Syntheses of Z-Iodovinylfurans and 2-Acyl Furans via Controllable Cyclization of Ynenones

Article abstract of DOI:10.1021/acs.joc.9b01852

A divergent synthesis of Z-iodovinylfurans and 2-acyl furans promoted by NIS via controllable cyclization of ynenones is reported. The reaction proceeded by sequential 5-exo-dig electrophilic cyclization to intermediate 2-(iodomethylene)-2H-furanium catio

Full text of DOI:10.1021/acs.joc.9b01852

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Article
Syntheses of Z-Iodovinylfurans and 2-Acyl
Furans via Controllable Cyclization of Ynenones
Mengxue Li, Fang Yang, Ting Yuan, Haoyang Li, Jian Li, Zi-Sheng Chen, and Kegong Ji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01852 • Publication Date (Web): 17 Sep 2019
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Syntheses of Z-Iodovinylfurans and 2-Acyl Furans via Controllable
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Cyclization of Ynenones
Mengxue Li,‡ Fang Yang,‡ Ting Yuan, Haoyang Li, Jian Li, Zi-Sheng Chen, Kegong
Ji*
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College of Chemistry and Pharmacy, Northwest A&F University; Shaanxi Key Laboratory of
Natural Products & Chemical Biology, 3 Taicheng Road, Yangling, 712100, Shaanxi (P.R. China).
R1
R1
R2
R1
R2
O
O
R2
O
I
NIS
NIS , N2
DCE , rt
O
DMSO , rt
R
R
R
3
2
1
15 examples
up to 98% yield
11 examples
up to 96% yield
Ynenone
I
O
N
O
R1
R1
R2
R1
R2
R2
O
O
S
O
O
DMSO
I
R
I
I
R
H
R
Int D
ABSTRACT: A divergent synthesis of Z-iodovinylfurans and 2-acyl furans promoted by NIS via
controllable cyclization of ynenones is reported. The reaction proceeded by sequential 5-exo-dig
electrophilic cyclization to intermediate 2-(iodomethylene)-2H-furanium cation D, providing a
range of synthetically valuable and useful tri-substituted furan derivatives 2 and 3 in moderate to
excellent yields. This approach is metal-free, mild and atom-economic, with good selectivity and
high stereoselectivity.
INTRODUCTION
Furan motif is a common structure pattern found in natural products,1 pharmaceuticals2 and
functional materials,3 which is also served as a building block in organic synthesis.4 Driven by this
prevalence, much attention has been paid to the synthesis of substituted furans to increase their
structural diversity and which are valuable in medicinal chemistry and drug discovery.5 In spite of
several well-established general approaches for furan synthesis, 6 metal-catalyzed reactions7-11 and
organocatalyst-promoted ractions12-13 were reported successively in recent years.14 However, these
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methods have been used less frequently in medicinal chemistry and drug discovery.5 So, the
development of new and more efficient methods, especially non-metal participated, for the
synthesis of furans is a general interest to organic chemists.
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Ynenones, serving as the carbene precursors, were reported for the synthesis of furan
derivatives in the presence of gold, palladium and copper catalysts, respectively15-17(Scheme 1a).
Moreover, Lewis acids, such as zinc and silver complexes, were also reported to catalyze
ynenones to construct furan derivatives via the intermediate furanium cation B8b,18,19 as shown in
Scheme 1b. In contrast, the number of non-metal participated examples is limited.12,13 Only
phosphine and sulfur were reported as organocatalysts to synthesize highly substituted furan
derivatives12, 13(Scheme 1c). We envisioned that electrophilic regent, such as N-iodosuccinimide,
could react with ynenone to form the 2-(iodomethylene)-2H-furanium intermediate D, followed by
nucleophile trapping (Scheme 1d).
Scheme 1. Strategies for the Synthesis of Furans from Ynenones
Previous work:
a) Sun, Xu and Zhou
R1
R1
R2
R2
R3
R4
R3
R2
R1
O
O
M
NuH
R4
Nu
[M]
M = Au, Pd, Cu
R3
O
R4
A
Int
b) Vicente and Xu
R1
R1
R2
R4
R3
R2
R1
O
O
LA
NuH
R4
Nu
R3
R2
[LA]
LA = Zn, Ag
R3
O
R4
B
Int
c) Clark and Kuroda
R1
R1
R2
R2
R3
R4
Y
R3
R2
R1
O
O
organocatalyst
PR3, R2S
R4
R3
Int
O
R4
R
C
This work:
d)
R2
R1
condition a
condition b
I
R1
O
R2
R1
O
O
electrophilic
regent
R2
R
2
O
H
NIS
R
R2
R1
I
O
R
D
Int
1
R
3
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Herein, we report the first NIS-promoted tandem cyclization of ynenones to synthesize
Z-iodovinylfuran and 2-acyl furan derivatives selectively. This approach is metal-free, mild,
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efficient and atom-economic, with good selectivity and high stereoselectivity (Scheme 1d).
RESULTS AND DISCUSSION
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At the beginning, we employed ynenone 1a for the reaction discovery and condition optimization,
and some results are shown in Table 1. The reaction was initially carried out in chlorobenzene
(PhCl) at room temperature under nitrogen for 20 minutes with N-iodosuccinimide (NIS, 1.1
equiv.)
(Z)-1-(5-(1-iodopent-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one 2a was obtained in 64% yield,
along with 72% yield of succinimide and less than 2% of
as
the
initiator.
To
our
delight,
the
product
1
1-(4-acetyl-5-methylfuran-2-yl)pentan-1-one 3a was observed from crude H NMR (entry 1).
Screening of various other solvents, revealed that aprotic solvent DCE (entry 2) was the most
effective (entries 2-7). To our surprise, no desired product 2a was observed by employing
dimethylsulfoxide (DMSO) as the solvent, but 3a was obtained in 94% yield, which revealed that
the solvent (DMSO) may be served as one of oxidants during the reaction (entry 8). Furthermore,
neither decreasing nor increasing the loading of NIS (entries 9-11) improved the yield of 2a.
Excessive NIS causes a messy reaction, indicating that 2a is unstable in the presence of excess
NIS. Other electrophilic regents I2 and NBS (N-bromosuccinimide)22 were also investigated with
no better results. Meanwhile, no reaction was observed with iodide-anion (KI) instead of NIS.
Table 1. Optimization of the Reaction Conditionsa
O
O
I
O
O
O
NIS , N2
solv. , rt
+
nBu
O
O
nBu
1a
2a
3a
NISb
time
(min)
yield (%)
2a 3a
entry
solvent
(equiv)
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1.1
1.1
1.1
1.1
PhCl
DCE
DCM
THF
Toluen
e
20
20
60
60
64
70
62
42
< 2
< 2
< 2
< 2
5
1.1
60
52
< 2
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7
1.1
PhF
20
20
69
47
0
< 2
< 2
94
1.1 CHCl3
1.1 DMSO
8
50
9
1.0
1.2
1.5
1.1
1.1
DCE
DCE
DCE
DCE
DCE
30
65
55
33
31
0
< 2
< 2
< 2
< 2
0
10
11
12c
13d
20
20
70
24 h
aThe reactions were conducted in the capped vial with a
septum under a nitrogen atmosphere. Initially, [1a] = 0.1
M. bThe loading of NIS. cReplaced NIS with I2. dReplaced
NIS with KI.
With the optimal conditions (Table 1, entry 2) in hand, the reaction scope was examined. As
shown in Scheme 2. Ynenones 1a−1e possessing aliphatic R groups reacted as expected, despite
of exhibiting moderate yields. Different functional groups at the end of the alkyl chain, such as Cl,
OBn, OTBS and OPh, were readily tolerated. Other substrates like 1f-1h, with OTIPS, OBn and
Ph installed at the β-carbon position of ynenones, reacted smoothly to afford Z-iodovinylfurans
2f-2h in good yields. The relative configuration of the product 2h was unambiguously assigned by
X-ray crystallography (CCDC 1906176) (see the Supporting Information). Ynenone 1i with a
phenyl group at the end of carbonyl group provided excellent yield of the product. The reaction
tolerated phosphate and ester R2 groups as well, the desired products 2j-2k were obtained in 59%
and 56% yields respectively.
Scheme 2. Reaction Scopea,b
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R1
R1
R2
O
I
NIS (1.1 equiv) , N2
O
R2
R
DCE , rt
R
1
2
I
O
I
O
I
O
O
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O
O
Cl
BnO
, 20 min, 54%
2c
2a
2b
, 20 min, 70%
, 30 min, 59%
I
O
I
I
O
O
O
O
O
OBn
, 10 min, 59%
OPh
TBSO
, 20 min, 54%
2f
2e
2h
, 20 min, 73%
2d
2g
Ph
I
O
I
I
O
O
O
O
O
OTIPS
Ph
Ph
2i
, 25 min, 96%
, 30 min, 72%
, 20 min, 51%
I
I
O
O
O
O
P
O
OEt
2k
O
, 20 min, 56%
2j
, 1h, 59%
a
1
All reactions were performed with (0.2 mmol, 1.0 equiv) and NIS (0.22
mmol, 1.1 equiv) in DCE 2 mL at rt under a static nitrogen atmosphere.
bThe products were isolated as single isomer.
Furthermore, more useful reactions of ynenone was investigated, namely the synthesis of 2-acyl
furans. The optional condition was that the reaction was carried out in DMSO at room temperature
with 1.0 equivalent of NIS in the air (see the Supporting Information). Thus, a tandem predictably
cyclization of ynenones 1a−1o proceeded smoothly to provide various 2-acyl furans 3a−3o in
good to excellent yields. The reaction works well with aliphatic R groups. Different functional
groups at the end of the alkyl chain, such as Cl, OBn, OTBS, OPh and Ph groups, were readily
tolerated and the corresponding products 3b-3i were obtained in excellent yields (up to 98% yield).
The reaction also tolerated phosphate and ester R2 groups, like 1j-k, and provided the 3j-k in
excellent yields. Ynenone bearing a sulfonyl R2 group provided a moderate yield of 3l because of
the poor solubility of 1l. To our delight, different substituted 2-acyl furans, like 3m-n, were also
formed efficiently through this process. Additionally, transformation of ynenone 1o with
trimethylsilyl group at the end of alkyne to useful furan-2-yl(trimethylsilyl)methanone 3o was also
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realized in a 97% yield.
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Scheme 3. Reaction scopea
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R1
R1
O
O
R2
1.0 equiv NIS
O
R3
R2
DMSO , rt
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R3
1
3
O
O
O
O
O
O
O
O
O
O
nBu
Cl
BnO
3c
, 70 min, 93%
3a
3b
, 1 h, 94%
O
, 3 h, 95%
O
O
O
O
O
O
O
O
O
BnO
TBSO
PhO
3d
3e
3f
, 3 h, 91%
, 3 h, 93%
, 50 min, 98%
Ph
O
O
O
O
O
O
O
nBu
TIPSO
Ph
, 1 h, 96%
Ph
3g
3h
3i
, 3 h, 95%
, 4 h, 93%
O
O
O
O
Ph
O
O
O
nBu
O
O
nBu
P
nBu
O
PhO2S
O
OEt
3j
3k
3l
, 48 h, 65%
, 2 h, 96%
O
, 2 h, 96%
O
O
O
O
O
O
O
Si
TIPSO
3m
3n
3o,
2 h, 97%
, 40 min, 89%
, 3 h, 76%
aReaction conditions: 1a (0.2 mmol, 1.0 equiv) and NIS as
initiator in DMSO (2 mL) in the air.
In order to gather experimental evidence for the mechanism, the ynenone 1a was tested in DCE,
with NIS (1.0 equiv) and DMSO (10 equiv) at room temperature, as shown in Scheme 4. To our
delight, a 98% yield of desired product 3a was isolated in 1 h, as well as no Z-iodovinylfuran 2a
was observed, which indicated that DMSO acted as a source of oxygen. Moreover, we also carried
out the reaction in the presence of H2O (10 equiv) in DCE without DMSO; however, less than
10% yield of 3a was observed in 1 h. The reaction was also attempted in the presence of H2O18
(10 equiv) and DMSO (10 equiv) in DCE at room temperature, and minor O18 labeled product 3a′
was detected from HRMS, indicating that the new oxygen of 3a was major from the DMSO and
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H2O existed in the reaction system can not only serve as a less efficient oxygen donor but also a
consequence of NIS inactivation with arising hydroiodic acid leading to molecular iodine.
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Scheme 4. Control Experiments.
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DMSO (10 equiv)
3a
+
+
2a
0%
DCE, rt, 1 h
98%
O
O
H2O (10 equiv)
DCE, rt, 1 h
3a
2a
63%
9%
nBu
1a
18O
nBu
DMSO (10 equiv)
H218O (10 equiv)
O
+
3a
94%
DCE, rt, 1 h
3a'
O
3a:3a'
= 6.9 :1
3a
3a'
HRMS[M+H] : 211.1211
HRMS[M+H] : 209.1177
On the basis of the above observations, we propose the following plausible mechanisms for this
transformation (Scheme 5). (i) Electrophile I+ generated from NIS first coordinates selectively
with C−C triple bonds of ynenone 1 to give iodirenium intermediate C’, subsequently the oxygen
from carbonyl group attacks iodirenium intermediate C’ via 5-exo-dig cyclization to generate
oxonium intermediate D. (ii) Succinimide anion generated from NIS eliminates the α-H of
oxonium intermediate D to form Z-iodovinylfurans 2. (iii) If the reaction is carried out in DMSO,
DMSO serves as a nucleophile to attack iodirenium intermediate D and gives sulfonium salt
intermediate F, where one molecular of DMSO or succinimide anion as nucleophile attacks the
sulfonium salt intermediate F and drives the iodine anion away to give the 2-acyl furan 3 and
Scheme 5. Proposed mechanisms
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R2
R2
R1
I2
S
O
+
I
R3
R1
1
O
O
R3
I-
3
2
NIS
S
HI
O
O
N
H
O
Nu
R1
O
R1
O
R1
R2
R2
R2
R1
R2
OH
I
O
O
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R3
O
E
F
R3
S
I
G
I
I
Nu-
R3
R3
C'
O
O
N
Path 2
H2O
O
O
N
O
O
N
H
Path 1
R1
R2
R3
R3
R1
R2
O
O
O
O
Nu-=
or
O
N
H
O
N
O
S
I
I
DMSO
D
D
sulfonium salt H, which is reduced by iodine anion to iodine and dimethyl sulfide23. (iv)
Moreover, H2O existed in the reaction system can also serve as a less efficient nucleophile to
attack iodirenium intermediate D and gives intermediate G, which is unstable and quickly
transfers to 2-acyl furan 3.
We also carried out 1i at a gram scale (1.265g, 4 mmol) with NIS as the initiator，where the
desired Z-iodovinylfuran 2i and 2-acyl furan 3i were isolated in 77% and 92% yields respectively.
The synthetic utility of the Z-iodovinylfuran products were also examined by using 2i as an
illustrative example, as shown in Scheme 6. Several palladium-catalyzed processes performed
well, including Heck reaction, Suzuki coupling and Sonogashira coupling, and the desired
products 4a-4c were synthesized in excellent yields.
Scheme 6. Transformations of 2i
O
O
Ph
O
O
NIS (1.0 equiv)
DMSO, rt
Ph
Ph
O
nBu
Ph
nBu
4 mmol 1.265g
1i
3i,
92%
NIS (1.1 equiv)
DCE, N2, rt
Ph
CO2Et
Ph
Ph
O
I
O
PhB(OH)2
Pd(PPh3)2Cl2
Ph
Ethyl acrylate
Pd(PPh3)2Cl2
O
O
O
Pr
Pr
O
Pr
℃
K2CO3, 80
H2O , Toluene
Et3N , DMF
Ph
Ph
℃
80
Ph
2i,
77%
4b,
90%
4a,
85%
Ph
Pd(PPh3)2Cl2/CuI
Et3N , rt , 10 h
Ph
Ph
O
O
Pr
Ph
4c,
87%
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We have reported an efficient strategy starting from ynenones to construct substituted
Z-iodovinylfurans 2 and 2-acyl furan derivatives 3 selectively via a N-iodosuccinimide promoted
tandem cyclization. This approach is metal-free, mild and efficient. And the Z-iodovinylfuran
product 2i readily undergo further transformations, substantially broaden the scope of accessible
multi-substituted furan products and notably enhance the synthetic utility of these cascade
reactions. Meanwhile, a useful transformation product furan-2-yl(trimethylsilyl)methanone 3o can
be synthesized in the yield of 97% from simple ynenone. Control experiments suggest that DMSO
is an efficient oxygen donor in the synthesis of 2-acyl furans 3.
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EXPERIMENTAL SECTION
General Information. Ethyl acetate (ACS grade), hexanes (ACS grade), diethyl ether (ACS grade)
and anhydrous 1,2-dichloroethane (anhydride, 99.8%) were purchased from Fisher Scientific and
used without further purification. Methylene chloride and tetrahydrofuran were purified using
MBraun Solvent Purifier. Commercially available reagents were used without further purification.
Reactions were monitored by thin layer chromatography (TLC) using Sorbent Technologies’
pre-coated silica gel plates. Flash column chromatography was performed over Sorbent
Technologies’ silica gel (230-400 mesh). 1H{13C} NMR and 13C{1H}NMR spectra were recorded
on Bruker 500 MHz spectrometers using residue solvent peaks as internal standards. Mass spectra
were recorded with Micromass Thermo Scientific LTQ Orbitrap XL and AB SCIEX Triple
TOF5600+ using electron spray ionization or Waters GCT Premier time-of-flight mass
spectrometer with a field ionization (FI) ion source. 13C{1H} NMR spectra were recorded on a
Bruker AV-500 spectrometer and a Bruker AV-500 spectrometer in chloroform-d3. Chemical
shifts are reported in ppm with the internal chloroform signal at 7.26 and 77.0 ppm as a standard
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and CD3OD signal at 3.31 and 49.0 ppm as a standard.
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General Procedure for the Synthesis of 1. Example for the Synthesis of 1b. Piperidine (75.0 mg,
0.8 mmol, 0.1 equiv), acetic acid (317.0 mg, 5.3 mmol, 0.6 equiv) and magnesium sulfate (1.10 g,
8.8 mmol, 1.0 equiv) were added to a stirred solution of 6-chlorohex-2-ynal (1.15 g, 8.8 mmol, 1.0
equiv) and acetylacetone (889.9 mg, 8.8 mmol, 1.01 equiv) in toluene (25 mL) at ambient
temperature. The reaction mixture was stirred at 35°C for overnight with oil bath and the reaction
was quenched by the addition of water (30 cm3). The aqueous layer was extracted with ethyl
acetate (3 × 100 cm3) and the combined organic layers were dried (magnesium sulfate) and
concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent:
hexanes/ethyl acetate = 20:1 ) and 1b was isolated in 729.9 mg, 3.4 mmol, 39%, yellow liquid.
3-(hept-2-yn-1-ylidene)pentane-2,4-dione (1a).20 Isolated by column chromatography
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(hexanes/ethyl acetate = 30:1 ) in 299.9 mg, 1.56 mmol, 82%, yellow liquid. H{13C} NMR (500
MHz, CDCl3) δ: 6.69 (1H, td, J = 2.5, 1.0 Hz), 2.46 (3H, d, J = 1.0 Hz), 2.43 (2H, tdd, J = 7.5, 2.5,
1.0 Hz), 2.30 (3H, d, J = 1.0 Hz), 1.57 - 1.52 (2H, m), 1.45 - 1.37 (2H, m), 0.92 (3H, td, J = 7.5,
1.0 Hz).
3-(6-chlorohex-2-yn-1-ylidene)pentane-2,4-dione (1b). 729.9 mg, 3.4 mmol, 39%, yellow liquid.
1H{13C} NMR (500 MHz, CDCl3) δ: 6.65 - 6.64 (1H, t, J = 2.5 Hz), 3.64 - 3.61 (2H, t, J = 6.0
Hz), 2.65 - 2.62 (2H, td, J = 2.5, 7.0 Hz), 2.44 (3H, s), 2.30 (3H, s), 2.03 - 1.98 (2H, m). 13C{1H}
NMR (125 MHz, CDCl3) δ: 201.1, 195.6, 150.1, 122.4, 107.4, 77.4, 43.3, 30.8, 30.6, 27.0, 17.5.
HRMS (ESI) m/z calcd for C11H14ClO2+ (M+H)+ 213.0677, found 213.0676.
3-(6-(benzyloxy)hex-2-yn-1-ylidene)pentane-2,4-dione (1c). Isolated by column chromatography
1
( hexanes/ethyl acetate = 25:2 ) in 341.2 mg, 1.2 mmol, 13%, yellow liquid. H{13C} NMR (500
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MHz, CDCl3) δ: 7.36 - 7.31 (4H, m), 7.30 - 7.27 (1H, m), 6.66 - 6.65 (1H, t, J = 2.5 Hz), 4.51 (2H,
s), 3.56 - 3.53 (2H, t, J = 6.3 Hz), 2.59 - 2.56 (2H, td, J = 7.1, 2.2 Hz), 2.44 (3H, s), 2.31 (3H, s),
1.89 - 1.83 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 201.0, 195.5, 149.5, 138.1, 128.2, 127.4,
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+
122.7, 122.7, 109.3, 76.8, 72.8, 68.2, 30.7, 28.1, 26.9, 16.9. HRMS (ESI) m/z calcd for C18H21O3
(M+H)+ 285.1485, found 285.1488.
3-(6-((tert-butyldimethylsilyl)oxy)hex-2-yn-1-ylidene)pentane-2,4-dione (1d). Isolated by column
chromatography ( hexanes/ethyl acetate = 20:1 ) in 431.9 mg, 1.4 mmol, 16%, yellow liquid.
1H{13C} NMR (500 MHz, CDCl3) δ: 6.68 - 6.67 (1H, t, J = 2.5 Hz), 3.68 - 3.65 (2H, t, J = 5.8
Hz), 2.54 - 2.51 (2H, td, J = 7.1, 2.5 Hz), 2.46 (3H, s), 2.30 (3H, s), 1.77 - 1.72 (2H, m), 0.88 (9H,
s), 0.04 (6H, s) . 13C{1H} NMR (125 MHz, CDCl3) δ: 201.2, 195.7, 149.6, 123.1, 110.0, 76.9,
61.2, 31.1, 30.9, 27.2, 25.8, 18.2, 16.7, -5.4. HRMS (ESI) m/z calcd for C17H29O3Si+ (M+H)+
309.1881, found 309.1881.
3-(6-phenoxyhex-2-yn-1-ylidene)pentane-2,4-dione (1e). Isolated by column chromatography
( hexanes/ethyl acetate = 20:1 ) in 621.8 mg, 2.3 mmol, 21%, yellow liquid. H{13C} NMR (500
1
MHz, CDCl3) δ: 7.30 - 7.25 (2H, m), 6.96 - 6.93 (1H, t, J = 6.8 Hz), 6.90 - 6.89 (2H, d, J = 8.0
Hz), 6.66 (1H, s), 4.05 - 4.03 (2H, t, J = 6.0 Hz), 2.68 - 2.66 (2H, t, J = 7.0 Hz), 2.42 (3H, s), 2.30
(3H, s), 2.06 - 2.01 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 201.2, 195.7, 158.7, 149.9,
129.5, 122.8, 120.8, 114.4, 108.7, 77.2, 65.8, 30.9, 27.9, 27.1, 17.0. HRMS (ESI) m/z calcd for
C17H19O3+ (M+H)+ 271.1329, found 271.1330.
3-(5-(benzyloxy)pent-2-yn-1-ylidene)pentane-2,4-dione (1f). Isolated by column chromatography
( hexanes/ethyl acetate = 10:1 ) in 973.2 mg, 3.6 mmol, 23%, yellow liquid. 1H{13C} NMR (500
MHz, CDCl3) δ: 7.37 - 7.28 (5H, m), 6.68 – 6.67 (1H, t, J = 2.3 Hz), 4.54 (2H, s), 3.64 – 3.61 (2H,
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t, J = 6.8 Hz), 2.76 – 2.73 (2H, td, J = 6.5, 2.0 Hz), 2.45 (3H, s), 2.30 (3H, s). 13C{1H} NMR (125
MHz, CDCl3) δ : 201.1, 195.7, 149.8, 137.7, 128.4, 127.8, 127.7, 122.6, 106.6, 77.5, 73.1, 67.5,
30.9, 27.2, 21.7. HRMS (ESI) m/z calcd for C17H18O3Na+ (M+Na)+ 293.1148, found 293.1143;
HRMS (ESI) m/z calcd for C17H19O3+ (M+H)+ 271.1329, found 271.1329.
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3-(5-((triisopropylsilyl)oxy)pent-2-yn-1-ylidene)pentane-2,4-dione (1g). Isolated by column
chromatography ( hexanes/ethyl acetate = 30:1 ) in 605.8 mg, 1.8 mmol, 25%, yellow liquid.
1H{13C} NMR (500 MHz, CDCl3) δ: 6.69 - 6.68 (1H, t, J = 2.5 Hz), 3.85 - 3.83 (2H, t, J = 6.8
Hz), 2.69 - 2.66 (2H, td, J = 2.3, 6.8 Hz), 2.48 (3H, s), 2.30 (3H, s), 1.10 - 1.07 (3H, m), 1.06 -
1.05 (18H, d, J = 5.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 201.1, 195.7, 149.6, 122.9, 107.3,
77.7, 61.4, 31.0, 27.3, 24.7, 17.9, 11.9. HRMS (ESI) m/z calcd for C19H33O3Si+ (M+H)+ 337.2194,
found 337.2195.
3-(5-phenylpent-2-yn-1-ylidene)pentane-2,4-dione (1h).21 Isolated by column chromatography
1
( hexanes/ethyl acetate = 15:1 ) in 192.2 mg, 0.8 mmol, 50%, yellow liquid. H{13C} NMR (500
MHz, CDCl3) δ: 7.32 - 7.29 (2H, m), 7.24 - 7.19 (3H, m), 6.65 (1H, t, J = 2.5 Hz), 2.87 (2H, t, J =
7.3 Hz), 2.75 (2H, td, J = 7.4, 2.7 Hz), 2.34 (3H, s), 2.29 (3H, s). 13C{1H} NMR (125 MHz,
CDCl3) δ: 201.2, 195.7, 149.6, 139.7, 128.5, 128.3, 126.5, 122.7, 108.9, 77.4, 34.2, 30.8, 27.1,
22.1.
2-(hept-2-yn-1-ylidene)-1,3-diphenylpropane-1,3-dione (1i).12 Isolated by column chromatography
( hexanes/ethyl acetate = 100:1 ) in 348.0 mg, 1.1 mmol, 23%, yellow liquid. 1H{13C} NMR (500
MHz, CDCl3) δ: 7.96 - 7.94 (2H, m), 7.79 - 7.77 (2H, m), 7.58 - 7.51 (2H, m), 7.47 - 7.41 (4H, m),
6.72 (1H, t, J = 1.1 Hz), 2.19 (2H, td, J = 7.0, 2.2 Hz), 1.26 - 1.21 (2H, m), 1.17 - 1.10 (2H, m),
0.76 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 194.4, 193.1, 147.8, 136.9, 136.3,
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133.6, 132.7, 129.5, 129.2, 128.6, 128.5, 125.5, 109.7, 76.8, 29.8, 21.6, 19.6, 13.4.
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dimethyl (E)-(2-oxodec-3-en-5-yn-3-yl)phosphonate (1j).12 Isolated by column chromatography
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( hexanes/ethyl acetate = 5:2 ) in 309.9 mg, 1.2 mmol, 15%, orange liquid. H{13C} NMR (500
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MHz, CDCl3) δ: 6.95 - 6.90 (1H, dt, J = 21.8, 2.4 Hz), 3.78 - 3.75 (6H, d, J = 11 Hz), 2.50 (3H, s),
2.46 - 2.42 (2H, td, J = 7.0, 3.0 Hz), 1.58 - 1.52 (2H, m), 1.45 - 1.39 (2H, m), 0.92 - 0.89 (3H, t, J
= 7.3 Hz).
ethyl (E)-2-acetylnon-2-en-4-ynoate (1k).12 Isolated by column chromatography ( hexanes/ethyl
acetate = 50:1 ) in 367.8 mg, 1.6 mmol, 38%, yellow liquid. 1H{13C} NMR (500 MHz, CDCl3)
δ: 6.78 - 6.77 (1H, t, J = 2.8 Hz), 4.25 - 4.21 (2H, q, J = 7.0 Hz), 2.42 (3H, s), 2.41 - 2.38 (2H, td,
J = 7.2, 2.8 Hz), 1.54 - 1.49 (2H, m), 1.43 - 1.35 (2H, m), 1.29 - 1.26 (3H, t, J = 7.3 Hz), 0.91 -
0.88 (3H, t, J = 7.3 Hz).
(E)-1-phenyl-2-(phenylsulfonyl)non-2-en-4-yn-1-one (1l). Isolated by column chromatography
( hexanes/ethyl acetate = 20:1 ) in 761.3 mg, 2.2 mmol, 36%, white solid. 1H{13C} NMR (500
MHz, CDCl3) δ: 7.90 - 7.88 (4H, d, J = 7.5 Hz), 7.66 - 7.58 (2H, m), 7.56 - 7.53 (2H, t, J = 7.5
Hz), 7.47 - 7.44 (2H, t, J = 7.5 Hz), 7.16 - 7.15 (1H, t, J = 2.5 Hz), 2.10 - 2.07 (2H, td, J = 6.9, 2.8
Hz), 1.11 - 1.06 (2H, m), 1.02 - 0.97 (2H, m), 0.70 - 0.67 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125
MHz, CDCl3) δ: 190.1, 148.6, 139.7, 135.8, 134.2, 133.8, 129.9, 129.1, 128.6, 128.6, 124.9, 110.8,
74.9, 29.6, 21.5, 19.4, 13.3. HRMS (ESI) m/z calcd for C21H20O3SNa+ (M+Na)+ 375.1025, found
375.1028.
3-(3-cyclopropylprop-2-yn-1-ylidene)pentane-2,4-dione
(1m).10d
Isolated
by
column
chromatography ( hexanes/ethyl acetate = 20:1 ) in 405.3 mg, 2.3 mmol, 31%, yellow solid.
1H{13C} NMR (500 MHz, CDCl3) δ: 6.65 - 6.64 (1H, t, J = 2.5 Hz), 2.41 (3H, s), 2.26 (3H, s),
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1.45 - 1.43 (1H, m), 0.96 - 0.93 (2H, m), 0.81 - 0.79 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ:
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201.0, 195.7, 148.8, 123.6, 114.5, 72.7, 30.8, 27.2, 9.8, 1.1. HRMS (ESI) m/z calcd for C11H13O2
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(M+H)+ 177.0910, found 177.0913.
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3-(4-((triisopropylsilyl)oxy)pent-2-yn-1-ylidene)pentane-2,4-dione (1n). Isolated by column
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chromatography ( hexanes/ethyl acetate = 30:1 ) in 1.15 g, 3.4 mmol, 41%, white solid. H{13C}
NMR (500 MHz, CDCl3) δ: 6.71 (1H, s), 4.81 - 4.77 (1H, q, J = 6.5 Hz), 2.47 (3H, s), 2.31 (3H,
s), 1.49 - 1.48 (3H, d, J = 6.5 Hz), 1.11 - 1.05 (21H, m). 13C{1H} NMR (125 MHz, CDCl3) δ:
200.8, 195.5, 149.9, 121.7, 110.2, 78.8, 59.6, 30.9, 27.3, 25.0, 17.9, 12.1. HRMS (ESI) m/z calcd
for C19H33O3Si+ (M+H)+ 337.2194, found 337.2196.
3-(3-(trimethylsilyl)prop-2-yn-1-ylidene)pentane-2,4-dione
(1o).12
Isolated
by
column
chromatography ( hexanes/ethyl acetate = 50:1 ) in 748.8 mg, 3.6 mmol, 80%, yellow solid.
1H{13C} NMR (500 MHz, CDCl3) δ: 6.65 (1H, s), 2.48 (3H, s), 2.29 (3H, s), 0.20 (9H, s). 13C{1H}
NMR (125 MHz, CDCl3) δ: 200.8, 195.4, 150.6, 121.4, 114.7, 99.7, 30.8, 27.4, -0.7. HRMS (ESI)
m/z calcd for C11H17O2Si+ (M+H)+ 209.0992, found 209.0994.
General Procedure for the Synthesis of 2. Example for the Synthesis of 2a. Under nitrogen
atmosphere, 0.2 mmol 1a (38.5 mg, 1.0 equiv), 0.22 mmol N-iodosuccinimide (NIS) (49 mg, 1.1
equiv) and 2 mL dry DCE were added to a flamed dried Schlenk flask. The resulting mixture was
stirred at room temperature for about 20 minutes and the progress of the reaction was monitored
by TLC. Upon completion, the reaction mixture was concentrated under vacuum. The residue was
purified by chromatography on silica gel (eluent: hexanes/ethyl acetate = 50:1 ) to afford the
desired product 2a (44.3 mg) in 70% yield as a light yellow liquid.
(Z)-1-(5-(1-iodopent-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2a). 44.3 mg, light yellow liquid,
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70%. 1H{13C} NMR (500 MHz, CDCl3) δ: 6.68 (1H, s), 6.33 (1H, t, J = 7.0 Hz), 2.57 (3H, s), 2.40
(3H, s), 2.29 (2H, q, 7.2 Hz), 1.57 - 1.50 (2H, m), 0.99 (3H, t, J = 7.5 Hz). 13C{1H} NMR (125
MHz, CDCl3) δ: 194.0, 158.6, 151.3, 136.3, 122.6, 111.1, 88.4, 38.5, 29.1, 21.7, 14.6, 13.8.
HRMS (ESI) m/z calcd for C12H16IO2+ (M+H)+ 319.0190, found 319.0188.
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(Z)-1-(5-(4-chloro-1-iodobut-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2b). Isolated by short
column chromatography ( hexanes/ethyl acetate = 30:1 ) in 40.0 mg, yellow solid, 59%. 1H{13C}
NMR (500 MHz, CDCl3) δ: 6.74 (1H, s), 6.44 - 6.41 (1H, t, J = 6.8 Hz), 3.66 - 3.63 (2H, t, J = 6.8
Hz), 2.82 - 2.78 (2H, q, J = 6.7 Hz), 2.58 (3H, s), 2.41 (3H, s). 13C{1H} NMR (125 MHz, CDCl3)
δ: 193.8, 159.1, 150.7, 131.3, 122.7, 112.2, 90.9, 42.6, 39.6, 29.1, 14.7. HRMS (ESI) m/z calcd for
C11H13ClIO2+ (M+H)+ 338.9643, found 338.9645.
(Z)-1-(5-(4-(benzyloxy)-1-iodobut-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2c). Isolated by
short column chromatography ( hexanes/ethyl acetate = 15:1 ) in 42.8 mg, yellow liquid, 54%.
1H{13C} NMR (500 MHz, CDCl3) δ: 7.36 - 7.33 (4H, m), 7.31 - 7.28 (1H, m), 6.71 (1H, s), 6.45 -
6.42 (1H, t, J = 7.0 Hz), 4.56 (2H, s), 3.63 - 3.61 (2H, t, J = 6.5 Hz), 2.65 - 2.61 (2H, q, J = 6.7
Hz), 2.57 (3H, s), 2.41 (3H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.9, 158.8, 151.0, 138.1,
132.8, 128.4, 127.6, 127.6, 122.6, 111.4, 89.8, 72.9, 68.2, 37.2, 29.1, 14.6. HRMS (ESI) m/z calcd
for C18H20IO3+ (M+H)+ 411.0452, found 411.0453.
(Z)-1-(5-(4-((tert-butyldimethylsilyl)oxy)-1-iodobut-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2d).
Isolated by short column chromatography ( hexanes/ethyl acetate = 50:1 ) in 48.1 mg, light yellow
1
liquid, 54%. H{13C} NMR (500 MHz, CDCl3) δ: 6.69 (1H, s), 6.43 - 6.40 (1H, t, J = 7.0 Hz),
3.76 - 3.73 (2H, t, J = 6.8 Hz), 2.56 (3H, s), 2.55 - 2.51 (2H, q, J = 6.7 Hz), 2.40 (3H, s), 0.90 (9H,
s), 0.07 (6H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.9, 158.8, 151.1, 133.1, 122.6, 111.3,
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89.5, 61.4, 40.1, 29.1, 25.9, 18.3, 14.6, -5.3. HRMS (ESI) m/z calcd for C17H28IO3Si+ (M+H)+
435.0847, found 435.0849.
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(Z)-1-(5-(1-iodo-4-phenoxybut-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2e). Isolated by short
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column chromatography ( hexanes/ethyl acetate = 50:1 ) in 57.7 mg, white solid, 73%. H{13C}
NMR (500 MHz, CDCl3) δ: 7.31 - 7.28 (2H, t, J = 7.8 Hz), 6.98 - 6.92 (3H, m), 6.74 (1H, s), 6.53
- 6.50 (1H, t, J = 6.8 Hz), 4.11 - 4.09 (2H, t, J = 6.3 Hz), 2.83 - 2.79 (2H, q, J = 6.7 Hz), 2.58 (3H,
s), 2.41 (3H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.8, 158.9, 158.7, 151.0, 131.9, 129.5,
+
122.7, 120.9, 114.5, 111.7, 90.4, 65.9, 36.8, 29.1, 14.6. HRMS (ESI) m/z calcd for C17H18IO3
(M+H)+ 397.0295, found 397.0297.
(Z)-1-(5-(3-(benzyloxy)-1-iodoprop-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2f). Isolated by
short column chromatography ( hexanes/ethyl acetate = 20:1 ) in 46.7 mg, light yellow liquid,
59%. 1H{13C} NMR (500 MHz, CDCl3) δ: 7.37 – 7.29 (5H, m), 6.67 (1H, s), 6.64 - 6.62 (1H, t, J
= 5.8 Hz), 4.58 (2H, s), 4.30 – 4.28 (2H, d, J = 5.5 Hz), 2.57 (3H, s), 2.41 (3H, s). 13C{1H} NMR
(125 MHz, CDCl3) δ: 193.7, 159.3, 150.5, 137.8, 132.2, 128.4, 127.8, 127.8, 122.8, 112.4, 88.3,
74.2, 72.7, 29.1, 14.6. HRMS (ESI) m/z calcd for C17H17IO3Na+ (M+Na)+ 419.0115, found
419.0122.
(Z)-1-(5-(1-iodo-3-((triisopropylsilyl)oxy)prop-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one
(2g).
Isolated by short column chromatography ( hexanes/ethyl acetate = 50:1 ) in 46.7 mg, yellow
liquid, 51%. H{13C} NMR (500 MHz, CDCl3) δ: 6.74 (1H, s), 6.58 - 6.56 (1H, t, J = 5.5 Hz),
1
4.47 - 4.46 (2H, d, J = 5.0 Hz), 2.58 (3H, s), 2.41 (3H, s), 1.17 - 1.12 (3H, m), 1.10 - 1.08 (18H, d,
J = 6.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.8, 159.2, 150.6, 135.8, 122.8, 111.8, 85.0,
68.7, 29.1, 18.0, 14.7, 12.0. HRMS (ESI) m/z calcd for C19H32IO3Si+ (M+H)+ 463.1160, found
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(Z)-1-(5-(1-iodo-3-phenylprop-1-en-1-yl)-2-methylfuran-3-yl)ethan-1-one (2h). Isolated by short
column chromatography ( hexanes/ethyl acetate = 100:3 ) in 52.5 mg, yellow solid, 72%. 1H{13C}
NMR (500 MHz, CDCl3) δ: 7.37 - 7.34 (2H, m), 7.30 - 7.27 (3H, m), 6.78 (1H, s), 6.53 (1H, t, J =
7.3 Hz), 3.71 (2H, d, J = 7.0 Hz), 2.58 (3H, s), 2.44 (3H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
193.9, 158.9, 151.0, 138.5, 134.6, 128.7, 128.6, 126.6, 122.7, 111.9, 89.2, 42.4, 29.1, 14.6. HRMS
(ESI) m/z calcd for C16H16IO2+ (M+H)+ 367.0190, found 367.0185.
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(Z)-(5-(1-iodopent-1-en-1-yl)-2-phenylfuran-3-yl)(phenyl)methanone (2i). Isolated by short column
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chromatography ( hexanes/ethyl acetate = 150:1 ) in 84.9 mg, light yellow solid, 96%. H{13C}
NMR (500 MHz, CD3OD) δ: 8.60 - 8.59 (2H, m), 8.45 - 8.39 (3H, m), 8.29 - 8.25 (2H, m), 8.18 -
8.15 (3H, m), 7.61 (1H, s), 7.44 (1H, t, J = 7.0 Hz), 3.11 - 3.07 (2H, m), 2.36 - 2.28 (2H, m), 1.75
(3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CD3OD) δ: 200.1, 163.5, 161.3, 147.2, 146.6,
142.8, 138.8, 138.7, 138.4, 138.1, 138.0, 136. 5, 131.5, 122.6, 98.2, 47.6, 30.6, 23.2. HRMS (ESI)
m/z calcd for C22H20IO2+ (M+H)+ 443.0503, found 443.0508.
dimethyl (Z)-(5-(1-iodopent-1-en-1-yl)-2-methylfuran-3-yl)phosphonate (2j). Isolated by short
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column chromatography ( hexanes/ethyl acetate = 3:1 ) in 45.4 mg, orange liquid, 59%. H{13C}
NMR (500 MHz, CDCl3) δ: 6.51 (1H, d, J = 3.5 Hz), 6.33 - 6.30 (1H, t, J = 7.0 Hz), 3.74 (3H, s),
3.72 (3H, s), 2.50 (3H, d, J = 1.5 Hz), 2.30 - 2.25 (2H, q, J = 7.3 Hz), 1.56 - 1.48 (2H, m), 0.99 -
0.96 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 160.9 - 160.7 (d, J = 26.1 Hz), 152.7
- 152.6 (d, J = 15.8 Hz), 136.5, 112.8 - 112.7 (d, J = 11.8 Hz), 108.2, 106.5, 88.1, 52.4 (d, J = 5.4
Hz), 38.5, 21.7, 13.8. HRMS (ESI) m/z calcd for C12H19IO4P+ (M+H)+ 385.0060, found 385.0063.
ethyl (Z)-5-(1-iodopent-1-en-1-yl)-2-methylfuran-3-carboxylate (2k). Isolated by short column
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chromatography (hexanes/ethyl acetate = 100:1 ) in 36.2 mg, yellow solid, 56%. H{13C} NMR
(500 MHz, CDCl3) δ: 6.71 (1H, s), 6.32 - 6.29 (1H, t, J = 7.0 Hz), 4.30 - 4.26 (2H, q, J = 7.0 Hz),
2.56 (3H, s), 2.30 - 2.26 (2H, q, J = 7.3 Hz), 1.57 - 1.49 (2H, m), 1.36 - 1.33 (3H, t, J = 7.3 Hz),
1.00 - 0.97 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 163.8, 159.2, 151.3, 136.0,
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115.0, 111.3, 88.6, 60.2, 38.5, 21.7, 14.4, 14.0, 13.8. HRMS (ESI) m/z calcd for C13H18IO3
(M+H)+ 349.0295, found 349.0294.
General Procedure for the Synthesis of Products 3. Example for the Synthesis of 3a. To a 3 dram
vial containing 2 mL of DMSO were added sequentially the ynenone 1a (0.20 mmol) and
N-iodosuccinimide (NIS) (0.20 mmol, 45.0 mg, 1.0 equiv). The resulting mixture was stirred at
room temperature for about 3.5 hours, and the progress of the reaction was monitored by TLC.
Upon completion, the reaction mixture was quenched by H2O (8 mL), extracted by diethyl ether
and dried by Na2SO4 and then concentrated under vacuum. The residue was purified by
chromatography on silica gel (eluent: hexanes/ethyl acetate = 20:1) to afford the desired product
3a (38.5 mg) in 94% yield as a yellow solid.
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1-(4-acetyl-5-methylfuran-2-yl)pentan-1-one (3a).13a 38.5 mg, yellow solid, 94%. H{13C} NMR
(500 MHz, CDCl3) δ: 7.35 (1H, s), 2.76 (2H, t, J = 7.5 Hz), 2.65 (3H, s), 2.43 (3H, s), 1.70 - 1.64
(2H, m), 1.41 - 1.33 (2H, m), 0.92 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.3,
189.3, 162.1, 150.1, 123.1, 116.9, 38.0, 28.9, 26.3, 22.3, 14.8, 13.8. HRMS (ESI) m/z calcd for 3a
C12H17O3+ (M+H)+ 209.1172, found 209.1169.
1-(4-acetyl-5-methylfuran-2-yl)-4-chlorobutan-1-one (3b). Isolated by short column
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chromatography ( hexanes/ethyl acetate = 15:1 ) in 44.2 mg, yellow liquid, 95%. H{13C} NMR
(500 MHz, CDCl3) δ: 7.41 (1H, s), 3.65 - 3.63 (2H, t, J = 6.3 Hz), 3.02 - 2.99 (2H, t, J = 7.0 Hz),
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2.67 (3H, s), 2.45 (3H, s), 2.22 - 2.17 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.2, 187.7,
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162.4, 149.8, 123.2, 117.3, 44.3, 35.0, 29.0, 26.4, 14.8. HRMS (ESI) m/z calcd for C11H14ClO3
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(M+H)+ 229.0626, found 229.0626.
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1-(4-acetyl-5-methylfuran-2-yl)-4-(benzyloxy)butan-1-one (3c). Isolated by short column
chromatography ( hexanes/ethyl acetate = 8:1 ) in 55.4 mg, light yellow solid, 93%. 1H{13C} NMR
(500 MHz, CDCl3) δ: 7.36 (1H, s), 7.33 - 7.29 (4H, m), 7.28 - 7.25 (1H, m), 4.48 (2H, s), 3.56 -
3.64 (2H, t, J = 6.0 Hz), 2.93 - 2.90 (2H, t, J = 7.3 Hz), 2.66 (3H, s), 2.42 (3H, s), 2.06 - 2.01 (2H,
m). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.3, 188.7, 162.2, 145.0, 138.3, 128.3, 127.5, 123.0,
117.2, 72.8, 69.1, 34.9, 28.9, 24.2, 14.8. HRMS (ESI) m/z calcd for C18H21O4+ (M+H)+ 301.1434,
found 301.1439.
1-(4-acetyl-5-methylfuran-2-yl)-4-((tert-butyldimethylsilyl)oxy)butan-1-one (3d). Isolated by short
column chromatography ( hexanes/ethyl acetate = 12:1 ) in 59.0 mg, colorless liquid, 91%.
1H{13C} NMR (500 MHz, CDCl3) δ: 7.38 (1H, s), 3.69 - 3.67 (2H, t, J = 6.0 Hz), 2.90 - 2.87 (2H,
t, J = 7.5 Hz), 2.67 (3H, s), 2.45 (3H, s), 1.96 - 1.90 (2H, m), 0.88 (9H, s), 0.04 (6H, s). 13C{1H}
NMR (125 MHz, CDCl3) δ: 193.4, 189.1, 162.2, 150.1, 123.1, 117.1, 62.0, 34.7, 29.0, 27.3, 25.9,
18.3, 14.8, -5.4. HRMS (ESI) m/z calcd for C17H29O4Si+ (M+H)+ 325.1830, found 325.1831.
1-(4-acetyl-5-methylfuran-2-yl)-4-phenoxybutan-1-one (3e). Isolated by short column
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chromatography ( hexanes/ethyl acetate = 20:1 ) in 56.1 mg, white solid, 98%. H{13C} NMR
(500 MHz, CDCl3) δ: 7.39 (1H, s), 7.28 - 7.24 (2H, t, J = 8.0 Hz), 6.94 - 6.91 (1H, t, J = 7.8 Hz),
6.88 - 6.87 (2H, d, J = 7.5 Hz), 4.05 - 4.02 (2H, t, J = 5.3 Hz), 3.08 - 3.01 (2H, t, J = 7.5 Hz), 2.65
(3H, s), 2.41 (3H, s), 2.23 - 2.19 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.3, 188.4,
162.3, 158.7, 149.9, 129.4, 123.0, 120.7, 117.2, 114.3, 66.4, 34.7, 28.9, 23.7, 14.8. HRMS (ESI)
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m/z calcd for C17H19O4+ (M+H)+ 287.1278, found 287.1280.
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1-(4-acetyl-5-methylfuran-2-yl)-3-(benzyloxy)propan-1-one (3f). Isolated by short column
chromatography ( hexanes/ethyl acetate = 8:1 ) in 52.1 mg, light yellow solid, 91%. 1H{13C} NMR
(500 MHz, CDCl3) δ: 7.37 – 7.29 (5H, m), 6.67 (1H, s), 6.64 - 6.62 (1H, t, J = 5.8 Hz), 4.58 (2H,
s), 4.30 – 4.28 (2H, d, J = 5.5 Hz), 2.57 (3H, s), 2.41 (3H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
193.7, 159.3, 150.5, 137.8, 132.2, 128.4, 127.8, 127.8, 122.8, 112.4, 88.3, 74.2, 72.7, 29.1, 14.6.
HRMS (ESI) m/z calcd for C17H18O4Na+ (M+Na)+ 309.1097, found 309.1108.
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1-(4-acetyl-5-methylfuran-2-yl)-3-((triisopropylsilyl)oxy)propan-1-one (3g). Isolated by short
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column chromatography (hexanes/ethyl acetate = 15:1 ) in 67.1 mg, yellow solid, 95%. H{13C}
NMR (500 MHz, CDCl3) δ: 7.40 (1H, s), 4.10 - 4.08 (2H, t, J = 6.3 Hz), 3.01 - 2.99 (2H, t, J = 6.5
Hz), 2.66 (3H, s), 2.44 (3H, s), 1.08 - 1.03 (3H, m), 1.01 - 1.00 (18H, d, J = 6.0 Hz). 13C{1H}
NMR (125 MHz, CDCl3) δ: 193.3, 187.8, 162.5, 150.5, 123.1, 117.7, 59.5, 41.8, 29.0, 17.9, 14.8,
11.9. HRMS (ESI) m/z calcd for C19H33O4Si+ (M+H)+ 353.2143, found 353.2146.
1-(4-acetyl-5-methylfuran-2-yl)-3-phenylpropan-1-one (3h). Isolated by short column
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chromatography ( hexanes/ethyl acetate = 12:1 ) in 48.8 mg, yellow solid, 96%. H{13C} NMR
(500 MHz, CDCl3) δ: 7.34 (1H, s), 7.30 - 7.27 (2H, m), 7.24 - 7.18 (3H, m), 3.12 (2H, t, J = 7.8
Hz), 3.04 (2H, t, J = 7.8 Hz), 2.65 (3H, s), 2.43 (3H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
193.3, 188.0, 162.3, 149.9, 140.7, 128.5, 128.4, 126.2, 123.1, 117.2, 40.0, 29.9, 29.0, 14.8. HRMS
(ESI) m/z calcd for C16H17O3+ (M+H)+ 257.1172, found 257.1177.
1-(4-benzoyl-5-phenylfuran-2-yl)pentan-1-one (3i). Isolated by short column chromatography
( hexanes/ethyl acetate = 80:1 ) in 62.0 mg, yellow liquid, 93%. 1H{13C} NMR (500 MHz, CDCl3)
δ: 7.84 - 7.83 (2H, m), 7.80 - 7.78 (2H, m), 7.55 (1H, t, J = 7.3 Hz), 7.43 - 7.33 (6H, m), 2.89 (2H,
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t, J = 7.3 Hz), 1.79 - 1.73 (2H, m), 1.47 - 1.40 (2H, m), 0.97 (3H, t, J = 7.3 Hz). 13C{1H} NMR
(125 MHz, CDCl3) δ: 190.8, 189. 6, 158.1, 150.4, 137.3, 133.4, 130.3, 129.7, 128.6, 128.6, 128.5,
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128.0, 122.5, 119.6, 38.4, 26.4, 22.4, 13.9. HRMS (ESI) m/z calcd for C22H21O3 (M+H)+
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333.1485, found 333.1489.
dimethyl (2-methyl-5-pentanoylfuran-3-yl)phosphonate (3j). Isolated by short column
chromatography ( hexanes/ethyl acetate = 1:1 ) in 52.9 mg, yellow liquid, 96%. H{13C} NMR
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(500 MHz, CDCl3) δ: 7.21 (1H, d, J = 3.5 Hz), 3.77 (3H, s), 3.75 (3H, s), 2.77 - 2.74 (2H, t, J =
7.8 Hz), 2.60 - 2.59 (3H, d, J = 2.0 Hz), 1.71 - 1.65 (2H, m), 1.41 - 1.34 (2H, m), 0.94 - 0.91 (3H,
t, J = 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 189.0, 164.3 - 164.1 (d, J = 26.1 Hz), 151.3,
119.8 - 119.7 (d, J = 11.1 Hz), 109.9, 108.2, 52.7 - 52.6 (d, J = 5.5 Hz), 38.1, 26.4, 22.4, 14.0 -
13.8 (d, J = 25.0 Hz). HRMS (ESI) m/z calcd for C12H20O5P+ (M+H)+ 275.1043, found 275.1044.
ethyl 2-methyl-5-pentanoylfuran-3-carboxylate (3k).13a Isolated by short column chromatography
(hexanes/ethyl acetate = 30:1 ) in 48.3 mg, yellow liquid, 96%. 1H{13C} NMR (500 MHz, CDCl3)
δ: 7.38 (1H, s), 4.32 - 4.28 (2H, q, J = 7.0 Hz), 2.77 - 2.74 (2H, t, J = 7.5 Hz), 2.65 (3H, s), 1.71 -
1.65 (2H, m), 1.41 - 1.34 (5H, m), 0.94 - 0.91 (3H, t, J = 7.3 Hz); 13C{1H} NMR (125 MHz,
CDCl3) δ: 189.1, 162.9, 150.0, 118.0, 115.8, 60.6, 38.0, 26.5, 22.4, 14.3, 14.2, 13.8.
1-(5-phenyl-4-(phenylsulfonyl)furan-2-yl)pentan-1-one (3l). Isolated by short column
chromatography ( hexanes/ethyl acetate = 15:1 ) in 47.9 mg, light yellow solid, 65%. H{13C}
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NMR (500 MHz, CDCl3) δ: 7.94 - 7.93 (2H, d, J = 7.5 Hz), 7.79 - 7.78 (2H, d, J = 7.5 Hz), 7.55 -
7.40 (7H, m), 2.85 - 2.81 (2H, t, J = 7.3 Hz), 1.74 - 1.68 (2H, m), 1.44 - 1.36 (2H, m), 0.96 - 0.93
(3H, t, J = 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 189.0, 157.2, 150.0, 141.0, 133.7, 131.2,
129.2, 129.1, 128.5, 127.2, 126.2, 118.3, 38.3, 26.1, 22.3, 13.8. HRMS (ESI) m/z calcd for
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C21H21O4S+ (M+H)+ 369.1155, found 369.1158.
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chromatography ( hexanes/ethyl acetate = 20:1 ) in 34.3 mg, white solid, 89%. H{13C} NMR
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(500 MHz, CDCl3) δ: 7.42 (1H, s), 2.68 (3H, s), 2.55 - 2.51 (1H, m), 2.45 (3H, s), 1.24 - 1.22 (2H,
m), 1.04 - 1.02 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 193.4, 188.9, 162.1, 150.6, 123.1,
+
116.6, 29.0, 17.2, 14.8, 11.5. HRMS (ESI) m/z calcd for C11H13O3 (M+H)+ 193.0859, found
193.0857.
1-(4-acetyl-5-methylfuran-2-yl)-2-((triisopropylsilyl)oxy)propan-1-one (3n). Isolated by short
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column chromatography ( hexanes/ethyl acetate = 20:1 ) in 53.5 mg, yellow solid, 76%. H{13C}
NMR (500 MHz, CDCl3) δ: 7.75 (1H, s), 4.72 - 4.68 (1H, q, J = 6.7 Hz), 2.68 (3H, s), 2.43 (3H,
s), 1.51 - 1.50 (3H, d, J = 6.5 Hz), 1.14 - 1.08 (3H, m), 1.06 - 1.03 (18H, t, J = 6.7 Hz). 13C{1H}
NMR (125 MHz, CDCl3) δ: 193.3, 190.5, 162.9, 147.0, 122.8, 120.6, 74.5, 28.9, 22.9, 17.9, 14.8,
12.1. HRMS (ESI) m/z calcd for C19H33O4Si+ (M+H)+ 353.2143, found 353.2145.
1-(2-methyl-5-((trimethylsilyl)carbonyl)furan-3-yl)ethan-1-one (3o). Isolated by short column
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chromatography ( hexanes/ethyl acetate = 40:1 ) in 43.3 mg, yellow solid, 97%. H{13C} NMR
(500 MHz, CDCl3) δ: 7.24 (1H, s), 2.67 (3H, s), 2.45 (3H, s), 0.34 (9H, s). 13C{1H} NMR (125
MHz, CDCl3) δ: 221.1, 193.5, 161.8, 155.3, 123.0, 115.0, 29.0, 14.8, -2.4. HRMS (ESI) m/z calcd
for C11H17O3Si+ (M+H)+ 225.0942, found 225.0940.
The data of diphenyl sulfide (6a). Isolated by short column chromatography ( hexanes/ethyl
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acetate = 80:1 ) in 8.0 mg, light yellow liquid, 21%. H{13C} NMR (500 MHz, CDCl3) δ: 7.36 –
7.34 (4H, m), 7.32 – 7.29 (4H, m), 7.27 – 7.23 (2H, m).
The ynenone 1i was carried out on a larger scale to desire the product Z-iodovinylfuran 2i.
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Under nitrogen atmosphere, 4.4 mmol N-iodosuccinimide (NIS) (990 mg, 1.1 equiv) and 20 mL
dry DCE was added to a flamed dried Round-bottomed flask (50 mL), then 4.0 mmol 1i (1.265 g,
1.0 equiv) was added into the reaction. The resulting mixture was stirred at room temperature for
about 20 minutes and the progress of the reaction was monitored by TLC. Upon completion, the
reaction mixture was concentrated under vacuum. The residue was purified by chromatography on
silica gel (eluent: hexanes/ethyl acetate = 50:1 ) to afford the desired product Z-iodovinylfuran 2i
(1.37 g) in 77% yield as a light yellow solid.
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The ynenone 1i was carried out on a larger scale to desire the product 2-acyl furan 3i.
The ynenone 1i (4.0 mmol, 1.265 g, 1.0 equiv) and N-iodosuccinimide (NIS) (4.0 mmol, 900 mg,
1.0 equiv) were added to a 50 mL Round-bottomed flask with 20 mL of DMSO was added. The
resulting mixture was stirred at room temperature open to the air overnight, and the progress of the
reaction was monitored by TLC. Upon completion, the reaction mixture was quenched by H2O (80
mL), extracted by diethyl ether and dried by Na2SO4 and then concentrated under vacuum. The
residue was purified by chromatography on silica gel (eluent: hexanes/ethyl acetate = 20:1) to
afford the desired product 2-acyl furan 3i (1.22 g) in 92% yield as a yellow liquid.
Preparation of products 4
ethyl (2E,4E)-4-(4-benzoyl-5-phenylfuran-2-yl)octa-2,4-dienoate (4a). To a solution of 2i (119.4
mg, 0.27 mmol, 1.0 equiv) , Pd(PPh3)2Cl2 (5.6 mg, 0.0081 mmol, 3 mol %), Et3N (32.8 mg, 0.32
mmol, 1.2 equiv) and ethyl acrylate (75.7 mg, 0.76 mmol, 2.8 equiv) in DMF (5 mL). The reaction
mixture was heated at 80℃ for 2 h with oil bath. After the completion of reaction quenched by
aqueous NH4Cl (10 mL) and reaction mixture was stirred for 30 min. The mixture was extracted
with EtOAc (2 x 5 mL) organic layer was washed with H2O (5 mL), brine (5 mL), dried over
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Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography on silica
gel ( hexanes/ethyl acetate = 80:1 ) and the product was isolated in 70.4 mg, yellow liquid, yield =
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85%. H{13C} NMR (500 MHz, CDCl3) δ : 7.86 - 7.84 (2H, d, J = 8.0 Hz), 7.70 - 7.68 (3H, m),
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7.53 - 7.49 (1H, t, J = 7.5 Hz), 7.40 - 7.37 (2H, t, J = 7.3 Hz), 7.31 - 7.29 (3H, m), 6.62 (1H, s),
6.48 - 6.45 (1H, t, J = 7.8 Hz), 6.29 - 6.26 (1H, d, J = 16 Hz), 4.27 - 4.21 (2H, m), 2.45 - 2.40 (2H,
q, J = 7.7 Hz), 1.60 - 1.54 (2H, m), 1.33 - 1.30 (3H, t, J = 7.3 Hz), 1.02 - 0.99 (3H, t, J = 7.0 Hz).
13C{1H} NMR (125 MHz, CDCl3) δ : 191.6, 167.0, 154.7, 151.3, 139.4, 137.9, 137.8, 132.9,
129.7, 129.6, 129.0, 128.4, 128.3, 128.3, 127.5, 126.4, 122.2, 110.8, 60.6, 30.7, 22.6, 14.3, 13.8.
HRMS (ESI) m/z calcd for C27H27O4+ (M+H)+ 415.1904, found 415.1907.
(E)-phenyl(2-phenyl-5-(1-phenylpent-1-en-1-yl)furan-3-yl)methanone (4b). To a solution of 2i
(119.4 mg, 0.2 mmol, 1.0 equiv), K2CO4 (69.1 mg, 0.5 mmol 2.5 equiv), Pd(PPh3)2Cl2 (1.4 mg,
0.002 mmol, 1 mol %) and phenylboronic acid (25.6 mg, 0.21 mmol, 1.05 equiv) in toluene (5
mL) and water (1 mL) was degassed with N2 for 20 min. The reaction mixture was heated at 80℃
for 6 h with oil bath. After the completion of reaction, DMF was removed under vacuum, and the
residue was dissolved in EtOAc (5 mL), filtered through celite and concentrated in vacuo. The
crude was purified by column chromatography on silica gel ( hexanes/ethyl acetate = 100:1 ) and
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the product was isolated in 70.6 mg, yellow liquid, yield = 90%. H{13C} NMR (500 MHz,
CDCl3) δ : 7.81 - 7.79 (2H, d, J = 7.5 Hz), 7.72 - 7.71 (2H, d, J = 7.0 Hz), 7.48 - 7.45 (1H, t, J =
7.3 Hz), 7.42 - 7.30 (10H, m), 6.53 – 6.50 (1H, t, J = 7.5 Hz), 6.05 (1H, s), 2.12 – 2.08 (2H, q, J =
7.3 Hz), 1.54 – 1.46 (2H, m), 0.94 – 0.91 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ :
191.8, 154.5, 154.1, 137.9, 136.8, 132.7, 131.1, 129.8, 129.7, 129.1, 128.8, 128.3, 128.3, 128.2, 127.5,
+
127.4, 127.2, 122.5, 110.7, 31.0, 22.9, 13.9. HRMS (ESI) m/z calcd for C28H25O2 (M+H)+ 393.1849,
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found 393.1852. Z : E = 7:1.
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(E)-phenyl(2-phenyl-5-(1-phenylhept-3-en-1-yn-3-yl)furan-3-yl)methanone (4c). To a solution of 2i
( 119.4 mg, 0.27 mmol, 1.0 equiv) in trethylamine (3 mL) was added to a mixture of Pd(PPh3)2Cl2
(1.9 mg, 0.0027 mmol, 1 mol %) and copper(I)iodide (1.0 mg, 0.0054 mmol, 2 mol %) in a flame
dried flask. The mixture was degassed with N2 for 15 min. Phenylacetylene (27.5 mg, 0.27 mmol,
1.0 equiv) was added, and the mixture was stirred at room temperature overnight. After the
completion of reaction, the mixture was diluted with Water (3 mL) and then the mixture was
extracted with EtOAc (10 mL x 2). The combined organic layers were dried with anhydrous
Na2SO4, filtered through celite, and concentrated in vacuo. The crude was purified by column
chromatography on silica gel ( hexanes/ethyl acetate = 30:1 ) and the product was isolated in 72.4
mg, red liquid, yield = 87%. 1H{13C} NMR (500 MHz, CDCl3) δ : 7.90 - 7.88 (2H, d, J = 7.5 Hz),
7.74 - 7.72 (2H, d, J = 6.0 Hz), 7.52 - 7.51 (3H, d, J = 5.0 Hz), 7.41 - 7.38 (2H, t, J = 7.3 Hz), 7.35
- 7.31 (6H, m), 6.77 (1H, s), 6.74 - 6.71 (1H, t, J = 7.8 Hz), 2.60 - 2.56 (2H, q, J = 7.2 Hz), 1.65 -
1.61 (2H, m), 1.07 - 1.04 (3H, t, J = 7.3 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ : 191.7, 154.8,
151.1, 137.9, 137.3, 132.9, 131.6, 129.8, 129.7, 129.0, 128.5, 128.4, 128.3, 128.3, 127.4, 122.9,
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+
122.5, 113.8, 110.4, 94.1, 83.7, 32.8, 22.4, 13.9. HRMS (ESI) m/z calcd for C30H25O2 (M+H)+
417.1849, found 417.1854.
■ AUTHOR INFORMATION
Corresponding Author
*E-mail: jikegong@nwsuaf.edu.cn.
ORCID
Zi-Sheng Chen: 0000-0001-8778-8889
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Kegong Ji: 0000-0001-5707-894X
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Author Contributions
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‡These authors contributed equally.
Notes
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The authors declare no competing financial interest.
■ ASSOCIATED CONTENT
Supporting Information: concise list of types of data or files found in the SI.
Reaction conditions optimization, the data of X-ray structure of 2h, the spectra of HRMS (ESI)
m/z calcd for 3a and 3a’ and copies of characterization data (1H{13C}, 13C{1H} NMR) (PDF)
■ ACKNOWLEDGMENTS
We are grateful for the financial support from National Natural Science Foundation of China
(21702170) and Natural Science Foundation of Shaanxi (2018JQ2072) and the Youth Training
Programme of Northwest A&F University (Nos. 2452016006, 2452017034).
REFERENCES
(1) (a) Boto, A.; Alvarez, L.;Majumdar, K. C.; Chattopadhyay, S. K. Eds.; Wiley-VCH:
Weinheim. Heterocycles in Natural Product Synthesis. 2011; pp 99−152. (b) Barancelli, D. A.;
Mantovani, A. C.; Jesse, C.; Nogueira, C. W.; Zeni, G. Synthesis of Natural Polyacetylenes
Bearing Furan Rings. J. Nat. Prod. 2009, 72, 857. (c) Kobayashi, J. i.; Watanabe, D.;
Kawasaki, N.; Tsuda, M. Nakadomarin A, a Novel Hexacyclic Manzamine-Related Alkaloid
from Amphimedon Sponge. J. Org. Chem. 1997, 62, 9236. (d) Rodríguez, A. D. The natural
products chemistry of West Indian gorgonian octocorals. Tetrahedron 1995, 51, 4571.
(2) (a) Wang, Y.; Luo, Y.-C.; Hu, X.-Q.; Xu, P.-F. A Powerful Cascade Approach for Expeditious
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1
2
3
4
5
6
7
8
9
Synthesis of Trifluoromethylated Furans. Org. Lett. 2011, 13, 5346. (b) Tikhomirov, A. S.;
Shchekotikhin, A. E.; Lee, Y.-H.; Chen, Y.-A.; Yeh, C.-A.; Jr., V. V. T.; Dezhenkova, L. G.;
Glazunova, V. A.; Balzarini, J.; Shtil, A. A.; Preobrazhenskaya, M. N.; Chueh, P. J. Synthesis
and Characterization of 4,11-Diaminoanthra[2,3-b]furan-5,10-diones: Tumor Cell Apoptosis
through tNOX-Modulated NAD+/NADH Ratio and SIRT1. J. Med. Chem. 2015, 58, 9522. (c)
Riley, A. P.; Groer, C. E.; Young, D.; Ewald, A. W.; Kivell, B. M.; Prisinzano, T. E. Synthesis
and κ-Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues. J. Med. Chem.
2014, 57, 10464.
10
11
12
13
14
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16
17
18
19
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21
22
23
24
25
26
27
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47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3) Selected examples: (a) Gandini, A.; Belgacem, M. N. Furans in polymer chemistry. Prog.
Polym. Sci. 1997, 22, 1203. (b) Wu, C.-C.; Hung, W.-Y.; Liu, T.-L. Hole-transport properties
of a furan-containing oligoaryl. J. Appl. Phys. 2003, 93, 5465. (c) Ripaud, E.; Demeter, D.;
Rousseau, T.; Boucard-Cétol, E.; Allain, M.; Po, R.; Leriche, P.; Roncali, J.
Structure-properties relationships in conjugated molecules based on diketopyrrolopyrrole for
organic photovoltaics. Dyes Pigm. 2012, 95, 126.
(4) (a) Lipshutz, B. H. Five-membered heteroaromatic rings as intermediates in organic synthesis.
Chem. Rev. 1986, 86, 795. (b) Achmatowicz, O.; Bukowski, P.; Szechner, B.; Zwierzch, Z.;
Zamojski, A. Synthesis of methyl 2,3-dideoxy-DL-alk-2-enopyranosides from furan
compounds : A general approach to the total synthesis of monosaccharides. Tetrahedron 1971,
27, 1973. (c) Ciufolini, M. A.; Wood, C. Y. The aza-achmatowicz rearrangement: A route to
useful building blocks for N- containing structures. Tetrahedron Lett. 1986, 27, 5085.
(5) Clark, J. S.; Romiti, F.; Hogg, K. F.; Hamid, M. H. S. A.; Richter, S. C.; Boyer, A.; Redman, J.
C.; Farrugia, L. J. Synthesis of Cyclopropyl‐Substituted Furans by Brønsted Acid Promoted
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2
3
4
Cascade Reactions. Angew. Chem. Int. Ed. 2015, 54, 5744.
5
6
7
8
9
(6) (a) Feist, F. Studies on the furan and pyrrole group. Ber. Dtsch. Chem. Ges. 1902, 35, 1537.
(b) Benary, E. Synthesis of Pyridine Derivatives from Dichloroether and β-Aminocrotonic
Ester. Ber. Dtsch. Chem. Ges. 1911, 44, 489.(7) (a) Barluenga, J.; Riesgo, L.; Vicente, R.;
López, L. A.; Tomás, M. Cu(I)-Catalyzed Regioselective Synthesis of Polysubstituted Furans
from Propargylic Esters via Postulated (2-Furyl)carbene Complexes. J. Am. Chem. Soc. 2008,
130, 13528. (b) Yang, J.; Wang, C.; Xie, X.; Li, H.; Lia, E.; Li, Y. Pd/Cu-catalyzed cascade
Sonogashira coupling/cyclization reactions to highly substituted 3-formyl furans. Org. Biomol.
Chem. 2011, 9, 1342.
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11
12
13
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19
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21
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23
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27
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58
59
60
(8) (a) González, J.; González, J.; Pérez-Calleja, C.; López, L. A.; Vicente, R. Zinc-Catalyzed
Synthesis of Functionalized Furans and Triarylmethanes from Enynones and Alcohols or
Azoles: Dual X-H Bond Activation by Zinc. Angew. Chem. 2013, 125, 5965. (b) González, J.;
González, J.; Pérez-Calleja, C.; López, L. A.; Vicente, R. Zinc-Catalyzed Synthesis of
Functionalized Furans and Triarylmethanes from Enynones and Alcohols or Azoles: Dual X-H
Bond Activation by Zinc. Angew. Chem. Int. Ed. 2013, 52, 5853. (c) Vicente, R.; González, J.;
Riesgo, L.; González, J.; López, L. A. Catalytic Generation of Zinc Carbenes from Alkynes:
Zinc-Catalyzed Cyclopropanation and Si-H Bond Insertion Reactions. Angew. Chem. Int. Ed.
2012, 51, 8063.
(9) (a)Xia, Y.; Qu, S.; Xiao, Q.; Wang, Z.-X.; Qu, P.; Chen, L.; Liu, Z.; Tian, L.; Huang, Z.;
Zhang, Y.; Wang, J. Palladium-Catalyzed Carbene Migratory Insertion Using Conjugated
Ene-Yne-Ketones as Carbene Precursors. J. Am. Chem. Soc. 2013, 135, 13502. (b) Mao, S.;
Tang, L.; Wu, C.; Tu, X.; Gao, Q.; Deng, G. Ag(I)-Catalyzed Tandem Reaction of Conjugated
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7
Ene-yne-ketones in the Presence of PhI(OAc)2 and Triethylamine: Synthesis of
2-Alkenylfurans Org. Lett. 2019, 21, 2416.
8
9
(10) (a) Corma, A.; Leyva-Pérez, A.; Sabater, M. J. Gold-Catalyzed Carbon-Heteroatom
Bond-Forming Reactions. Chem. Rev. 2011, 111, 1657. (b) Hashmi, A. S. K. Gold-Catalyzed
Organic Reactions. Chem. Rev. 2007, 107, 3180. (c) Li, Z.; Brouwer, C.; He, C.
Gold-Catalyzed Organic Transformations. Chem. Rev. 2008, 108, 3239. (d) Ma, J.; Jiang, H.;
Zhu, S. NHC–AuCl/Selectfluor: A Highly Efficient Catalytic System for Carbene-Transfer
Reactions. Org. Lett. 2014, 16, 4472.
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11
12
13
14
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19
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22
23
24
25
26
27
28
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60
(11) (a) Wu, W.; Yi, S.; Huang, w.; Luo, D.; Jiang, H. Ag-Catalyzed Oxidative Cyclization
Reaction of 1,6-Enynes and Sodium Sulfinate: Access to Sulfonylated Benzofurans. Org. Lett.
2017, 19, 2825. (b) Marshall, J. A.; Wang, X. J. Synthesis of furans by silver(I)-promoted
cyclization of allenyl ketones and aldehydes. J. Org. Chem. 1991, 56, 960.
(12) Clark, J. S.; Boyer, A.; Aimon, A.; García, P. E.; Lindsay, D. M.; Symington, A. D. F.;
Danoy, Y. Organocatalytic Synthesis of Highly Substituted Furfuryl Alcohols and Amines.
Angew. Chem. Int. Ed. 2012, 51, 12128.
(13) (a) Xu, C.; Wittmann, S.; Gemander, M.; Ruohonen, V.; Clark, J. S.
Trialkylphosphine-Mediated Synthesis of 2-Acyl Furans from Ynenones. Org. Lett. 2017, 19,
3556. (b) Kuroda, H.; Hanaki, E.; Izawa, H.; Kano, M.; Itahashi, H. A convenient method for
the preparation of α-vinylfurans by phosphine-initiated reactions of various substituted enynes
bearing a carbonyl group with aldehydes. Tetrahedron 2004, 60, 1913−1920.
(14) (a) Gulevich, A. V.; Dudnik, A. S.; Chernyak, N.; Gevorgyan, V. Transition Metal-Mediated
Synthesis of Monocyclic Aromatic Heterocycles. Chem. Rev. 2013, 113, 3084. (b) Miki, K.;
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