Synthesis of substituted phenanthrofurans

Article abstract of DOI:10.1016/j.tet.2015.10.060

A three-step protocol toward phenanthrofurans 1 starting with deoxybenzoins 3 is developed with moderate to good yield. A facile process is carried out for the (1) α-propargylation of 3 with NaH and propargyl bromide 2 in refluxing THF, (2) Bi(OTf)₃-mediated cycloisomerization of γ-ynones 4 with 4 ? molecular sieves in MeNO₂ at rt, and (3) photolytic Scholl annulation of 2,3-diarylfurans 5 with I₂ in EtOAc at rt. The key structures of 1 are confirmed by X-ray crystallographic analysis.

Full text of DOI:10.1016/j.tet.2015.10.060

Tetrahedron xxx (2015) 1e9
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of substituted phenanthrofurans
*
Chieh-Kai Chan, Yi-Chia Chen, Yeh-Long Chen, Meng-Yang Chang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A three-step protocol toward phenanthrofurans 1 starting with deoxybenzoins 3 is developed with
moderate to good yield. A facile process is carried out for the (1) -propargylation of 3 with NaH and
propargyl bromide 2 in refluxing THF, (2) Bi(OTf)3-mediated cycloisomerization of
molecular sieves in MeNO2 at rt, and (3) photolytic Scholl annulation of 2,3-diarylfurans 5 with I2 in
EtOAc at rt. The key structures of 1 are confirmed by X-ray crystallographic analysis.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 24 September 2015
Received in revised form 19 October 2015
Accepted 21 October 2015
Available online xxx
a
ꢀ
g
-ynones 4 with 4 A
Keywords:
Phenanthrofurans
Cycloisomerization
Scholl annulation
1. Introduction
phenanthro[9,10-b]furan 1 starting from deoxybenzoin 3 using an
easy-operational, high-yielding and efficient sequence of a-prop-
Applications for a phenanthro-based furan core system have
been developed in electronic devices from BASF SE, especially in
electroluminescent devices.1 This core skeleton may function with
phosphorescent materials to provide improved efficiency, stability,
manufacturability, or spectral characteristics of electroluminescent
devices. To the best of our knowledge, few synthetic routes for
preparing the skeleton of phenanthrofuran have been early re-
ported.2 For its analogues, phenanthro-fused benzofurans are also
large planar building blocks in the supramolecular field of molec-
ular materials.3,4 Depending on literature reports, 1 can be obtained
in great quantities via photolytic irradiation of 2,3-diarylfurans.2a,b
Although prepared protocols of 1, with a specific substitution pat-
tern, have been investigated, newly prepared methodologies are
needed. Based on the above encouraged interests in the structural
framework of phenanthro-conjugated oxygen-containing hetero-
cycles, we envisage a three-step synthetic route to functionalized
argylation, Bi(OTf)3-mediated cycloisomerization, and photolytic
Scholl annulation, as shown in Scheme 1.
2. Results and discussion
In continuation of our investigation on the skeleton of metal
triflate-mediated reactions,5 a facile three-step route toward 1 is
explored, including (1) a-propargylation of 3 with NaH and 2 in
refluxing THF, (2) Bi(OTf)3-mediated (3þ2) cycloisomerization of
g-
ꢀ
ynone 4 with 4 A molecular sieves (MS) in MeNO2 at rt, and (3)
photolytic Scholl annulation of 2,3-diarylfuran 5 with I2 in EtOAc at
rt, as shown in Scheme 2.
Scheme 2. Three-step synthesis of 1.
Initially, treatment of the mode substrate deoxybenzoin 3a
(X¼H, Ar¼Ph, prepared from PPA/TFAA-mediated FriedeleCrafts
acylation of benzene with phenylacetic acid in MeCN) with NaH
and propargyl bromide (2, 1.2 equiv) in boiling THF produces 4a
with an 85% yield, as shown in Table 1. Next, the reaction of 4a with
catalytic amounts of Bi(OTf)3 (2 mol %) in the presence of molecular
Scheme 1. Synthetic analysis of 1.
ꢀ
sieves (4 A, MS) in MeNO2 affords furan 5a with the 2,3-diphenyl
group in an 88% yield. The 5-exo-dig cycloisomerization provides
facile, mild, less-toxic, and atom-economic conditions. Among
* Corresponding author. Tel.: þ886 7 3121101x2220; e-mail address: mychang@
kmu.edu.tw (M.-Y. Chang).
http://dx.doi.org/10.1016/j.tet.2015.10.060
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
Table 1
Table 2
Synthesis of 5a,b
Synthesis of 1a
X
X
X
NaH, THF
Bi(OTf)
3
Me
Br
2
MeNO , MS
O
2
Ar
O
Ar
O
Ar
3a-u
5a-u
4a-u
Entry
3, X¼, Ar¼
3a, H, Ph
4 (%)c
5 (%)c
1
4a, 85
4b, 80
4c, 76
4d, 75
4e, 72
4f, 77
4g, 80
4h, 74
4i, 70
4j, 80
4k, 82
4l, 80
4m, 76
4n, 78
4o, 82
4p, 78
4q, 80
4r, 82
4s, 80
4t, 73
4u, 74
5a, 88
5b, 86
5c, 82
5d, 84
5e, 79
5f, 80
5g, 80
5h, 83
5i, 75
5j, 77
5k, 80
5l, 81
5m, 76
5n, 78
5o, 76
5p, 80
5q, 76
5r, 73
5s, 74
5t, 75
5u, 74
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
3b, H, 4-FC6H4
3c, H, 4-MeOC6H4
3d, 4-Me, 4-MeOC6H4
3e, 4-F, 4-MeOC6H4
3f, 4-OMe, 4-MeOC6H4
3g, 4-CF3, 4-MeOC6H4
3h, 3,5-F2, 4-MeOC6H4
3i, 4-Ph, 4-MeOC6H4
3j, 2-naphthalene, 4-MeOC6H4
3k, H, 3,4-(MeO)2C6H3
3l, 4-Me, 3,4-(MeO)2C6H3
3m, 4-F, 3,4-(MeO)2C6H3
3n, 4-OMe, 3,4-(MeO)2C6H3
3o, 4-Ph, 3,4-(MeO)2C6H3
3p, 3,5-F2, 3,4-(MeO)2C6H3
3q, 4-F, 2,3,4-(MeO)3C6H2
3r, 3,4-(OMe)2, 4-MeO-naphthalene
3s, 3,4-CH2O2, 4-MeO-naphthalene
3t, 3,4-CH2O2, 4-nBuO-naphthalene
3u, 3,4-CH2O2, 4,7-(MeO)2-naphthalene
a
The reaction was run on 3 (1.0 mmol), 2 (1.2 mmol), NaH (60% in oil, 120 mg,
3.0 mmol), THF (10 mL), reflux, 8 h.
b
The reaction was run on 4 (1.0 mmol), Bi(OTf)3 (13 mg, 2 mol %), MeNO2 (5 mL),
ꢀ
MS (4 A, 100 mg), rt, 3 h.
c
Isolated yields.
these routes, transition metals (Pd2þ, Agþ/Au3þ, In3þ or Zn2þ
promoting cycloisomerization of diversified -alkynones represent
)
g
a major pathway.6,7 With the results in hand, different aryl sub-
stituents (X¼H, 4-Me, 4-F, 4-MeO, 4-CF3, 3,5-F2, 4-Ph, 2-
naphthalene, 3,4-(OMe)2, 3,4-CH2O2; Ar¼Ph, 4-FC6H4, 4-
MeOC6H4, 3,4-(MeO)2C6H3, 2,3,4-(MeO)3C6H2, 4-MeO-naphtha-
lene, 4-nBuO-naphthalene, 4,7-(MeO)2-naphthalene) are examined
to investigate the synthetic pathway of 5. In Table 1, entries 1e21
show that 4a-u and 5a-u are isolated in a range of 70%e85% and
73%e88% yields, respectively. From the above results, we observe
that no obvious yield changes were exhibited for the generation of
4 and 5 among the electron-donating, electron-neutral, and
electron-withdrawing groups.
In order to synthesize the phenanthro-based furan core struc-
ture 1,8 the Scholl ring-closure of 5 is studied according to pre-
vious experiences.9 By the addition of molecular iodine and 1,2-
epoxybutane, 1a is isolated in an 80% yield in ethyl acetate at rt
for 80 h under a 254 nm wavelength irradiation. A number of
processes are available for the Scholl reaction. The following
combination of Lewis acid (or oxidant) and a reaction solvent has
been reported in literature: FeCl3 in CH2Cl2,10a MoCl5 in CH2Cl2,10b
CuCl2/AlCl3 in CS2,10c Tl(OTf)3 in CF3CO2H,10d PhI(OTf)2/BF3eOEt2
in CH2Cl2,10e MsOH/DDQ in CH2Cl2,10f and I2/photolysis in benze-
ne.10g Attempts to apply Lewis acid-mediated Scholl annulation of
5a failed to afford 1 due to the low stability of the furan ring. Of
these methods in previous literature, the photolytic Scholl oxida-
tive annulation provides the most convenient operation and
higher yields. As shown in Table 2, functionalized phenan-
throfurans 1aek with a tetracyclic skeleton and 1lem with
a polycyclic skeleton are isolated in 74%e85% yields by photolytic
annulation of 5aeg, 5ken and 5teu. The structural skeletons of
1d, 1e and 1k (see Fig. 1) were determined by single-crystal X-ray
crystallography.11
Fig. 1. X-ray structure of 1k.
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C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
3
3. Conclusion
J¼8.8 Hz, 2H), 7.29e7.19 (m, 2H), 7.05e6.92 (m, 4H), 4.21 (s, 2H),
3.87 (s, 3H).
We have developed a three-step protocol toward phenan-
throfurans 1 starting with deoxybenzoins 3. The facile process was
4.2.6. 1,2-Bis-(4-methoxyphenyl)-ethanone
(538 mg); 1H NMR (200 MHz, CDCl3):
(3f).12b Yield¼70%
carried out for the (1)
a-propargylation of 3 with NaH and prop-
d
8.01 (d, J¼8.8 Hz, 2H), 7.17
argylic bromide 2 in refluxing THF, (2) Bi(OTf)3-mediated cyclo-
(d, J¼8.4 Hz, 2H), 7.04 (d, J¼8.8 Hz, 2H), 6.86 (d, J¼8.4 Hz, 2H), 4.22
ꢀ
isomerization of
g
-ynones 4 with 4 A MS in MeNO2 at rt, and (3)
(s, 2H), 3.83 (s, 3H), 3.71 (s, 3H).
photolytic Scholl annulation of 2,3-diarylfurans 5 with I2 in EtOAc
at rt in acceptable yields. The key structures were confirmed by X-
ray crystallographic analysis. This synthesis begins with simple
starting materials and reagents, and provides a potential method-
ology for electroluminescent research.
4.2.7. 1-(4-Methoxyphenyl)-2-(4-trifluoromethylphenyl)-ethanone
(3g).12c Yield¼75% (662 mg); 1H NMR (200 MHz, CDCl3):
d 8.00 (d,
J¼8.8 Hz, 2H), 7.58 (d, J¼8.0 Hz, 2H), 7.38 (d, J¼8.0 Hz, 2H), 6.94 (d,
J¼8.8 Hz, 2H), 4.30 (s, 2H), 3.87 (s, 3H).
4. Experimental section
4.1. General
4.2.8. 2-(3,5-Difluorophenyl)-1-(4-methoxyphenyl)-ethanone
(3h). HRMS (ESI, Mþþ1) calcd for C15H13F2O2 263.0884, found
263.0885; Yield¼76% (597 mg); 1H NMR (200 MHz, CDCl3):
d 8.00
(d, J¼8.8 Hz, 2H), 6.91e6.85 (m, 4H), 6.67 (tt, J¼2.4, 8.8 Hz, 1H), 4.23
All other reagents and solvents were obtained from commercial
sources and used without further purification. Reactions were
routinely carried out under an atmosphere of dry nitrogen with
magnetic stirring. Products in organic solvents were dried with
anhydrous magnesium sulfate before concentration in vacuo.
Melting points were determined with a SMP3 melting apparatus.
1H and 13C NMR spectra were recorded on a Varian INOVA-400
spectrometer operating at 200/400 and at 100 MHz, respectively.
(s, 2H), 3.89 (s, 3H).
4.2.9. 2-Biphenyl-4-yl-1-(4-methoxyphenyl)-ethanone
(3i).12d Yield¼80% (725 mg); 1H NMR (200 MHz, CDCl3):
d 8.02 (d,
J¼8.8 Hz, 2H), 7.58e7.54 (m, 4H), 7.41e7.38 (m, 2H), 7.31e7.36 (m,
3H), 6.95 (d, J¼8.8 Hz, 2H), 4.28 (s, 2H), 3.87 (s, 3H).
4.2.10. 1-(4-Methoxyphenyl)-2-naphthalen-2-yl-ethanone
Chemical shifts (d) are reported in parts per million (ppm) and the
(3j).12e Yield¼76% (629 mg); 1H NMR (200 MHz, CDCl3):
d 8.08 (d,
coupling constants (J) are given in Hertz. High resolution mass
spectra (HRMS) were measured with a mass spectrometer Fin-
nigan/Thermo Quest MAT 95XL. X-ray crystal structures were ob-
tained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa
CCD).
J¼8.8 Hz, 2H), 7.85e7.75 (m, 3H), 7.71 (br s, 1H), 7.54e7.43 (m, 2H),
7.42e7.36 (m, 1H), 6.98 (d, J¼8.8 Hz, 2H), 4.38 (s, 2H), 3.81 (s, 3H).
4 . 2 .11. 1 - ( 3 , 4 - D i m e t h o x y p h e nyl ) - 2 - p h e nyl - e t h a n o n e
(3k).12f Yield¼78% (599 mg); 1H NMR (200 MHz, CDCl3):
d 7.58 (dd,
J¼2.0, 8.4 Hz, 1H), 7.45 (d, J¼2.0 Hz, 1H), 7.24e7.20 (m, 5H), 6.82 (d,
J¼8.4 Hz, 1H), 4.15 (s, 2H), 3.85 (s, 3H), 3.82 (s, 3H).
4.2. A representative synthetic procedure of skeleton 3 is as
follows
4. 2 .12 . 1 -(3 , 4-D imet hox yphenyl )- 2-p -tol yl- e than on e
PPA (H6P4O13, polyphosphoric acid, 1.7 g, 5.0 mmol) was added
to a solution of substituted arenes (3.3 mmol) and phenylacetic
acids (3.0 mmol) in MeCN (10 mL) at rt. The reaction mixture was
stirred at rt for 10 min. TFAA (trifluoroacetic anhydride, 850 mg,
4.0 mmol) was added to the reaction mixture at rt. The reaction
mixture was stirred at rt for 8 h. The solvent was concentrated. The
residue was diluted with water (10 mL) and the mixture was
extracted with CH2Cl2 (3ꢀ20 mL). The combined organic layers
were washed with brine, dried, filtered and evaporated to afford
crude product under reduced pressure. Purification on silica gel
(hexanes/EtOAc¼8/1e4/1) afforded 3.
(3l). Yield¼74% (599 mg); HRMS (ESI, Mþþ1) calcd for C17H19O3
271.1334, found 271.1335; 1H NMR (200 MHz, CDCl3):
d 7.56 (dd,
J¼2.0, 8.0 Hz, 1H), 7.48 (d, J¼2.0 Hz, 1H), 7.16 (d, J¼8.4 Hz, 2H), 7.06
(d, J¼8.0 Hz, 2H), 6.69 (d, J¼8.4 Hz, 1H), 4.18 (s, 2H), 3.84 (s, 3H),
3.82 (s, 3H), 2.20 (s, 3H).
4.2.13. 1-(3,4-Dimethoxyphenyl)-2-(4-fluorophenyl)-ethanone
(3m).12f Yield¼70% (575 mg); 1H NMR (200 MHz, CDCl3):
d 7.55 (dd,
J¼2.0, 8.4 Hz,1H), 7.48 (d, J¼2.0 Hz,1H), 7.27e7.23 (m, 2H), 6.98e6.91
(m, 2H), 6.76 (d, J¼8.4 Hz, 1H), 4.17 (s, 2H), 3.85 (s, 3H), 3.82 (s, 3H).
4.2.14. 1-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)-ethanone
4.2.1. 1,2-Diphenyl-ethanone (3a).12a Yield¼58% (341 mg); 1H NMR
(3n).12g Yield¼72% (618 mg); 1H NMR (200 MHz, CDCl3):
d 7.58 (dd,
(200 MHz, CDCl3):
d
8.04e7.99 (m, 2H), 7.56e7.45 (m, 3H),
J¼2.0, 8.4 Hz, 1H), 7.55 (d, J¼2.0 Hz, 1H), 7.23 (d, J¼8.4 Hz, 2H), 6.81
(d, J¼8.4 Hz, 2H), 6.78 (d, J¼8.4 Hz, 1H), 4.18 (s, 2H), 3.87 (s, 3H),
3.86 (s, 3H), 3.83 (s, 3H).
7.33e7.24 (m, 5H), 4.29 (s, 2H).
4.2.2. 1-(4-Fluorophenyl)-2-phenyl-ethanone
(3b).12a Yield¼32%
7.98e7.94 (m, 2H),
(205 mg); 1H NMR (200 MHz, CDCl3):
d
4.2.15. 2-Biphenyl-4-yl-1-(3,4-dimethoxyphenyl)-ethanone
7.29e7.19 (m, 5H), 7.02e6.99 (m, 2H), 4.17 (s, 2H).
(3o). Yield¼76% (757 mg); HRMS (ESI, Mþþ1) calcd for C22H21O3
333.1491, found 333.1492; 1H NMR (200 MHz, CDCl3):
d 7.65e7.52
4.2.3. 1-(4-Methoxyphenyl)-2-phenyl-ethanone (3c).12a Yield¼75%
(m, 6H), 7.47e7.29 (m, 5H), 6.82 (d, J¼8.4 Hz, 1H), 4.22 (s, 2H), 3.87
(509 mg); 1H NMR (200 MHz, CDCl3):
d
7.95e7.92 (m, 2H),
(s, 3H), 3.86 (s, 3H).
7.29e7.15 (m, 5H), 6.85e6.83 (m, 2H), 4.16 (s, 2H), 3.70 (s, 3H).
4.2.16. 2-(3,5-Difluorophenyl)-1-(3,4-dimethoxyphenyl)-ethanone
(3p). Yield¼70% (613 mg); HRMS (ESI, Mþþ1) calcd for C16H15F2O3
4.2.4. 1-(4-Methoxyphenyl)-2-p-tolyl-ethanone (3d).12a Yield¼80%
(576 mg); 1H NMR (200 MHz, CDCl3):
d
7.93 (d, J¼8.0 Hz, 2H),
293.0989, found 293.0985; 1H NMR (200 MHz, CDCl3):
d 7.54 (dd,
7.12e7.05 (m, 4H), 6.81 (d, J¼8.0 Hz, 2H), 4.09 (s, 2H), 3.68 (s, 3H),
J¼2.0, 8.4 Hz,1H), 7.52 (d, J¼2.0 Hz,1H), 6.89e6.83 (m, 2H), 6.81 (br s,
2.24 (s, 3H).
1H), 6.66 (tt, J¼2.4, 8.8 Hz,1H), 4.21 (s, 2H), 3.87 (s, 3H), 3.84 (s, 3H).
4.2.5. 2-(4-Fluorophenyl)-1-(4-methoxyphenyl)-ethanone
4.2.17. 2-(4-Fluorophenyl)-1-(2,3,4-trimethoxyphenyl)-ethanone
(3e).12b Yield¼76% (556 mg); 1H NMR (200 MHz, CDCl3):
d
8.00 (d,
(3q).12h Yield¼68% (620 mg); 1H NMR (200 MHz, CDCl3):
d 7.33 (d,
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4
C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
J¼8.8 Hz, 1H), 7.26e7.20 (m, 2H), 6.95e6.90 (m, 2H), 6.60 (d,
J¼8.8 Hz, 1H), 4.25 (s, 2H), 3.86 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H).
13C NMR (100 MHz, CDCl3):
d
196.22, 165.48 (d, J¼254.0 Hz), 137.83,
132.41 (d, J¼3.0 Hz), 131.39 (d, J¼9.1 Hz, 2ꢀ), 129.02 (2ꢀ), 127.94
(2ꢀ), 127.61, 115.57 (d, J¼21.2 Hz, 2ꢀ), 82.03, 69.84, 52.86, 23.25.
4.2.18. 2-(3,4-Dimethoxyphenyl)-1-(4-methoxynaphthalen-1-yl)-
ethanone (3r). Yield¼60% (605 mg); HRMS (ESI, Mþþ1) calcd for
4.3.3. 1-(4-Methoxyphenyl)-2-phenylpent-4-yn-1-one
(4c).5b Yield¼76% (201 mg); Colorless solid; mp¼77e78 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C18H17O2 265.1229, found 265.1232; 1H NMR (400 MHz, CDCl3):
C
21H21O4 337.1440, found 337.1447; 1H NMR (200 MHz, CDCl3):
d
8.76e8.73 (m, 1H), 8.27 (dd, J¼1.6, 8.4 Hz, 1H), 7.99 (d, J¼8.0 Hz,
1H), 7.57 (dt, J¼1.6, 8.4 Hz, 1H), 7.48 (dt, J¼1.6, 8.4 Hz, 1H), 6.89 (dd,
J¼2.0, 8.4 Hz, 1H), 6.85 (d, J¼2.0 Hz, 1H), 6.74 (d, J¼8.4 Hz, 1H), 6.70
(d, J¼8.4 Hz, 1H), 4.28 (s, 2H), 4.00 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H).
d
7.96 (d, J¼8.8 Hz, 2H), 7.39e7.27 (m, 4H), 7.24e7.20 (m, 1H), 6.85
(d, J¼8.8 Hz, 2H), 4.75 (t, J¼7.2 Hz,1H), 3.77 (s, 3H), 3.04 (ddd, J¼2.8,
7.2, 16.8 Hz, 1H), 2.71 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.95 (t, J¼2.8 Hz,
4.2.19. 2-Benzo[1,3]dioxol-5-yl-1-(4-methoxynaphthalen-1-yl)-etha-
1H); 13C NMR (100 MHz, CDCl3):
d 196.26, 163.31, 138.41, 131.01
none (3s). Yield¼60% (576 mg); HRMS (ESI, Mþþ1) calcd for
(2ꢀ), 128.98, 128.85 (2ꢀ), 127.93 (2ꢀ), 127.34, 113.62 (2ꢀ), 82.31,
C
20H17O4 321.1127, found 321.1131; 1H NMR (200 MHz, CDCl3):
69.66, 55.24, 52.42, 23.23.
d
8.78 (d, J¼8.4 Hz, 1H), 8.25 (d, J¼8.4 Hz, 1H), 7.97 (d, J¼8.4 Hz, 1H),
7.63e7.55 (m, 1H), 7.50e7.47 (m, 1H), 6.85 (d, J¼2.0 Hz, 1H), 6.80
(dd, J¼2.0, 8.0 Hz, 1H), 6.75 (d, J¼2.8 Hz, 1H), 6.70 (d, J¼2.8 Hz, 1H),
5.87 (s, 2H), 4.22 (s, 2H), 3.99 (s, 3H).
4.3.4. 1-(4-Methoxyphenyl)-2-p-tolylpent-4-yn-1-one
(4d). Yield¼75% (209 mg); Colorless solid; mp¼86e88 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C
19H19O2 279.1385, found 279.1385; 1H NMR (400 MHz, CDCl3):
4.2.20. 2-Benzo[1,3]dioxol-5-yl-1-(4-butoxynaphthalen-1-yl)-etha-
d
7.98 (d, J¼9.2 Hz, 2H), 7.24 (d, J¼8.4 Hz, 2H), 7.12 (d, J¼8.0 Hz, 2H),
none (3t). Yield¼55% (597 mg); HRMS (ESI, Mþþ1) calcd for
6.85 (d, J¼8.8 Hz, 2H), 4.74 (t, J¼7.2 Hz, 1H), 3.76 (s, 3H), 3.04 (ddd,
J¼2.8, 7.6, 16.8 Hz, 1H), 2.71 (ddd, J¼2.8, 7.6, 16.8 Hz, 1H), 1.97 (t,
C
23H23O4 363.1596, found 363.1598; 1H NMR (200 MHz, CDCl3):
d
8.81 (d, J¼8.8 Hz, 1H), 8.32 (d, J¼8.4 Hz, 1H), 7.96 (d, J¼8.4 Hz, 1H),
J¼2.8 Hz, 1H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 196.32,
7.60e7.57 (m, 1H), 7.50e7.46 (m, 1H), 6.85 (d, J¼1.6 Hz, 1H), 6.81
(dd, J¼1.6, 8.0 Hz, 1H), 6.71 (d, J¼8.0 Hz, 1H), 6.69 (d, J¼8.0 Hz, 1H),
5.88 (s, 2H), 4.18 (s, 2H), 4.20e4.14 (m, 2H), 1.93e1.87 (m, 2H),
1.63e1.52 (m, 2H), 1.00 (t, J¼7.2 Hz, 3H).
163.19, 136.91, 135.35, 130.94 (2ꢀ), 129.51 (2ꢀ), 128.90, 127.71 (2ꢀ),
113.52 (2ꢀ), 82.41, 69.56, 55.14, 51.97, 23.17, 20.84.
4.3.5. 2-(4-Fluorophenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one
(4e).5b Yield¼72% (203 mg); Colorless solid; mp¼83e84 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C18H16FO2 283.1134, found 283.1139; 1H NMR (400 MHz, CDCl3):
4.2.21. 2-Benzo[1,3]dioxol-5-yl-1-(4,7-dimethoxynaphthalen-1-yl)-
ethanone (3u). Yield¼50% (525 mg); HRMS (ESI, Mþþ1) calcd for
C
21H19O5 351.1233, found 351.1239; 1H NMR (200 MHz, CDCl3):
d
7.93 (d, J¼8.8 Hz, 2H), 7.30e7.26 (m, 2H), 7.01e6.96 (m, 2H), 6.86
d
8.46 (d, J¼2.0 Hz, 1H), 8.18 (d, J¼8.8 Hz, 1H), 8.02 (d, J¼8.8 Hz, 1H),
(d, J¼8.8 Hz, 2H), 4.72 (t, J¼7.6 Hz,1H), 3.80 (s, 3H), 2.97 (ddd, J¼2.4,
7.6, 16.8 Hz, 1H), 2.68 (ddd, J¼2.4, 7.6, 16.8 Hz, 1H), 1.94 (t, J¼2.4 Hz,
7.15 (dd, J¼2.8, 8.8 Hz, 1H), 6.84 (d, J¼2.0 Hz, 1H), 6.81 (dd, J¼2.0,
8.0 Hz,1H), 6.73 (d, J¼8.0 Hz,1H), 6.62 (d, J¼8.4 Hz,1H), 5.88 (s, 2H),
4.22 (s, 2H), 3.98 (s, 3H), 3.95 (s, 3H).
1H); 13C NMR (100 MHz, CDCl3):
d 196.25, 163.49, 162.00 (d,
J¼244.8 Hz), 134.16 (d, J¼3.0 Hz), 131.03 (2ꢀ), 129.59 (d, J¼7.6 Hz,
2ꢀ), 128.80, 115.79 (d, J¼21.2 Hz, 2ꢀ), 113.73 (2ꢀ), 82.06, 69.95,
55.31, 51.47, 23.32.
4.3. A representative synthetic procedure of skeleton 4 is as
follows
4.3.6. 1,2-Bis-(4-methoxyphenyl)pent-4-yn-1-one (4f).5b Yield¼77%
(226 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C19H19O3
NaH (120 mg, 60% in oil, 3.0 mmol) was added to a solution of 3
(1.0 mmol) in THF (10 mL) at rt. The reaction mixture was stirred at
rt for 10 min. Propargyl bromide (140 mg, 1.2 mmol) was added to
the reaction mixture at rt. The reaction mixture was stirred at reflux
for 8 h. The reaction mixture was cooled to rt and the solvent was
concentrated. The residue was diluted with water (10 mL) and the
mixture was extracted with CH2Cl2 (3ꢀ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered and evaporated
to afford crude product under reduced pressure. Purification on
silica gel (hexanes/EtOAc¼8/1e4/1) afforded 4.
295.1334, found 295.1336; 1H NMR (400 MHz, CDCl3):
d 7.94 (d,
J¼8.8 Hz, 2H), 7.22 (d, J¼8.8 Hz, 2H), 6.85e6.80 (m, 4H), 4.68 (t,
J¼7.2 Hz, 1H), 3.77 (s, 3H), 3.71 (s, 3H), 2.97 (ddd, J¼2.4, 7.6, 16.8 Hz,
1H), 2.66 (ddd, J¼2.4, 7.6, 16.8 Hz, 1H), 1.94 (t, J¼2.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3):
d
196.47, 163.24, 158.73, 130.97 (2ꢀ),
130.39, 128.96 (2ꢀ), 114.23 (2ꢀ), 114.14, 113.57 (2ꢀ), 82.45, 69.59,
55.23, 54.97, 51.52, 23.25.
4.3.7. 1-(4-Methoxyphenyl)-2-(4-trifluoromethylphenyl)pent-4-yn-
1-one (4g). Yield¼80% (266 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C19H16F3O2 333.1102, found 333.1105; 1H NMR (400 MHz,
4.3.1. 1,2-Diphenylpent-4-yn-1-one (4a). Yield¼78% (183 mg);
Colorless solid; mp¼59e61 ꢁC (recrystallized from hexanes and
EtOAc); HRMS (ESI, Mþþ1) calcd for C17H15O 235.1123, found
CDCl3):
d
7.93 (d, J¼8.8 Hz, 2H), 7.57 (d, J¼8.4 Hz, 2H), 7.45 (d,
J¼8.4 Hz, 2H), 6.88 (d, J¼8.8 Hz, 2H), 4.80 (dd, J¼6.8, 8.0 Hz, 1H),
3.82 (s, 3H), 3.01 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 2.73 (ddd, J¼2.8, 7.2,
16.8 Hz, 1H), 1.95 (t, J¼2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
235.1122; 1H NMR (400 MHz, CDCl3):
d 8.01e7.98 (m, 2H),
7.50e7.22 (m, 8H), 4.83 (t, J¼7.2 Hz, 1H), 3.08 (ddd, J¼2.8, 7.2,
16.8 Hz, 1H), 2.74 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.97 (t, J¼2.8 Hz, 1H);
d
195.74, 163.74, 142.35, 131.12 (2ꢀ), 130.81, 129.87, 128.66, 128.47
13C NMR (100 MHz, CDCl3):
d
197.76, 137.92, 135.98, 132.97, 128.91
(2ꢀ), 125.94 (d, J¼3.8 Hz, 2ꢀ), 125.84 (d, J¼2.8 Hz, 2ꢀ), 81.66, 70.30,
(2ꢀ), 128.69 (2ꢀ), 128.41 (2ꢀ), 127.98 (2ꢀ), 127.46, 82.11, 69.77,
55.41, 52.04, 23.22.
52.76, 23.23.
4.3.8. 2-(3,5-Difluorophenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one
(4h). Yield¼74% (222 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C18H15F2O2 301.1040, found 301.1045; 1H NMR (400 MHz,
4 . 3 . 2 . 1 - ( 4 - F l u o r o p h e nyl ) - 2 - p h e nyl p e n t - 4 - y n - 1 - o n e
(4b). Yield¼80% (202 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C17H14FO 253.1029, found 253.1032; 1H NMR (400 MHz, CDCl3):
CDCl3):
d
7.92 (d, J¼8.8 Hz, 2H), 6.91e6.85 (m, 4H), 6.67 (tt, J¼2.4,
d
8.02e7.97 (m, 2H), 7.32e7.30 (m, 4H), 7.27e7.22 (m, 1H),
8.8 Hz,1H), 4.69 (dd, J¼6.8, 7.6 Hz,1H), 3.82 (s, 3H), 2.95 (ddd, J¼2.8,
7.06e7.01 (m, 2H), 4.75 (t, J¼7.2 Hz, 1H), 3.05 (ddd, J¼2.8, 7.6,
7.2, 16.8 Hz, 1H), 2.70 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.97 (t, J¼2.8 Hz,
16.8 Hz, 1H), 2.71 (ddd, J¼2.8, 7.6, 16.8 Hz,1H), 1.96 (t, J¼2.8 Hz,1H);
1H); 13C NMR (100 MHz, CDCl3):
d 195.32, 163.79, 163.14 (d,
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060

C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
5
J¼247.9 Hz), 163.01 (d, J¼247.9 Hz), 142.00 (t, J¼9.1 Hz), 131.07 (2ꢀ),
128.55, 113.90 (2ꢀ), 111.12 (d, J¼25.0 Hz), 111.12 (d, J¼11.4 Hz),
103.08 (t, J¼25.0 Hz), 81.42, 70.42, 55.40, 51.69, 23.10.
J¼8.4 Hz, 2H), 6.82 (d, J¼8.8 Hz, 2H), 6.79 (d, J¼8.4 Hz, 1H), 4.69 (t,
J¼7.6 Hz, 1H), 3.86 (s, 6H), 3.72 (s, 3H), 2.97 (ddd, J¼2.8, 6.8, 16.8 Hz,
1H), 2.66 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 1.93 (t, J¼2.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3):
d 196.57, 158.80, 153.09, 148.83, 130.56,
4.3.9. 2-Biphenyl-4-yl-1-(4-methoxyphenyl)pent-4-yn-1-one
(4i). Yield¼70% (238 mg); Colorless solid; mp¼104e106 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C24H21O2 341.1542, found 341.1547; 1H NMR (400 MHz, CDCl3):
129.11, 128.93 (2ꢀ),123.46,114.30 (2ꢀ), 110.83,109.86, 82.45, 69.58,
55.89, 55.75, 55.06, 51.55, 23.33.
4.3.15. 2-Biphenyl-4-yl-1-(3,4-dimethoxyphenyl)pent-4-yn-1-one
(4o). Yield¼82% (303 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C25H23O3 371.1647, found 371.1652; 1H NMR (400 MHz, CDCl3):
d
8.00 (d, J¼8.8 Hz, 2H), 7.56e7.52 (m, 4H), 7.45e7.30 (m, 5H), 6.88
(d, J¼8.8 Hz, 2H), 4.79 (t, J¼7.2 Hz,1H), 3.81 (s, 3H), 3.07 (ddd, J¼2.4,
7.6, 16.8 Hz, 1H), 2.74 (ddd, J¼2.4, 7.6, 16.8 Hz, 1H), 1.97 (t, J¼2.4 Hz,
d
7.64e7.52 (m, 6H), 7.48e7.30 (m, 5H), 6.83 (d, J¼8.4 Hz, 1H), 4.80
1H); 13C NMR (100 MHz, CDCl3):
d
196.34, 163.47, 140.41, 140.28,
(t, J¼7.2 Hz, 1H), 3.90 (s, 6H), 3.07 (ddd, J¼2.4, 7.2, 16.8 Hz, 1H), 2.74
137.44, 131.16 (2ꢀ), 129.05, 128.70 (2ꢀ), 128.41 (2ꢀ), 127.65 (2ꢀ),
(ddd, J¼2.4, 7.2, 16.8 Hz, 1H), 1.96 (t, J¼2.4 Hz, 1H); 13C NMR
127.30, 126.94 (2ꢀ), 113.74 (2ꢀ), 82.38, 69.77, 55.38, 52.14, 23.32.
(100 MHz, CDCl3):
d 196.42, 153.33, 148.99, 140.37, 137.58, 129.21,
128.73 (2ꢀ), 128.36 (2ꢀ), 127.70 (2ꢀ), 127.43, 127.35, 127.30, 126.96
4.3.10. 1-(4-Methoxyphenyl)-2-naphthalen-2-yl-pent-4-yn-1-one
(4j).5b Yield¼80% (251 mg); Colorless solid; mp¼93e94 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H19O2 315.1385, found 315.1388; 1H NMR (400 MHz, CDCl3):
(2ꢀ), 123.64, 110.93, 109.98, 69.78, 56.00, 55.87, 52.13, 23.38.
4.3.16. 2-(3,5-Difluorophenyl)-1-(3,4-dimethoxyphenyl)pent-4-yn-
1-one (4p). Yield¼78% (257 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C19H17F2O3 331.1146, found 331.1152; 1H NMR
d
8.37 (d, J¼8.4 Hz,1H), 7.90 (dd, J¼0.8, 8.0 Hz,1H), 7.87 (d, J¼9.2 Hz,
2H), 7.75 (d, J¼8.0 Hz, 1H), 7.67 (dt, J¼1.2, 8.4 Hz, 1H), 7.56 (dt, J¼1.2,
8.0 Hz,1H), 7.34 (t, J¼8.4 Hz,1H), 7.27 (dd, J¼1.2, 8.4 Hz,1H), 6.74 (d,
J¼8.8 Hz, 2H), 5.53 (dd, J¼5.6, 8.4 Hz, 1H), 3.72 (s, 3H), 3.19 (ddd,
J¼2.8, 8.4, 16.8 Hz, 1H), 2.75 (ddd, J¼2.8, 8.4, 16.8 Hz, 1H), 1.93 (t,
(400 MHz, CDCl3):
d
7.54 (dd, J¼2.0, 8.4 Hz, 1H), 7.52 (d, J¼2.0 Hz,
1H), 6.89e6.83 (m, 2H), 6.82 (s, 1H), 6.68 (tt, J¼2.4, 8.8 Hz, 1H),
4.70 (dd, J¼6.8, 7.6 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H), 2.95 (ddd,
J¼2.8, 7.2, 16.8 Hz, 1H), 2.70 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.96 (t,
J¼2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
196.47, 163.27, 134.92,
J¼2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 195.41, 163.19 (d,
134.27, 130.84 (2ꢀ), 130.71, 129.28, 129.02, 128.13, 126.83, 125.86,
125.62,125.37, 122.54, 113.64 (2ꢀ), 82.67, 69.53, 55.25, 48.06, 22.78.
J¼247.9 Hz), 163.06 (d, J¼248.7 Hz), 153.68, 142.09 (t, J¼9.1 Hz),
128.71, 123.54 (2ꢀ), 111.06 (d, J¼25.8 Hz), 111.06 (d, J¼11.3 Hz),
109.98 (2ꢀ), 103.15 (t, J¼24.2 Hz), 81.39, 70.41, 56.04, 55.89, 51.62,
23.16.
4.3.11. 1-(3,4-Dimethoxyphenyl)-2-phenylpent-4-yn-1-one
(4k). Yield¼82% (241 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H19O3 295.1334, found 295.1336; 1H NMR (400 MHz, CDCl3):
4.3.17. 2-(4-Fluorophenyl)-1-(2,3,4-trimethoxyphenyl)pent-4-yn-1-
one (4q). Yield¼80% (274 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C20H20FO4 343.1346, found 343.1348; 1H NMR (400 MHz,
d
7.56 (dd, J¼2.0, 8.4 Hz, 1H), 7.51 (d, J¼2.0 Hz, 1H), 7.31e7.25 (m,
2H), 7.27 (d, J¼8.4 Hz, 2H), 7.21e7.16 (m, 1H), 6.75 (d, J¼8.4 Hz, 1H),
4.73 (t, J¼7.6 Hz, 1H), 3.82 (s, 6H), 3.00 (ddd, J¼2.4, 7.2, 16.8 Hz, 1H),
2.67 (ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.92 (t, J¼2.4 Hz, 1H); 13C NMR
CDCl3):
d
7.35 (d, J¼8.8 Hz, 1H), 7.27e7.22 (m, 2H), 6.98e6.92 (m,
2H), 6.63 (d, J¼8.8 Hz, 1H), 4.86 (t, J¼7.6 Hz, 1H), 3.86 (s, 3H), 3.82
(s, 3H), 3.81 (s, 3H), 2.99 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 2.62 (ddd,
J¼2.8, 6.8, 16.8 Hz, 1H), 1.92 (t, J¼2.8 Hz, 1H); 13C NMR (100 MHz,
(100 MHz, CDCl3):
d 196.23, 153.06, 148.74, 138.99, 128.99, 128.83
(2ꢀ), 127.79 (2ꢀ), 127.33, 123.43, 110.72, 109.79, 82.22, 69.61, 55.78,
55.64, 52.31, 23.20.
CDCl3):
d
199.32, 162.00 (d, J¼244.9 Hz), 157.26, 153.38, 141.88,
133.94 (d, J¼3.1 Hz), 129.96 (d, J¼8.3 Hz, 2ꢀ), 125.87, 125.56,
115.40 (d, J¼21.2 Hz, 2ꢀ), 107.07, 82.38, 69.59, 61.76, 60.85, 55.99,
54.99, 23.19.
4.3.12. 1-(3,4-Dimethoxyphenyl)-2-p-tolylpent-4-yn-1-one
(4l). Yield¼80% (246 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C20H21O3 309.1491, found 309.1493; 1H NMR (400 MHz, CDCl3):
d
7.55 (dd, J¼2.0, 8.4 Hz, 1H), 7.49 (d, J¼2.0 Hz, 1H), 7.17 (d, J¼8.0 Hz,
4.3.18. 2-(3,4-Dimethoxyphenyl)-1-(4-methoxynaphthalen-1-yl)
pent-4-yn-1-one (4r). Yield¼82% (307 mg); Colorless gum; HRMS
(ESI, Mþþ1) calcd for C24H23O4 375.1596, found 375.1601; 1H NMR
2H), 7.04 (d, J¼8.0 Hz, 2H), 6.69 (d, J¼8.4 Hz, 1H), 4.69 (t, J¼7.6 Hz,
1H), 3.77 (s, 3H), 3.75 (s, 3H), 2.97 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 2.64
(ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 2.19 (s, 3H), 1.93 (t, J¼2.8 Hz, 1H); 13
C
(400 MHz, CDCl3):
d
8.76e8.73 (m, 1H), 8.26 (ddd, J¼0.8, 1.6,
NMR (100 MHz, CDCl3):
d
196.07, 152.79, 148.50, 136.68, 135.29,
8.4 Hz, 1H), 7.96 (d, J¼8.0 Hz, 1H), 7.58 (dt, J¼1.6, 8.4 Hz, 1H), 7.48
(dt, J¼1.6, 8.4 Hz, 1H), 6.88 (dd, J¼2.0, 8.4 Hz, 1H), 6.86 (d,
J¼2.0 Hz, 1H), 6.76 (d, J¼8.4 Hz, 1H), 6.72 (d, J¼8.4 Hz, 1H), 4.78 (d,
J¼7.6 Hz, 1H), 4.00 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.12 (ddd,
J¼2.8, 6.8, 16.8 Hz, 1H), 2.73 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 1.97 (t,
129.30 (2ꢀ), 128.77, 127.44 (2ꢀ), 123.17, 110.50, 109.60, 82.18, 69.44,
55.46, 55.32, 51.67, 22.97, 20.58.
4.3.13. 1-(3,4-Dimethoxyphenyl)-2-(4-fluorophenyl)pent-4-yn-1-one
(4m). Yield¼76% (237 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C19H18FO3 313.1240, found 313.1241; 1H NMR (400 MHz,
J¼2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 200.24, 158.86, 149.09,
148.24, 132.22, 130.99, 130.51, 128.50, 127.55, 125.91, 125.77,
125.73, 122.05, 120.41, 111.28, 110.52, 101.97, 82.60, 71.76, 69.72,
55.81, 55.68, 54.64, 23.57.
CDCl3):
d
7.54 (dd, J¼2.0, 8.4 Hz, 1H), 7.49 (d, J¼2.0 Hz, 1H),
7.28e7.24 (m, 2H), 6.97e6.92 (m, 2H), 6.76 (d, J¼8.4 Hz, 1H), 4.72 (t,
J¼7.6 Hz, 1H), 3.82 (s, 6H), 2.94 (ddd, J¼2, 7.2, 16.8 Hz, 1H), 2.65
(ddd, J¼2.8, 7.2, 16.8 Hz, 1H), 1.94 (t, J¼2.4 Hz, 1H); 13C NMR
4.3.19. 2-Benzo[1,3]dioxol-5-yl-1-(4-methoxynaphthalen-1-yl)pent-
4-yn-1-one (4s). Yield¼80% (286 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C23H19O4 359.1283, found 359.1285; 1H NMR
(100 MHz, CDCl3):
d
196.09, 161.78 (d, J¼244.8 Hz), 153.13, 148.76,
134.13 (d, J¼3.2 Hz), 129.35 (d, J¼8.3 Hz, 2ꢀ), 128.68, 123.32, 115.62
(d, J¼21.2 Hz, 2ꢀ), 110.57, 109.73, 81.88, 69.87, 55.68, 55.53, 51.15,
23.15.
(400 MHz, CDCl3):
d
8.79 (d, J¼8.8 Hz, 1H), 8.27 (dd, J¼1.2, 8.4 Hz,
1H), 7.98 (d, J¼8.4 Hz, 1H), 7.62e7.57 (m, 1H), 7.51e7.47 (m, 1H),
6.86 (d, J¼1.6 Hz, 1H), 6.81 (dd, J¼1.6, 8.0 Hz, 1H), 6.72 (d, J¼2.8 Hz,
1H), 6.70 (d, J¼2.8 Hz, 1H), 5.88 (d, J¼1.2 Hz, 1H), 5.87 (d, J¼1.2 Hz,
1H), 4.77 (t, J¼7.6 Hz, 1H), 3.99 (s, 3H), 3.11 (ddd, J¼2.8, 6.8, 16.8 Hz,
1H), 2.73 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 1.99 (t, J¼2.8 Hz, 1H); 13C
4.3.14. 1-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)pent-4-yn-1-
one (4n). Yield¼78% (253 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C20H21O4 325.1440, found 325.1442; 1H NMR (400 MHz,
CDCl3):
d
7.57 (dd, J¼2.0, 8.4 Hz, 1H), 7.53 (d, J¼2.0 Hz, 1H), 7.22 (d,
NMR (100 MHz, CDCl3): d 199.74, 158.96, 147.94, 146.85, 132.29,
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060

6
C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
132.22, 130.72, 129.56, 127.18, 125.84, 125.77, 125.74, 122.01, 121.39,
108.54, 108.12, 101.98, 101.02, 82.47, 69.81, 55.68, 54.46, 23.51.
2H), 6.15 (d, J¼0.8 Hz, 1H), 3.80 (s, 3H), 2.38 (d, J¼0.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d 158.76, 150.69, 146.89, 134.82, 128.49
(2ꢀ), 128.46 (2ꢀ), 127.51 (2ꢀ), 126.70, 124.35, 121.67, 113.78 (2ꢀ),
4.3.20. 2-Benzo[1,3]dioxol-5-yl-1-(4-butoxynaphthalen-1-yl)pent-4-
yn-1-one (4t). Yield¼73% (292 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C26H25O4 401.1753, found 401.1755; 1H NMR
109.73, 55.21, 13.54.
4.4.4. 2-(4-Methoxyphenyl)-5-methyl-3-p-tolyl-furan
(5d). Yield¼84% (234 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H19O2 279.1385, found 279.1391; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
8.79 (d, J¼8.8 Hz, 1H), 8.30 (dd, J¼0.8, 8.4 Hz,
1H), 7.97 (d, J¼8.4 Hz, 1H), 7.61e7.58 (m, 1H), 7.51e7.47 (m, 1H),
6.84 (d, J¼1.6 Hz, 1H), 6.80 (dd, J¼1.6, 8.0 Hz, 1H), 6.72 (d, J¼8.0 Hz,
1H), 6.70 (d, J¼8.0 Hz, 1H), 5.89 (d, J¼1.6 Hz, 1H), 5.88 (d, J¼1.6 Hz,
1H), 4.76 (t, J¼7.6 Hz, 1H), 4.21e4.14 (m, 2H), 3.09 (ddd, J¼2.4, 7.2,
16.8 Hz, 1H), 2.72 (ddd, J¼2.4, 7.2, 16.8 Hz, 1H), 1.97 (t, J¼2.4 Hz, 1H),
1.93e1.88 (m, 2H),1.63e1.54 (m, 2H),1.02 (t, J¼7.2 Hz, 3H); 13C NMR
d
7.47 (d, J¼8.8 Hz, 2H), 7.30 (d, J¼8.0 Hz, 2H), 7.16 (d, J¼8.0 Hz, 2H),
6.84 (d, J¼8.8 Hz, 2H), 6.15 (d, J¼0.8 Hz, 1H), 3.81 (s, 3H), 2.38 (s,
6H); 13C NMR (100 MHz, CDCl3):
158.63, 150.56, 146.63, 136.35,
d
131.78, 129.21 (2ꢀ), 128.29 (2ꢀ), 127.40 (2ꢀ), 124.45, 121.57, 113.72
(2ꢀ), 109.80, 55.18, 21.17, 13.53.
(100 MHz, CDCl3):
d 199.72, 158.57, 147.96, 146.87, 132.42, 132.35,
130.94, 128.57, 126.86, 125.91, 125.89, 125.70, 122.15, 121.42, 108.57,
108.16, 102.63, 101.05, 82.53, 69.78, 68.15, 54.44, 31.09, 23.57, 19.40,
13.83.
4.4.5. 3-(4-Fluorophenyl)-2-(4-methoxyphenyl)-5-methyl-furan
(5e).5b Yield¼79% (223 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C18H16FO2 283.1134, found 283.1133; 1H NMR (400 MHz,
CDCl3):
d
7.40 (d, J¼8.8 Hz, 2H), 7.35e7.32 (m, 2H), 7.04e7.00 (m,
4.3.21. 2-Benzo[1,3]dioxol-5-yl-1-(4,7-dimethoxynaphthalen-1-yl)
pent-4-yn-1-one (4u). Yield¼74% (287 mg); Colorless gum; HRMS
(ESI, Mþþ1) calcd for C24H21O5 389.1389, found 389.1390; 1H NMR
2H), 6.83 (d, J¼8.8 Hz, 2H), 6.11 (d, J¼0.8 Hz, 1H), 3.81 (s, 3H), 2.37
(d, J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 161.80 (d,
J¼244.1 Hz), 158.82, 150.78, 146.90, 130.79 (d, J¼3.0 Hz), 130.03 (d,
J¼7.6 Hz, 2ꢀ), 127.47 (2ꢀ), 124.13, 120.65, 115.44 (d, J¼21.2 Hz, 2ꢀ),
113.84 (2ꢀ), 109.63, 55.22, 13.52 (d, J¼2.3 Hz); Anal. Calcd for
(400 MHz, CDCl3):
d
8.45 (d, J¼2.4 Hz, 1H), 8.17 (d, J¼9.2 Hz, 1H),
8.04 (d, J¼8.4 Hz, 1H), 7.13 (dd, J¼2.8, 9.2 Hz, 1H), 6.85 (d, J¼1.6 Hz,
1H), 6.82 (dd, J¼2.0, 8.0 Hz, 1H), 6.71 (d, J¼8.0 Hz, 1H), 6.61 (d,
J¼8.4 Hz, 1H), 5.89 (d, J¼1.6 Hz, 1H), 5.88 (d, J¼1.6 Hz, 1H), 4.79 (t,
J¼7.6 Hz, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.08 (ddd, J¼2.8, 6.8, 16.8 Hz,
1H), 2.71 (ddd, J¼2.8, 6.8, 16.8 Hz, 1H), 1.97 (t, J¼2.8 Hz, 1H); 13C
C18H15FO2: C, 76.58; H, 5.36. Found: C, 76.82; H, 5.55.
4.4.6. 2,3-Bis-(4-methoxyphenyl)-5-methyl-furan (5f).5b Yield¼80%
(235 mg); Colorless solid; mp¼95e97 ꢁC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C19H19O3 295.1334,
NMR (100 MHz, CDCl3):
d 199.62, 160.22, 159.48, 147.95, 146.83,
134.41, 132.66, 132.57, 125.11, 123.73, 121.32, 120.75, 118.03, 108.57,
108.05, 104.73, 101.04, 100.52, 82.57, 69.76, 55.65, 55.31, 54.15,
23.68.
found 295.1339; 1H NMR (400 MHz, CDCl3):
d
7.43 (d, J¼8.8 Hz, 2H),
7.31 (d, J¼8.8 Hz, 2H), 6.88 (d, J¼8.8 Hz, 2H), 6.82 (d, J¼8.8 Hz, 2H),
6.11 (d, J¼1.2 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 2.37 (d, J¼0.8 Hz,
3H); 13C NMR (100 MHz, CDCl3):
d 158.60, 158.47, 150.52, 146.44,
4.4. A representative synthetic procedure of skeleton 5 is as
follows
129.56 (2ꢀ), 127.33 (2ꢀ), 127.15, 124.49, 121.28, 113.95 (2ꢀ), 113.75
(2ꢀ), 109.82, 55.22, 55.20, 13.54; Anal. Calcd for C19H18O3: C, 77.53;
H, 6.16. Found: C, 77.82; H, 6.01. Single-crystal X-ray diagram:
crystal of compound 5f was grown by slow diffusion of EtOAc into
a solution of compound 5f in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the orthorhombic crystal system, space
ꢀ
Bi(OTf)3 (13 mg, 0.02 mmol) and molecular sieves (4 A MS,
100 mg) was added to a solution of 4 (1.0 mmol) in dry MeNO2
(5 mL) at rt. The reaction mixture was stirred at rt for 3 h. The re-
action mixture was diluted with CH2Cl2 (10 mL), filtered, and
concentrated. The residue was diluted with water (10 mL) and the
mixture was extracted with CH2Cl2 (3ꢀ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered and evaporated
to afford crude product under reduced pressure. Purification on
silica gel (hexanes/EtOAc¼10/1e4/1) afforded 5.
ꢀ
ꢀ
ꢀ
group P b c n, a¼7.867 (2) A, b¼9.448 (3) A, c¼21.293 (6) A,
3
ꢀ
V¼1582.5 (7) A , Z¼4, dcalcd¼1.235 g/cm3, F(000)¼624, 2
q range
1.913e26.588ꢁ, R indices (all data) R1¼0.0931, wR2¼0.1279.
4.4.7. 2-(4-Methoxyphenyl)-5-methyl-3-(4-trifluoromethylphenyl)-
furan (5g). Yield¼80% (266 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C19H16F3O2 333.1102, found 333.1103; 1H NMR (400 MHz,
4.4.1. 5-Methyl-2,3-diphenyl-furan (5a). Yield¼88% (206 mg); Col-
orless gum; HRMS (ESI, Mþþ1) calcd for C17H15O 235.1123, found
CDCl3):
d
7.57 (d, J¼8.0 Hz, 2H), 7.49 (d, J¼8.0 Hz, 2H), 7.42 (d,
J¼8.8 Hz, 2H), 6.86 (d, J¼8.8 Hz, 2H), 6.17 (d, J¼0.8 Hz, 1H), 3.82 (s,
235.1126; 1H NMR (400 MHz, CDCl3):
d
7.54e7.51 (m, 2H), 7.43e7.19
3H), 2.39 (d, J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 159.16,
(m, 8H), 6.18 (d, J¼0.8 Hz, 1H), 2.41 (d, J¼0.8 Hz, 3H); 13C NMR
151.26, 147.81, 138.56, 128.49 (2ꢀ), 127.84 (2ꢀ), 125.47 (d, J¼3.8 Hz,
2ꢀ), 125.40 (d, J¼3.8 Hz, 2ꢀ), 123.73, 120.32, 113.96 (2ꢀ), 109.17,
55.22, 13.49.
(100 MHz, CDCl3):
d
151.27, 146.76, 134.69, 131.46, 128.56 (2ꢀ),
128.53 (2ꢀ), 128.29 (2ꢀ), 127.01, 126.92, 125.90 (2ꢀ), 123.13, 110.12,
13.56; Anal. Calcd for C17H14O: C, 87.15; H, 6.02. Found: C, 87.38; H,
6.18.
4.4.8. 3-(3,5-Difluorophenyl)-2-(4-methoxyphenyl)-5-methyl-furan
(5h). Yield¼83% (249 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C18H15F2O2 301.1040, found 301.1042; 1H NMR (400 MHz,
4 . 4 . 2 . 2 - ( 4 - F l u o r o p h e n yl ) - 5 - m e t hyl - 3 - p h e n yl - f u ra n
(5b). Yield¼86% (217 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C17H14FO 253.1029, found 253.1031; 1H NMR (400 MHz, CDCl3):
CDCl3):
d
7.41 (d, J¼8.8 Hz, 2H), 6.92e6.84 (m, 4H), 6.72e6.66 (m,
1H), 6.12 (d, J¼1.2 Hz, 1H), 3.82 (s, 3H), 2.37 (d, J¼0.8 Hz, 3H); 13C
d
7.53e7.28 (m, 7H), 7.00e6.94 (m, 2H), 6.17 (d, J¼0.8 Hz, 1H), 2.39
NMR (100 MHz, CDCl3):
d
163.15 (d, J¼245.7 Hz), 163.02 (d,
(s, 3H); 13C NMR (100 MHz, CDCl3):
d
161.83 (d, J¼245.6 Hz), 151.24,
J¼245.6 Hz), 151.22, 147.87, 138.08, 127.96 (2ꢀ), 123.47, 119.65,
114.29, 114.00 (2ꢀ), 111.02 (d, J¼25.0 Hz), 111.02 (d, J¼11.4 Hz),
108.97, 102.00 (t, J¼25.0 Hz), 55.25, 13.47.
145.90, 134.45, 131.26, 129.20, 128.60 (2ꢀ), 128.47 (2ꢀ), 127.70 (d,
J¼7.6 Hz, 2ꢀ), 127.11, 115.29 (d, J¼21.9 Hz, 2ꢀ), 110.01, 13.51.
4. 4. 3. 2-(4-Methoxyphenyl)-5-methyl-3-phenyl-furan
(5c).5b Yield¼82% (216 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C18H17O2 265.1229, found 265.1230; 1H NMR (400 MHz,
4.4.9. 3-Biphenyl-4-yl-2-(4-methoxyphenyl)-5-methyl-furan
(5i). Yield¼75% (255 mg); Colorless solid; mp¼126e128 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C24H21O2 341.1542, found 341.1545; 1H NMR (400 MHz, CDCl3):
CDCl3):
d
7.44 (d, J¼9.2 Hz, 2H), 7.42e7.24 (m, 5H), 6.82 (d, J¼9.2 Hz,
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060

C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
7
d
7.65e7.62 (m, 2H), 7.60e7.56 (m, 2H), 7.51e7.43 (m, 6H),
127.24, 127.06 (2ꢀ), 126.85 (2ꢀ), 124.40, 121.51, 118.74, 111.01,
7.37e7.33 (m, 1H), 6.85 (d, J¼8.8 Hz, 2H), 6.20 (d, J¼1.2 Hz, 1H), 3.82
109.71, 109.41, 55.79, 55.60, 13.56.
(s, 3H), 2.40 (d, J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 158.82,
150.83, 147.04, 140.73, 139.37, 133.78, 128.77 (2ꢀ), 128.74 (2ꢀ),
127.64 (2ꢀ), 127.21, 127.15 (2ꢀ), 126.90 (2ꢀ), 124.32, 121.22, 113.81
(2ꢀ), 109.59, 55.22, 13.57.
4.4.16. 3-(3,5-Difluorophenyl)-2-(3,4-dimethoxyphenyl)-5-methyl-
furan (5p). Yield¼80% (264 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C19H17F2O3 331.1146, found 331.1147; 1H NMR (400 MHz,
CDCl3):
d
7.05 (dd, J¼2.0, 8.4 Hz, 1H), 7.01 (d, J¼2.0 Hz, 1H),
4.4.10. 2-(4-Methoxyphenyl)-5-methyl-3-naphthalen-2-yl-furan
(5j).5b Yield¼77% (242 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C22H19O2 315.1385, found 315.1389; 1H NMR (400 MHz,
6.94e6.89 (m, 2H), 6.82 (d, J¼8.4 Hz,1H), 6.72e6.66 (m,1H), 6.12 (d,
J¼0.8 Hz, 1H), 3.89 (s, 3H), 3.77 (s, 3H), 2.37 (d, J¼1.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d
163.09 (d, J¼246.3 Hz), 162.96 (d,
CDCl3):
d
7.92 (d, J¼8.4 Hz, 1H), 7.91 (d, J¼8.4 Hz, 1H), 7.87 (dd,
J¼245.6 Hz), 151.24, 148.77, 147.70, 138.07 (t, J¼9.8 Hz), 123.56,
119.87, 119.22, 111.17 (d, J¼25.8 Hz), 111.18 (d, J¼9.1 Hz, 2ꢀ), 109.64,
109.09, 102.02 (t, J¼25.0 Hz, 2ꢀ), 55.83, 55.70, 13.46.
J¼1.6, 8.0 Hz, 1H), 7.52e7.39 (m, 4H), 7.25 (d, J¼8.8 Hz, 2H), 6.67 (d,
J¼8.8 Hz, 2H), 6.16 (d, J¼0.8 Hz, 1H), 3.71 (s, 3H), 2.46 (d, J¼1.2 Hz,
3H); 13C NMR (100 MHz, CDCl3):
d 158.29, 150.23, 147.68, 133.85,
132.97, 132.13, 128.21, 127.68, 127.63, 126.23 (2ꢀ), 126.21, 126.05,
4.4.17. 3-(4-Fluorophenyl)-5-methyl-2-(2,3,4-trimethoxyphenyl)-fu-
ran (5q). Yield¼76% (260 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C20H20FO4 343.1346, found 343.1348; 1H NMR (400 MHz,
125.88, 125.66, 124.16, 119.41, 113.67 (2ꢀ), 111.76, 55.09, 13.63.
4.4.11. 2-(3,4-Dimethoxyphenyl)-5-methyl-3-phenyl-furan
(5k). Yield¼80% (235 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H19O3 295.1334, found 295.1336; 1H NMR (400 MHz, CDCl3):
CDCl3):
d
7.26e7.21 (m, 2H), 7.02 (d, J¼8.8 Hz, 1H), 6.96e6.91 (m,
2H), 6.65 (d, J¼8.4 Hz, 1H), 6.25 (d, J¼0.8 Hz, 1H), 3.88 (s, 3H), 3.87
(s, 3H), 3.64 (s, 3H), 2.37 (d, J¼0.4 Hz, 3H); 13C NMR (100 MHz,
d
7.43e7.40 (m, 2H), 7.37e7.32 (m, 2H), 7.29e7.25 (m, 1H), 7.10 (dd,
CDCl3):
d
161.44 (d, J¼243.4 Hz), 154.09, 152.24, 151.48, 144.27,
J¼2.0, 8.4 Hz, 1H), 7.01 (d, J¼2.0 Hz, 1H), 6.79 (d, J¼8.4 Hz, 1H), 6.16
142.38, 130.37 (d, J¼3.0 Hz), 128.72 (d, J¼7.6 Hz, 2ꢀ), 125.74, 122.44,
118.41, 115.06 (d, J¼21.2 Hz, 2ꢀ), 107.60, 107.06, 60.88, 60.84, 55.89,
13.57.
(d, J¼0.8 Hz, 1H), 3.87 (s, 3H), 3.70 (s, 3H), 2.39 (d, J¼0.8 Hz, 3H); 13
C
NMR (100 MHz, CDCl3):
d 150.66, 148.49, 148.13, 146.71, 134.79,
128.62 (2ꢀ), 128.40 (2ꢀ), 126.78, 124.38, 121.92, 118.50, 110.96,
109.82, 109.26, 55.75, 55.50, 13.51.
4.4.18. 3-(3,4-Dimethoxyphenyl)-2-(4-methoxynaphthalen-1-yl)-5-
methyl-furan (5r). Yield¼73% (273 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C24H23O4 375.1596, found 375.1596; 1H NMR
4.4.12. 2-(3,4-Dimethoxyphenyl)-5-methyl-3-p-tolyl-furan
(5l). Yield¼81% (249 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C20H21O3 309.1491, found 309.1486; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
8.30 (dd, J¼1.2, 8.4 Hz, 1H), 7.79 (dd, J¼1.2,
8.4 Hz, 1H), 7.47 (d, J¼7.6 Hz, 2H), 7.44e7.39 (m, 1H), 6.85e6.81 (m,
2H), 6.69 (d, J¼8.4 Hz, 1H), 6.63 (d, J¼1.6 Hz, 1H), 6.40 (d, J¼0.8 Hz,
d
7.32e7.29 (m, 2H), 7.16e7.14 (m, 2H), 7.09 (dd, J¼2.0, 8.4 Hz, 1H),
7.04 (d, J¼2.0 Hz, 1H), 6.79 (d, J¼8.4 Hz, 1H), 6.14 (d, J¼0.8 Hz, 1H),
1H), 4.03 (s, 3H), 3.80 (s, 3H), 3.34 (s, 3H), 2.42 (d, J¼1.2 Hz, 3H); 13
C
3.87 (s, 3H), 3.72 (s, 3H), 2.38 (s, 3H), 2.37 (s, 3H); 13C NMR
NMR (100 MHz, CDCl3): d 156.01, 151.55, 148.42, 147.42, 146.10,
(100 MHz, CDCl3):
d
150.57, 148.54, 148.08, 146.51, 136.44, 131.78,
132.99, 129.27, 126.95, 126.53, 125.93, 125.67, 125.32, 123.50,
122.04, 122.01, 119.31, 110.98, 110.58, 107.11, 103.39, 55.71, 55.58,
55.24, 13.72.
129.12 (2ꢀ), 128.48 (2ꢀ), 124.58, 121.88, 118.51, 110.98, 109.93,
109.29, 55.78, 55.58, 21.14, 13.54; Anal. Calcd for C20H20O3: C, 77.90;
H, 6.54. Found: C, 78.02; H, 6.80.
4.4.19. 5-[2-(4-Methoxynaphthalen-1-yl)-5-methyl-furan-3-yl]-
benzo[1,3]dioxole (5s). Yield¼74% (265 mg); Colorless solid;
mp¼140e142 ꢁC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C23H19O4 359.1283, found 359.1286; 1H NMR
4.4.13. 2-(3,4-Dimethoxyphenyl)-3-(4-fluorophenyl)-5-methyl-furan
(5m). Yield¼76% (237 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C19H18FO3 313.1240, found 313.1245; 1H NMR (400 MHz,
CDCl3):
d
7.37e7.33 (m, 2H), 7.06e7.01 (m, 3H), 6.98 (d, J¼2.0 Hz,
(400 MHz, CDCl3):
d
8.31 (dd, J¼1.2, 8.4 Hz, 1H), 7.78 (dd, J¼1.2,
1H), 6.79 (d, J¼8.4 Hz,1H), 6.11 (d, J¼0.8 Hz,1H), 3.87 (s, 3H), 3.72 (s,
8.4 Hz,1H), 7.49e7.40 (m, 3H), 6.81 (d, J¼8.4 Hz,1H), 6.71 (dd, J¼1.6,
8.0 Hz, 1H), 6.66 (d, J¼1.6 Hz, 1H), 6.61 (d, J¼8.0 Hz, 1H), 6.33 (d,
J¼1.2 Hz, 1H), 5.85 (s, 2H), 4.03 (s, 3H), 2.41 (d, J¼0.8 Hz, 3H); 13C
3H), 2.38 (d, J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 161.79 (d,
J¼244.0 Hz), 150.78, 148.60, 148.25, 146.75, 130.77 (d, J¼3.0 Hz),
130.21 (d, J¼7.6 Hz, 2ꢀ), 124.19, 120.88, 118.58, 115.35 (d, J¼21.2 Hz,
2ꢀ), 111.01, 109.76, 109.22, 55.78, 55.58, 13.51.
NMR (100 MHz, CDCl3):
d 156.07, 151.51, 147.44, 146.32, 145.91,
133.04, 129.23, 127.96, 126.89, 125.81, 125.77, 125.30, 123.60, 122.10,
121.70, 120.77, 108.23, 107.85, 107.49, 103.46, 100.73, 55.55, 13.69.
4.4.14. 2-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-5-methyl-fu-
ran (5n). Yield¼78% (253 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C20H21O4 325.1440, found 325.1442; 1H NMR (400 MHz,
4.4.20. 5-[2-(4-Butoxynaphthalen-1-yl)-5-methyl-furan-3-yl]-benzo
[1,3]dioxole (5t). Yield¼75% (300 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C26H25O4 401.1753, found 401.1752; 1H NMR
CDCl3):
d
7.33 (d, J¼8.8 Hz, 2H), 7.08 (dd, J¼2.0, 8.4 Hz, 1H), 7.03 (d,
J¼2.0 Hz, 1H), 6.89 (d, J¼8.8 Hz, 2H), 6.79 (d, J¼8.4 Hz, 1H), 6.11 (d,
(400 MHz, CDCl3):
d
8.35 (dd, J¼1.6, 7.6 Hz, 1H), 7.78 (dd, J¼1.2,
J¼0.8 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.72 (s, 3H), 2.38 (d,
7.6 Hz,1H), 7.49e7.40 (m, 3H), 6.80 (d, J¼8.0 Hz,1H), 6.72 (dd, J¼1.2,
8.0 Hz, 1H), 6.68 (d, J¼1.2 Hz, 1H), 6.62 (d, J¼8.0 Hz, 1H), 6.34 (d,
J¼0.8 Hz, 1H), 5.85 (s, 2H), 4.18 (t, J¼6.4 Hz, 2H), 2.41 (d, J¼1.2 Hz,
J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 158.53, 150.52, 148.55,
148.05, 146.32, 129.72 (2ꢀ), 127.11, 124.60, 121.56, 118.43, 113.86
(2ꢀ), 111.02, 109.94, 109.22, 55.78, 55.59, 55.21, 13.51.
3H), 1.98e1.91 (m, 2H), 1.68e1.89 (m, 2H), 1.05 (t, J¼7.2 Hz, 3H); 13
C
NMR (100 MHz, CDCl3):
d 155.54, 151.46, 147.41, 146.39, 145.87,
4.4.15. 3-Biphenyl-4-yl-2-(3,4-dimethoxyphenyl)-5-methyl-furan
(5o). Yield¼76% (281 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C25H23O3 371.1647, found 371.1649; 1H NMR (400 MHz,
133.02, 129.29,127.96,126.82,125.92,125.72,125.16,123.49,122.22,
121.34, 120.74, 108.22, 107.83, 107.45, 104.12, 100.71, 67.84, 31.32,
19.49, 13.94, 13.70.
CDCl3):
d 7.64e7.58 (m, 4H), 7.51e7.44 (m, 4H), 7.38e7.34 (m, 1H),
7.15 (dd, J¼2.0, 8.4 Hz, 1H), 7.08 (d, J¼2.0 Hz, 1H), 6.82 (d,
4.4.21. 5-[2-(4,7-Dimethoxynaphthalen-1-yl)-5-methyl-furan-3-yl]-
benzo[1,3]dioxole (5u). Yield¼74% (287 mg); Colorless gum; HRMS
(ESI, Mþþ1) calcd for C24H21O5 389.1389, found 389.1390; 1H NMR
J¼8.4 Hz, 1H), 6.21 (d, J¼0.8 Hz, 1H), 3.89 (s, 3H), 3.74 (s, 3H), 2.41
(d, J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 150.83, 148.57,
148.25, 146.92, 140.66, 139.48, 133.79, 128.95 (2ꢀ), 128.77 (2ꢀ),
(400 MHz, CDCl3):
d
8.19 (d, J¼9.2 Hz, 1H), 7.49 (d, J¼8.0 Hz, 1H),
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060

8
C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
7.08 (dd, J¼2.4, 9.2 Hz, 1H), 7.02 (d, J¼2.4 Hz, 1H), 6.73 (d, J¼8.0 Hz,
1H), 6.72 (d, J¼8.0 Hz, 1H), 6.67 (d, J¼1.2 Hz, 1H), 6.62 (d, J¼8.0 Hz,
1H), 6.33 (s, 1H), 5.85 (s, 2H), 4.01 (s, 3H), 3.61 (s, 3H), 2.41 (s, 3H);
F(000)¼1168,
R1¼0.0622, wR2¼0.1816.
2q R indices (all data)
range 1.063e26.407ꢁ,
13C NMR (100 MHz, CDCl3):
d
158.33, 156.19, 151.49, 147.48, 146.30,
4.5.5. 6-Fluoro-9-methoxy-2-methyl-1-oxa-cyclopenta[l]phenan-
threne (1e). Yield¼80% (45 mg); Colorless solid; mp¼120e122 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C18H14FO2 281.0978, found 281.0982; 1H NMR (400 MHz,
145.94, 133.77, 129.75, 128.12, 123.78, 123.16, 120.82, 120.73, 120.66,
117.50, 108.24, 107.84, 107.66, 104.49, 101.83, 100.74, 55.48, 54.94,
13.67.
CDCl3):
d
8.20 (dd, J¼2.4, 11.6 Hz, 1H), 8.19 (d, J¼8.8 Hz, 1H), 7.99
4.5. A representative synthetic procedure of skeleton 1 is as
follows
(dd, J¼6.0, 8.8 Hz, 1H), 7.90 (d, J¼2.4 Hz, 1H), 7.37 (dt, J¼2.4, 8.4 Hz,
1H), 7.32 (dd, J¼2.4, 8.8 Hz, 1H), 6.77 (d, J¼0.8 Hz, 1H), 4.02 (s, 3H),
2.58 (d, J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 160.30 (d,
5 (0.2 mmol) and I2 (100 mg, 0.4 mmol) was dissolved in EtOAc
(15 mL) at rt. Then,1,2-epoxybutane (440 mg, 6.0 mmol) was added
to the reaction mixture and irradiated under a nitrogen atmosphere
J¼240.3 Hz), 157.48, 153.66, 129.07, 128.84 (d, J¼7.6 Hz), 127.46,
125.70 (d, J¼8.3 Hz), 124.38 (d, J¼1.5 Hz), 121.81, 119.16, 117.34,
115.49 (d, J¼23.5 Hz), 113.82, 108.82 (d, J¼22.0 Hz), 105.37, 102.08,
55.51, 14.16. Single-crystal X-ray diagram: crystal of compound 1b
was grown by slow diffusion of EtOAc into a solution of compound
1a in CH2Cl2 to yield colorless prisms. The compound crystallizes in
ꢀ
with a lamp (
l
¼2540 A), using a Pyrex glass filter at rt for 80 h. The
solvent was evaporated to afford crude product. Purification on
silica gel (hexanes/EtOAc¼8/1e2/1) afforded 1.
ꢀ
the monoclinic crystal system, space group P 21/c, a¼31.469 (3) A,
3
ꢀ
ꢀ
ꢀ
4.5.1. 2-Methyl-1-oxa-cyclopenta[l]phenanthrene (1a). Yield¼80%
(37 mg); Colorless solid; mp¼122e124 ꢁC (recrystallized from
b¼5.0480 (4) A, c¼17.5880 (15) A, V¼2704.4 (4) A , Z¼4,
dcalcd¼1.377 mg/cm3, F(000)¼1168, 2
q
range 0.668e26.686ꢁ, R in-
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C17H13
O
dices (all data) R1¼0.0549, wR2¼0.1368.
233.0966, found 233.0968; 1H NMR (400 MHz, CDCl3):
d 8.72e8.69
(m, 2H), 8.30 (dd, J¼1.6, 7.6 Hz, 1H), 8.08 (dd, J¼1.6, 7.6 Hz, 1H),
4.5.6. 6,9-Dimethoxy-2-methyl-1-oxa-cyclopenta[l]phenanthrene
(1f). Yield¼79% (46 mg); Colorless solid; mp¼128e130 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C19H17O3 293.1178, found 293.1182; 1H NMR (400 MHz, CDCl3):
7.68e7.58 (m, 4H), 6.87 (q, J¼1.2 Hz, 1H), 2.62 (d, J¼1.2 Hz, 3H); 13
C
NMR (100 MHz, CDCl3):
d 154.28, 148.16, 127.96, 127.42, 126.89,
126.76, 125.89, 125.19, 124.86, 123.90, 123.54, 123.41, 122.40, 121.40,
120.16, 102.42, 14.23.
d
8.19 (d, J¼8.8 Hz, 1H), 7.99e7.94 (m, 3H), 7.29 (dt, J¼2.4, 8.8 Hz,
2H), 6.76 (t, J¼1.2 Hz, 1H), 4.02 (s, 3H), 4.01 (s, 3H), 2.58 (s, 3H); 13
C
4.5.2. 9-Fluoro-2-methyl-1-oxa-cyclopenta[l]phenanthrene
(1b). Yield¼82% (41 mg); Colorless solid; mp¼82e84 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
NMR (100 MHz, CDCl3): d 157.25, 156.91, 153.36, 147.28, 129.21,
128.66, 125.23, 122.26, 121.70, 119.44, 117.47, 116.34, 116.07, 106.11,
105.90, 102.08, 55.57, 55.56, 14.15.
C
17H12FO 251.0872, found 251.0875; 1H NMR (400 MHz, CDCl3):
d
8.53 (d, J¼8.4 Hz, 1H), 8.28 (dd, J¼2.4, 11.6 Hz, 1H), 8.24 (dd, J¼6.0,
4.5.7. 9-Methoxy-2-methyl-6-trifluoromethyl-1-oxa-cyclopenta[l]
phenanthrene (1g). Yield¼88% (58 mg); Colorless solid;
mp¼84e86 ꢁC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C19H14F3O2 331.0946, found 331.0950; 1H NMR
8.8 Hz, 1H), 8.04 (d, J¼7.6 Hz, 1H), 7.65 (dt, J¼0.8, 8.0 Hz, 1H), 7.58
(dt, J¼0.8, 8.0 Hz, 1H), 7.39 (dt, J¼2.0, 8.4 Hz, 1H), 6.82 (s, 1H), 2.59
(s, 3H); 13C NMR (100 MHz, CDCl3):
d
160.79 (d, J¼241.8 Hz), 154.13,
147.80, 129.96 (d, J¼7.5 Hz), 128.55 (d, J¼12.2 Hz), 127.86, 127.32,
124.85, 123.97, 123.69, 122.16 (d, J¼8.3 Hz), 120.68, 119.12, 115.65 (d,
J¼23.5 Hz), 108.79 (d, J¼22.7 Hz), 102.30, 14.14.
(400 MHz, CDCl3):
d
8.86 (s, 1H), 8.26 (d, J¼8.8 Hz, 1H), 8.14 (d,
J¼8.4 Hz,1H), 8.07 (d, J¼2.0 Hz,1H), 8.20 (dd, J¼2.0, 8.4 Hz,1H), 7.36
(dd, J¼2.0, 8.8 Hz, 1H), 6.86 (d, J¼0.8 Hz, 1H), 4.06 (s, 3H), 2.61 (d,
J¼0.8 Hz, 3H).
4.5.3. 9-Methoxy-2-methyl-1-oxa-cyclopenta[l]phenanthrene
(1c). Yield¼83% (43 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C18H15O2 263.1072, found 263.1077; 1H NMR (400 MHz, CDCl3):
4.5.8. 9,10-Dimethoxy-2-methyl-1-oxa-cyclopenta[l]phenanthrene
(1h). Yield¼78% (46 mg); Colorless solid; mp¼95e97 ꢁC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C19H17O3 293.1178, found 293.1186; 1H NMR (400 MHz, CDCl3):
d
8.62 (dd, J¼0.8, 8.4 Hz, 1H), 8.22 (d, J¼8.8 Hz, 1H), 8.09 (d,
J¼2.4 Hz, 1H), 8.06 (ddd, J¼0.8, 1.2, 8.0 Hz, 1H), 7.63 (dt, J¼1.2,
8.4 Hz, 1H), 7.57 (dt, J¼1.2, 8.4 Hz, 1H), 7.31 (dd, J¼2.4, 8.8 Hz, 1H),
6.84 (d, J¼1.2 Hz, 1H), 4.03 (s, 3H), 2.60 (d, J¼0.8 Hz, 3H); 13C NMR
d
8.56e8.54 (m, 1H), 8.07e8.05 (m, 1H), 8.04 (s, 1H), 7.65 (s, 1H),
7.61e7.54 (m, 2H), 6.86 (d, J¼0.8 Hz, 1H), 4.13 (s, 3H), 4.12 (s, 3H),
(100 MHz, CDCl3):
d
157.53, 153.46, 148.42, 129.87, 127.90, 127.43,
2.61 (d, J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 153.52, 149.73,
126.86, 124.47, 123.98, 123.56, 121.69, 119.46, 117.15, 116.56, 105.47,
102.23, 55.51, 14.19.
148.23,129.25,127.40,126.64,125.77,124.50,124.02,122.99,122.75,
120.11, 117.21, 104.62, 102.40, 100.67, 56.06, 56.03, 14.21.
4.5.4. 9-Methoxy-2,6-dimethyl-1-oxa-cyclopenta[l]phenanthrene
(1d). Yield¼85% (47 mg); Colorless solid; mp¼123e125 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C19H17O2 277.1229, found 277.1230; 1H NMR (400 MHz, CDCl3):
4.5.9. 9,10-Dimethoxy-2,6-dimethyl-1-oxa-cyclopenta[l]phenan-
threne (1i). Yield¼74% (45 mg); Colorless solid; mp¼104e106 ꢁC
(recrystallized fromhexanesandEtOAc); HRMS (ESI, Mþþ1) calcd for
C
20H19O3 307.1334, found 307.1336;1H NMR (400 MHz, CDCl3):
d 8.31
d
8.39 (br s,1H), 8.20 (d, J¼8.8 Hz,1H), 8.07 (d, J¼2.4 Hz,1H), 7.95 (d,
(s, 1H), 8.03 (s, 1H), 7.95 (d, J¼8.4 Hz,1H), 7.63 (s,1H), 7.41 (dd, J¼1.2,
J¼8.0 Hz, 1H), 7.46 (dd, J¼1.2, 8.0 Hz, 1H), 7.29 (dd, J¼2.4, 8.8 Hz,
1H), 6.80 (d, J¼0.8 Hz, 1H), 4.04 (s, 3H), 2.63 (s, 3H), 2.58 (d,
8.0 Hz,1H), 6.83 (d, J¼0.8 Hz,1H), 4.14 (s, 3H), 4.11 (s, 3H), 2.63 (s, 3H),
2.60 (d, J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 153.39, 149.67,
J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
157.40, 153.31, 148.01,
148.11, 147.67, 133.98, 130.88, 127.46, 124.45, 123.91, 122.76, 120.08,
117.34, 104.76, 104.68, 102.37, 100.68, 56.09, 56.05, 22.05, 14.21.
133.93, 129.58, 128.48, 127.49, 125.64, 123.84, 123.38, 121.63, 119.41,
117.25, 116.45, 105.42, 102.18, 55.55, 22.01, 14.18. Single-crystal X-
ray diagram: crystal of compound 1d was grown by slow diffusion
of EtOAc into a solution of compound 1d in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the monoclinic crystal sys-
4.5.10. 6-Fluoro-9,10-dimethoxy-2-methyl-1-oxa-cyclopenta[l]phen-
anthrene (1j). Yield¼76% (47 mg); Colorless solid; mp¼135e137 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C19H16FO3 311.1084, found 311.1088; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
tem, space group P 21/c, a¼19.7036 (8) A, b¼13.6382 (6) A,
c¼10.8241 (4) A, V¼2827.6 (2) A , Z¼8, dcalcd¼1.298 mg/cm3,
d
8.05 (dd, J¼2.4, 11.2 Hz, 1H), 7.76 (dd, J¼2.0, 8.8 Hz, 1H), 7.75 (s,
3
ꢀ
ꢀ
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060

C.-K. Chan et al. / Tetrahedron xxx (2015) 1e9
9
1H), 7.53 (d, J¼1.2 Hz, 1H), 7.29 (dt, J¼2.4, 8.0 Hz, 1H), 6.75 (t,
References and notes
J¼1.2 Hz, 1H), 4.09 (s, 3H), 4.08 (s, 3H), 2.58 (d, J¼0.8 Hz, 3H); 13C
1. (a) Schaefer, T.; Schildknecht, C.; Murer, P.; Lennartz, C.; Langer, N.; Wagenblast,
G.; Metz, S. 2012, U.S. Patent 2012/0095222 A1. (b) Welker, M.; Schafer, T.;
Chebotareva, N.; Dubner, M.; Turbiez, M. G. R. 2013, WO2013149897 A1.
2. (a) Horspool, W. M.; Khalaf, A. I. Tetrahedron Lett. 1983, 24, 3745; (b) Horspool,
W. M.; Khalaf, A. I. J. Chem. Soc., Perkin Trans. 1 1989, 1147; (c) Sivavec, T. M.;
Katz, T. J.; Chiang, M. Y.; Yang, G. X.-Q. Organometallics 1989, 8, 1620; (d) Mu-
eller, P.; Pautex, N. Helv. Chim. Acta 1988, 71, 1630; (e) Nicolaides, D. N.; Ada-
mopoulos, S. G.; Lefkaditis, D. A.; Litinas, K. E. J. Chem. Soc., Perkin Trans. 1 1992,
2479; (f) Nicolaides, D. N.; Litinas, K. E.; Lefkaditis, D. A.; Adamopoulos, S. G.;
Raptoulou, C. P.; Terzis, A. J. Chem. Soc., Perkin Trans. 1 1994, 2107.
3. Churruca, F.; SanMartin, R.; Tellitu, I.; Dominguez, E. Eur. J. Org. Chem. 2005,
2481 and cited references therein.
NMR (100 MHz, CDCl3):
d
160.31 (d, J¼239.6 Hz), 153.61, 150.05,
148.11, 147.43 (d, J¼2.3 Hz), 128.67 (d, J¼7.6 Hz), 125.67 (d,
J¼7.6 Hz),123.05,121.88,119.73,117.43,114.35 (d, J¼23.5 Hz),108.03
(d, J¼22.7 Hz), 104.44, 102.20, 100.52, 56.01, 55.93, 14.14.
4.5.11. 6,9,10-Trimethoxy-2-methyl-1-oxa-cyclopenta[l]phenan-
threne (1k). Yield¼75% (48 mg); Colorless solid; mp¼210e212 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C20H19O4 323.1283, found 323.1288; 1H NMR (400 MHz, CDCl3):
4. (a) Kojima, T.; Yokota, R.; Kitamura, C.; Kurata, H.; Tanaka, M.; Ikeda, H.; Ka-
wase, T. Chem. Lett. 2014, 43, 696; (b) Zhou, J.; Yang, W.; Wang, B.; Ren, H.
Angew. Chem., Int. Ed. 2012, 51, 12293; (c) West, P. R.; Chaudhary, S. K.; Vernon,
J. M.; Mitchell, R. H. J. Chem. Soc., Chem. Commun. 1984, 613.
5. (a) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K.; Huang, G. G. Tetrahedron 2015, 71,
2095; (b) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 1264; (c) Chang,
M.-Y.; Lu, Y.-J.; Cheng, Y.-C. Tetrahedron 2015, 71, 6840; (d) Chang, M.-Y.; Cheng,
Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 3142.
6. For Pd(II)-mediated cyclizations of 4-alkynones, see: (a) Arcadi, A.; Cacchi, S.;
Fabrizi, G.; Marinelli, F.; Parisi, L. M. Tetrahedron 2003, 59, 4661; (b) Picquet, M.;
Bruneau, C.; Dixneuf, P. H. Tetrahedron 1999, 55, 3937; (c) Cacchi, S.; Fabrizi, G.;
Moro, L. J. Org. Chem. 1997, 62, 5327; (d) Li, Y.; Yu, Z. J. Org. Chem. 2009, 74,
8904; (e) Arcadi, A.; Rossi, E. Tetrahedron Lett. 1996, 37, 6811; (f) Saito, A.;
Enomoto, Y.; Hanzawa, Y. Tetrahedron Lett. 2011, 52, 4299 For Ag(I)/Au(III)-
mediated cyclizations of 4-alkynones, see: (g) Arcadi, A.; Alfonsi, M.; Chiarini,
M.; Marinelli, F. J. Organomet. Chem. 2009, 694, 576; (h) Belting, V.; Krause, N.
Org. Biomol. Chem. 2009, 7, 1221; (i) Wang, T.; Zhang, J. Dalton Trans. 2010, 39,
4270.
d
7.98 (d, J¼8.8 Hz, 1H), 7.93 (s, 1H), 7.92 (d, J¼2.4 Hz, 1H), 7.62 (s,
1H), 7.25 (d, J¼2.4, 8.8 Hz, 1H), 6.80 (q, J¼0.8 Hz, 1H), 4.11 (s, 6H),
4.02 (s, 3H), 2.59 (d, J¼0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
156.97, 153.46, 149.90, 148.01, 146.97, 128.68, 125.33, 122.04,
121.11, 120.10, 117.62, 114.82, 105.80, 104.86, 102.27, 100.72, 56.12,
56.06, 55.65, 14.21; Anal. Calcd for C20H18O4: C, 74.52; H, 5.63.
Found: C, 74.69; H, 5.58. Single-crystal X-ray diagram: crystal of
compound 1k was grown by slow diffusion of EtOAc into a solution
of compound 1k in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P 21/
ꢀ
ꢀ
ꢀ
c, a¼7.7621 (4) A, b¼8.1857 (5) A, c¼24.7632 (13) A, V¼1563.14
(15) A , Z¼4, dcalcd¼1.370 mg/cm3, F(000)¼680,
2
q range
3
ꢀ
1.655e26.435ꢁ, R indices (all data) R1¼0.0596, wR2¼0.0962.
7. For other metal-mediated cyclizations of 4-alkynones, For Ag, see: (a) Das, R.;
Chakraboty, D. Appl. Organomet. Chem. 2012, 26, 722 For Hg(II), see: (b) Imag-
awa, H.; Kurisaki, T.; Nishizawa, M. Org. Lett. 2004, 6, 3679 In(III), see: (c) Feng,
X.; Tan, Z.; Chen, D.; Shen, Y.; Guo, C.-C.; Xiang, J.; Zhu, C. Tetrahedron Lett. 2008,
49, 4110; (d) Tsuji, H.; Yamagata, K.-i.; Ueda, Y.; Nakamura, E. Synlett 2011, 1015
For Zn(II), see: (e) Liu, C.-R.; Li, M.-B.; Yang, C.-F.; Tian, S. Chem.dEur. J. 2009, 15,
793.
8. For the representative examples on the synthesis of 2,3-diarylfurans, see: (a)
Dudnik, A. S.; Gevorgyan, V. Angew. Chem., Int. Ed. 2007, 46, 5195; (b) Dudnik, A.
S.; Sromek, A. W.; Rubina, M.; Kim, J. T.; Kelin, A. V.; Gevorgyan, V. J. Am. Chem.
Soc. 2008, 130, 1440; (c) Mothe, S. R.; Lauw, S. J. L.; Kothandaraman, P.; Chan, P.
W. H. J. Org. Chem. 2012, 77, 6937.
4.5.12. Compound (1l). Yield¼80% (64 mg); Colorless solid;
mp¼170e172 ꢁC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C26H23O4 399.1596, found 399.1601; 1H NMR
(400 MHz, CDCl3):
d
9.66 (d, J¼8.4 Hz, 1H), 8.48 (dd, J¼0.8, 8.4 Hz,
1H), 7.99 (s, 1H), 7.78 (dt, J¼1.6, 8.4 Hz, 1H), 7.12 (s, 1H), 7.66 (dt,
J¼1.2, 8.4 Hz, 1H), 7.44 (s, 1H), 6.82 (s, 1H), 6.12 (s, 2H), 4.35 (t,
J¼6.0 Hz, 2H), 2.70 (s, 3H), 2.06e1.99 (m, 2H), 1.74e1.65 (m, 2H),
1.09 (t, J¼7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 153.25, 152.61,
149.02, 147.59, 146.68, 129.65, 127.36, 127.26, 126.85, 125.90, 125.74,
123.52, 123.06, 121.96, 121.79, 112.63, 101.95, 101.60, 101.33, 101.24,
99.31, 67.84, 31.50, 19.60, 14.43, 14.01.
9. (a) Chang, M.-Y.; Lee, N.-C. Synlett 2011, 1875; (b) Chang, M.-Y.; Wu, M.-H.
Tetrahedron 2013, 69, 129; (c) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Tetrahedron
2015, 71, 782.
10. (a) Boden, N.; Bushby, R. J.; Headdock, G.; Lozman, O. R.; Wood, A. Liq. Cryst.
2001, 28, 139; (b) King, B. T.; Kroulik, J.; Robertson, C. R.; Rempala, P.; Hilton, C.
L.; Korinek, J. D.; Gortari, L. M. J. Org. Chem. 2007, 72, 2279; (c) Simpson, C. D.;
Mattersteig, G.; Martin, K.; Gherghel, L.; Bauer, R. E.; Rader, H. J.; Mullen, K. J.
Am. Chem. Soc. 2004, 126, 3139; (d) McKillop, A.; Turrell, A. G.; Young, D. W.;
Taylor, E. C. J. Am. Chem. Soc. 1980, 102, 6504; (e) Churruca, F.; SanMartin, R.;
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Zhang, X.; Jiang, X.; Zhang, K.; Mao, L.; Luo, J.; Chi, C.; Chan, H. S. O.; Wu, J. J. Org.
Chem. 2010, 75, 8069.
11. CCDC 1063475 (1d), 1063476 (1e) and 1406420 (1k) contain the supplementary
crystallographic data for this paper. This data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: þ44 1223 336033; e-mail: deposit@ccdc.cam.ac.
uk).
12. For 3aed, see: (a) Yu, J.-W.; Mao, S.; Wang, Y.-Q. Tetrahedron Lett. 2015, 56, 1575
For 3eef, see: (b) Salehi, M.; Ostad, S. N.; Riazi, G. H.; Assadieskandar, A.;
Cheraghi-Shavi, T.; Shafiee, A.; Amini, M. Med. Chem. Res. 2014, 23, 1465 For 3g,
see: (c) Wang, D.; Zhang, Z. Org. Lett. 2003, 5, 4645 For 3i, see: (d) Zhang, W.;
Ready, J. M. Angew. Chem., Int. Ed. 2014, 53, 8980 For 3j, see: (e) Chen, J.; Liu, S.;
Zhou, Y.; Li, S.; Lin, C.; Bian, Z.; Fan, B. Organometallics 2015, 34, 4318 For 3k and
3m, see: (f) Churruca, F.; SanMartin, R.; Carril, M.; Tellitu, I.; Dominguez, E.
Tetrahedron 2004, 60, 2393 For 3n, see: (g) Napolitano, E.; Giannone, E.; Fiaschi,
R.; Marsili, A. J. Org. Chem. 1983, 48, 3653 For 3q, see: (h) Salehi, M.; Amini, M.;
Ostad, S. N.; Riazi, G. H.; Assadieskandar, A.; Shafiei, B.; Shafiee, A. Bioorg. Med.
Chem. 2013, 21, 7648.
4.5.13. Compound (1m). Yield¼80% (62 mg); Colorless solid;
mp>230 ꢁC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C24H19O5 387.1233, found 387.1236; 1H NMR
(400 MHz, CDCl3):
d
9.11 (s, 1H), 8.35 (d, J¼8.8 Hz, 1H), 7.99 (s, 1H),
7.58 (s, 1H), 7.44 (s, 1H), 7.29 (dd, J¼2.4, 8.8 Hz, 1H), 6.82 (s, 1H), 6.12
(s, 2H), 4.18 (s, 3H), 4.09 (s, 3H), 2.68 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d 158.98, 157.74, 153.35, 152.87, 149.02, 146.68, 132.67,
131.07, 127.53, 123.42, 123.15, 117.38, 116.21, 112.33, 111.01, 108.16,
102.07, 101.60, 101.36, 101.27, 96.68, 55.43, 55.28, 14.33.
Acknowledgements
The authors would like to thank the Ministry of Science and
Technology of the Republic of China for financial support (MOST
104-2113-M-037-012).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.10.060.
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.060