, 4j). Delightfully, the corresponding product 4a
obtained in good yield when 3-phenylpropiolic acid and was obtained in 33% yield when using 1-bromo-2-((2-
trimethyl(phenylethynyl)silane were used to replace 2a under the methylallyl)oxy)benzene as substrate under the optimized reaction
optimized reaction conditions (Table 1, Entries 10-11). Considering conditions for alkynylation.
the atom economy, we chose 2a as the best substrate in our
Scheme 3 Substrate scope of alkynylation a, b
reaction system.
Table 2 Optimization of the reaction conditions of alkynylation a
Entry
1
Catalyst
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)2Cl2
PdCl2
Base
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Et3N
Ligand
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
-
Solvent
DMF
Yieldb (%)
15
20
2
DMSO
3
MeCN
38
4
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
85（83）
70
5
6
78
7
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
-
75
8
80
9
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
-
82
10c
11d
12
13e
14
83
78
n.d.
32
Pd(OAc)2
Pd(OAc)2
PPh3
12
a Reaction conditions: 1a (0.3 mmol), 2a (0.36 mmol), Pd catalyst (5 mol %), PPh3
b
(15 mol %) , base (1 equiv.), solvent (1.5 mL), 80 °C, under N2, 8 h. Yield was
a Reaction condition: 1 (0.3 mmol), 2 (0.36 mmol), Pd(OAc)2 (5 mol %), PPh3 (15 mol %),
Cs2CO3 (1 equiv), toluene (1.5 mL), 80 oC, N2 balloon, 8 h. b Yields of isolated products
were given. c 1-bromo-2-((2-methylallyl)oxy)benzene was uesd as 1a. d Pent-2-ynoic
acid was used as 2i. e 1a (0.6 mmol), propiolic acid was uesd as 2ab.
determined by NMR analysis using dibromomethane as the internal standard.
c
Isolated yield of product was in parentheses. n.d. = not detected. 2a was
d
replaced
by
3-phenylpropiolic
acid.
2a
was
replaced
by
trimethyl(phenylethynyl)silane. e Without ligand.
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As a demonstration of the scalability of this transformation, 1-
Journal Name
Pd(OAc)2
iodo-2-((2-methylallyl)oxy)benzene (1a) with ethynylbenzene (2a)
was performed at the gram scale (Scheme 4). Analytically pure 4a
was isolated in 83% yield (0.7525 g) through a pad of silica gel. We
also selectively reduced the alkyne in product 4a under H2 (20 Mpa)
with Lindlar catalyst in methanol, and analytically pure 5a was
isolated in nearly 99% yield (Scheme 5).
L
Pd0Ln
I
3a
R1
O
O
1a
4a
O
Vl
Ph
Scheme 4 Experiment of gram scale a
CsF.HI
CsF
Ln
Pd
III
R2
Ph
PdII
Ln
O
2a
O
I
lll
I
LnPdII
Cs2CO3.HI
O
R2
O
V
a Reaction condition: 1a (3.66 mmol), 2a (4.39 mmol), Pd(OAc)2 (5 mol %), PPh3 (15
Cs2CO3
Path a
2a
mol %), Cs2CO3 (1 equiv.), toluene (1.5 mL), 80 oC, N2 balloon.
CO
I
PdII
Ln
Path b
Scheme 5 Experiment of hydrogenation. a
O
II
Conclusions
a Reaction condition: 4a (0.3 mmol), Lindlar catalyst (5 mol %), H2 (20 MPa), MeOH (1.5
In summary, we have established a simple and efficient method
for the synthesis of different types ynones with high selectivity,
which could be got by commercially available substrates. Notably,
this protocol could also be used for direct alkynylation to construct
functionalized dihydrobenzofurans. Importantly, readily available
starting materials, broad substrate scope, high regioselectivity and
excellent functional group compatibility make this protocol practical
and attractive.
mL), 80 oC.
Based on the experimental results obtained above, a possible
mechanism for this Pd-catalyzed Heck-type cascade annulation
reaction was outlined (Scheme 6).14 Initially, the oxidative addition
of 1a gave the aryl palladium species I, followed by intramolecular
insertion of alkene to generate the intermediate II. Subsequently,
the reaction might occur through two different paths. In path a, the
intermediate II was captured by 2a leading to the intermediate III,
while in path b, it firstly occurred the insertion of CO to generate
intermediate V, which went through the same route of path a to
give the intermediate VI. Eventually, both of intermediates III and
VI would undergo the reductive elimination to form 3a and 4a.3-6
Experimental section
Materials and methods
1H and 13C NMR spectra were recorded on a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.24
and 77.0 ppm, respectively, and chloroform was used as a solvent
with TMS as the internal standard. IR spectra were obtained with an
infrared spectrometer on either potassium bromide pellets or liquid
films between two potassium bromide pellets. GC-MS data were
obtained using electron ionization. HRMS was carried out on a high-
resolution mass spectrometer (LCMS-IT-TOF). TLC was performed
using commercially available 100−400 mesh silica gel plates (GF254).
Unless otherwise noted, purchased chemicals were used without
further purification. All terminal alkynes 2 were commercially
available.
Scheme 6 Possible reaction mechanism
General Procedure for the Carbonylation Products 3
To a 25 mL test tube equipped with a magnetic stirring bar was
added 1 (0.3 mmol), Pd(OAc)2 (5 mol%), 2 (0.45 mmol), CsF (1
equiv), L2 (15 mol %), 1,4-dioxane (2 mL) under CO atmosphere.
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o
The resulting mixture was vigorously stirred at 60 C in an oil bath. (m, 1H), 7.36 (t, J = 6.0 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H), 4.68 (d, J =
After 8 h, the resulting solution was cooled to room temperature, 8.0 Hz, 1H), 4.50 (d, J = 8.0 Hz, 1H), 3.86 (s, 3H), 3.21 (d, J = 16.0 Hz,
added water (5 mL), and extracted with EtOAc (3 × 5 mL). The 1H), 3.04 (d, J = 16.0 Hz, 1H), 1.49 (s, 3H); 13C NMR (100 MHz, CDCl3)
combined organic phases were dried over anhydrous Na2SO4, δ 184.8, 166.7, 163.2, 134.7, 133.0, 131.6, 130.9, 128.6, 124.8,
filtered and concentrated in vacuo. Further purification by flash 122.9, 119.5, 109.6, 91.6, 88.2, 83.1, 54.7, 51.8, 43.6, 25.5;
column chromatography on silica gel (eluting with petroleum νmax(KBr)/cm-1 3888, 3679, 2934, 2195, 1710, 1596, 1440, 1269,
ether/ethyl acetate) provided the pure product 3.
1064, 758; HRMS-ESI (m/z): calcd for C21H18NaO4, [M+Na]+:
357.1097, found 357.1089.
General Procedure for the Alkynylation Products 4
1-(5-Fluoro-3-methyl-2,3-dihydrobenzofuran-3-yl)-4-phenylbut-3-
1
To a 25 mL test tube equipped with a magnetic stirring bar was yn-2-one (3d): Yield: (45.9 mg, 52%), yellow oil; H NMR (400 MHz,
added 1 (0.3 mmol), Pd(OAc)2 (5 mol %), 2 (0.36 mmol), Cs2CO3 (1 CDCl3) δ 7.53 (d, J = 8.0 Hz, 2H), 7.46 (t, J = 6.0 Hz, 1H), 7.37 (t, J =
equiv), PPh3 (15 mol %), toluene (2 mL) under N2 atmosphere. The 6.0 Hz, 2H), 6.87 (dd, J = 8.0, 2.8 Hz, 1H), 6.81 (td, J = 8.8, 2.8 Hz,
resulting mixture was vigorously stirred at 80 oC in an oil bath. After 1H), 6.70 (dd, J = 8.8, 4.0 Hz, 1H), 4.61 (d, J = 9.2 Hz, 1H), 4.41 (d, J =
8 h, the resulting solution was cooled to room temperature, added 9.2 Hz, 1H), 3.12 (d, J = 16.0 Hz, 1H), 3.02 (d, J = 16.0 Hz, 1H), 1.47
water (5 mL), and extracted with EtOAc (3 × 5 mL). The combined (s, 3H); 13C NMR (100 MHz, CDCl3) δ 184.7, 157.6 (d, J = 238 Hz),
organic phases were dried over anhydrous Na2SO4, filtered and 154.9, 135.6 (d, J = 8 Hz), 133.0, 130.9, 128.6, 119.6, 114.8 (d, J = 24
concentrated in vacuo. Further purification by flash column Hz), 110.2 (d, J = 7 Hz), 110.0 (d, J = 9 Hz), 91.4, 88.3, 82.7, 54.5,
chromatography on silica gel (eluting with petroleum ether/ethyl 44.5 (d, J = 2 Hz), 24.9; νmax(KBr)/cm-1 3676, 2966, 2196, 1666, 1475,
acetate) provided the pure product 4.
1252, 1168, 1063, 754, 680; HRMS-ESI (m/z): calcd for C19H16FO2,
[M+H]+: 295.1129, found 295.1133.
Procedure for the Gram-Scale Synthesis of 4a
1-(6-Chloro-3-methyl-2,3-dihydrobenzofuran-3-yl)-4-phenylbut-3-
1
A 100 mL round-bottom flask equipped with a magnetic stirring bar yn-2-one (3e): Yield: (57.8 mg, 62%), yellow oil; H NMR (400 MHz,
was added 1a (3.66 mmol, 1.0017g), Pd(OAc)2 (5 mol %), 2a (4.39 CDCl3) δ 7.53 - 7.51 (m, 2H), 7.47 - 7.44 (m, 1H), 7.37 (t, J = 8.0 Hz,
mmol), Cs2CO3 (1 equiv), PPh3 (15 mol %), toluene (50 mL) under N2 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.87 - 6.84 (m, 1H), 6.80 (d, J = 4.0 Hz,
atmosphere. The resulting mixture was vigorously stirred at 80 oC in 1H), 4.62 (d, J = 8.0 Hz, 1H), 4.42 (d, J = 8.0 Hz, 1H), 3.13 (d, J = 16.0
an oil bath. After 8 h, the resulting solution was cooled to room Hz, 1H), 2.99 (d, J = 16.0 Hz, 1H), 1.46 (s, 3H); 13C NMR (100 MHz,
temperature, added water (50 mL), and extracted with EtOAc (50 CDCl3) δ 184.8, 159.9, 133.9, 133.0, 130.9, 128.6, 123.5, 120.8,
mL × 3). The combined organic phases were dried over anhydrous 119.5, 110.7, 91.5, 88.3, 82.9, 54.7, 43.8, 25.2; νmax(KBr)/cm-1 2962,
Na2SO4, filtered and concentrated in vacuo. Further purification by 2196, 1665, 1594, 1475, 1065, 974, 861, 753, 684; HRMS-ESI (m/z):
flash column chromatography on silica gel (eluting with petroleum calcd for C19H15ClNaO2, [M+Na]+:333.0653, found 333.0652.
ether/ethyl acetate) provided the pure product 4a (0.7525 g, 3.03 4-(4-Ethylphenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3-
1
mmol).
yn-2-one (3f): Yield: (53.9 mg, 59%), brown oil; H NMR (400 MHz,
CDCl3) δ 7.45 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.16 - 7.12
(m, 2H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.62 (d, J =
1-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-4-phenylbut-3-yn-2-one
(3a): Yield: (61.3 mg, 74%), yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.0 Hz, 0H), 4.40 (d, J = 8.0 Hz, 1H), 3.15 (d, J = 16.0 Hz, 1H), 3.01 (d,
7.56 (d, J = 8.0 Hz, 2H), 7.49 (t, J = 6.0 Hz, 1H), 7.40 (t, J = 6.0 Hz, J = 16.0 Hz, 1H), 2.67 (q, J = 8.0 Hz, 2H), 1.48 (s, 3H), 1.24 (t, J = 8.0
2H), 7.20 - 7.15 (m, 2H), 6.92 (t, J = 7.4 Hz, 1H), 6.84 (d, J = 8.0 Hz, Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 185.3, 159.0, 147.8, 134.4,
1H), 4.65 (d, J = 8.0 Hz, 1H), 4.43 (d, J = 8.0 Hz, 1H), 3.19 (d, J = 16.0 133.2, 128.6, 128.2, 122.8, 120.7, 116.7, 109.9, 92.0, 88.3, 82.2,
Hz, 1H), 3.05 (d, J = 16.0 Hz, 1H), 1.52 (s, 3H); 13C NMR (100 MHz, 54.8, 44.2, 29.0, 25.1, 15.1; νmax(KBr)/cm-1 3876, 3676, 2964, 2873,
CDCl3) δ 185.2, 159.0, 134.3, 133.0, 130.9, 128.6, 122.8, 120.7, 2193, 1665, 1596, 1470, 1063, 749; HRMS-ESI (m/z): calcd for
119.7, 109.9, 91.3, 88.4, 82.2, 54.9, 44.2, 25.1; νmax(KBr)/cm-1 3880, C21H20NaO2, [M+Na]+:327.1356, found 327.1352.
3671, 3459, 2965, 2194, 1662, 1598, 1471, 1060, 751; HRMS-ESI 4-(4-(tert-Butyl)phenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-
(m/z): calcd for C19H16NaO2, [M+Na]+: 299.1043, found 299.1041.
yl)but-3-yn-2-one (3g): Yield: (68.8 mg, 69%), yellow oil; 1H NMR
(400 MHz, CDCl3) δ 7.52 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H),
1-(3-Methyl-5-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)-4-
phenylbut-3-yn-2-one (3b): Yield: (69.2 mg, 67%), yellow oil; 1H 7.21 - 7.16 (m, 2H), 6.93 (t, J = 8.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H),
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2H), 7.47 - 7.35 (m, 5H), 4.67 (d, J = 8.0 Hz, 1H), 4.45 (d, J = 8.0 Hz, 1H), 3.19 (d, J = 16.0 Hz,
6.85 (d, J = 8.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.49 (d, J = 12.0 Hz, 1H), 3.06 (d, J = 16.0 Hz, 1H), 1.53 (s, 3H), 1.36 (s, 9H); 13C NMR (100
1H), 3.19 (d, J = 16.0 Hz, 1H), 3.04 (d, J = 16.0 Hz, 1H), 1.50 (s, 3H); MHz, CDCl3) δ 185.2, 159.0, 154.6, 134.3,132.9, 128.5, 125.7, 122.8,
13C NMR (100 MHz, CDCl3) 184.6, 161.9, 135.2, 133.1, 131.0, 128.7, 120.6, 116.5, 109.9, 91.9, 88.3, 82.2, 54.8, 44.1, 35.0, 31.0, 25.1;
126.7 (q, J = 4.0 Hz), 125.9, 123.16 (q, J = 32.5 Hz, 1H), 120.4 (q, J = νmax(KBr)/cm-1 3681, 2957, 2191, 1665, 1592, 1489, 1061, 970, 829,
4.0 Hz), 119.5, 110.1, 91.7, 88.3, 83.0, 54.6, 43.9, 25.4; 744; HRMS-ESI (m/z): calcd for C23H24NaO2, [M+Na]+: 355.1669,
ν
max(KBr)/cm-1 3806, 3676, 3322, 2966, 2196, 1667, 1322, 1059, found 355.1661.
977, 751; HRMS-ESI (m/z): calcd for C20H15F3NaO2, [M+Na]+: 4-(4-Butylphenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3-
1
367.0916, found 367.0913.
yn-2-one (3h): Yield: (67.8 mg, 68%), yellow oil; H NMR (400 MHz,
CDCl3) δ 7.45 (d, J = 8.0 Hz, 1H), 7.10 - 7.12 (m, 4H), 6.89 (t, J = 8.0
3-Methyl-3-(2-oxo-4-phenylbut-3-yn-1-yl)-2,3-dihydrobenzofuran-
5-carboxylate (3c): Yield: (67.2 mg, 67%), brown oil; 1H NMR (400 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.63 (d, J = 8.0 Hz, 1H), 4.40 (d, J =
MHz, CDCl3) δ 7.90 - 7.86 (m, 2H), 7.53 - 7.50 (m, 1H), 7.47 - 7.43 8.0 Hz, 1H), 3.15 (d, J = 16.0 Hz, 1H), 3.01 (d, J = 16.0 Hz, 1H), 2.63
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(t, J=8.0 Hz, 1H), 1.63 - 1.56 (m, 2H), 1.48 (s, 3H), 1.37 - 1.32 (m, 2H), 134.0, 132.7, 131.8, 129.6, 128.6, 124.1, 122.8, 120.7, 109.9, 89.8,
0.92 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 185.3, 159.0, 89.3, 82.0, 54.9, 52.4, 44.1, 25.1; νmax(KBr)/cm-1 3679, 2961, 2197,
146.6, 134.4, 133.1, 128.8, 128.6, 122.8, 120.7, 116.7, 109.9, 92.1, 1721, 1587, 1467, 1273, 1054, 840, 755; HRMS-ESI (m/z): calcd for
88.4, 82.2, 54.8, 44.2, 35.7, 33.1, 25.1, 22.2, 13.8; νmax(KBr)/cm-1 C21H18NaO4, [M+Na]+:357.1097, found 357.1099.
3810, 3668, 3568, 2937, 2192, 1664, 1595, 1466, 1006, 745; HRMS- 4-(3-Methoxyphenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-
ESI (m/z): calcd for C23H24NaO2, [M+Na]+:355.1669, found 355.1675. 3-yn-2-one (3n): Yield: (57.9 mg, 63%), yellow oil; 1H NMR (400
1-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-4-(4-pentylphenyl)but-3- MHz, CDCl3) δ 7.26 (d, J = 8.0 Hz, 1H), 7.17 - 7.11 (m, 3H), 7.03 - 6.99
1
yn-2-one (3i): Yield: (72.8 mg, 70%), brown oil; H NMR (400 MHz, (m, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.61 (d, J =
CDCl3) δ 7.44 (d, J = 8.0 Hz, 2H), 7.19 - 7.14 (m, 4H), 6.89 (t, J = 8.0 8.0 Hz, 1H), 4.40 (d, J = 8.0 Hz, 1H), 3.81 (s, 3H), 3.15 (d, J = 16.0 Hz,
Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.62 (d, J = 8.0 Hz, 1H), 4.40 (d, J = 1H), 3.02 (d, J = 16.0 Hz, 1H), 1.49 (s, 3H); 13C NMR (100 MHz, CDCl3)
8.0 Hz, 1H), 3.12 (d, J = 16.0 Hz, 1H), 3.03 (d, J = 16.0 Hz, 1H), 2.62 δ 185.2, 159.4, 159.0, 134.3, 129.7, 128.6, 125.5, 122.8, 120.7,
(t, J = 8.0 Hz, 1H), 1.65 - 1.57 (m, 2H), 1.48 (s, 3H), 1.33 - 1.30 (m, 120.6, 117.7, 117.5, 109.9, 91.2, 88.1, 82.2, 55.4, 54.9, 44.2, 25.1;
4H), 0.89 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 185.2, νmax(KBr)/cm-1 3683, 2958, 2192, 1666, 1587, 1472, 1210, 1053,
159.0, 146.6, 134.4, 133.1, 128.8, 128.6, 122.8, 120.6, 116.7, 109.9, 749, 680; HRMS-ESI (m/z): calcd for C20H18NaO3, [M+Na]+: 329.1148,
92.1, 88.4, 82.2, 54.8, 44.1, 36.0, 31.3, 30.7, 25.1, 22.4, 13.9; found 329.1149.
νmax(KBr)/cm-1 3685, 2933, 2861, 2192, 1665, 1591, 1466, 1060, 1-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-4-(m-tolyl)but-3-yn-2-
827, 744; HRMS-ESI (m/z): calcd for C24H26NaO2, [M+Na]+:369.1825, one (3o): Yield: (56.6 mg, 65%), brown oil; 1H NMR (400 MHz,
found 369.1829.
CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.50 - 7.45 (m, 2H), 7.34 (t, J = 8.0
Hz, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H), 7.03 (t, J = 8.0
1-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-4-(4-
(pentyloxy)phenyl)but-3-yn-2-one (3j): Yield: (70.7 mg, 65%), Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.26 (d, J =
yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 12.0 Hz, 2H), 7.17 12.0 Hz, 1H), 3.25 (d, J = 16.0 Hz, 1H), 2.93 (d, J = 16.0 Hz, 1H), 2.46
(dd, J = 13.6, 7.2 Hz, 2H), 6.94 - 6.89 (m, 3H), 6.84 (d, J = 8.0 Hz, 1H), (s, 3H), 1.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 194.9, 184.1,
4.66 (d, J = 9.2 Hz, 1H), 4.43 (d, J = 9.2 Hz, 1H), 4.00 (t, J = 8.0 Hz, 161.1, 142.3, 135.8, 133.5, 130.9, 129.8, 127.9, 125.8, 121.6, 119.4,
2H), 3.17 (d, J = 16.0 Hz, 1H), 3.03 (d, J = 16.0 Hz, 1H), 1.86 - 1.79 119.4, 117.7, 92.1, 90.5, 74.0, 48.2, 44.4, 20.5, 19.1; νmax(KBr)/cm-1
(m, 2H), 1.51 (s, 3H), 1.49 - 1.39 (m, 4H), 0.97 (t, J = 8.0 Hz, 3H); 13
C
3672, 3060, 2965, 2190, 1664, 1468, 1058, 973, 826, 746; HRMS-ESI
NMR (100 MHz, CDCl3) δ 185.0, 161.3, 158.9, 135.0, 134.3, 128.4, (m/z): calcd for C20H18NaO2, [M+Na]+:313.1199, found 313.1198.
122.7, 120.5, 114.7, 111.0, 109.8, 92.6, 88.4, 82.1, 68.1, 54.6, 44.1, 4-(2-Bromophenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3-
28.6, 28.0, 25.1, 22.3, 13.9; νmax(KBr)/cm-1 3681, 2943, 2860, 2189, yn-2-one (3p): Yield: (75.7 mg, 71%), brown oil; H NMR (400 MHz,
1
1664, 1593, 1475, 1247, 1060, 744; HRMS-ESI (m/z): calcd for CDCl3) δ 7.64 - 7.62 (m, 1H), 7.56 - 7.53 (m, 1H), 7.35 - 7.28 (m, 2H),
C
24H26NaO2, [M+Na]+:385.1774, found 385.1781.
7.17 - 7.12 (m, 2H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H),
4.64 (d, J = 8.0 Hz, 1H), 4.40 (d, J = 8.0 Hz, 1H), 3.20 (d, J = 16.0 Hz,
4-(4-Fluorophenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3-
yn-2-one (3k): Yield: (59.2 mg, 67%), brown oil; H NMR (400 MHz, 1H), 3.06 (d, J = 16.0 Hz, 1H), 1.50 (s, 3H); 13C NMR (100 MHz, CDCl3)
CDCl3) δ 7.49 (dd, J = 8.8, 5.6 Hz, 2H), 7.13 (dd, J = 15.6, 8.0 Hz, 2H), δ 185.1, 159.0, 134.9, 134.3, 132.8, 131.9, 128.6, 127.3, 126.8,
7.04 (t, J = 8.0 Hz, 2H), 6.87 (t, J = 6.0 Hz, 1H), 6.80 (d, J = 8.0 Hz, 122.9, 122.2, 120.7, 110.0, 91.6, 89.1, 82.2, 54.8, 44.2, 25.1;
1
1H), 4.59 (d, J = 9.2 Hz, 1H), 4.37 (d, J = 9.2 Hz, 1H), 3.13 (d, J = 16.0
ν
max(KBr)/cm-1 3681, 2958, 2200, 1669, 1591, 1468, 1230, 1069,
Hz, 1H), 2.99 (d, J = 16.0 Hz, 1H), 1.47 (s, 3H); 13C NMR (100 MHz, 970, 750; HRMS-ESI (m/z): calcd for
CDCl3) δ 184.7, 163.8 (d, J = 254 Hz), 158.9, 135.2 (d, J = 9 Hz), 377.0148, found 377.0156.
C
19H15BrNaO2, [M+Na]+:
134.1, 128.5, 122.7, 120.5, 116.0 (d, J = 22 Hz), 115.6 (d, J = 4Hz), 4-Cyclopropyl-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3-yn-2-
109.8, 89.9, 88.2, 81.9, 54.6, 44.0, 25.0; νmax(KBr)/cm-1 3681, 2965, one (3q): Yield: (30.3 mg, 42%), yellow oil; 1H NMR (400 MHz,
2881, 2197, 1668, 1591, 1487, 1224, 1062, 827; HRMS-ESI (m/z): CDCl3) δ 7.15 - 7.09 (m, 2H), 6.87 (t, J = 8.0 Hz, 1H), 6.79 (d, J = 8.0
calcd for C19H15FNaO2, [M+Na]+:317.0948, found 317.0953.
Hz, 1H), 4.54 (d, J = 8.0 Hz, 1H), 4.35 (d, J = 8.0 Hz, 1H), 2.98 (d, J =
4-(4-Chlorophenyl)-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-3- 16.0 Hz, 1H), 2.85 (d, J = 16.0 Hz, 1H), 1.42 (s, 3H), 1.35 (m, 1H), 0.96
1
yn-2-one (3l): Yield: (68.1 mg, 73%), brown oil; H NMR (400 MHz, (m, 2H), 0.87 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 185.0, 159.0,
CDCl3) δ 7.43 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.16 - 7.11 134.4, 128.5, 122.7, 120.5, 109.8, 99.4, 82.1, 54.6, 44.0, 25.1, 9.7,
(m, 2H), 6.88 (t, J = 8.0 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 4.59 (d, J = 0.4; νmax(KBr)/cm-1 3681, 3559, 3254, 2965, 2197, 1659, 1466, 1037,
8.0 Hz, 1H), 4.38 (d, J = 8.0 Hz, 1H), 3.14 (d, J = 16.0 Hz, 1H), 3.00 (d, 829, 754; HRMS-ESI (m/z): calcd for C16H16NaO2, [M+Na]+: 263.1043,
J = 16.0 Hz, 1H), 1.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 185.0, found 263.1049.
159.0, 137.2, 134.1, 134.1, 129.0, 128.6, 122.8, 120.6, 118.1, 109.9, (R)-5-cyclohexyl-1-(3-methyl-2,3-dihydrobenzofuran-3-yl)pent-3-
1
89.7, 89.0, 82.0, 54.8, 44.1, 25.1; νmax(KBr)/cm-1 2960, 2197, 1666, yn-2-one (3r): Yield: (28.4 mg, 32%), yellow oil; H NMR (400 MHz,
1590, 1475, 1069, 970, 826, 746, 597; HRMS-ESI (m/z): calcd for CDCl3) δ 7.16 - 7.09 (m, 2H), 6.88 (t, J = 8.0 Hz, 1H), 6.80 (d, J =
C19H15ClNaO2, [M+Na]+:333.0653, found 333.0659.
8.0Hz, 1H), 4.55 (d, J = 8.0 Hz, 1H), 4.36 (d, J = 8.0Hz, 1H), 3.02 (d, J
= 8.0Hz, 1H), 2.89 (d, J = 8.0 Hz, 1H), 2.22 (d, J = 8 Hz, 2H), 1.81 -
Methyl-4-(3-(3-methyl-2,3-dihydrobenzofuran-3-yl)prop-1-yn-1-
yl)benzoate (3m): Yield: (65.2 mg, 65%), yellow oil; 1H NMR (400 1.65 (m, 5H), 1.44 (s, 3H), 1.33 (s, 1H), 1.25 - 1.09 (m, 3H), 1.06 -
MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.12 – 0.94 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 185.4, 159.0, 134.4,
7.17 (m, 2H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.50 128.5, 122.8, 120.6, 109.9, 94.2, 82.5, 82.2, 54.9, 44.0, 36.7, 32.7,
(dd, J = 80.7, 9.2 Hz, 1H), 3.93 (s, 1H), 3.10 (dd, J = 53.0, 16.5 Hz, 26.7, 26.0, 25.9, 25.1; νmax(KBr)/cm-1 3729, 2921, 2349, 2207, 1756,
1H), 1.49 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 185.0, 165.9, 159.0,
6 | J. Name., 2012, 00, 1-3
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1668, 2597, 1466, 1181, 964, 744; HRMS-ESI (m/z): calcd for 1.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.4, 133.9, 132.8, 131.6,
C20H24NaO2, [M+Na]+: 319.1669, found 319.1674.
128.3, 128.0, 123.6, 123.3, 120.7, 110.6, 86.2, 83.0, 82.7, 45.0, 31.5,
3-Methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-dihydrobenzofuran (4a): 24.2; νmax(KBr)/cm-1 3682, 3358, 2923, 1725, 1595, 1477, 1264, 982,
1
Yield: (68.5 mg, 92%), yellow oil; H NMR (400 MHz, CDCl3) δ 7.38 - 754, 691; HRMS-ESI (m/z): calcd for C18H15ClNaO, [M+Na]+:
7.37 (m, 2H), 7.28 - 7.27 (m, 3H), 7.22 (d, J = 8.0 Hz, 1H), 7.15 (t, J = 305.0704, found 305.0708.
8.0 Hz, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 4.54 (d, J 6-Bromo-3-methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-
= 8.0 Hz, 1H), 4.22 (d, J = 8.0 Hz, 1H), 2.67 (s, 2H), 1.53 (s, 3H); 13C dihydrobenzofuran (4g): Yield: (34.4 mg, 35%), yellow oil; 1H NMR
NMR (100 MHz, CDCl3) δ 159.5, 134.0, 131.6, 128.5, 128.2, 127.8, (400 MHz, CDCl3) δ 7.38 - 7.36 (m, 2H), 7.29 - 7.28 (m, 3H), 7.08 (d, J
123.5, 122.9, 120.6, 109.8, 86.7, 82.5, 82.3, 45.3, 31.5, 24.2; = 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.97 (s, 1H), 4.55 (d, J = 8.0 Hz,
νmax(KBr)/cm-1 3833, 3783, 3681, 3361, 2924, 2854, 1593, 1478, 1H), 4.24 (d, J = 8.0 Hz, 1H), 2.65 (s, 2H), 1.50 (s, 3H); 13C NMR (100
1023 752; HRMS-ESI (m/z): calcd for C18H17O, [M+H]+: 249.1274, MHz, CDCl3) δ 160.5, 133.3, 131.6, 128.3, 127.9, 124.1, 123.6, 123.3,
found 249.1269.
121.6, 113.4, 86.2, 82.9, 82.7, 45.0, 31.4, 24.2; νmax(KBr)/cm-1 3839,
3666, 2963, 1593, 1474, 1416, 1117, 976, 754, 691; HRMS-ESI (m/z):
5-Fluoro-3-methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-
dihydrobenzofuran (4b): Yield: (41.5 mg, 52%), yellow oil; H NMR calcd for C18H15BrNaO, [M+Na]+: 349.0198, found 349.0196.
(400 MHz, CDCl3) δ 7.38 (dd, J = 6.5, 2.9 Hz, 2H), 7.33 – 7.26 (m, 3H), 1-Methyl-1-(3-phenylprop-2-yn-1-yl)-1,2-dihydronaphtho[2,1-
6.94 (dd, J = 8.0, 2.7 Hz, 1H), 6.84 (td, J = 8.8, 2.7 Hz, 1H), 6.71 (dd, J b]furan (4h): Yield: (62.7 mg, 70%), yellow oil; 1H NMR (400 MHz,
= 8.8, 4.0 Hz, 1H), 4.55 (d, J = 8.0 Hz, 1H), 4.25 (d, J = 8.0 Hz, 1H), CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.68 (d, J =
2.67 (s, 2H), 1.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.32 - 7.29 (m, 2H), 7.26 (d, J =
236 Hz), 155.3, 135.4 (d, J = 8.0 Hz), 131.6, 128.3, 128.0, 123.3, 8.0 Hz, 3H), 7.10 (d, J = 8.0 Hz, 1H), 4.80 (d, J = 8.0 Hz, 1H), 4.33 (d, J
114.7 (d, J = 24 Hz), 110.3 (d, J = 24 Hz), 110.0 (d, J = 8 Hz), 86.1, = 8.0 Hz, 1H), 3.10 (d, J = 16.8 Hz, 1H), 2.93 (d, J = 16.8 Hz, 1H), 1.81
82.8, 82.8, 45.7, 31.3, 24.1; νmax(KBr)/cm-1 3883, 3689, 3352, 2924, (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6, 131.6, 130.4, 130.2,
2849, 1723, 1584, 1483, 1055, 754; HRMS-ESI (m/z): calcd for 130.0, 129.5, 128.2, 127.8, 126.6, 123.6, 123.5, 122.6, 121.7, 112.5,
1
C
18H15FNaO, [M+Na]+: 289.0999, found 289.1004.
86.7, 82.8, 82.5, 47.3, 30.6, 24.3; νmax(KBr)/cm-1 3682, 3356, 2969,
1718, 1587, 1437, 1368, 1244, 999, 749; HRMS-ESI (m/z): calcd for
C
22H19O, [M+H]+: 299.1430, found 299.1428.
3-Methyl-3-(3-phenylprop-2-yn-1-yl)-5-(trifluoromethyl)-2,3-
1
dihydrobenzofuran (4c): Yield: (63.6 mg, 67%), yellow oil; H NMR
(400 MHz, CDCl3) δ 7.50 (s, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 - 7.36 3-Methyl-3-(pent-2-yn-1-yl)-2,3-dihydrobenzofuran (4i): Yield:
1
(m, 2H), 7.29 - 7.28 (m, 3H), 6.86 (d, J = 8.0 Hz, 1H), 4.61 (d, J = 8.0 (52.9 mg, 88%), yellow oil; H NMR (400 MHz, CDCl3) δ 7.21 (d, J =
Hz, 1H), 4.31 (d, J = 8.0 Hz, 1H), 2.69 (s, 2H), 1.55 (s, 3H); 13C NMR 8.0 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 8.0 Hz, 1H), 6.84 (d, J
(100 MHz, CDCl3) δ 162.2, 134.8, 131.6, 128.3, 128.0, 126.6 (q, J = 4 = 8.0 Hz, 1H), 4.53 (d, J = 8.0 Hz, 1H), 4.22 (d, J = 8.0 Hz, 1H), 2.47 (s,
Hz), 125.9, 123.25 (q, J = 24 Hz), 123.2, 120.6 (q, J = 4 Hz), 109.9, 2H), 2.24 - 2.18 (m, 2H), 1.50 (s, 3H), 1.17 (t, J = 8.0 Hz, 3H);
85.8, 83.1, 83.0, 45.1, 31.6, 24.2; νmax(KBr)/cm-1 3926, 3711, 2968,
ν
max(KBr)/cm-1; 13C NMR (100 MHz, CDCl3) δ 159.4, 134.3, 128.3,
1614, 1490, 1326, 1267, 1160, 1115, 754; HRMS-ESI (m/z): calcd for 122.8, 120.4, 109.7, 83.7, 82.2, 75.9, 45.1, 30.8, 24.2, 14.2, 12.3;
C19H16F3O, [M+H]+: 317.1148, found 317.1145.
νmax(KBr)/cm-1 3660, 3302, 2963, 1741, 1592, 1525, 1469, 1376,
822, 753; HRMS-ESI (m/z): calcd for C14H16NaO, [M+Na]+: 223.1093,
5-(tert-Butyl)-3-methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-
1
dihydrobenzofuran (4d): Yield: (69.4 mg, 76%), yellow oil; H NMR found 223.1099.
(400 MHz, CDCl3) δ 7.39 (d, J = 4.0 Hz, 1H), 7.27 - 7.26 (m, 4H), 7.18 3-Methyl-3-(oct-2-yn-1-yl)-2,3-dihydrobenzofuran (4j): Yield: (58.2
(d, J = 8.04 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 4.51 (d, J = 8.0 Hz, 1H), mg, 80%), yellow oil; 1H NMR (400 MHz, CDCl3) δ 1H NMR (400
4.21 (d, J = 8.0 Hz, 1H), 2.68 (s, 2H), 1.54 (s, 3H), 1.29 (s, 9H); 13C MHz, CDCl3) δ 7.15 (d, J = 8.0 Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.86
NMR (100 MHz, CDCl3) δ 157.2, 143.6, 133.6, 131.6, 128.2, 127.8, (t, J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 4.47 (d, J = 8.0 Hz, 1H),
125.4, 123.6, 119.8, 108.9, 86.9, 82.6, 82.5, 45.4, 34.4, 31.7, 31.6, 4.16 (d, J = 8.0 Hz, 1H), 2.42 (s, 2H), 2.15 - 2.12 (m, 2H), 1.49 - 1.44
24.0; νmax(KBr)/cm-13833, 3059, 2959, 1695, 1487, 1365, 1223, (m, 5H), 1.33 - 1.32 (m, 4H), 0.90 (t, J = 8.0 Hz, 3H); 13C NMR (100
1059, 753; HRMS-ESI (m/z): calcd for C22H25O, [M+H]+: 305.1900, MHz, CDCl3) δ 159.4, 134.3, 128.3, 122.8, 120.4, 109.7, 82.4, 82.2,
found 305.1901.
45.1, 30.9, 30.9, 28.6, 24.3, 22.2, 18.6, 13.9; νmax(KBr)/cm-1 2932,
2865, 1598, 1466, 1376, 1646, 1223, 978, 831, 750; HRMS-ESI (m/z):
3-Methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-dihydrobenzofuran-5-yl
acetate (4e): Yield: (73.5 mg, 80%), yellow oil; 1H NMR (400 MHz, calcd for C17H13O, [M+H]+: 243.1743, found 243.1746.
CDCl3) δ 7.87 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.29 - 7.28 (m, 2H), Trimethyl(3-(3-methyl-2,3-dihydrobenzofuran-3-yl)prop-1-yn-1-
7.18 (s, 3H), 6.73 (d, J = 8.0 Hz, 1H), 4.55 (d, J = 8.0 Hz, 1H), 4.23 (d, J yl)silane (4k): Yield: (51.3 mg, 70%), yellow oil; 1H NMR (400 MHz,
= 8.0 Hz, 1H), 3.78 (s, 3H), 2.60 (s, 2H), 1.45 (s, 3H); 13C NMR (100 CDCl3) δ 7.20 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 6.90 (t, J =
MHz, CDCl3) δ 166.8, 163.6, 134.3, 131.6, 128.2, 127.9, 125.0, 123.2, 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 4.49 (d, J = 8.0 Hz, 1H), 4.20 (d, J
122.8, 109.5, 86.0, 83.2, 82.8, 51.7, 44.9, 31.6, 24.4; νmax(KBr)/cm-1 = 8.0 Hz, 1H), 2.51 (s, 2H), 1.50 (s, 3H), 0.18 (s, 9H); 13C NMR (100
2953, 1713, 1604, 1446, 1253, 1107, 977, 839, 758, 686; HRMS-ESI MHz, CDCl3) δ 159.4, 133.9, 128.5, 122.9, 120.4, 109.7, 103.7, 86.9,
(m/z): calcd for C20H19O3, [M+H]+: 307.1329, found 307.1341.
6-Chloro-3-methyl-3-(3-phenylprop-2-yn-1-yl)-2,3-
dihydrobenzofuran (4f): Yield: (52.6 mg, 62%), yellow oil; 1H NMR
82.2, 44.9, 31.9, 23.9, -0.04; νmax(KBr)/cm-1 3826, 3744, 3565, 3385,
2927, 1646, 1537, 1395, 1005, 754; HRMS-ESI (m/z): calcd for
C15H21OSi, [M+H]+: 245.1356, found 245.1359.
(400 MHz, CDCl3) δ 7.41 (dd, J = 6.4, 3.2 Hz, 2H), 7.33 - 7.32 (m, 3H), 1,3-Dimethyl-3-(3-phenylprop-2-yn-1-yl)indoline (4l): Yield: (64.3
7.16 (d, J = 8.0 Hz, 2H), 6.91 (dd, J = 8.0, 1.6 Hz, 1H), 6.85 (d, J = 1.6 mg, 82%), brown oil; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz,
Hz, 1H), 4.60 (d, J = 8.0 Hz, 1H), 4.30 (d, J = 8.0 Hz, 1H), 2.70 (s, 2H), 1H), 7.33 - 7.28 (m, 6H), 7.12 (t, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz,
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1H), 3.26 (s, 3H), 2.94 (d, J = 16.0 Hz, 1H), 2.71 (d, J = 16.0 Hz, 1H), Ethyl
4-(3-(3-methyl-2,3-dihydrobenzofuran-3-yl)prop-1-yn-1-
1.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 179.5, 143.1, 133.3, 131.5, yl)benzoate (4r): Yield: (78.8 mg, 82%), yellow oil; 1H NMR (400
128.2, 128.2, 127.8, 123.4, 123.3, 122.6, 107.9, 85.4, 82.8, 47.2, MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.21 -
28.9, 26.3, 21.7; νmax(KBr)/cm-1 3667, 3308, 2951, 2836, 1677, 1469, 7.15 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 4.53 (d,
1242, 1141, 747, 683; HRMS-ESI (m/z): calcd for C19H20N, [M+H]+: J = 8.0 Hz, 1H), 4.24 (d, J = 8.0 Hz, 1H), 2.71 (s, 2H), 1.53 (s, 3H); 13C
262.1590, found 262.1591.
NMR (100 MHz, CDCl3) δ 166.0, 159.4, 133.7, 131.4, 129.5, 129.3,
1-(3-Methyl-3-(3-phenylprop-2-yn-1-yl)indolin-1-yl)ethan-1-one
128.6, 128.0, 122.8, 120.6, 109.8, 89.9, 82.2, 81.9, 61.0, 45.2, 31.6,
(4m): Yield: (63.4 mg, 73%), yellow oil; H NMR (400 MHz, CDCl3) δ 24.2, 14.2; νmax(KBr)/cm-1 3850, 2971, 1714, 1599, 1468, 1370,
8.26 (d, J = 8.0 Hz, 1H), 7.39 - 7.38(m, 2H), 7.32 - 7.30 (m, 4H), 7.27 - 1270, 1102, 845, 752; HRMS-ESI (m/z): calcd for C21H21O3, [M+H]+:
7.25 (m, 2H), 7.09 (t, J = 6.0 Hz, 1H), 4.14 (d, J = 10.4 Hz, 1H), 3.80 321.1485, found 321.1479.
1
(d, J = 10.54 Hz, 1H), 2.70 (s, 2H), 2.26 (s, 3H), 1.57 (s, 3H); 13C NMR 3-(3-(4-Methoxyphenyl)prop-2-yn-1-yl)-3-methyl-2,3-
(100 MHz, CDCl3) δ 168.5, 142.0, 137.7, 131.5, 128.3, 128.2, 127.9, dihydrobenzofuran (4s): Yield: (72.6 mg, 87%), yellow oil; 1H NMR
123.7, 123.2, 122.2, 116.9, 86.1, 82.7, 61.2, 43.6, 32.4, 25.4, 24.2; (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 4.0 Hz, 1H),
νmax(KBr)/cm-1 3879, 3749, 3587, 3354, 1654, 1473, 1336, 1013, 7.07 (t, J = 8.0 Hz, 1H), 6.80 (t, J = 8.0 Hz, 1H), 6.73 (d, J = 8.0 Hz,
752, 687; HRMS-ESI (m/z): calcd for C20H20N, [M+H]+: 290.1539, 2H), 4.45 (d, J = 8.0 Hz, 1H), 4.13 (d, J = 8.0 Hz, 1H), 3.69 (s, 3H), 2.57
found 290.1532.
(s, 2H), 1.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4, 159.2,
3-(3-(4-Fluorophenyl)prop-2-yn-1-yl)-3-methyl-2,3-
134.1, 132.9, 128.5, 122.9, 120.5, 115.6, 113.8, 109.7, 85.0, 82.3,
dihydrobenzofuran (4n): Yield: (71.1 mg, 89%), yellow oil; H NMR 82.2, 55.2, 45.3, 31.5, 24.2; νmax(KBr)/cm-1 3882, 3681, 2942, 2838,
(400 MHz, CDCl3) δ 7.25 (dd, J = 8.8, 5.6 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1724, 1594, 1505, 1246, 1035, 830, 755; HRMS-ESI (m/z): calcd for
1H), 7.07 (t, J = 8.0 Hz, 1H), 6.88 (t, J = 8.0 Hz, 2H), 6.81 (t, J = 8.0 Hz, C19H19O2, [M+H]+: 279.1380, found 279.1379.
1
1H), 6.73 (d, J = 8.0 Hz, 1H), 4.44 (d, J = 8.0 Hz, 1H), 4.15 (d, J = 8.0 3-Methyl-3-(3-(p-tolyl)prop-2-yn-1-yl)-2,3-dihydrobenzofuran (4t):
Hz, 1H), 2.57 (s, 2H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.2 Yield: (68.5 mg, 87%), yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.27
(d, J = 248 Hz), 159.4, 133.9, 133.37 (d, J = 8 Hz), 128.6, 122.9, (d, J = 4.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H),
120.6, 119.5 (d, J = 4Hz), 115.4 (d, J = 22 Hz), 109.8, 86.3, 82.2, 81.4, 7.09 (d, J = 8.0 Hz, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz,
45.3, 31.5, 24.2; νmax(KBr)/cm-1 3784, 3689, 3576, 3049, 2965, 1595, 1H), 4.54 (d, J = 8.0 Hz, 1H), 4.22 (d, J = 8.0 Hz, 1H), 2.66 (s, 2H), 2.33
1486, 1221, 827, 747; HRMS-ESI (m/z): calcd for C18H16FO, [M+H]+: (s, 3H), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4, 137.9,
267.1180, found 267.1176.
134.1, 131.5, 128.9, 128.5, 123.0, 120.5, 120.4, 109.8, 85.8, 82.5,
82.3, 45.3, 31.6, 24.2, 21.4; νmax(KBr)/cm-1 3663, 3037, 2958, 1598,
3-(3-(4-Chlorophenyl)prop-2-yn-1-yl)-3-methyl-2,3-
1
dihydrobenzofuran (4o): Yield: (72.1 mg, 85%), yellow oil; H NMR 1469, 1220, 1110, 982, 819, 748; HRMS-ESI (m/z): calcd for C19H19O,
(400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), [M+H]+: 263.1430, found 263.1435.
7.19 (d, J = 8.0 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 6.88 (t, J = 6.0 Hz, 3-(3-(4-Ethylphenyl)prop-2-yn-1-yl)-3-methyl-2,3-
1
1H), 6.81 (d, J = 8.0 Hz, 1H), 4.52 (d, J = 8.0 Hz, 1H), 4.21 (d, J = 8.0 dihydrobenzofuran (4u): Yield: (70.5 mg, 85%), yellow oil; H NMR
Hz, 1H), 2.65 (s, 2H), 1.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (400 MHz, CDCl3) δ 7.30 (d, J = 8.0 Hz, 2H), 7.22 (dd, J = 7.2, 0.8 Hz,
159.4, 133.9, 133.8, 132.8, 128.6, 128.5, 122.9, 121.9, 120.6, 109.8, 1H), 7.12 (dd, J = 13.6, 4.8 Hz, 3H), 6.88 (t, J = 8.0 Hz, 1H), 6.81 (d, J
87.7, 82.2, 81.4, 45.2, 31.6, 24.2; νmax(KBr)/cm-1 3783, 3050, 2965, = 8.0 Hz, 1H), 4.53 (d, J = 8.0 Hz, 1H), 4.21 (d, J = 8.0 Hz, 1H), 2.66 (s,
2879, 1587, 1498, 1091, 979, 826, 749; HRMS-ESI (m/z): calcd for 2H), 2.61 (q, J = 8.0 Hz, 2H), 1.52 (s, 3H), 1.21 (t, J = 8.0 Hz, 3H); 13C
C
18H16ClO, [M+H]+: 283.0884, found 283.0886.
3-Methyl-3-(3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-yl)-2,3-
NMR (100 MHz, CDCl3) δ 159.4, 144.2), 134.1, 131.5, 128.5, 127.8,
122.9, 120.7, 120.5, 109.8, 85.8, 82.5, 82.3, 45.3, 31.5, 28.7, 24.2,
dihydrobenzofuran (4p): Yield: (84.5 mg, 89%), yellow oil; H NMR 15.4; νmax(KBr)/cm-1 3041, 2960, 1600, 1468, 1318, 1221, 980, 833,
(400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 749, 544; HRMS-ESI (m/z): calcd for C20H21O, [M+H]+: 277.1587,
7.26 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 8.0 Hz, 1H), 6.95 (t, J = 6.0 Hz, found 277.1594.
1
1H), 6.87 (d, J = 8.0 Hz, 1H), 4.58 (d, J = 8.0 Hz, 1H), 4.28 (d, J = 8.0 3-(3-(4-Butylphenyl)prop-2-yn-1-yl)-3-methyl-2,3-
Hz, 1H), 2.74 (s, 2H), 1.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ dihydrobenzofuran (4v): Yield: (81.3 mg, 89%), yellow oil; 1H NMR
159.5, 133.7, 131.8, 128.7, 125.2 (q, J = 3 Hz), 122.9, 120.6, 109.9, (400 MHz, CDCl3) δ 7.21 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1H),
89.5, 82.2, 81.3, 45.3, 31.6, 24.2; νmax(KBr)/cm-1 2880, 1605, 1473, 7.06 (dd, J = 11.2, 4.0 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 6.79 (t, J = 8.0
1323, 1228, 1124, 1064, 976, 839, 749; HRMS-ESI (m/z): calcd for Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 4.45 (d, J = 8.0 Hz, 1H), 4.13 (d, J =
C19H16F3O, [M+H]+: 317.1148, found 317.1150.
8.0 Hz, 1H), 2.57 (s, 3H), 2.49 (t, J = 8.0 Hz, 2H), 1.50 - 1.44 (m, 2H),
1.43 (s, 3H), 1.27 - 1.22 (m, 2H), 0.83 (t, J = 8.0 Hz, 3H); 13C NMR
4-(3-(3-Methyl-2,3-dihydrobenzofuran-3-yl)prop-1-yn-1-
1
yl)benzonitrile (4q): Yield: (65.6 mg, 80%), yellow oil; H NMR (400 (100 MHz, CDCl3) δ 159.4, 142.9, 134.1, 131.5, 128.5, 128.3, 122.9,
1
MHz, CDCl3) δ H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 2H), 120.6, 120.5, 109.8, 85.8, 82.6, 82.3, 45.3, 35.5, 33.4, 31.5, 24.2,
7.43 (d, J = 8.0 Hz, 2H), 7.21 - 7.15 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 22.2, 13.9; νmax(KBr)/cm-1 3042, 2941, 1600, 1469, 1220, 983, 829,
6.82 (d, J = 8.0 Hz, 1H), 4.53 (d, J = 8.0 Hz, 1H), 4.24 (d, J = 8.0 Hz, 749, 544; HRMS-ESI (m/z): calcd for C20H21O, [M+H]+: 305.1900,
1H), 2.71 (s, 2H), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4, found 305.1908.
133.6, 132.1, 131.9, 128.7, 128.4, 122.8, 120.6, 118.5, 111.2, 109.9, 3-(3-(3-Methyl-2,3-dihydrobenzofuran-3-yl)prop-1-yn-1-
91.8, 82.1, 81.2, 45.3, 31.7, 24.2; νmax(KBr)/cm-1 3927, 3680, 2962, yl)pyridine (4w): Yield: (24.7 mg, 33%), yellow oil; 1H NMR (400
2223, 1597, 1473, 977, 835, 749, 553; HRMS-ESI (m/z): calcd for MHz, CDCl3) δ 8.53 - 8.41 (m, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.18 - 7.06
C19H16O, [M+H]+: 274.1126, found 274.1128.
(m, 3H), 6.82 (t, J = 8.0 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 4.45 (d, J =
8 | J. Name., 2012, 00, 1-3
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8.0 Hz, 1H), 4.15 (d, J = 8.0 Hz, 1H), 2.62 (s, 2H), 1.45 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 159.4, 152.2, 148.1, 138.4, 133.6, 128.6,
122.9, 122.8, 120.6, 109.8, 90.3, 82.1, 79.2, 45.2, 31.5, 24.2;
νmax(KBr)/cm-1 3042, 2960, 2885, 1596, 1470, 1320, 1218, 979, 816,
748; HRMS-ESI (m/z): calcd for C17H16NO, [M+H]+: 250.1226, found
250.1220.
Acknowledgements
The authors thank the National Key Research and Development
Program of China (2016YFA0602900), the National Natural
Science Foundation of China (21490572 and 21420102003) and
Guangdong Province Science Foundation (2017B090903003) for
financial support.
3-(3-([1,1'-Biphenyl]-4-yl)prop-2-yn-1-yl)-3-methyl-2,3-
1
dihydrobenzofuran (4x): Yield: (46.7 mg, 48%), yellow oil; H NMR
(400 MHz, CDCl3) δ 7.41 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H),
7.30 - 7.25 (m, 4H), 7.18 (t, J = 8.0 Hz, 1H), 7.08 (t, J = 6.4 Hz, 1H),
7.01 (t, J = 8.0 Hz, 1H), 6.75 (t, J = 8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz,
1H), 4.40 (d, J = 8.0 Hz, 1H), 4.09 (d, J = 8.0 Hz, 1H), 2.54 (s, 2H), 1.39
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.5, 140.6, 140.4, 134.0,
132.0, 128.8, 128.6, 127.5, 127.0, 126.9, 123.0, 122.4, 120.6, 109.8,
87.4, 82.3, 82.3, 45.3, 31.6, 24.2; νmax(KBr)/cm-1 3903, 3801, 3365,
2953, 1592, 1471, 1009, 830, 747, 559; HRMS-ESI (m/z): calcd for
C24H21O, [M+H]+: 325.1587, found 325.1592.
Notes and references
1
2
3
N. D. Rode, I. Abdalghani, A. Arcadi, M. Aschi, M. Chiarini, F.
Marinelli, J. Org. Chem., 2018, 83, 6354-6362.
P, Fricero, L. Bialy, W. Czechtizky, M. Mendez, J. P. A. Harrity,
Org. Lett., 2018, 20, 198
−200
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a) T. Zhang, H. Maekawa, Org. Lett., 2017, 19, 6602-6605; b)
A. Jeevanandam, K. Narkunan, Y.-C. Ling, J. Org. Chem., 2001,
66, 6014-6020; c) A. V. Kel’in, V. Gevorgyan, J. Org. Chem.,
2002, 67, 95-98.
4
5
K. Utimoto, H. Miwa, H. Nozaki, Tetrahedron Lett., 1981, 22,
4277-4278.
3-(3-(4,6-Dihydropyren-1-yl)prop-2-yn-1-yl)-3-methyl-2,3-
1
a) S. N. Knezz, T. A. Waltz, B. C. Haenni, N. J. Burrmann, R. J.
McMahon, J. Am. Chem. Soc., 2016, 138, 12596-12604. b) O.
Hamed, P. M. Henry, D. P. Becker, Tetrahedron Lett., 2010,
51, 3514-3517. c) R. S. Coleman, X. Lu, I. Modolo, J. Am.
Chem. Soc., 2007, 129, 3826-3827. d) D. Muri, E. M. Carreira,
J. Org. Chem., 2009, 74, 8695-8712.
dihydrobenzofuran (4y): Yield: (91.0 mg, 81%), brown oil; H NMR
(400 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 8.03 (dd, J = 11.2, 7.2 Hz,
2H), 7.95 (d, J = 8.0 Hz, 1H), 7.92 (s, 2H), 7.88 (d, J = 4.0 Hz, 0H), 7.86
(s, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.14 - 7.20 (m, 1H), 6.85 (t, J = 8.0 Hz,
1H), 6.79 (d, J = 8.0 Hz, 1H), 4.62 (d, J = 8.0 Hz, 1H), 4.23 (d, J = 8.8
Hz, 1H), 2.81 (m, 2H), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.6, 134.0, 131.9, 131.2, 131.0, 130.8, 129.6, 128.6, 128.1, 127.8,
127.1, 126.1, 125.4, 125.4, 125.3, 124.3, 124.2, 123.0, 120.7, 118.1,
109.9, 92.3, 82.3, 81.5, 45.6, 32.0, 24.8; νmax(KBr)/cm-1 3668, 3354,
2932, 1727, 1590, 1219, 1050, 915, 838, 750; HRMS-ESI (m/z): calcd
for C28H23O, [M+H]+: 375.1743, found 375.1746.
6
a) H. C. Brown, C. P. Garg, J. Am. Chem. Soc., 1961, 83, 2952-
2953. b) Y. Maeda, N. Kakiuchi, S. Matsumura, T. Nishimura,
T. Kawamura, S. Uemura, J. Org. Chem., 2002, 67, 6718-
6724. c) D. A. Alonso, C. Nájera, M. C. Pacheco, J. Org. Chem.,
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2-methyl-5-(3-methyl-2,3-dihydrobenzofuran-3-yl)pent-3-yn-2-ol
(4z): Yield: (19.3 mg, 28%), yellow oil; 1H NMR (400 MHz, CDCl3) δ
7.41 (d, J = 8.0 Hz, 1H), 7.29 - 7.23 (m, 1H), 6.95- 6.84 (m, 2H), 5.22
(s, 1H), 5.02 (s, 1H), 4.49 (s, 2H), 2.17 (s, 1H), 1.89 (s, 3H), 1.65 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 159.2, 140.6, 133.4, 129.6, 120.6,
112.5, 112.3, 112.2, 97.9, 78.6, 72.0, 65.7, 31.5, 19.3; νmax(KBr)/cm-
1: 3851, 3072, 2920, 2855, 1662, 1579, 1447, 1248, 1146, 900, 743;
HRMS-ESI (m/z): calcd for C15H18NaO2, [M+Na]+: 253.1199, found
253.1201.
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,
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8
9
W. Sun, Y. Wang, X. Wu, X. Yao, Green Chem., 2013, 15,
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11868-11871.
1,4-bis(3-methyl-2,3-dihydrobenzofuran-3-yl)but-2-yne
(4ab):
1
,
Yield: (71.6 mg, 75%), yellow oil; H NMR (400 MHz, CDCl3) δ 7.08 -
6.95 (m, 4H), 6.82 - 6.75 (m, 2H), 6.71 (t, J = 7.7 Hz, 2H), 4.33 (dd, J =
14.8, 8.8 Hz, 2H), 4.03 (dd, J = 10.1, 9.0 Hz, 2H), 2.42 - 2.23 (m, 4H),
1.28 (d, J = 8.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 159.4, 134.1,
128.4, 122.7, 120.5, 109.7, 82.0, 78.7, 45.1, 30.8, 24.7; νmax(KBr)/cm-
1: 3053, 2955, 2895, 1600, 1468, 1220, 978, 747; HRMS-ESI (m/z):
calcd for C22H22NaO2, [M+Na]+:341.1512, found 341.1514.
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1306.
3-Methyl-3-(3-phenylpropyl)-2,3-dihydrobenzofuran (5a): Yield:
(75.0 mg, 99%), yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.16 (t, J =
8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 1H), 7.05 – 6.99 (m, 3H), 6.94 (d, J =
8.0 Hz, 1H), 6.76 (t, J = 7.4 Hz, 0H), 6.68 (d, J = 8.0 Hz, 0H), 4.23 (d, J
= 8.6 Hz, 0H), 4.04 (d, J = 8.6 Hz, 0H), 2.46 (t, J = 7.2 Hz, 1H), 1.54
(dd, J = 11.6, 6.0 Hz, 1H), 1.43 – 1.29 (m, 0H), 1.22 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 159.5, 142.1, 135.1, 128.3, 128.3, 127.9, 125.7,
122.8, 120.4, 109.5, 82.4, 45.1, 40.4, 36.2, 26.4, 25.6; νmax(KBr)/cm-1
3660, 3305, 3027, 2938, 1744, 1595, 1475, 1373, 835, 697; HRMS-
ESI (m/z): calcd for C18H21O, [M+H]+: 253.1587, found 253.1591.
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