Transition-metal-free C-C σ-bond activation of α-aryl ketones and subsequent Zn-catalyzed intramolecular cyclization: synthesis of tetrasubstituted furans

Article abstract of DOI:10.1039/c9ob00081j

A highly atom-economical protocol for the synthesis of tetrasubstituted furans has been developed. This process is realized through the tandem reactions of Cs₂CO₃ promoted C-C σ-bond activation of α-aryl ketones followed by Zn-cataly

Full text of DOI:10.1039/c9ob00081j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

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DOI: 10.1039/C9OB00081J
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Transition-metal-free C-C σ-Bonds Activation of α-Aryl Ketones
and Subsequent Zn-catalyzed Intramolecular Cyclization:
Synthesis of Tetrasubstituted Furans
Received 00th January 20xx,
Accepted 00th January 20xx
Yang Yuan,† Hailu Tan,† Lingkai Kong,† Zhong Zheng,† Murong Xu,† Jiaqi Huang,† and Yanzhong Li*a
DOI: 10.1039/x0xx00000x
A highly atom-economical protocol for the synthesis of tetrasubstituted furans has been developed. This process is
realized through the tandem reactions of Cs2CO3 promoted C-C σ-bonds activation of α-aryl ketones followed by Zn-
catalyzed intramolecular cyclization. This represents the first example for the preparation of tetrasubstituted furans
through rearrangement of molecular skeletons and subsequent transformations. Mild reaction conditions and readily
www.rsc.org/
accessible
starting
material
make
the
protocol
attractive
in
organic
synthesis.
Yu's work: Fe-catalyzed C-H functionalization
COR3
R2
O
O
EWG
R1S
EWG
R1S
H
Introduction
Fe(OAc)2 cat.
DMA, 120 o
R2
R3
+
(a)
(b)
SR1
C
O
H
Highly substituted furans are of great importance because they
exhibit a wide range of biological activities and appear as key
structural units in many natural products, pharmaceuticals,
and agrochemicals1, examples include two sesquiterpenoids (I
and II)1e and dimethylfuroguaiacin (III)1f (Figure 1). Moreover,
they are versatile building blocks in synthetic organic
chemistry.2 Many synthetic routes for their preparation have
been developed, such as direct functionalization of furan
rings,3 the Paal-Knorr synthesis from 1,4-dicarbonyl
compounds,4 the Feist- Bénary synthesis,5 and transition-
metal-catalyzed cycloisomerization of alkynyl or allenyl
ketones.6 However, literature reports for the syntheses of
tetrasubstituted furans are relatively rare.7 Polysubstituted
furans were synthesized through Iron-catalyzed C-H/C-H
coupling of activated carbonyl methylenes with S, S-
functionalized olefins (Scheme 1, a).7c Ag-catalyzed coupling of
two (sp3)C –H groups afforded tetrasubstituted furans
(Scheme 1, b).7h DBU-mediated tandem Michael addition/
Wang's work: Ag-catalyzed C-H/C-H coupling
Ar2
R2
Ar1
R1
O
O
i) AgF cat., xylene, 140 o
R2
ii) TsOH (1.5 equiv)
C
+
Ar1
Ar2
R1
O
This work:


Base-promoted C-C -bonds activation of -aryl ketones and subsequent
intramolecular cyclization to tetrasubstituted furans
O
R3
O
O
R4
(c)
i) Cs2CO3, DMF, RT
ii) ZnI2, K2S2O8, 50oC
R2
+
R1
R4
R3
O
R2
R1
Scheme 1 synthesis of tetrasubstituted furans using keto-methylenes.
effective, more diverse and atom-economical procedures are
strongly demanded for highly functionalized furans. In this
context, processes initiated from the C-C σ-bonds activation
toward tetrasubstituted furans would be very attractive,
because it can reorganize the molecular skeleton and form two
carbon-carbon bonds simultaneously without any byproducts.8
cycloisomerization of keto-methylenes and enynes also gave As a continuation of our interest in the C-H and C-C σ-bonds
tetrasubstituted furans.7f
Although these methods are
activation chemistry, we report herein the one-pot procedure
of Cs2CO3 mediated C-C bond insertion of alkynones into α–
aryl ketones and subsequent Zn-catalyzed intramolecular
cyclization (Scheme 1, c).9a The reaction produces the
corresponding tetrasubstituted furans in good yields with
easily accessible starting materials. This is the first example for
the synthesis of tetrasubstituted furans through transition-
metal-free carbon-carbon -bonds cleavage of unstrained
molecules, as far as our knowledge.
O
O
HO
OMe
OMe
MeO
MeO
O
O
OH
O
O
OH
OH
O
OH
I
II
III
Dimethylfuroguaiacin
Sesquiterpenoids
Figure 1 Some naturally occurring compounds containing substituted furans.
a. Y. Yuan, H. Tan, L. Kong, Z. Zheng, M. Xu, J. Huang, Prof. Dr. Y. Li
Shanghai Key Laboratory of Green Chemistry and Chemical Processes
School of Chemistry and Molecular Engineering
East China Normal University, 500 Dongchuan Road
E-mail: yzli@chem.ecnu.edu.cn
Results and discussion
We initially conducted the reactions of 1,3-diphenylprop-
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
2-yn-1-one (1a) with 1,2-diphenylethanone (2a) (1.0 equiv) in
This journal is © The Royal Society of Chemistry 20xx
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the presence of Cs2CO3 (2.0 equiv) in DMF under N2 at room
temperature. After the C-C bond cleavage product was formed
2
O
O
O
View Article Online
Ph
R
Ph
i) Cs2CO3 (2.0 equiv)
DMF, rt, N2 , 3 h
Ph
O
DOI: 10.1039/C9OB00081J
+
R2
Ph
Ph
Ph
and
Ph
ii) ZnI2 (20 mol %)
K2S2O8 (2.0 equiv)
50 oC, air, 8 h
Table 1 Screening of the reaction conditions for the synthesis of 3a
R1
R2
O
O
R1
R1
2a
1
O
3
3'
O
O
Ph
Ph
Ph
Ph
Cs2CO3 (2.0 equiv) catalyst, [O]
Ph
+
O
O
O
Ph
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Temp, air, 8 h
DMF, rt, N2, 3 h
Ph
O
Ph
O
2a
1a
Ph
3a
O
O
O
O
temp (oC)
yield (%)a
CN
OMe
Cl
Me
3a,
3b,
3e,
78%
O
59%
3d,
83%
67%
O
entry
cat.
[O] (equiv)
_
3c, 81%
O
Ph
Ph
Ph
Ph
F
O
Ph
Ph
Ph
1
ZnI2 (20 mol%)
ZnI2 (20 mol%)
ZnI2 (20 mol%)
50
50
80
NP
Me
Ph
F
+
2
K2S2O8 [2]
78%
78%
Ph
Cl
O
O
Ph
O
Ph
3
4
5
K2S2O8 [2]
O
3f,
3g, 73%
69%
Ph
3h+3h',
(4:3)76%
Br
ZnI2 (20 mol%)
_
K2S2O8 [2]
K2S2O8 [2]
30
50
31%
39%
Cl
O
O
Ph
Ph
Ph
O
O
Ph
Ph
Br
Cl
6
7
8
9
ZnI2 (10 mol%)
ZnI2 (50 mol%)
ZnI2 (20 mol%)
ZnI2 (20 mol%)
K2S2O8 [2]
K2S2O8 [2]
K2S2O8 [1]
K2S2O8 [3]
50
50
50
50
67%
77%
54%
63%
+
+
Ph
Ph
Ph
Ph
Ph
Ph
O
O
O
O
O
3i+3i',
3j+3j',
(1:1) 79%
(1:1) 72%
MeO
Me
Ph
O
O
Ph
Ph
Ph
O
O
Ph
Ph
Ph
MeO
Me
10
11
12
13
14
15
16
17
CuI (20 mol%)
FeCl3 (20 mol%)
ZnCl2 (20 mol%)
Zn(OTf)2 (20 mol%)
ZnI2 (20 mol%)
ZnI2 (20 mol%)
ZnI2 (20 mol%)
ZnI2 (20 mol%)
K2S2O8 [2]
K2S2O8 [2]
K2S2O8 [2]
K2S2O8 [2]
(NH4)2S2O8 [2]
TBHP [2]
50
50
50
50
50
50
50
50
64%
50%
38%
37%
55%
26%
NP
+
+
Ph
Ph
3k+3k',
Ph
(4:1) 52%
Ph
Ph
O
O
O
3l+3l',
(1.4:1) 83%
Figure 2 The scope of alkynone 1 for the synthesis of furan 3. Reaction
conditions: 1 (0.2 mmol), 2a (0.2 mmol), Cs2CO3 (0.4 mmol), DMF (2.0 mL),
ZnI2 (0.04 mmol), K2S2O8 (0.4 mmol), isolated yields.
DTBP [2]
donating groups on the aryl ring underwent the reaction
smoothly to afford the desired substituted furans in good to
high yields (Figure 2, 3a-3g). With electron-withdrawing groups
on the para-position of the aryl ring such as p-CN and p-Cl, the
corresponding products 3b or 3c were obtained in 59% and
81% yields, respectively. With electron-donating groups on the
aryl ring such as p-Me or p-OMe, the desired tetrasubstituted
furans were also produced in high yields (3d, 3e). A methyl
group on the ortho-position of the aryl ring afforded the target
compound 3f in a yield of 69%. A meta-chloro substituted aryl
ring produced the desired furan 3g in 73% yield. Next, the R2
substituents of the aryl ring on the carbonyl carbon were
explored (Figure 2, 3h-3l). It was worth noting when
substituents on the carbonyl carbon of substrates 1 and 2
were different, two isomers would be obtained. With an
electron-withdrawing group on the para-position of the aryl
ring such as p-F, two isomerized products 3h and 3h’ were
obtained in a combined yield of 76% with a ratio of 4:3. The
results indicated that there was competitively enolization
between two carbonyl group of the C-C cleavage intermediate.
Other electron-withdrawing groups such as p-Cl and p-Br were
tolerable to the reaction conditions, affording (3i, 3i’) and (3j,
3j’) as two isomers in high yields. Substrates bearing electron-
donating groups such as p-Me and p-OMe cyclized readily
under the standard reaction conditions to afford the
corresponding tetrasubstituted furans (3k, 3k’) and (3l, 3l’) in
83% and 52% yields, respectively.
H2O2 [2]
trace
aReaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), Cs2CO3 (0.4 mmol), DMF (2.0
mL), 50 oC, isolated yields. NP = No Product.
as monitored by TLC, several reaction parameters were
screened in order to achieve subsequent further
transformations, the results are depicted in Table 1. When ZnI2
(20 mol %) was added and the reaction temperature was
o
increased to 50 C, no new product was observed (entry 1).
Interestingly, when K2S2O8 (2.0 equiv) was employed, the
corresponding tetrasubstituted furan 3a was formed in 78%
o
yield (entry 2). A higher temperature of 80 C gave the same
o
result as that of 50 C (entry 3). A lower reaction temperature
(30 oC) resulted in only 31% yield of 3a (entry 4). It is worth to
note that the subsequent reaction could also occur in the
absence of ZnI2 to give a low yield of the desired product
(entry 5). Reducing the catalyst loading of ZnI2 to 10 mol %
achieved 3a in 67% yield (entry 6). 50 mol % of catalyst loading
gave almost the same outcome as that of 20 mol % (entry 7 vs
entry 2). Then, the amount of K2S2O8 was tested. Decreasing or
increasing the amount of K2S2O8 made lower yields of the
desired furan (entries 8, 9). Next, other metal salts were
screened. It was found that CuI, FeCl3, ZnCl2 and Zn(OTf)2 could
also catalyze the reaction, however, the yields of 3a were in
the range of 37-64% (entries 10-13). Lastly, different oxidants
were tested. (NH4)2S2O8 and tert-butyl hydroperoxide (TBHP)
afforded the desired 3a in 55% and 26% yields, respectively
(entries 14, 15). Whereas, di-tert-butyl peroxide (DTBP) and
H2O2 are not effective for this reaction.
To investigate whether our synthetic strategy is effective
for alkyl-substituted alkynones, we next introduced tert-butyl
and ethyl groups on the carbonyl side of the alkynone 1.
Interestingly, the desired tetrasubstituted furans (3m, 3m’)
and (3n, 3n’) were obtained as well in good yields of 61% and
63% as two isomers, respectively (Figure 3, a). However, when
the alkyne terminus was an n-butyl, only complex reaction
mixture was observed in the first step reaction (Figure 3, b).
Encouraged by the above results, we next examined the
substrate scope toward the synthesis of diverse
tetrasubstituted furans by varying substituents on alkynones
under the conditions shown in Table 1, entry 2. The results are
depicted in Figure 2. First, we investigated the effect of
different substituents (R1) of the aryl rings on the triple bond.
It was found that both electron-withdrawing and electron-
2 | J. Name., 2012, 00, 1-3
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O
O
O
Ph
R
R
Ph
i) Cs2CO3 (2.0 equiv)
DMF, rt, N2 , 3 h
Ph
Ph
View Article Online
O
O
R
O
DOI: 10.1039/C9OB00081J
+
Ph
O
(a)
Cs2CO3 (2.0 equiv)
Ph
+
Ph
Ph
ii) ZnI2 (20 mol %)
K2S2O8 (2.0 equiv)
50 oC, air, 8 h
(a)
Ph
+
O
O
Ph
DMF, rt, N2, 3 h
1
2a
3
3'
Ph
HO
Ph
3m 3m'
+
: R = tBu, 61% 1.2:1
: R = Et, 63% 16.7:1
4a,
%
84
1a
2a
3n 3n'
+
O
O
Cs2CO3 (2.0 equiv)
DMF, rt, N2 ,3 h
O
+
complex mixture
(b)
ZnI2 (20 mol %)
K2S2O8 (2.0 equiv)
(b)
(c)
4a
Figure 3 Synthesis of furans using alkyl substituted alkynones.
50 oC, air, 8 h
O
3a,
%
64
The scope of the α-aryl ketone 2 was also examined
(Figure 4). In order to synthesize only one isomer, we tried to
keep R2 and R3 as the same groups. For R4 substituent, both
electron-withdrawing and -donating groups on the aryl ring
readily delivered the corresponding furans in good yields (3o-
3s). A variety of functional groups such as nitro (3o), fluoro
(3p), chloro (3q), bromo (3r), and methyl (3s) were tolerated
well. The structure of 3q was confirmed by comparing with the
reported compound.7a For R3 substituent, again, both electron-
withdrawing and -donating character of the substituents on
the aryl ring, such as p-Cl, p-Br, p-Me and p-OMe were well
tolerated (3t-3w), providing the products in 51-82% yields.
Interestingly, when R3 as p-Br was employed to react with 1,3-
diphenylprop-2-yn-1-one (1a), the corresponding 3j and 3j’
were formed in a combined yield of 71%. We can find a similar
result from Figure 2 for the preparation of 3j and 3j’. In that
case, the desired substituted furans were produced from the
reaction of 1-(4-bromophenyl)-3-phenylprop-2-yn-1-one with
1,2-diphenylethanone (2a). Moreover, bicyclic substituent
smoothly underwent to this reaction, offering the desired
furan 3x in 51% yield, demonstrating the synthetic potential
ZnI2 (20 mol %)
K2S2O8 (2.0 equiv)
TEMPO (3.0 equiv)
4a
3a,
%
55
50 oC, air, 8 h
Scheme 2 Control experiments.
method. When R1 substituent of substrate 1 with p-Cl or p-Me
groups were used, the corresponding furans (3y, 3z) were
obtained both in 70% yield. With a 2-thienyl group in the
alkyne side, the corresponding furan 3za was also produced in
58% yield. However, when acetophenone was used, since the
first step of the reaction cannot occur, the target product 3zb
cannot be obtained. To demonstrate the practical utility of this
methodology, the gram scale reaction was conducted for the
synthesis of 3a, and the desired product 3a was obtained in
73% (1.47 g) yield.
In order to clarify the reaction mechanism, we carried out
the following control experiments (Scheme 2). First, the
reaction of 1a with 2a was performed under the optimized
reaction conditions for the first step. An intermediate 4a was
obtained in 84% yield after 3 h (Scheme 2, a). Treatment of 4a
with the general reaction conditions for the second step of our
system, the desired furan 3a was formed in 64% isolated yield
within 8 h (Scheme 2, b). The result implicates that 4a is the
reaction intermediate for the formation of 3a in the one-pot
reaction. When the reaction was carried out with the addition
of a radical scavenger TEMPO (3.0 equiv), a 55% yield of 3a
was obtained as well (Scheme 2, c). This indicates that a racical
for the construction of complex organic molecules by this
O
R3
O
i) Cs2CO3 (2.0 equiv)
DMF, rt, N2 ,3 h
R4
O
+
R2
R4
ii) ZnI2 (20 mol%)
K2S2O8 (2.0 equiv)
50 oC,air, 8 h
R1
R2
O
R3
R1
2
1
3
NO2
Cl
F
Br
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
reaction pathway may not be involved in the reaction process.
Ph
Ph
Ph
3p,
Ph
3r,
R1
O
O
O
O
R1
O
3o,
61%
83%
3q, 70%
75%
O
O
O
Ar4
Ar3
2
Me
R2
R2
Ar4
Br
R2
Cl
Me
O
Ar3
O
Ph
Base
R1
R1
O
O
Ph
Ar4
O
O
Ph
Ph
Ph
Ar3
Br
B
A
Me
1
Cl
Ph
Ph
Ph
Ph
R1
R1
O
O
O
O
3s,
86%
3t,
3u,
82%
75%
3v,
80%
O
O
O
Me
Cl
H2O
MeO
4a
O
R2
R2
O
Ph
Ar4
Ph
O
O
Ar4
R2
Ar4
O
Ar3
Ph
Ph
Ar3
O
Ar3
O
Me
Cl
MeO
C
D
E
R1
Ph
Ph
O
O
O
O
R1
[O]
path a:
ZnI2
R1
3w,
51%
3x,
3y,
3z,
70%
51%
70%
Me
Cl
O
R2
O
O
R2
ZnI2
Ar4
H2O
3
D
Me
R2
ZnI
Ar4
O
Ph
Ph
Zn(II)
O
Ar3
Ar4
Ar3
Ar3
O
O
O
G
Me
F
H
Ph
S
R1
O
O
R1
R1
2
=acetophenone
3zb,
O
path b:
O
3za,
58%
0%
Ar3
Ar3
O
ZnI2
Ar4
H2O
ZnI2
[O]
Figure 4 The scope of -aryl ketone 2. Reaction conditions: 1 (0.2 mmol), 2 (0.2
mmol), Cs2CO3 (0.4 mmol), DMF (2.0 mL), ZnI2 (0.04 mmol), K2S2O8 (0.4 mmol),
isolated yields.
ZnI
Ar4
Ar3
3'
R2
E
R2
Ar4
O
O
Zn(II)
O
R2
I
K
J
Scheme 3 A plausible reaction mechanism.
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Based on the above observation and our previous reduced pressure. Purification by column chromatography
View Article Online
reports,9 a plausible reaction mechanism is depicted in Scheme with petroleum ether/ethyl acetate = 5/1-10:1 as the eluent
DOI: 10.1039/C9OB00081J
3. In the presence of a base, 1 is attacked by α-aryl ketone 2 to afforded the substituted alkynol.
give an intermediate A, which undergoes an intramolecular
To a solution of substituted alkynol (10 mmol) in DMSO (20 mL)
nucleophilic addition/ring-opening to give a formal alkyne
in round-bottom flask, IBX (12 mmol, 3.36 g) was added at
insertion product C. Tautermerization of C leads to the
room temperature. The reaction was stirred in air until the full
formation of D or E, which delivers intermediate 4a after
conversion of substituted alkynol monitored by thin-layer
hydrolysis. There are two possible pathways to achieve the
chromatography. The resulting mixture was quenched with
final products 3 and 3’. In path a, coordination of the double
water (20 mL) and filtered. Then the filtrate was extracted with
bond of D to ZnI2 affords F. Nucleophilic attack of the carbonyl
ethyl acetate (20 mL × 3). The organic layers was combined,
O atom to the activated double bond gives G. Hydrolysis of G
washed with brine, dried over anhydrous Na2SO4, filtered and
followed by oxidative aromatization offers furan 3. In path b,
concentrated under reduced pressure. Purification by column
coordination of the double bond of E to ZnI2 produces I.
chromatography with petroleum ether/ethyl acetate = 10/1-
Nucleophilic attack of the carbonyl O atom to a double bond
20:1 as the eluent afforded the acetylenic ketones.
gives J. Hydrolysis of J followed by aromatization affords furan
3’.
4,4-dimethyl-1-phenylpent-1-yn-3-one and 1-phenylpent-1-
yn-3-one were synthesized according to the references 10a
and 10b, respectively.
Conclusions
Typical Procedure for the Synthesis of 2.9a
In summary, we have developed a one-pot procedure for
To a Schlenk tube with a magnetic stirring bar were charged
the respective nitrile (1.0 mmol), arylboronic acid (2.0 mmol),
Pd(OAc)2 (5 mol %, 11.2 mg ), bpy (10 mol%, 15.6 mg), TFA (10
equiv, 0.74 ml ), THF (5 mL), and H2O (1 mL) under N2
atmosphere. The reaction mixture was stirred at 80 oC for 36 h.
After cooling to r.t., the mixture was poured into EtOAc (5 mL),
which was washed with sat. aq NaHCO3 (2 × 10 mL) and then
brine (1 × 10 mL). After extracting the aqueous layer with
EtOAc (3 × 10 mL), the combined organic layers were dried
over anhydrous Na2SO4, and evaporated under vacuum.
Purification by column chromatography with petroleum
ether/ethyl acetate = 5/1-10:1 as the eluent afforded the alkyl
aryl ketones 2.
the atom-economical synthesis of tetrasubstituted furans from
α-aryl ketones and alkynones under mild conditions. This
reaction proceeds through the base-promoted cleavage of a
unstrained C-C single bond of ketones followed by the
subsequent Zn-catalyzed intramolecular cyclization.
Experimental
General Information.
All reactions were performed in flame-dried glassware under
an atmosphere of dry nitrogen, unless otherwise noted.
Anhydrous DMF were prepared by distillation from CaH2.
Unless noted, all commercial reagents were used without
further purification. Reactions were monitored by thin layer
chromatography. Preparation of ynones and diaryl ketones
were using reported methods.9a-9j, 10 Purification of reaction
products was carried out by flash chromatography on silica gel
Typical Procedure for the Synthesis of 3
In a schlenk tube, acetylenic ketone 1a (0.2 mmol, 40.2 mg), 2-
phenylacetophenone 2a (0.2 mmol, 39.2 mg), Cs2CO3 (0.4
mmol, 130.3 mg) and DMF (2.0 mL) were stirred at room
temperature under N2. After 3 h, then ZnI2 (0.04 mmol, 12.8
mg) and K2S2O8 (0.4 mmol, 108.1 mg) were added. After the
completion of the addition, the reaction mixture was allowed
to react at 50 °C for 8 h. Then, the reaction mixture was cooled
to room temperature and was treated with H2O, then
extracted with EA and dried over anhydrous Na2SO4. After
removal of the EA, the residue was purified by
chromatography on basic silica gel (PE: EA = 30: 1) to afford 3a
(yellow solid, 62.5 mg, 78%).
1
(200~300 mesh). H NMR spectra were recorded at 400 MHz,
13C NMR spectra were recorded at 100 MHz, and in CDCl3
(containing 0.03% TMS) solutions. 1H NMR spectra was
recorded with tetramethylsilane (δ= 0.00 ppm) as internal
reference; 13C NMR spectra was recorded with CDCl3(δ= 77.00
ppm) as internal reference. High-resolution mass spectra were
performed on a mass spectrometer with a TOF (for EI or ESI) or
FT-ICR (for MALDI) analyzer.
Typical Procedure for the Synthesis of 1
Phenyl(2,4,5-triphenylfuran-3-yl)methanone (3a). yellow
solid, obtained in 11 h and purified by chromatography on
silica gel (petroleum ether/ethyl acetate = 30:1); yield: 78%,
62.5 mg, m.p. 185-187 oC. 1H NMR (400 MHz, CDCl3) δ 7.83 (d,
J = 8.0 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.54 (d, J = 7.6 Hz, 2H),
7.42-7.37 (m, 1H), 7.35-7.15 (m, 13H). 13C NMR (100 MHz,
CDCl3) δ 194.0, 151.3, 148.4, 137.7, 133.6, 132.4, 130.4, 130.0,
129.8, 128.8, 128.7, 128.6, 128.1, 127.9, 126.5, 126.2, 124.3,
To a solution of alkyne (12 mmol) in anhydrous THF (30 mL), n-
BuLi (2.5M, 10 mmol, 4 mL) was added at -78 oC. The resulting
mixture was stirred at -78 oC for 1 hour, then the aldehyde (10
mmol) was added and the reaction temperature was raised to
room temperature till aldehyde disappeared by TLC analysis.
The resulting mixture was quenched with a saturated solution
of NH4Cl and extracted with ethyl acetate (20 mL × 3). The
combined organic layers were washed with brine and dried
over anhydrous Na2SO4, filtered, and concentrated under
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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124.0. HRMS (ESI) calcd for C29H20NaO2 [M+Na]+: 423.1356;
found: 423.1361.
4-(4-Benzoyl-2,5-diphenylfuran-3-yl)benzonitrile
(4-(3-chlorophenyl)-2,5-diphenylfuran-3-
yl)(phenyl)methanone (3g). yellow solidD, OobI:t1a0i.n10e3d9/iCn91O1B0h00a8n1dJ
(3b). purified by chromatography on silica gel (petroleum
View Article Online
yellow solid, obtained in 11 h and purified by chromatography ether/ethyl acetate = 30:1); yield: 73%, 63.3 mg, m.p. 136-138
on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 59%, oC. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 2H), 7.62 (d,
50.5 mg, m.p. 134-136 oC. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.52 (d, J = 7.2 Hz, 2H), 7.44-7.39 (m, 1H), 7.33-
J = 8.0 Hz, 2H), 7.60 (d, J = 7.2 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.23 (m, 9H), 7.19-7.13 (m, 3H). 13C NMR (100 MHz, CDCl3) δ
7.49-7.42 (m, 3H), 7.41-7.37 (m, 2H), 7.36-7.25 (m, 8H). 13C 193.5, 151.7, 148.8, 137.6, 134.5, 134.3, 133.7, 130.1, 130.0,
NMR (100 MHz, CDCl3) δ 193.2, 152.4, 149.3, 137.7, 137.4, 129.9, 129.5, 128.9, 128.8, 128.6, 128.4, 128.1, 126.6, 126.3,
134.0, 132.6, 130.8, 130.0, 129.6, 129.3, 129.1, 128.9, 128.8, 123.6, 122.8. HRMS (ESI) calcd for C29H19ClNaO2 [M+Na]+:
128.8, 126.8, 126.6, 123.1, 122.5, 118.8, 111.5. HRMS (ESI) 457.0966; found: 457.0964.
calcd for C30H19NNaO2 [M+Na]+: 448.1308; found: 448.1323.
(4-Fluorophenyl)(2,4,5-triphenylfuran-3-yl)methanone and
(2-(4-fluorophenyl)-4,5-diphenylfuran-3-
(4-(4-Chlorophenyl)-2,5-diphenylfuran-3-
yl)(phenyl)methanone (3c). yellow solid, obtained in 11 h and yl)(phenyl)methanone (3h+3h'). yellow solid, obtained in 11 h
purified by chromatography on silica gel (petroleum and purified by chromatography on silica gel (petroleum
1
ether/ethyl acetate = 30:1); yield: 81%, 70.2 mg, mp 137-139 ether/ethyl acetate = 30:1); yield: 76%, 63.5 mg. H NMR (400
oC. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.6 Hz, 2H), 7.60 (d, MHz, CDCl3) Obtained as 4: 3 isomer. Major isomer: δ 7.89-
J = 7.2 Hz, 2H), 7.52 (d, J = 6.4 Hz, 2H), 7.45-7.41 (m, 1H), 7.32- 7.78 (m, 2H), 7.66-7.60 (m, 2H), 7.57-7.50 (m, 2H), 7.46-7.36
7.25 (m, 7H), 7.25-7.17 (m, 5H). 13C NMR (100 MHz, CDCl3) δ (m, 1H), 7.32-7.20 (m, 10H), 6.95-6.88 (m, 2H); minor isomer: δ
193.7, 151.6, 148.7, 137.5, 133.9, 133.8, 131.4, 130.9, 130.1, 7.12-6.96 (m, 2H); other peaks are overlapped with the other
130.0, 129.6, 129.1, 128.8, 128.7, 128.4, 126.6, 126.3, 123.7, isomer. 13C NMR (100 MHz, CDCl3) δ 193.8, 192.3, 167.5, 164.9,
123.1. HRMS (ESI) calcd for C29H19ClNaO2 [M+Na]+: 457.0966; 164.3, 161.8, 151.3, 150.6, 148.5, 148.4, 137.6, 134.1, 134.1,
found: 457.0972.
133.7, 133.3, 132.7, 132.6, 132.3, 130.3, 130.0, 130.0, 129.7,
(2,5-Diphenyl-4-(p-tolyl)furan-3-yl)(phenyl)methanone (3d). 128.8, 128.8, 128.7, 128.6, 128.5, 128.5, 128.2, 128.0, 127.9,
yellow solid, obtained in 11 h and purified by chromatography 126.5, 126.2, 124.3, 124.2, 123.8, 123.7, 116.0, 115.8, 115.8,
on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 83%, 115.6. HRMS (ESI) calcd for C29H19FNaO2 [M+Na]+: 441.1261;
69.2 mg, m.p. 148-150 oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, found: 441.1266.
J = 8.0 Hz, 2H), 7.61 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 7.6 Hz, 2H),
(4-Chlorophenyl)(2,4,5-triphenylfuran-3-yl)methanone and
7.45-7.38 (m, 1H), 7.33-7.21 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), (2-(4-chlorophenyl)-4,5-diphenylfuran-3-
7.03 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H). 13C NMR (100 MHz, CDCl3) yl)(phenyl)methanone (3i+3i'). yellow solid, obtained in 11 h
δ 194.1, 151.0, 148.4, 137.7, 137.6, 133.6, 130.5, 130.1, 129.8, and purified by chromatography on silica gel (petroleum
1
129.5, 129.2, 128.8, 128.7, 128.6, 128.0, 126.5, 126.2, 124.4, ether/ethyl acetate = 30:1); yield: 79%, 68.3 mg. H NMR (400
124.1, 21.0. HRMS (ESI) calcd for C30H22NaO2 [M+Na]+: MHz, CDCl3) Obtained as 1: 1 isomer. Isomer 1: δ 7.82 (d, J =
437.1512; found: 437.1516.
8.0 Hz, 2H), 7.64-7.51 (m, 4H), 7.46-7.36 (m, 1H), 7.30-7.20 (m,
(4-(4-Methoxyphenyl)-2,5-diphenylfuran-3-
12H); isomer 2: δ 7.76 (d, J = 8.0 Hz, 2H); other peaks are
yl)(phenyl)methanone (3e). yellow solid, obtained in 11 h and overlapped with the other isomer. 13C NMR (100 MHz, CDCl3) δ
purified by chromatography on silica gel (petroleum 193.8, 192.6, 151.4, 150.0, 148.7, 148.6, 140.1, 137.5, 136.0,
ether/ethyl acetate = 30:1); yield: 67%, 57.8 mg, m.p. 104-106 134.6, 133.8, 132.2, 132.1, 131.3, 130.2, 130.2, 130.0, 129.6,
oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 2H), 7.62 (d, 129.1, 128.9, 128.9, 128.8, 128.7, 128.6, 128.3, 128.2, 128.0,
J = 7.6 Hz, 2H), 7.56 (d, J = 7.6 Hz, 2H), 7.45-7.39 (m, 1H), 7.34- 127.9, 127.6, 126.5, 126.3, 126.2, 124.4, 124.1, 123.5. HRMS
7.23 (m, 8H), 7.19 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 8.4 Hz, 2H), (ESI) calcd for C29H19ClNaO2 [M+Na]+: 457.0966; found:
3.75 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 194.2, 159.4, 151.0, 457.0967.
148.3, 137.7, 133.6, 131.2, 130.5, 130.0, 129.8, 128.8, 128.7,
(4-Bromophenyl)(2,4,5-triphenylfuran-3-yl)methanone and
128.6, 128.0, 126.4, 126.1, 124.4, 124.1, 124.0, 114.2, 55.0. (2-(4-bromophenyl)-4,5-diphenylfuran-3-
HRMS (ESI) calcd for C30H22NaO3 [M+Na]+: 453.1461; found: yl)(phenyl)methanone (3j+3j'). yellow solid, obtained in 11 h
453.1467.
and purified by chromatography on silica gel (petroleum
1
(2,5-diphenyl-4-(o-tolyl)furan-3-yl)(phenyl)methanone (3f). ether/ethyl acetate = 30:1); yield: 72%, 68.9 mg. H NMR (400
yellow solid, obtained in 11 h and purified by chromatography MHz, CDCl3) Obtained as 1: 1 isomer. Isomer 1: δ 7.82 (d, J =
on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 69%, 8.0 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H), 7.55-7.38 (m, 5H), 7.32-
57.5 mg, m.p. 163-165 oC. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, 7.20 (m, 10H); isomer 2: δ 7.69 (d, J = 8.4 Hz, 2H); other peaks
J = 7.6 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 7.6 Hz, 2H), are overlapped with the other isomer. 13C NMR (100 MHz,
7.42-7.36 (m, 1H), 7.32-7.13 (m, 11H), 7.12-7.05 (m, 1H), 2.15 CDCl3) δ 193.8, 192.8, 151.5, 150.0, 148.7, 148.6, 137.5, 136.4,
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 193.5, 151.4, 148.2, 137.6, 133.8, 132.2, 132.1, 132.0, 131.9, 131.4, 130.2, 130.2, 130.0,
137.4, 133.4, 131.8, 130.7, 130.6, 130.4, 129.8, 129.7, 128.8, 129.6, 128.9, 128.8, 128.7, 128.7, 128.3, 128.2, 128.0, 128.0,
128.7, 128.7, 128.4, 128.4, 127.9, 126.7, 126.1, 125.0, 124.3, 127.8, 126.5, 126.3, 126.2, 124.5, 124.4, 124.2, 123.5, 122.8.
123.5, 19.8. HRMS (ESI) calcd for C30H22NaO2 [M+Na]+: HRMS (ESI) calcd for C29H19BrNaO2 [M+Na]+: 501.0461; found:
437.1512; found: 437.1515.
501.0461.
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J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
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COMMUNICATION
Journal Name
P-tolyl(2,4,5-triphenylfuran-3-yl)methanone and (4,5- 20.9, 12.3. HRMS (ESI) calcd for C25H20NaO2: [M+Na]+:
View Article Online
DOI: 10.1039/C9OB00081J
diphenyl-2-(p-tolyl)furan-3-yl)(phenyl)methanone (3k+3k'). 375.1356 found: 375.1354.
yellow solid, obtained in 11 h and purified by chromatography
(5-(4-Nitrophenyl)-2,4-diphenylfuran-3-
on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 83%, yl)(phenyl)methanone (3o). yellow solid, obtained in 11 h and
1
69.0 mg. H NMR (400 MHz, CDCl3) Obtained as 1.4: 1 isomer. purified by chromatography on silica gel (petroleum
Major isomer: δ 7.76 (d, J = 7.6 Hz, 2H), 7.64-7.50 (m, 4H), ether/ethyl acetate = 30:1); yield: 61%, 54.5 mg, m.p. 157-159
7.45-7.35 (m, 1H), 7.30-7.20 (m, 10H), 7.13-7.03 (m, 2H), 2.30 oC. 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.8 Hz, 2H), 7.82 (d,
(s, 3H); minor isomer: δ 7.83 (d, J = 7.6 Hz, 2H); other peaks are J = 7.6 Hz, 2H), 7.72-7.60 (m, 4H) , 7.45-7.40 (m, 1H), 7.35-7.23
overlapped with the other isomer. 13C NMR (100 MHz, CDCl3) δ (m, 10H). 13C NMR (100 MHz, CDCl3) δ 193.2, 152.8, 146.8,
194.1, 193.7, 151.6, 150.6, 148.4, 148.1, 144.7, 138.8, 137.8, 146.0, 137.3, 136.3, 133.9, 131.4, 129.9, 129.7, 129.4, 129.2,
135.2, 133.5, 132.5, 132.4, 130.5, 130.2, 130.0, 130.0, 130.0, 129.1, 128.9, 128.7, 128.0, 126.7, 126.0, 124.5, 124.1. HRMS
129.8, 129.5, 129.4, 128.8, 128.8, 128.7, 128.5, 128.1, 128.0, (ESI) calcd for C29H19NNaO4 [M+Na]+: 468.1206; found:
127.8, 127.8, 127.0, 126.5, 126.3, 126.2, 126.2, 124.3, 124.3, 468.1207.
124.2, 123.4, 21.4, 21.0. HRMS (ESI) calcd for C30H22NaO2
[M+Na]+: 437.1512; found: 437.1513.
(4-Methoxyphenyl)(2,4,5-triphenylfuran-3-yl)methanone
(5-(4-Fluorophenyl)-2,4-diphenylfuran-3-
yl)(phenyl)methanone (3p). yellow solid, obtained in 11 h and
purified by chromatography on silica gel (petroleum
and
(2-(4-methoxyphenyl)-4,5-diphenylfuran-3- ether/ethyl acetate = 30:1); yield: 83%, 69.3 mg, m.p. 150-152
yl)(phenyl)methanone (3l+3l'). yellow solid, obtained in 11 h oC. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.6 Hz, 2H), 7.62 (d,
and purified by chromatography on silica gel (petroleum J = 7.6 Hz, 2H), 7.54-7.47 (m, 2H) , 7.43-7.38 (m, 1H), 7.32-7.21
ether/ethyl acetate = 10:1); yield: 52%, 44.8 mg. H NMR (400 (m, 10H), 7.02-6.94 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 193.8,
1
MHz, CDCl3) Obtained as 4: 1 isomer. Major isomer: δ 7.84 (d, J 162.7 (J = 248.6 Hz), 151.3, 147.6, 137.6, 133.6, 132.2, 130.0,
= 8.8 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H),7.54 (d, J = 7.2 Hz, 2H), 130.0, 129.7, 128.9, 128.8, 128.7, 128.6, 128.1 (J = 8.1 Hz),
7.33-7.20 (m, 11H), 6.76 (d, J = 8.4 Hz, 2H), 3.78 (s, 3H); minor 128.0, 126.6 (J = 3.3 Hz), 126.5, 124.0, 123.9, 115.7 (J = 21.8
isomer: δ 7.42-7.37 (m, 1H), 6.82 (d, J = 8.8 Hz, 2H); other Hz). HRMS (ESI) calcd for C29H19FNaO2 [M+Na]+: 441.1261;
peaks are overlapped with the other isomer. 13C NMR (100 found: 441.1264.
MHz, CDCl3) δ 192.5, 164.2, 150.4, 148.3, 133.4, 132.5, 130.8,
(5-(4-Chlorophenyl)-2,4-diphenylfuran-3-
130.5, 130.0, 130.0, 130.0, 129.9, 128.8, 128.8, 128.7, 128.7, yl)(phenyl)methanone (3q). white solid, obtained in 11 h and
128.5, 128.5, 128.2, 128.0, 127.9, 127.9, 127.8, 126.2, 126.1, purified by chromatography on silica gel (petroleum
124.3, 124.2, 114.2, 113.8, 55.3, 55.1. HRMS (ESI) calcd for ether/ethyl acetate = 30:1); yield: 70%, 60.9 mg, m.p. 178-180
C30H22NaO3: [M+Na]+: 453.1461 found: 453.1467.
2,2-dimethyl-1-(2,4,5-triphenylfuran-3-yl)propan-1-one and J = 7.2 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.42-7.37 (m, 1H), 7.35-
(2-(tert-butyl)-4,5-diphenylfuran-3-yl)(phenyl)methanone
7.14 (m, 12H). 13C NMR (100 MHz, CDCl3) δ 193.7, 151.5, 147.4,
oC. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.62 (d,
(3m+3m'). white solid, obtained in 11 h and purified by 137.6, 133.9, 133.7, 132.0, 130.0, 129.9, 129.6, 128.9, 128.9,
chromatography on silica gel (petroleum ether/ethyl acetate = 128.8, 128.8, 128.6, 128.1, 127.4, 126.5, 124.8, 124.0. HRMS
50:1); yield: 61%, 46.6 mg. 1H NMR (400 MHz, CDCl3) Obtained (ESI) calcd for C29H19ClNaO2 [M+Na]+: 457.0966; found:
as 1.2: 1 isomer. Major isomer: δ 7.78 (d, J = 7.6 Hz, 2H), 7.53 457.0970 .
(d, J = 6.8 Hz, 2H), 7.45-7.11 (m, 11H), 1.36 (s, 9H); minor
(5-(4-Bromophenyl)-2,4-diphenylfuran-3-
isomer: δ 7.65 (d, J = 8.0 Hz, 2H), 0.82 (s, 9H); other peaks are yl)(phenyl)methanone (3r). yellow solid, obtained in 11 h and
overlapped with the other isomer. 13C NMR (100 MHz, CDCl3) δ purified by chromatography on silica gel (petroleum
212.7, 195.4, 159.8, 148.2, 147.6, 146.0, 138.6, 133.4, 133.2, ether/ethyl acetate = 30:1); yield: 75%, 72.0 mg, m.p. 164-166
132.8, 130.8, 130.8, 130.5, 130.3, 129.9, 129.0, 128.9, 128.6, oC. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 2H), 7.62 (d,
128.6, 128.5, 128.4, 128.1, 128.0, 127.5, 127.5, 126.2, 126.0, J = 7.2 Hz, 2H), 7.42-7.36 (m, 5H), 7.30-7.21 (m, 10H). 13C NMR
125.8, 125.2, 123.0, 122.6, 122.0, 45.7, 34.1, 29.2, 26.5. HRMS (100 MHz, CDCl3) δ 193.7, 151.5, 147.4, 137.5, 133.7, 132.0,
(ESI) calcd for C27H24NaO2: [M+Na]+: 403.1669 found: 403.1669. 131.9, 130.0, 129.9, 129.5, 129.2, 128.9, 128.8, 128.8, 128.6,
1-(2,4,5-triphenylfuran-3-yl)propan-1-one and (2-ethyl-4,5- 128.1, 127.6, 126.5, 124.9, 124.0, 122.0. HRMS (ESI) calcd for
diphenylfuran-3-yl)(phenyl)methanone (3n+3n'). yellow oil, C29H19BrNaO2 [M+Na]+: 501.0461; found: 501.0466.
obtained in 11 h and purified by chromatography on silica gel
(2,4-Diphenyl-5-(p-tolyl)furan-3-yl)(phenyl)methanone (3s).
and purified by
(petroleum ether/ethyl acetate = 50:1); yield: 63%, 44.6 mg. 1H yellow solid, obtained in 11
h
NMR (400 MHz, CDCl3) Obtained as 16.7: 1 isomer. Major chromatographyon silica gel (petroleum ether/ethyl acetate =
isomer: δ 7.71 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 7.2 Hz, 2H),7.54- 30:1); yield: 86%, 71.3 mg, m.p. 140-142 oC. 1H NMR (400 MHz,
7.36 (m, 1H), 7.29-7.12 (m, 10H), 2.75 (q, J = 7.6 Hz, 2H), 1.31 (t, CDCl3) δ 7.84 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2H), 7.45-
3H); minor isomer: δ 7.98 (d, J = 7.6 Hz, 2H), 2.31 (q, J = 7.6 Hz, 7.36 (m, 3H) , 7.31-7.18 (m, 10H), 7.10 (d, J = 8.0 Hz, 2H), 2.33
2H), 0.94 (t, 3H); other peaks are overlapped with the other (s, 3H). 13C NMR (100 MHz, CDCl3) δ 194.1, 151.0, 148.7, 138.1,
isomer. 13C NMR (100 MHz, CDCl3) δ 193.1, 159.9, 147.5, 138.7, 137.7, 133.6, 132.5, 130.0, 129.8, 129.4, 128.8, 128.7, 128.6,
135.1, 132.9, 132.8, 130.6, 130.1, 129.6, 129.2, 129.2, 128.8, 128.5, 127.7, 127.6, 126.5, 126.2, 123.9, 123.7, 21.0. HRMS
128.5, 128.5, 128.2, 127.7, 127.4, 127.2, 126.1, 123.3, 122.5, (ESI) calcd for C30H22NaO2 [M+Na]+: 437.1512; found: 437.1516.
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
(4-Chlorophenyl)(2-(4-chlorophenyl)-4,5-diphenylfuran-3-
yl)methanone (3t). yellow solid, obtained in 11 h and purified 7.46 (m, 4H), 7.35-7.16 (m, 11H). C NMR (100 MHz, CDCl3) δ
by chromatography on silica gel (petroleum ether/ethyl 192.2, 150.4, 149.2, 140.6, 135.7, 135.0, 134.2, 131.3, 130.5,
acetate = 30:1); yield: 82%, 76.9 mg, m.p. 147-149 oC. 1H NMR 129.7, 129.3, 129.2, 128.9, 128.7, 127.9, 127.7, 126.4, 123.6,
(400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 123.0. HRMS (ESI) calcd for C29H17Cl3NaO2 [M+Na]+: 525.0186;
2H), 7.52 (d, J = 7.2 Hz, 2H), 7.32-7.18 (m, 12H). 13C NMR (100 found: 525.0200.
COMMUNICATION
oC. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H), 7.56-
1
View Article Online
13
DOI: 10.1039/C9OB00081J
MHz, CDCl3) δ 192.5, 150.2, 148.8, 140.3, 135.8, 134.8, 132.0,
(5-Phenyl-2,4-di-p-tolylfuran-3-yl)(p-tolyl)methanone (3z).
131.3, 130.0, 129.9, 129.2, 129.0, 128.9, 128.7, 128.4, 128.1, yellow solid, obtained in 11 h and purified by chromatography
127.6, 126.3, 124.2, 123.9. HRMS (ESI) calcd for C29H18Cl2NaO2 on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 70%,
[M+Na]+: 491.0576; found: 491.0577.
(4-Bromophenyl)(2-(4-bromophenyl)-4,5-diphenylfuran-3-
62.3 mg, m.p. 64-66 oC. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
7.6 Hz, 2H), 7.55 (d, J = 7.6 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H),
yl)methanone (3u). yellow solid, obtained in 11 h and purified 7.30-7.22 (m, 3H), 7.18-7.00 (m, 8H), 2.3-2.2 (m, 9H). 13C NMR
by chromatography on silica gel (petroleum ether/ethyl (100 MHz, CDCl3) δ 193.8, 150.8, 147.9, 144.6, 138.5, 137.5,
acetate = 30:1); yield: 75%, 83.2 mg, m.p. 193-195 oC. 1H NMR 135.3, 130.7, 130.2, 129.8, 129.5, 129.5, 129.4, 128.6, 127.8,
(400 MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 2H), 7.54-7.40 (m, 8H), 127.1, 126.3, 126.1, 124.3, 123.6, 21.4, 21.0, 21.0. HRMS (ESI)
7.32-7.20 (m, 8H). 13C NMR (100 MHz, CDCl3) δ 192.7, 150.2, calcd for C32H26NaO2 [M+Na]+: 465.1825; found: 465.1828.
148.9, 136.2, 132.1, 132.0, 131.9, 131.4, 130.0, 129.9, 129.2,
(5-phenyl-4-(thiophen-2-yl)-2-(p-tolyl)furan-3-yl)(p-
128.9, 128.8, 128.5, 128.4, 128.1, 127.8, 126.3, 124.2, 124.0, tolyl)methanone (3za). yellow solid, obtained in 11 h and
123.0. HRMS (ESI) calcd for C29H18Br2NaO2 [M+Na]+: 578.9566; purified by chromatography on silica gel (petroleum
found: 578.9577.
ether/ethyl acetate = 30:1); yield: 58%, 50.4 mg, m.p. 177-179
(4,5-Diphenyl-2-(p-tolyl)furan-3-yl)(p-tolyl)methanone (3v). oC. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.62 (d,
yellow solid, obtained in 11 h and purified by chromatography J = 6.8 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.35-7.26 (m, 3H), 7.23-
on silica gel (petroleum ether/ethyl acetate = 30:1); yield: 80%, 7.18 (m, 1H), 7.14-7.06 (m, 4H), 6.97-6.92 (m, 1H), 6.92-6.87
68.6 mg, m.p. 168-170 oC. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, (m, 1H), 2.33 (S, 3H), 2.30 (S, 3H). 13C NMR (100 MHz, CDCl3) δ
J = 8.0 Hz, 2H), 7.55-7.47 (m, 4H), 7.30-7.18 (m, 8H), 7.12-7.03 193.4, 150.8, 149.4, 144.8, 138.8, 135.2, 132.6, 130.2, 130.1,
(m, 4H), 2.29 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 193.7, 151.0, 129.5, 129.4, 128.7, 128.6, 128.3, 127.5, 126.9, 126.7, 126.4,
148.0, 144.6, 138.6, 135.3, 132.5, 130.5, 130.2, 130.0, 129.5, 126.2, 123.8, 116.8, 21.5, 21.0. HRMS (ESI) calcd for
129.3, 128.7, 128.6, 127.9, 127.8, 127.1, 126.3, 126.2, 124.3, C29H22NaO2S [M+Na]+: 457.1233; found: 457.1239.
123.5, 21.4, 21.0. HRMS (ESI) calcd for C31H24NaO2 [M+Na]+:
Typical Procedure for the Synthesis of 4a.
451.1669; found: 451.1678.
In a schlenk tube acetyenic ketone 1a (0.2 mmol, 41.2 mg),
(4-Methoxyphenyl)(2-(4-methoxyphenyl)-4,5-
Cs2CO3 (0.4 mmol, 130.3 mg), DMF (3.0 mL) and 2-
diphenylfuran-3-yl)methanone (3w). yellow oil, obtained in 11
phenylacetophenone 2a (0.2 mmol, 39.2 mg) was stirred at
h and purified by chromatography on silica gel (petroleum
room temperature under N2. After the reaction was completed
1
ether/ethyl acetate = 10:1); yield: 51%, 46.6 mg. H NMR (400
as monitored by thin-layer chromatography, the reaction
MHz, CDCl3) δ 7.83 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H),
mixture was then quenched by water, and the water layers
7.52 (d, J = 7.6 Hz, 2H), 7.29-7.20 (m, 8H), 6.82 (d, J = 8.4 Hz,
were extracted with ethyl acetate (10 mL × 3). The combined
2H), 6.75 (d, J = 8.8 Hz, 2H), 3.77 (s, 6H). 13C NMR (100 MHz,
organic layers were washed with brine, dried over anhydrous
CDCl3) δ 192.6, 164.1, 160.0, 150.9, 147.7, 132.6, 132.5, 130.9,
Na2SO4, filtered, and concentrated under reduced pressure.
130.6, 130.0, 128.7, 128.6, 127.9, 127.8, 127.8, 126.1, 124.3,
Purification by chromatography on silica gel (petroleum
122.8, 122.7, 114.2, 113.8, 55.3, 55.1. HRMS (ESI) calcd for
ether/ethyl acetate = 20/1) afforded desired compound 4a
C31H24NaO4 [M+Na]+: 483.1567; found: 483.1572.
(yellow solid, 67.6 mg, 84%).
Naphthalen-2-yl(2-(naphthalen-2-yl)-4,5-diphenylfuran-3-
(2Z,3Z)-2-(hydroxy(phenyl)methylene)-1,3,4-triphenylbut-
yl)methanone (3x). yellow solid, obtained in 11 h and purified
3-en-1-one (4a). yellow solid, obtained in 3.0 h and purified by
by chromatography on silica gel (petroleum ether/ethyl
chromatography on silica gel (petroleum ether/ethyl acetate =
acetate = 30:1); yield: 51%, 51.1 mg, m.p. 136-138 oC. 1H NMR
20:1); yield: 84%, 67.6 mg, m.p. 156-158 oC. 1H NMR (400 MHz,
(400 MHz, CDCl3) δ 8.38 (s, 1H), 8.20 (s,1H), 8.01 (d, J = 8.4 Hz,
CDCl3) δ 17.94 (s, 1H), 7.44-7.32 (m, 6H), 7.25-7.05 (m, 14H),
2H), 7.80-7.68 (m, 7H), 7.63 (d, J = 7.6 Hz, 2H), 7.53-7.47 (m,
6.64 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 190.7, 143.0, 137.8,
1H), 7.42-7.15 (m, 11H). 13C NMR (100 MHz, CDCl3) δ 194.0,
137.2, 137.0, 132.3, 130.6, 128.7, 128.5, 128.5, 127.7, 127.6,
151.0, 148.7, 136.0, 135.2, 133.4, 133.2, 132.9, 132.6, 132.4,
127.5, 127.2, 127.0, 110.7. HRMS (ESI) calcd for C29H22NaO2
130.4, 130.0, 129.9, 128.8, 128.8, 128.7, 128.6, 128.6, 128.2,
[M+Na]+: 425.1512; found: 425.1505.
127.9, 127.9, 127.8, 127.2, 126.8, 126.7, 126.7, 126.3, 125.6,
124.7, 124.7, 124.6, 123.8. HRMS (ESI) calcd for C37H24NaO2 Gram Scales.
[M+Na]+: 523.1669; found: 523.1681.
(2,4-Bis(4-chlorophenyl)-5-phenylfuran-3-yl)(4-
In a schlenk tube, acetyenic ketone 1a (5.0 mmol, 1031.2 mg),
chlorophenyl)methanone (3y). yellow solid, obtained in 11 h 2-phenylacetophenone 2a (5.0 mmol, 981.2 mg), Cs2CO3 (10.0
and purified by chromatography on silica gel (petroleum mmol, 3258.2 mg) and DMF (50 mL) were stirred at room
ether/ethyl acetate = 30:1); yield: 70%, 70.7 mg, m.p. 145-147 temperature under N2. After 3 h, then ZnI2 (1.0 mmol, 319.2mg)
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Organic & Biomolecular Chemistry
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(h) S. Mao, X.-Q. Zhu, Y.-R. Gao, D.-D. Guo, Y.-Q. Wang, Chem.- Eur. J.,
and K2S2O8 (10.0 mmol, 2703.2 mg) were added. After the
completion of the addition, the reaction mixture was allowed
to react at 50 °C for 8 h. Then, the reaction mixture was cooled
to room temperature and was treated with H2O, then
extracted with EA and dried over anhydrous Na2SO4. After
removal of the EA, the residue was purified by
chromatography on basic silica gel (PE: EA = 30: 1) to afford 3a
(yellow solid, 1469.3 mg, 73%).
View Article Online
2015, 21, 11335.
DOI: 10.1039/C9OB00081J
8
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We thank the National Natural Science Foundation of China
(Grant Nos. 21272074, 21871087) and the Program for
Changjiang Scholars and Innovative Research Team in
University (PCSIRT) for financial support.
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