Synthesis of dibenzocyclohepten-5-ones by electrophilic iodocyclization of 1-([1,1′-Biphenyl]-2-yl)alkynones

Article abstract of DOI:10.1021/jo5001803

A synthesis of iodo-substituted dibenzocyclohepten-5-ones by the iodine monochloride (or iodine)-induced intramolecular 7-endo-dig cyclization of 1-([1,1′-biphenyl]-2-yl)alkynones is reported. Detailed investigations on the substituent effects during the

Full text of DOI:10.1021/jo5001803

Article
pubs.acs.org/joc
Synthesis of Dibenzocyclohepten-5-ones by Electrophilic
Iodocyclization of 1‑([1,1′-Biphenyl]-2-yl)alkynones
Yu Chen,* Chenlong Huang, Xiaochen Liu, Eliyahu Perl, Zhiwei Chen, Jieun Namgung,
Gopal Subramaniam, Gan Zhang, and William H. Hersh
Department of Chemistry and Biochemistry, Queens College and the Graduate Center of the City University of New York, 65-30
Kissena Boulevard, Flushing, New York 11367, United States
S
* Supporting Information
ABSTRACT: A synthesis of iodo-substituted dibenzocyclo-
hepten-5-ones by the iodine monochloride (or iodine)-
induced intramolecular 7-endo-dig cyclization of 1-([1,1′-
biphenyl]-2-yl)alkynones is reported. Detailed investigations
on the substituent effects during the electrophilic iodocycliza-
tion of the alkynones show that they play a crucial role in
determining the reaction pathways of the cyclization. By
modifying the substitution pattern on the alkynone substrates,
the cyclization takes place regioselectively, leading to either dibenzocyclohepten-5-ones, via a 7-endo-dig cyclization, or
spiroconjugated compounds, via a 6-endo-dig cyclization.
Halogen-induced electrophilic cyclization reactions have
emerged as an indispensable method for the synthesis of cyclic
compounds, as they occur under relatively mild conditions.
Moreover, these reactions provide a facile approach toward the
synthesis of a variety of functionally substituted heterocyclic and
carbocyclic compounds, by the ready modification of the halide
functionality, and have therefore attracted a significant amount of
attention from synthetic chemists.16,17
On the basis of our continuing interest in synthesizing
biologically interesting cyclic compounds by the cyclization of
functionally substituted alkynes,18 our group has designed an
ICl-induced intramolecular cyclization of 1-([1,1′-biphenyl]-2-
yl)alkynones (1). From the outset of our experimentation, we
envisioned that a 7-endo-dig cyclization of substrate 1 would take
place in the presence of ICl, leading to the formation of 6-
iododibenzocyclohepten-5-ones (2) (eq 1).
INTRODUCTION
■
Colchicine, a naturally occurring molecule isolated from meadow
saffron (Colchicum autumnale), has long been known for its
potent antitumor effects;1 however, because of its cytotoxicity, its
therapeutic applications have been rather limited. Allocolchicine,
a degradation product of colchicine, has recently attracted the
attention of medicinal chemists. Both allocolchicine and its
derivatives display potent anticancer effects by inhibiting tubulin
polymerization (Figure 1),2 with the added benefit of having a
more-limited toxicity than their parent molecule. Accordingly,
various synthetic methods producing allocolchicine analogues
have been developed, including Wulff’s Diels−Alder reaction−
aromatization approach,3 Fagnou’s palladium-catalyzed intra-
molecular direct arylation,4 DeShong’s phenanthrol ring
expansion,5 Green’s intramolecular Nicholas reaction,6 Leo-
nard’s Ziegler−Ullmann coupling process,7 Kocienski’s sequen-
tial Suzuki−Miyaura coupling−asymmetric reduction8 preceded
by his earlier synthesis involving an intramolecular biaryl
oxidative coupling,9 Hanna’s sequential ring-closing enyne
metathesis−Diels−Alder reactions,10 and a thallium(III)-medi-
ated intramolecular nonphenolic biaryl oxidative coupling
originally developed by Sawyer11 and utilized in the asymmetric
synthesis of (−)-N-acetylcolchinol by Chong.12
From a synthetic point-of-view, dibenzocyclohepten-5-one is
the core structure of allocolchicine. However, there are only a few
known methods for the synthesis of dibenzocyclohepten-5-ones,
these being limited to Choi’s sequential Suzuki−Miyaura
coupling−aldol condensation synthesis,13 Satyanarayana’s palla-
dium-catalyzed domino homobiaryl coupling reaction,14 and
Waldvogel’s oxidative aryl−aryl coupling of 1,3-diarylpropene
derivatives.15 A facile synthetic route toward this core structure is
thus still in high demand.
Our results reveal that the ICl-induced cyclization of 1 is
strongly controlled by substituent effects. We show that the
attachment of different functional groups on the phenyl group
distal to the 1,1′-biphenyl bond modulates the electron density at
both the ipso and ortho positions, influencing the relative
nucleophilicity of the ipso and ortho sites on the distal phenyl
Received: January 24, 2014
Published: March 18, 2014
© 2014 American Chemical Society
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Figure 1. Colchicine, allocolchicine analogues, and dibenzocyclohepten-5-one.
ring. These substituent effects generate two alternative reaction
pathways: a 6-endo-dig and a 7-endo-dig cyclization, which
compete with each other during the process of the electrophilic
cyclization. The outcome of which process predominates
depends on the relative electron density at the ipso and ortho
positions of the phenyl ring distal to the 1,1′-biphenyl bond. We
show that when a strong electron-donating group such as a
methoxy is present at the para position of the distal phenyl ring, a
6-endo-dig cyclization is favored, leading to the formation the
spiroconjugated compounds 3 (eq 2).19 Conversely, when the
the following functionalizations at the para position of the distal
phenyl ring: benzyloxy, phenoxy, fluorine, chlorine, thiomethyl,
and methyl groups. Both benzyloxy- and phenoxy-substituted
substrates (1ab and 1ac) lead to the same spiroconjugated
compound (3aa) as the methoxy-substituted substrate 1aa
(Table 1, entries 1−3). In the presence of a p-fluorine group
(1ad), a mixture of dibenzocyclohepten-5-one (2ad) and the
spiroconjugated compound (3aa) is obtained in an approximate
1:2 ratio (Table 1, entry 4), while dibenzocyclohepten-5-one
(2ae) is obtained as the sole product when a p-chlorine group is
present (Table 1, entry 5). The cyclization of p-thiomethyl-
substituted substrate 1af leads to an equal mixture of the
spiroconjugated compound (3aa) and a chlorine-substituted
dibenzocyclohepten-5-one (2ae) (Table 1, entry 6). When a
methyl group is present at the para position, dibenzocyclohept-
en-5-one 2aga is obtained together with the minor product 2agb
(Table 1, entry 7). The latter is presumably formed via
chlorination of 2aga.
Because an electron-donating group at the ortho position of
the distal phenyl ring also enriches the electron-density at the
ipso position, we examined the cyclization of substrate 1b (Table
1, entry 8); a pair of spiroconjugated compounds, 3b and 3c,
results from this reaction. The structures of 3b and 3c were
strongly electron-donating group is removed from the para
position, a 7-endo-dig cyclization predominates, producing
dibenzocyclohepten-5-ones (2). Some of these results have
been communicated previously.19 Herein we report the full
details of these electrophilic iodocyclization reactions.
1
characterized by analysis of their H and 13C NMR and high
resolution mass spectra. In addition, the structure of 3c was
further confirmed by comparison of its spectra with those of the
regiospecific product from the cyclization of 1c (Table 1, entry
9).
RESULTS AND DISCUSSION
■
The starting materials 1-([1,1′-biphenyl]-2-yl)alkynones (1)
were prepared from 1-(2-bromoaryl)alkynones (4) and boronic
acids by a microwave-assisted Suzuki−Miyaura coupling.20 The
1-(2-bromoaryl)alkynones (4) used in this first reaction were
prepared from commercially available 2-bromobenzoyl chlorides
(5) and terminal alkynes by a Sonogashira coupling (Scheme 1;
see Experimental Section for details on the synthesis of
compounds 1 and 4).21
The resulting 1-([1,1′-biphenyl]-2-yl)alkynones (1) were then
subjected to an ICl-induced cyclization under the optimal
conditions established by our previous work.19 Building on this
work, we first studied the effect of the groups at the para position
of the phenyl ring distal to the 1,1′-biphenyl bond. Following our
study of the methoxy functionality,19 we investigated the
cyclization processes of the monosubstituted substrates bearing
Alkynone substrates with polysubstituted distal phenyl rings
were also investigated. In addition to the p-methoxy group, when
a second methoxy group is present at the ortho position to the
1,1′-biphenyl bond, the cyclization leads exclusively to the spiro
compound 3c (Table 1, entry 9), by amplification of the electron
density at the ipso position. When a second methoxy group is
introduced at the meta position of the distal phenyl ring, a
mixture of spiro compound 3d and dibenzocyclohepten-5-one
2d is produced (Table 1, entry 10). On the other hand, when
both a second and third methoxy group are present at the meta
positions, a 7-endo-dig cyclization takes place, leading exclusively
to the dibenzocyclohepten-5-one product 2e (Table 1, entry 11).
However, when two more weakly electron-donating methyl
Scheme 1. Preparation of 1-([1,1′-Biphenyl]-2-yl)alkynones (1)
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a
Table 1. Substituent Effects in the ICl-Induced Intramolecular Cyclization of 1-([1,1′-Biphenyl]-2-yl)alkynones
a
b
See Experimental Section for the general procedure. Isolated yields after column chromatography.
groups are placed at the meta positions of the distal phenyl ring, a
mixture of 3f and 2f is obtained (Table 1, entry 12). Our study
has also revealed a mild substituent effect on the phenyl ring
proximal to the 1,1′-biphenyl bond. When the proximal phenyl
ring bears a methoxy group at the para position to the 1,1′-
biphenyl bond, a mixture of dibenzocyclohepten-5-one 2g and
spiro compound 3g is obtained in a 1:10 ratio (Table 1, entry 13).
To investigate the formation of dibenzocyclohepten-5-ones by
a regioselective process, a variety of alkynone substrates were
employed in this cyclization reaction. When no substituent is
present at the distal phenyl ring (1h), dibenzocyclohepten-5-one
(2h) is exclusively obtained (Table 2, entry 1). Additionally,
substrates including 3′-methoxy-, 3′-fluoro-, 3′,5′-dimethyl-,
3′,5′-dimethoxy-, 2′,3′-dimethoxy-, and 3′-methoxy-4′-methyl-
substituted distal phenyl rings all lead exclusively to the
dibenzocyclohepten-5-one products, proceeding via a 7-endo-
dig cyclization (Table 2, entries 1−7).
Mild electron-withdrawing substituents (such as fluorine) and
strong electron-donating substituents (such as methoxy) are well
accommodated on the proximal phenyl group at the position
para to the 1,1′-biphenyl bond, with both leading to the
dibenzocyclohepten-5-one products (Table 2, entries 8 and 9).
The electronic effects of substituents at the distal position of the
alkynone triple bond were also investigated. Both electron-rich
and -deficient aryl, heteroaryl, and alkenyl groups are well
accommodated at the distal position of the alkynone triple bond
(Table 2, entries 10−14). It is worth noting that cyclization
products 2l, 2t, and 2u (Table 2, entries 5, 13, and 14) were
produced from a cyclization reaction involving I2, as the reaction
with ICl produced an inseparable mixture of products.
Finally, it should be noted that the electrophilic cyclizations of
the meta-substituted alkynones to give dibenzocyclohepten-5-
one product 2 take place regiospecifically at the less-hindered 6′
ortho position of the 1,1′-biphenyl bond. This phenomenon is
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Table 2. Synthesis of Dibenzocyclohepten-5-ones by ICl-Induced Intramolecular Cyclization of 1-([1,1′-Biphenyl]-2-
a
yl)alkynones
a
b
c
See Experimental Section for the general procedure. Isolated yields after column chromatography. Three equivalents of I2 was used instead of ICl,
for the cyclization of these products.
Figure 2. Position of electron density on the distal phenyl ring influenced by the substituent effects about the 1,1′-biphenyl bond.
supported by the 1H NMR spectra of these compounds, where a
proton doublet peak with long distance coupling of 4J is observed
on the original distal phenyl groups of 2i, 2j, 2o, 2p, 2s, 2t, and 2u
(Table 2, entries 2, 3, 8, 9, 12−14), and two isolated proton
singlets are observed on the original distal phenyl group of 2n
(Table 2, entry 7). The regiospecificity observed during the
cyclizations of alkynones 1i, 1j, 1n, 1o, 1p, 1s, 1t, and 1u is
presumably due to the steric effects induced by the meta
substituents on the distal phenyl ring.
On the basis of our results, the outcome of this regioselective
cyclization primarily depends on whether the electron-density is
concentrated at the ortho or ipso position of the phenyl ring
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Scheme 2. A Plausible Mechanism for the Formation of Dibenzocyclohepten-5-ones by the ICl-Induced Electrophilic Cyclization
of 1-([1,1′-Biphenyl]-2-yl)alkynones
Scheme 3. A Plausible Mechanism for the ICl-Induced Ipso-Electrophilic Cyclization of Alkynones 1aa and 1ab
Scheme 4. A Plausible Mechanism for the ICl-Induced Electrophilic Cyclization of Alkynones 1ac, 1ad, and 1af
distal to the 1,1′-biphenyl bond, which is in turn influenced by
the substitution pattern of the alkynone substrate 1. In the
absence of any substituent on either the proximal or distal phenyl
rings, a 7-endo-dig cyclization exclusively takes place, leading
only to dibenzocyclohepten-5-one (1h) (Table 2, entry 1).
When a strong electron-donating substituent such as methoxy is
present at either the para or ortho position of the distal phenyl
group, the ipso position on the phenyl ring becomes more
electron-dense than the ortho position (Figure 2, structures A
and B); therefore, only an ipso cyclization takes place. On the
other hand, when the donor substituent is present at the meta
position of the distal phenyl ring, or at the para position of the
proximal phenyl ring, the ortho position of the distal phenyl ring
becomes more electron-dense (Figure 2, structures C and D);
therefore, an ortho electrophilic cyclization is favored. When the
mild electron-withdrawing substituent fluorine or the electron-
donating thiomethyl group is present at the para position of the
distal phenyl ring, both ipso and ortho cyclizations take place,
affording a mixture of the spiro compound and dibenzocyclo-
hepten-5-one. Mesomeric effects presumably play a significant
role in determining the reaction pathways during the cyclizations
of 1ad and 1ae. The formation of a substantial amount of spiro
compound from the cyclization of alkynone 1ad but not for 1ae
is presumably due to the relatively stronger mesomeric effect
displayed by the fluorine atom than the chlorine atom. Similar
explanation also explicates the different outcome observed
during the cyclizations of alkynones 1af and 1ag.
Our results also demonstrate that the functional group distal to
the alkyne triple bond does not display any appreciable
substituent effects during the cyclization process. Additionally,
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while functionalization of the phenyl ring proximal to the 1,1′-
biphenyl bond induces a mild substituent effect, groups on the
distal phenyl ring induce a much stronger effect, partially due to
their proximity to the ortho and ipso positions.
Scheme 5. A Plausible Mechanism for the ICl-Induced
Electrophilic Cyclization of Alkynone 1b
When more than one substituent is present on the distal and
proximal phenyl groups, the outcome of the reaction depends on
the identity of the substituents, as well as on their positions. If all
substituents reinforce each other, only one product predom-
inates (e.g., Table 1, entry 9; Table 2, entries 4, 5, 8, and 9).
However, if multiple substituents shift electron density to both
the ipso and ortho positions, a mixture of both the
dibenzocyclohepten-5-ones and the spiro compound is afforded
(e.g., Table 1, entries 10, 12, and 13). The ratio of the mixture is
in turn determined by the strength of each substituent’s electron-
donating ability, as well as their proximity to either the ipso or the
ortho position of the distal phenyl ring. For instance, substrate 1g
generates a lower yield of a 7-endo-dig cyclization product than
substrate 1d, as the methoxy groups compete only in terms of
their proximity to the ipso or ortho positions on the distal phenyl
ring. The strength of the substituent groups also affects the
cyclization process, as demonstrated by the reactions of 1e and
1f. While compound 2e forms regiospecifically due to the
significant amplification of the substituent effects of the two meta
methoxy groups, a mixture of 2f and 3f is obtained when the
milder electron-donating methyl groups replace the two meta
methoxy groups in 1e.
A plausible reaction mechanism is proposed to account for the
formation of the dibenzocyclohepten-5-ones 2 (Scheme 2). First,
the iodonium intermediate 6 forms upon the interaction of the
electrophilic ICl with the alkynone (1) triple bond.17b,22 A 7-
endo-dig electrophilic aromatic substitution then takes place at
the ortho position of the distal phenyl group to form compound
2.
When a strong electron-donating group, such as a methoxy or
a benzyloxy, is the only substituent present at the para position of
the distal phenyl ring, a 6-endo-dig cyclization exclusively takes
place at the ipso position to form oxonium ion intermediate 7.
The methyl or benzyl group on 7 is then removed, in situ, by a
nucleophile such as chloride anion, and the spiro compound 3aa
forms.
Similarly, when a phenoxy is present at the para position of the
distal phenyl ring, a 6-endo-dig ipso-cyclization takes place on
intermediate 8, leading to the spiro intermediate 9 (Scheme 4,
path a). The nucleophilic addition of water to 9 leads to
intermediate 10. After the phenoxy group is expelled, a base
abstracts a proton from intermediate 11, generating the spiro
compound 3aa. When a fluorine or thiomethyl group is present
at the para position of the distal phenyl ring, two reaction
pathways are possible: (a) a 6-endo-dig ipso-cyclization similar to
the reaction of the phenoxy-substituted substrate 1ac (Scheme 4,
path a), or (b) a 7-endo-dig ortho electrophilic aromatic
substitution leading to dibenzocyclohepten-5-ones 2ad and
2ae (Scheme 4, path b). The formation of 2ae from 1af
presumably occurs from a nucleophilic aromatic substitution on
an intermediate compound 2af, with chloride replacing the
thiomethyl group. Our effort to trap the intermediate compound
2af was, however, unsuccessful.
of water to form intermediate 13 (Scheme 5, path b), which leads
to spiro compound 3c after oxidation (presumably by air or ICl).
CONCLUSION
■
A synthesis of dibenzocyclohepten-5-ones, the core structure of
allocolchicine, by the iodocyclization reaction of 1-([1,1′-
biphenyl]-2-yl)alkynones under mild reaction conditions is
described. Two reaction pathways were observed: a 7-endo-dig
and a 6-endo-dig cyclization for the alkynone substrates.
Substituent effects during the cyclization process have been
studied in detail and play a crucial role in determining which
reaction pathway predominates. By selecting the substituent
pattern on the alkynone substrates, we are able to selectively
prepare either dibenzocyclohepten-5-ones or spiroconjugated
compounds. The iodine functional group in the produced
compounds promises further elaboration of the core structure
through well-known palladium-catalyzed coupling reactions.
This method is particularly useful for combinatorial chemistry,
as it provides a direct route toward the library synthesis of
allocolchicine derivatives, potentiating the discovery of new
anticancer medications. Synthesis of a molecular library of
allocolchicine analogues using the developed method is currently
underway in our group. We expect this facile synthetic route will
soon find applications in high-throughput drug screening
processes.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out in sealed 6-
dram vials, unless otherwise indicated. All microwave irradiation
reactions were carried out in 20 mL Biotage microwave vials sealed
with an aluminum/Teflon crimp cap, which can be exposed to a
maximum of 250 °C and 20 bar internal pressure. The microwave
irradiation reactions were run using a Biotage-EXP Microwave synthesis
system, operating at a frequency of 2450 MHz, with continuous
irradiation power from 0 to 300 W. An IR sensor within the apparatus
measured the reaction temperatures by analysis of radiant heat from the
outer surfaces of the process vials. All commercially available chemicals
were used as received without further purification. All products were
purified by flash column chromatography on silica gel (230−400 mesh).
1H NMR spectra were recorded at 500 MHz using CDCl3 as the solvent.
13C NMR spectra were recorded at either 125 or 100 MHz using CDCl3
as the solvent. The chemical shifts of all 1H and 13C NMR spectra are
referenced to the residual signal of CDCl3 (δ 7.26 ppm for the 1H NMR
When a methoxy group is present at the ortho position of distal
phenyl ring, a 6-endo-dig cyclization takes place at the ipso
position, leading to the spiro intermediate 12, which upon the
loss of the methyl group forms spiro compound 3b (Scheme 5,
path a). Alternatively, intermediate 12 can also undergo a
different reaction pathway, by a nucleophilic conjugate addition
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spectra, and δ 77.23 ppm for the 13C NMR spectra). IR spectra were
recorded on a FT-IR spectrometer, at a resolution of 4.0 cm−1, with only
major peaks reported. The high resolution mass spectra were recorded
on a double focusing magnetic-sector mass spectrometer, using
electrospray ionization. The melting points are uncorrected.
1H), 7.60−7.64 (m, 3H), 7.45−7.48 (m, 1H), 7.37−7.40 (m, 2H),
7.07−7.11 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 176.0 (d, JC−F = 1.6
Hz), 161.4 (d, JC−F = 250.5 Hz), 138.7 (d, JC−F = 6.3 Hz), 136.4 (d, JC−F
= 7.2 Hz), 133.2, 131.3, 128.8, 120.7 (d, JC−F = 21.3 Hz), 119.6, 119.5 (d,
JC−F = 24.4 Hz), 115.5 (d, JC−F = 3.6 Hz), 95.0, 87.6; IR (CHCl3, cm−1) ν
3068, 2201, 1654, 1576, 1464, 1398, 1299, 1261, 1159, 758; HRMS
(ESI) calcd for C15H9BrFO (M + H)+ 302.9815, found 302.9817.
1-(2-Bromo-5-methoxyphenyl)-3-phenylprop-2-yn-1-one (4g).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a light brown oil (500.8 mg, 78% yield): 1H
NMR (500 MHz, CDCl3) δ 7.58−7.60 (m, 2H), 7.54 (d, J = 3.2 Hz,
1H), 7.50 (d, J = 8.7 Hz, 1H), 7.41−7.45 (m, 1H), 7.34−7.37 (m, 2H),
6.89 (dd, J = 8.8, 3.2 Hz, 1H), 3.80 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 177.2, 158.7, 137.9, 135.6, 133.1, 131.1, 128.7, 119.8, 119.4,
117.9, 111.4, 94.4, 87.9, 55.7; IR (CHCl3, cm−1) ν 2936, 2838, 2199,
1653, 1468, 1286, 1240, 1172, 1031, 757; HRMS (ESI) calcd for
C16H12BrO2 (M + H)+ 315.0015 found 315.0016.
General Procedure for the Preparation of 1-([1,1′-Biphenyl]-
2-yl)alkynones (1) from 1-(2-Bromophenyl)alkynones (4) and
Arylboronic Acids.26 A 20 mL microwave vial was charged with 1-(2-
bromophenyl)alkynone (4, 1.0 mmol), an arylboronic acid (1.2 mmol),
Pd(PPh3)4 (57.7 mg, 0.05 mmol), Cs2CO3 (570.2 mg, 1.75 mmol), and
THF (10 mL). The vial was flushed with nitrogen and sealed with an
aluminum/Teflon crimp cap. The reaction mixture was stirred at 120 °C
while undergoing microwave irradiation (300 W) for 2 h and then
diluted with ethyl acetate (30 mL) and washed with brine (30 mL). The
aqueous phase was extracted with ethyl acetate (2 × 20 mL), and the
combined organic layers were dried over anhydrous MgSO4 and
concentrated using a rotary evaporator, under reduced pressure (20
mmHg). The subsequent residue was then purified by flash column
chromatography on silica gel (eluent: hexanes/ethyl acetate).
General Procedure for the Preparation of 1-(2-Bromo-
phenyl)alkynones (4) from 2-Bromobenzoyl Chlorides (5) and
Terminal Alkynes.23 An oven-dried 6-dram vial was charged with 2-
bromobenzoyl chloride or its derivative (5, 2.0 mmol), a terminal alkyne
(2.0 mmol), Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol), CuI (3.8 mg, 0.02
mmol), and anhydrous Et3N (10 mL). The vial was then flushed with
nitrogen and sealed. The reaction mixture was stirred at room
temperature overnight, until the disappearance of starting material
was observed, as monitored by thin layer chromatography. The reaction
mixture was diluted with ethyl acetate (40 mL) and washed with brine
(40 mL), and the aqueous phase was then extracted with ethyl acetate (2
× 20 mL). The combined organic layers were dried over anhydrous
MgSO4 and concentrated using a rotary evaporator under reduced
pressure (20 mmHg); the resulting residue was purified by flash column
chromatography on silica gel (eluent: hexanes/ethyl acetate).
1-(2-Bromophenyl)-3-phenylprop-2-yn-1-one (4a). Eluent of col-
umn chromatography: hexanes/ethyl acetate 10:1. This compound was
1
obtained as a yellow oil (468.5 mg, 82% yield): H NMR (500 MHz,
CDCl3) δ 8.08 (dd, J = 7.7, 1.8 Hz, 1H), 7.71 (dd, J = 7.9, 1.1 Hz, 1H),
7.64−7.66 (m, 2H), 7.37−7.50 (m, 5H). The 1H NMR spectral data are
in good agreement with the literature data.18a
1-(2-Bromophenyl)-3-(4-methoxyphenyl)prop-2-yn-1-one (4b).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a beige solid, mp 46.0−46.9 °C; (453.6 mg,
1
72% yield): H NMR (500 MHz, CDCl3) δ 8.04 (dd, J = 7.7, 1.7 Hz,
1H), 7.69 (dd, J = 8.0, 1.0 Hz, 1H), 7.60−7.62 (m, 2H), 7.45 (dt, J = 7.5,
1.1 Hz, 1H), 7.37 (dt, J = 7.8, 1.8 Hz, 1H), 6.91−6.93 (m, 2H), 3.85 (s,
1-(4′-Methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1aa). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This compound was obtained as a yellow oil (247.6 mg, 79% yield): 1H
NMR (500 MHz, CDCl3) δ 7.93 (d, J = 7.7 Hz, 1H), 7.56 (t, J = 7.9 Hz,
1H), 7.41−7.45 (m, 2H), 7.34−7.35 (m, 3H), 7.26−7.29 (m, 4H), 6.94
(d, J = 7.2 Hz, 2H), 3.76 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 181.0,
159.7, 142.6, 138.1, 133.1, 132.9, 132.3, 131.1, 130.9, 130.5, 130.1, 128.4,
127.2, 120.3, 114.0, 93.8, 89.0, 55.4; IR (CHCl3, cm−1) ν 3016, 2935,
2835, 2194, 1636, 1299, 1246, 759; HRMS (ESI) calcd for C22H17O2 (M
+ H)+ 313.1223, found 313.1223.
1
3H). The H NMR spectral data are in good agreement with the
literature data.24
Methyl 4-(3-(2-Bromophenyl)-3-oxoprop-1-yn-1-yl)benzoate
(4c).25 Eluent of column chromatography: hexanes/ethyl acetate 5:1.
This compound was obtained as a yellow solid, by reacting 2-
bromobenzoyl chloride with methyl 4-ethynylbenzoate in the presence
of 1 equiv of Et3N in 10 mL of anhydrous THF (501.3 mg, 73% yield):
mp 89.9−90.5 °C; 1H NMR (500 MHz, CDCl3) δ 8.06−8.08 (m, 3H),
7.70−7.72 (m, 3H), 7.47 (dt, J = 7.6, 1.0 Hz, 1H), 7.40 (dt, J = 7.9, 1.7
Hz, 1H), 3.94 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 177.4, 166.3,
137.3, 135.2, 133.8, 133.09, 133.06, 132.0, 129.9, 127.7, 124.6, 121.6,
92.5, 89.6, 52.7; IR (CHCl3, cm−1) ν 3012, 2960, 2204, 1723, 1640,
1587, 1436, 1278, 1203, 1004, 768, 734; HRMS (ESI) calcd for
C17H12BrO3 (M + H)+ 342.9964, found 342.9966.
1-(2-Bromophenyl)-3-(thiophen-3-yl)prop-2-yn-1-one (4d). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a light brown oil (469.6 mg, 81% yield): 1H
NMR (500 MHz, CDCl3) δ 8.04 (dd, J = 7.7, 1.4 Hz, 1H), 7.82−7.83
(m, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.35−7.40 (m,
2H), 7.28−7.29 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 177.7, 137.6,
135.1, 134.5, 133.5, 132.9, 130.4, 127.6, 126.5, 121.4, 119.4, 89.9, 88.4;
IR (CHCl3, cm−1) ν 3018, 2197, 1644, 1290, 1216, 1012, 758; HRMS
(ESI) calcd for C13H8BrOS (M + H)+ 290.9474, found 290.9473.
1-(2-Bromophenyl)-3-(cyclohex-1-en-1-yl)prop-2-yn-1-one (4e).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a yellow oil (324.0 mg, 56% yield): 1H NMR
(500 MHz, CDCl3) δ 7.96 (dd, J = 7.7, 1.8 Hz, 1H), 7.66 (dd, J = 7.9, 1.1
Hz, 1H), 7.41 (dt, J = 7.5, 1.2 Hz, 1H), 7.34 (dt, J = 7.7, 1.8 Hz, 1H),
6.54−6.56 (m, 1H), 2.22−2.25 (m, 2H), 2.17−2.20 (m, 2H), 1.66−1.69
(m, 2H), 1.61−1.65 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 177.8,
143.5, 137.8, 134.9, 133.2, 132.7, 127.4, 121.1, 119.2, 97.0, 86.5, 28.2,
26.3, 22.0, 21.2; IR (CHCl3, cm−1) ν 3019, 2940, 2864, 2182, 1650,
1430, 1293, 1246, 1026, 757; HRMS (ESI) calcd for C15H14BrO (M +
H)+ 289.0223, found 289.0220.
1-(4′-(Benzyloxy)-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1ab). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This compound was obtained as a yellow solid (310.1 mg, 80% yield):
1
mp 104.4−105.3 °C; H NMR (500 MHz, CDCl3) δ 7.96−7.98 (m,
1H), 7.59 (t, J = 7.3 Hz, 1H), 7.46 (dd, J = 13.9, 7.7 Hz, 2H), 7.39−7.40
(m, 8H), 7.29−7.31 (m, 4H), 7.04−7.06 (m, 2H), 5.03 (s, 2H); 13C
NMR (125 MHz, CDCl3) δ 180.9, 158.9, 142.5, 138.0, 136.9, 133.1,
132.3, 131.0, 130.9, 130.5, 130.1, 128.7, 128.4, 128.1, 127.5, 127.2, 120.3,
114.9, 93.8, 89.0, 70.2 (fewer 13C signals were observed due to signal
overlapping); IR (CHCl3, cm−1) ν 3063, 3017, 2196, 1639, 1516, 1300,
1240, 1009, 758; HRMS (ESI) calcd for C28H21O2 (M + H)+ 389.1536,
found 389.1533.
1-(4′-Phenoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1ac). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This compound was obtained as an orange oil (322.8 mg, 86% yield): 1H
NMR (500 MHz, CDCl3) δ 7.93 (d, J = 7.7 Hz, 1H), 7.61 (d, J = 7.5 Hz,
1H), 7.44−7.49 (m, 2H), 7.42−7.43 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H),
7.31−7.35 (m, 4H), 7.22 (t, J = 7.7 Hz, 2H), 7.07 (t, J = 7.4 Hz, 1H), 7.03
(d, J = 8.3 Hz, 2H), 6.82 (d, J = 8.2 Hz, 2H); 13C NMR (125 MHz,
CDCl3) δ 180.8, 157.5, 156.9, 142.2, 138.2, 135.3, 133.1, 132.3, 131.1,
131.0, 130.7, 130.1, 130.0, 128.6, 127.5, 123.6, 120.2, 119.2, 118.6, 93.8,
89.1; IR (CHCl3, cm−1) ν 3061, 2196, 1636, 1591, 1488, 1304, 1239,
758, 689; HRMS (ESI) calcd for C27H19O2 (M + H)+ 375.1380, found
375.1378.
1-(4′-Fluoro-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1ad).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow oil (251.5 mg, 84% yield): 1H NMR
(500 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H),
7.43 (t, J = 7.4 Hz, 1H), 7.31−7.35 (m, 4H), 7.25−7.26 (m, 4H), 7.05 (t,
1-(2-Bromo-5-fluorophenyl)-3-phenylprop-2-yn-1-one (4f). Eluent
of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a yellow solid (357.3 mg, 59% yield): mp
59.2−60.1 °C; 1H NMR (500 MHz, CDCl3) δ 7.74 (dd, J = 8.8, 3.2 Hz,
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J = 8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 180.4, 162.7 (d, JC−F
=
1520, 1299, 1248, 1026, 758; HRMS (ESI) calcd for C23H19O3 (M +
H)+ 343.1329, found 343.1332.
247.0 Hz), 141.7, 137.9, 136.6 (d, JC−F = 3.5 Hz), 133.0, 132.4, 131.20
(d, JC−F = 1.9 Hz), 131.15, 130.6 (d, JC−F = 36.4 Hz), 128.6, 127.7, 120.0,
115.5, 115.3, 94.0, 88.9; IR (CHCl3, cm−1) ν 3063, 3020, 2197, 1642,
1513, 1303, 1223, 1204, 1010, 837, 758; HRMS (ESI) calcd for
C21H14FO (M + H)+ 301.1023, found 301.1023.
1-(4′-Chloro-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1ae).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
compound was obtained as a yellow oil (233.2 mg, 74% yield): 1H NMR
(500 MHz, CDCl3) δ 8.03 (dd, J = 7.7, 0.7 Hz, 1H), 7.60 (dt, J = 7.5, 1.2
Hz, 1H), 7.51 (dt, J = 7.7, 1.0 Hz, 1H), 7.38−7.42 (m, 4H), 7.29−7.35
(m, 6H); 13C NMR (125 MHz, CDCl3) δ 180.2, 141.6, 139.1, 137.7,
134.2, 133.0, 132.5, 131.2, 130.9, 130.8, 130.6, 128.64, 128.62, 128.0,
120.0, 94.3, 88.9; IR (CHCl3, cm−1) ν 3061, 3023, 2194, 1644, 1591,
1470, 1299, 1203, 1008, 758; HRMS (ESI) calcd for C21H14ClO (M +
H)+ 317.0728, found 317.0726.
3-Phenyl-1-(3′,4′,5′-trimethoxy-[1,1′-biphenyl]-2-yl)prop-2-yn-1-
one (1e). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as a colorless crystal (223.4 mg, 60%
yield): mp 121.0−122.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.89 (d, J =
7.9 Hz, 1H), 7.59 (dt, J = 7.7, 1.3 Hz, 1H), 7.46−7.50 (m, 2H), 7.35−
7.38 (m, 1H), 7.25−7.30 (m, 4H), 6.63 (s, 2H), 3.86 (s, 6H), 3.69 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 181.0, 153.3, 142.9, 138.5, 138.0,
136.3, 133.0, 132.3, 130.71, 130.69, 129.9, 128.6, 127.7, 120.3, 107.2,
93.7, 88.8, 60.9, 56.4; IR (CHCl3, cm−1) ν 3016, 2938, 2836, 2198, 1638,
1587, 1461, 1300, 1239, 1128, 1010, 760; HRMS (ESI) calcd for
C24H21O4 (M + H)+ 373.1434, found 373.1436.
1-(4′-Methoxy-3′,5′-dimethyl-[1,1′-biphenyl]-2-yl)-3-phenylprop-
2-yn-1-one (1f). Eluent of column chromatography: hexanes/ethyl
acetate 10:1. This product was obtained as a yellow oil (239.6 mg, 70%
yield): 1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.6 Hz, 1H), 7.56 (t, J
= 7.4 Hz, 1H), 7.41−7.45 (m, 2H), 7.34−7.36 (m, 1H), 7.23- 7.28 (m,
4H), 7.06 (s, 2H), 3.48 (s, 3H), 2.26 (s, 6H); 13C NMR (125 MHz,
CDCl3) δ 181.0, 157.0, 142.9, 138.3, 136.1, 133.0, 132.2, 130.9, 130.5,
130.3, 129.8, 128.4, 127.3, 120.4, 93.6, 89.0, 59.5, 16.3 (fewer 13C signals
were observed due to signal overlapping); IR (CHCl3, cm−1) ν 3017,
2935, 2199, 1637, 1472, 1300, 1234, 1010, 760; HRMS (ESI) calcd for
C24H21O2 (M + H)+ 341.1536, found 341.1536.
1-(4′-(Methylthio)-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1af). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (241.8 mg, 74% yield): H
NMR (500 MHz, CDCl3) δ 7.93 (dd, J = 7.8, 1.2 Hz, 1H), 7.55 (dt, J =
7.5, 1.3 Hz, 1H), 7.44 (dt, J = 7.6, 1.3 Hz, 1H), 7.38 (dd, J = 7.8, 1.1 Hz,
1H), 7.30−7.36 (m, 3H), 7.24−7.27 (m, 4H), 7.20−7.22 (m, 2H), 2.38
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.6, 142.4, 138.7, 137.9,
137.3, 133.0, 132.5, 131.1, 130.6, 130.4, 130.2, 128.5, 127.6, 126.5, 120.2,
94.2, 89.0, 15.9; IR (CHCl3, cm−1) ν 3060, 2982, 2922, 2198, 1734,
1642, 1293, 1243, 1010, 824, 690; HRMS (ESI) calcd for C22H17OS (M
+ H)+ 329.0995, found 329.0994.
1-(4,4′-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1g). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (212.0 mg, 62% yield): H
NMR (500 MHz, CDCl3) δ 7.43 (d, J = 2.7 Hz, 1H), 7.30−7.35 (m,
4H), 7.21−7.28 (m, 4H), 7.12 (dd, J = 8.5, 2.6 Hz, 1H), 6.92 (d, J = 8.7
Hz, 2H), 3.88 (s, 3H), 3.74(s, 3H); 13C NMR (125 MHz, CDCl3) δ
180.7, 159.4, 158.7, 138.7, 135.4, 133.1, 132.7, 132.3, 131.0, 130.5, 128.4,
120.3, 119.1, 114.0, 113.9, 94.1, 89.0, 55.8, 55.4; IR (CHCl3, cm−1) ν
3016, 2836, 2203, 1637, 1603, 1489, 1290, 1033, 757; HRMS (ESI)
calcd for C23H19O3 (M + H)+ 343.1329, found 343.1332.
1-(4′-Methyl-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1ag). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (228.1 mg, 77% yield): H
NMR (500 MHz, CDCl3) δ 7.96 (dd, J = 7.7, 0.7 Hz, 1H), 7.59 (dt, J =
7.6, 1.2 Hz, 1H), 7.46 (dt, J = 7.6, 0.8 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H),
7.37 (t, J = 7.3 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 8.0 Hz, 2H),
7.22−7.24 (m, 4H), 2.34 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.9,
143.0, 138.1, 137.9, 137.7, 133.1, 132.4, 131.2, 130.5, 130.2, 129.7, 129.3,
128.4, 127.4, 120.4, 93.9, 89.0, 21.4; IR (CHCl3, cm−1) ν 3060, 3023,
2922, 2198, 1645, 1592, 1489, 1442, 1300, 1202, 1008, 819, 757, 690;
HRMS (ESI) calcd for C22H17O (M + H)+ 297.1274, found 297.1273.
1-(2′-Methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1b). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1-([1,1′-Biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1h). Eluent of
column chromatography: hexanes/ethyl acetate 10:1. This product was
1
obtained as a yellow oil (208.3 mg, 74% yield): H NMR (500 MHz,
CDCl3) δ 7.96 (dd, J = 7.7, 0.6 Hz, 1H), 7.56 (dt, J = 7.5, 1.1 Hz, 1H),
7.38−7.47 (m, 6H), 7.31−7.34 (m, 2H), 7.22−7.26 (m, 4H); 13C NMR
(125 MHz, CDCl3) δ 180.7, 142.8, 140.4, 138.0, 133.0, 132.2, 131.1,
130.5, 130.1, 129.6, 128.44, 128.37, 127.9, 127.5, 120.1, 93.9, 88.9; IR
(CHCl3, cm−1) ν 3060, 3020, 2196, 1642, 1303, 1202, 1010, 748, 697;
HRMS (ESI) calcd for C21H15O (M + H)+ 283.1117, found 283.1124.
1-(3′-Methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1i). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (251.3 mg, 80% yield): H
NMR (500 MHz, CDCl3) δ 7.97 (dd, J = 7.8, 1.0 Hz, 1H), 7.61 (dt, J =
7.6, 1.3 Hz, 1H), 7.46 (dt, J = 7.7, 1.0 Hz, 1H), 7.37−7.40 (m, 3H),
7.29−7.34 (m, 5H), 7.10 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H),
3.75 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.1, 156.5, 138.4, 138.3,
133.2, 132.6, 131.7, 130.60, 130.55, 129.8, 129.6, 129.3, 128.5, 127.6,
121.3, 120.4, 110.8, 92.0, 88.5, 55.3; IR (CHCl3, cm−1) ν 3064, 3014,
2960, 2935, 2836, 2198, 1645, 1487, 1299, 1025, 753; HRMS (ESI)
calcd for C22H17O2 (M + H)+ 313.1223, found 313.1223.
1-(2′,4′-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-
one (1c). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as a yellow oil (257.9 mg, 75% yield):
1H NMR (500 MHz, CDCl3) δ 7.95 (dd, J = 7.8, 0.8 Hz, 1H), 7.58 (dt, J
= 7.5, 1.1 Hz, 1H), 7.43 (dt, J = 7.5, 0.7 Hz, 1H), 7.35−7.38 (m, 2H),
7.28−7.33 (m, 5H), 6.60 (dd, J = 8.3, 2.3 Hz, 1H), 6.45 (d, J = 2.3 Hz,
1H), 3.78 (s, 3H), 3.72 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.3,
161.3, 157.7, 138.3, 138.2, 133.1, 132.6, 131.6, 131.1, 130.5, 129.2, 128.4,
127.2, 122.4, 120.5, 105.1, 98.7, 91.9, 88.5, 55.6, 55.3; IR (CHCl3, cm−1)
ν 3009, 2958, 2935, 2834, 2198, 1610, 1461, 1304, 1207, 1158, 1034,
759; HRMS (ESI) calcd for C23H19O3 (M + H)+ 343.1329, found
343.1329.
1-(3′,4′-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-
one (1d). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This compound was obtained as a yellow oil (256.6 mg, 75%
yield): 1H NMR (500 MHz, CDCl3) δ 7.91 (dd, J = 8.2, 1.4 Hz, 1H),
7.57 (dt, J = 7.5, 1.3 Hz, 1H), 7.43−7.46 (m, 2H), 7.34−7.35 (m, 1H),
7.23−7.29 (m, 4H), 6.88−6.98 (m, 3H), 3.88 (s, 3H), 3.83 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 180.9, 149.1, 148.8, 142.6, 138.2, 133.2,
132.9, 132.2, 130.9, 130.5, 129.9, 128.4, 127.3, 122.3, 120.2, 113.0, 111.3,
93.6, 88.9, 56.1, 56.0; IR (CHCl3, cm−1) ν 3019, 2936, 2835, 2196, 1638,
1
This product was obtained as a yellow oil (214.1 mg, 69% yield): H
NMR (500 MHz, CDCl3) δ 7.94 (d, J = 7.8 Hz, 1H), 7.59 (dt, J = 7.5, 1.0
Hz, 1H), 7.48 (dt, J = 7.6, 0.6, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.36−7.39
(m, 1H), 7.28−7.34 (m, 5H), 6.98−7.00 (m, 2H), 6.87 (dd, J = 8.4, 1.8
Hz, 1H), 3.80 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.9, 159.7,
142.7, 142.0, 138.3, 133.1, 132.3, 131.0, 130.6, 130.0, 129.6, 128.5, 127.7,
122.5, 120.3, 115.2, 113.6, 93.9, 88.9, 55.5; IR (CHCl3, cm−1) ν 3061,
2956, 2935, 2834, 2196, 1641, 1299, 1209, 1008, 757, 693; HRMS (ESI)
calcd for C22H17O2 (M + H)+ 313.1223, found 313.1226.
1-(3′-Fluoro-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1j).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow oil (230.7 mg, 77% yield): 1H NMR
(500 MHz, CDCl3) δ 8.02 (d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H),
7.52 (t, J = 7.5 Hz, 1H), 7.39−7.42 (m, 2H), 7.30−7.37 (m, 5H), 7.15−
7.19 (m, 2H), 7.03 (dt, J = 5.8, 1.4 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 180.2, 162.7 (d, JC−F = 246.2 Hz), 142.8 (d, JC−F = 7.9 Hz),
141.4 (d, JC−F = 1.6 Hz), 137.9, 133.0, 132.4, 131.0, 130.8, 130.4, 129.9
(d, JC−F = 8.4 Hz), 128.6, 128.0, 125.6 (d, JC−F = 2.7 Hz), 120.0, 116.3 (d,
JC−F = 21.8 Hz), 114.7 (d, JC−F = 21.0 Hz), 94.0, 88.8; IR (CHCl3, cm−1)
ν 3065, 2925, 2196, 1769, 1643, 1587, 1487, 1292, 1266, 757, 691;
HRMS (ESI) calcd for C21H14FO (M + H)+ 301.1023, found 301.1026.
1-(3′,5′-Dimethyl-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1k). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This compound was obtained as a yellow oil (255.0 mg, 82% yield): 1H
NMR (500 MHz, CDCl3) δ 7.92 (d, J = 7.8 Hz, 1H), 7.56 (dt, J = 7.5, 1.0
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Hz, 1H), 7.41−7.46 (m, 2H), 7.35−7.38 (m, 1H), 7.23−7.29 (m, 4H),
7.03 (s, 2H), 6.95 (s, 1H), 2.32 (s, 6H); 13C NMR (125 MHz, CDCl3) δ
181.0, 143.3, 140.6, 138.3, 138.0, 133.0, 132.2, 131.1, 130.5, 130.0, 129.7,
128.4, 127.6, 127.4, 120.4, 93.7, 89.0, 21.5; IR (CHCl3, cm−1) ν 3020,
2920, 2198, 1644, 1594, 1301, 1204, 1010, 758, 693; HRMS (ESI) calcd
for C23H19O (M + H)+ 311.1430, found 311.1428.
NMR (125 MHz, CDCl3) δ 180.9, 161.6, 142.7, 140.6, 138.3, 135.2,
132.1, 131.2, 130.1, 129.7, 128.5, 127.9, 127.5, 114.2, 112.0, 95.3, 89.0,
55.5; IR (CHCl3, cm−1) ν 3019, 2841, 2190, 1635, 1601, 1510, 1292,
1253, 1215, 1171, 1031, 760; HRMS (ESI) calcd for C22H17O2 (M +
H)+ 313.1223, found 313.1222.
1-(4′-Chloro-[1,1′-biphenyl]-2-yl)-3-(4-methoxyphenyl)prop-2-
yn-1-one (1r). Eluent of column chromatography: hexanes/ethyl
acetate 10:1. This product was obtained as a yellow oil (231.9 mg,
67% yield): 1H NMR (500 MHz, CDCl3) δ 8.00 (dd, J = 7.7, 0.8 Hz,
1H), 7.58 (dt, J = 7.5, 1.1 Hz, 1H), 7.48 (dt, J = 7.5, 0.8 Hz, 1H), 7.33−
7.38 (m, 5H), 7.24−7.26 (m, 2H), 6.82 (d, J = 8.7 Hz, 2H), 3.82 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 180.1, 161.7, 141.4, 139.2, 137.8, 135.1,
1-(3′,5′-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-
one (1l). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (257.8 mg, 75% yield): H
NMR (500 MHz, CDCl3) δ 7.91 (d, J = 7.7 Hz, 1H), 7.58 (dt, J = 7.6, 1.1
Hz, 1H), 7.47 (dd, J = 16.0, 7.7 Hz, 2H), 7.36−7.39 (m, 1H), 7.27−7.32
(m, 4H), 6.57 (d, J = 2.2 Hz, 2H), 6.41−6.42 (m, 1H), 3.76 (s, 6H); 13C
NMR (125 MHz, CDCl3) δ 180.6, 160.7, 142.7, 142.6, 138.3, 133.0,
132.1, 130.6, 130.5, 129.7, 128.4, 127.7, 120.2, 108.0, 100.0, 93.6, 88.7,
55.4; IR (CHCl3, cm−1) ν 3011, 2961, 2938, 2838, 2198, 1638, 1590,
1458, 1420, 1300, 1204, 1156, 1063, 1027, 1013; HRMS (ESI) calcd for
C23H19O3 (M + H)+ 343.1329, found 343.1329.
1-(2′,3′-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-
one (1m). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as a yellow oil (256.6 mg, 75% yield):
1H NMR (500 MHz, CDCl3) δ 8.05 (d, J = 7.8 Hz, 1H), 7.59 (t, J = 7.3
Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.34−7.39 (m,
3H), 7.27−7.31 (m, 2H), 7.12 (t, J = 7.8 Hz, 1H), 6.92 (d, J = 7.1 Hz,
1H), 6.90 (d, J = 8.2 Hz, 1H), 3.81 (s, 3H), 3.57 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 179.6, 152.7, 146.2, 138.4, 137.9, 134.8, 133.0, 132.2,
131.6, 130.4, 129.9, 128.4, 127.6, 124.2, 122.9, 120.4, 112.6, 92.5, 88.5,
60.4, 55.9; IR (CHCl3, cm−1) ν 3007, 2936, 2197, 1644, 1476, 1301,
1264, 1010, 690; HRMS (ESI) calcd for C23H19O3 (M + H)+ 343.1329,
found 343.1330.
1-(3′-Methoxy-4′-methyl-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-
yn-1-one (1n). Eluent of column chromatography: hexanes/ethyl
acetate 10:1. This product was obtained as a yellow oil (262.7 mg, 80%
yield): 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = 7.3 Hz, 1H), 7.59 (t, J
= 7.5 Hz, 1H), 7.46−7.49 (m, 2H), 7.36−7.38 (m, 1H), 7.29 (t, J = 7.7
Hz, 2H), 7.23−7.24 (m, 2H), 7.19 (d, J = 7.4 Hz, 1H), 6.96 (d, J = 7.5
Hz, 1H), 6.92 (s, 1H), 3.84 (s, 3H), 2.23 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 180.8, 157.6, 143.0, 139.2, 138.1, 132.8, 132.2, 130.9, 130.6,
130.4, 129.9, 128.4, 127.4, 126.5, 121.8, 120.2, 111.5, 93.7, 88.8, 55.4,
16.1; IR (CHCl3, cm−1) ν 3061, 3011, 2938, 2197, 1641, 1301, 1225,
1204, 1134, 1011; HRMS (ESI) calcd for C23H19O2 (M + H)+ 327.1380,
found 327.1379.
134.0, 132.3, 131.1, 130.9, 130.5, 128.5, 127.8, 114.3, 111.7, 95.5, 88.9,
55.5; IR (CHCl3, cm−1) ν 3012, 2962, 2933, 2839, 2189, 1639, 1603,
1510, 1292, 1253, 1207, 1171, 1090, 1028, 833, 757; HRMS (ESI) calcd
for C22H16ClO2 (M + H)+ 347.0833, found 347.0834.
Methyl 4-(3-(3′-Methoxy-[1,1′-biphenyl]-2-yl)-3-oxoprop-1-yn-1-
yl)benzoate (1s). Eluent of column chromatography: hexanes/ethyl
acetate 5:1. This product was obtained as a yellow oil (237.0 mg, 64%
yield); 1H NMR (500 MHz, CDCl3) δ 7.91−7.95 (m, 3H), 7.60 (dt, J =
7.5, 1.2 Hz, 1H), 7.48 (dt, J = 7.7, 1.0 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H),
7.29−7.33 (m, 3H), 6.98−6.99 (m, 2H), 6.85−6.88 (m, 1H), 3.91 (s,
3H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.5, 166.3, 159.7,
142.9, 141.9, 138.0, 132.8, 132.5, 131.4, 131.0, 130.0, 129.6, 129.4, 127.8,
124.8, 122.6, 115.2, 113.7, 91.9, 90.5, 55.5, 52.6; IR (CHCl3, cm−1) ν
3018, 2952, 2837, 2199, 1724, 1640, 1437, 1280, 1213, 1107, 1005, 758;
HRMS (ESI) calcd for C24H19O4 (M + H)+ 371.1278, found 371.1272.
1-(3′-Methoxy-[1,1′-biphenyl]-2-yl)-3-(thiophen-3-yl)prop-2-yn-
1-one (1t). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as an orange oil (236.1 mg, 74% yield):
1H NMR (500 MHz, CDCl3) δ 7.92 (dd, J = 7.8, 0.9 Hz, 1H), 7.59 (dt, J
= 7.5, 1.3 Hz, 1H), 7.48 (dd, J = 7.6, 1.1 Hz, 1H), 7.43−7.46 (m, 2H),
7.32 (t, J = 7.8 Hz, 1H), 7.22 (dd, J = 5.0, 3.1 Hz, 1H), 6.98−7.00 (m,
2H), 6.94 (dd, J = 5.0, 1.0 Hz, 1H), 6.88−6.90 (m, 1H), 3.81 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 180.6, 159.6, 142.7, 142.0, 138.2, 133.3,
130.9, 130.4, 129.9, 129.5, 127.7, 125.9, 122.5, 119.6, 115.2, 113.6, 89.3,
89.1, 55.5, 55.4; IR (CHCl3, cm−1) ν 3106, 3005, 2937, 2835, 2196,
1636, 1278, 1215, 1019, 787, 759; HRMS (ESI) calcd for C20H15O2S (M
+ H)+ 319.0787, found 319.0788.
3-(Cyclohex-1-en-1-yl)-1-(3′-methoxy-[1,1′-biphenyl]-2-yl)prop-
2-yn-1-one (1u). Eluent of column chromatography: hexanes/ethyl
acetate 10:1. This product was obtained as a yellow oil (154.4 mg, 49%
yield): 1H NMR (500 MHz, CDCl3) δ 7.86 (dd, J = 7.7, 1.2 Hz, 1H),
7.54 (td, J = 7.6, 1.2 Hz, 1H), 7.43 (td, J = 7.6, 1.2 Hz, 1H), 7.39 (dd, J =
7.7, 1.2 Hz, 1H), 7.30 (dd, J = 8.8, 7.6 Hz, 1H), 6.90−6.94 (m, 3H),
6.17−6.18 (m, 1H), 3.82 (s, 3H), 2.05−2.07 (m, 2H), 1.89−1.90 (m,
2H), 1.52−1.57 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 181.0, 159.6,
142.4, 142.2, 142.0, 138.6, 131.9, 130.8, 129.9, 129.3, 127.5, 122.3, 119.1,
114.9, 113.5, 96.4, 87.3, 55.4, 28.2, 26.2, 22.0, 21.2; IR (CHCl3, cm−1) ν
3016, 2938, 2182, 1640, 1599, 1473, 1288, 1215, 1049, 757; HRMS
(ESI) calcd for C22H21O2 (M + H)+ 317.1536, found 317.1535.
General Procedure for the ICl-Induced Intramolecular
Electrophilic Cyclization of 1-([1,1′-Biphenyl]-2-yl)alkynones
(1). A 4-dram vial was charged with 1-([1,1′-biphenyl]-2-yl)alkynones
(1, 0.5 mmol, 1 equiv), Na2HPO4 (142.0 mg, 1.0 mmol, 2 equiv), ICl
(243.6 mg, 1.5 mmol, 3 equiv), and acetonitrile (5 mL). The reaction
mixture was stirred at room temperature for 1 h. The reaction mixture
was diluted with 25 mL of ethyl acetate and washed with a 0.5 M
aqueous Na2S2O3 solution (30 mL), and the aqueous phase was
extracted with ethyl acetate (2 × 15 mL). The combined organic layers
were dried over anhydrous MgSO4 and concentrated using a rotary
evaporator under reduced pressure (20 mmHg). The subsequent
residue was purified by flash column chromatography on silica gel
(eluent: hexanes/ethyl acetate) to afford the corresponding cyclization
product.
1-(4-Fluoro-3′-methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-
1-one (1o). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as an orange oil (266.2 mg, 81% yield):
1H NMR (500 MHz, CDCl3) δ 7.62 (dd, J = 9.0, 2.7 Hz, 1H), 7.37−7.43
(m, 2H), 7.27−7.33 (m, 6H), 6.94−6.96 (m, 2H), 6.87 (dd, J = 8.5, 2.2
Hz, 1H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.2 (d, JC−F
=
1.7 Hz), 161.9 (d, JC−F = 248.6 Hz), 151.6, 140.9, 139.5 (d, JC−F = 6.3
Hz), 138.7 (d, JC−F = 3.4 Hz), 133.1, 132.7 (d, JC−F = 7.5 Hz), 130.8,
129.6, 128.4, 122.5, 119.9, 119.2 (d, JC−F = 21.2 Hz), 116.5 (d, JC−F
=
23.5 Hz), 115.3, 113.6, 94.5, 88.5, 55.3; IR (CHCl3, cm−1) ν 3065, 3016,
2937, 2836, 2200, 1640, 1609, 1477, 1294, 1226, 1161, 1044, 758;
HRMS (ESI) calcd for C22H16FO2 (M + H)+ 331.1129, found 331.1129.
1-(3′,4-Dimethoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one
(1p). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as an orange oil (200.3 mg, 58% yield): 1H
NMR (500 MHz, CDCl3) δ 7.44 (d, J = 2.6 Hz, 1H), 7.36−7.39 (m,
2H), 7.25−7.32 (m, 5H), 7.14 (dd, J = 8.5, 2.8 Hz, 1H), 6.97−6.99 (m,
2H), 6.85 (dd, J = 8.4, 2.1 Hz, 1H), 3.91 (s, 3H), 3.80 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 180.7, 159.6, 159.1, 141.8, 139.1, 135.5, 133.1,
132.2, 130.6, 129.5, 128.4, 122.7, 120.3, 118.9, 115.4, 114.0, 113.3, 94.1,
88.9, 55.8, 55.4; IR (CHCl3, cm−1) ν 3001, 2938, 2835, 2202, 1639,
1604, 1476, 1290, 1231, 1029, 761, 687; HRMS (ESI) calcd for
C23H19O3 (M + H)+ 343.1329, found 343.1329.
1-([1,1′-Biphenyl]-2-yl)-3-(4-methoxyphenyl)prop-2-yn-1-one
(1q). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as an orange oil (285.5 mg, 91% yield): 1H
NMR (500 MHz, CDCl3) δ 7.96 (d, J = 7.4 Hz, 1H), 7.59 (dt, J = 7.4, 0.6
Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.40−7.46 (m, 5H), 7.33−7.36 (m,
1H), 7.21 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H); 13C
3′-Iodo-2′-phenyl-4′H-spiro[cyclohexa[2,5]diene-1,1′-naphtha-
lene]-4,4′-dione (3aa). Eluent of column chromatography: hexanes/
ethyl acetate 3:1. This product was obtained as a white solid (208.9 mg,
99% yield): mp 228.2−229.0 °C; 1H NMR (500 MHz, CDCl3) δ 8.32
(dd, J = 7.9, 1.3 Hz, 1H), 7.60 (dt, J = 7.5, 1.5 Hz, 1H), 7.53 (dt, J = 7.9,
3460
dx.doi.org/10.1021/jo5001803 | J. Org. Chem. 2014, 79, 3452−3464

The Journal of Organic Chemistry
Article
1.2 Hz, 1H), 7.32−7.38 (m, 3H), 7.28−7.30 (m, 1H), 6.99−7.03 (m,
2H), 6.73−6.76 (m, 2H), 6.29−6.33 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 184.6, 178.8, 160.5, 147.8, 141.5, 138.4, 133.9, 130.3, 129.4,
129.14, 129.05, 128.25, 128.23, 127.4, 114.7, 53.3 (fewer 13C signals
were observed due to signal overlapping); IR (CHCl3, cm−1) ν 3048,
3024, 1659, 1620, 1594, 1570, 1393, 1300, 1243, 1219, 1174, 1126,
1029, 759; HRMS (ESI) calcd for C21H14IO2 (M + H)+ 425.0033, found
425.0030.
9-Fluoro-6-iodo-7-phenyldibenzocyclohepten-5-one (2ad). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a light yellow solid (58.9 mg, 28% yield); mp
160.8−162.0 °C: 1H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 7.8 Hz,
1H), 7.71 (dt, J = 7.4, 1.6 Hz, 1H), 7.67 (dd, J = 8.9, 5.9 Hz, 1H), 7.62
(dd, J = 7.7, 1.3 Hz, 1H), 7.56 (dt, J = 7.5, 1.0 Hz, 1H), 7.42−7.47 (m,
3H), 7.21−7.22 (m, 2H), 7.10−7.14 (m, 1H), 6.81 (dd, J = 10.3, 2.6 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 195.3, 161.4 (d, JC−F = 248.8 Hz),
149.3, 145.0, 139.5, 136.3 (d, JC−F = 7.7 Hz), 135.7, 133.9 (d, JC−F = 3.0
Hz), 133.3 (d, JC−F = 8.4 Hz), 131.9, 129.3, 129.2, 128.9, 128.82, 128.76,
127.2, 118.1 (d, JC−F = 23.9 Hz), 116.3 (d, JC−F = 21.6 Hz), 103.4; IR
(CHCl3, cm−1) ν 3061, 3020, 2924, 2852, 1675, 1597, 1478, 1233, 1207,
756; HRMS (ESI) calcd for C21H13FIO (M + H)+ 426.9990, found
426.9993.
9-Chloro-6-iodo-7-phenyldibenzocyclohepten-5-one (2ae). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow solid (160.5 mg, 73% yield) from 1ae;
mp 213.7−216.3 °C: 1H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.8 Hz,
1H), 7.72 (t, J = 7.5 Hz, 1H), 7.56−7.63 (m, 3H), 7.41−7.47 (m, 3H),
7.37 (dd, J = 8.4, 2.1 Hz, 1H), 7.22 (s, broad, 2H), 7.09 (d, J = 2.2 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 195.2, 149.0, 144.8, 139.6, 136.0,
135.9, 135.5, 133.7, 132.7, 132.0, 131.3, 129.3, 129.1, 128.9, 128.8, 127.2,
103.5 (fewer 13C signals were observed due to signal overlapping); IR
(CHCl3, cm−1) ν 3061, 3020, 2925, 2853, 1676, 1590, 1475, 1437, 1258,
1108, 756, 702; HRMS (ESI) calcd for C21H13ClIO (M + H)+ 442.9694,
found 442.9697.
6-Iodo-9-methyl-7-phenyldibenzocyclohepten-5-one (2aga). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a white solid (179.1 mg, 85% yield); mp 152.3−
153.3 °C: 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz, 1H), 7.69
(td, J = 7.7, 1.8 Hz, 1H), 7.62 (dd, J = 7.7, 1.6 Hz, 1H), 7.59 (d, J = 8.1
Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.39−7.46 (m, 3H), 7.22−7.25 (m,
3H), 6.91 (d, J = 1.8 Hz, 1H), 2.24 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 195.7, 150.4, 145.6, 139.5, 137.6, 136.5, 134.9, 134.3, 132.0,
131.7, 131.2, 129.8, 129.3, 129.1, 128.6, 128.41, 128.35, 127.0, 102.0,
21.3; IR (CHCl3, cm−1) ν 3058, 3022, 2920, 1676, 1592, 1478, 1439,
1294, 1260, 1218, 1114, 827, 755; HRMS (ESI) calcd for C22H16IO (M
+ H)+ 423.0240, found 423.0241.
9-(Chloromethyl)-6-iodo-7-phenyldibenzocyclohepten-5-one
(2agb). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as a yellow solid (25.6 mg, 11% yield); mp
170.8−172.0 °C: 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz,
1H), 7.70−7.74 (m, 2H), 7.62 (d, J = 7.7 Hz, 1H), 7.57 (t, J = 7.2 Hz,
1H), 7.42−7.47 (m, 4H), 7.23−7.24 (m, 2H), 7.08 (d, J = 1.3 Hz, 1H),
4.45 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 195.5, 149.7, 145.1, 139.8,
137.6, 137.0, 135.9, 134.8, 131.93, 131.90, 131.7, 129.4, 129.3, 129.1,
128.84, 128.78, 128.68, 127.2, 102.8, 45.5; IR (CHCl3, cm−1) ν 3020,
2928, 1679, 1440, 1217, 758; HRMS (ESI) calcd for C22H15ClIO (M +
H)+ 456.9851, found 456.9853.
3′-Iodo-2′-phenyl-4′H-spiro[cyclohexa[2,4]diene-1,1′-naphtha-
lene]-4′,6-dione (3b). Eluent of column chromatography: hexanes/
ethyl acetate 5:1. This product was obtained as a yellow solid (66.3 mg,
31% yield): sublime at 189.0−190.0 °C; 1H NMR (500 MHz, CDCl3) δ
8.31−8.33 (m, 1H), 7.48−7.53 (m, 2H), 7.32−7.39 (m, 3H), 7.15−7.16
(m, 1H), 7.05 (s, 1H), 6.92−6.98 (m, 2H), 6.32−6.37 (m, 2H), 6.04 (d,
J = 9.7 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 195.1, 179.8, 159.4,
142.8, 141.8, 141.5, 139.3, 133.6, 129.2, 129.1, 128.9, 128.6, 127.5, 126.5,
126.3, 122.5, 114.6, 63.8 (fewer 13C signals were observed due to signal
overlapping); IR (CHCl3, cm−1) ν 3064, 3017, 2927, 1664, 1594, 1301,
1221, 1132, 753; HRMS (ESI) calcd for C21H14IO2 (M + H)+ 425.0033,
found 425.0032.
3′-Iodo-2-methoxy-2′-phenyl-4′H-spiro[cyclohexa[2,5]diene-1,1′-
naphthalene]-4,4′-dione (3c). Eluent of column chromatography:
hexanes/ethyl acetate 5:1. This product was obtained as a yellow solid
from 1c (196.3 mg, 86% yield): mp 258.4−259.4 °C; H NMR (500
MHz, CDCl3) δ 8.32 (dd, J = 7.8, 0.7 Hz, 1H), 7.59 (dt, J = 7.6, 1.0 Hz,
1H), 7.53 (t, J = 7.2 Hz, 1H), 7.31−7.36 (m, 3H), 7.23 (d, J = 7.7 Hz,
1H), 6.99 (d, J = 7.0 Hz, 1H), 6.92−6.93 (m, 1H), 6.43 (d, J = 9.6 Hz,
1H), 6.26 (dd, J = 9.7, 0.5 Hz, 1H), 5.56 (s, 1H), 3.59 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 187.2, 179.0, 172.8, 160.2, 143.5, 141.1, 139.2,
134.0, 129.3, 129.2, 128.9, 128.8, 128.7, 128.6, 128.2, 127.2, 126.94,
126.91, 115.1, 105.1, 56.2, 55.5; IR (CHCl3, cm−1) ν 3017, 2941, 2846,
1655, 1592, 1453, 1338, 1302, 1221, 1080, 982, 856, 761; HRMS (ESI)
calcd for C22H16IO3 (M + H)+ 455.0139, found 455.0138.
1
6-Iodo-9,10-dimethoxy-7-phenyldibenzocyclohepten-5-one (2d).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow solid (135.4 mg, 58% yield): mp
1
187.5−188.0 °C; H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 7.9 Hz,
1H), 7.69 (dt, J = 7.4, 1.4 Hz, 1H), 7.62 (dd, J = 7.7, 1.3 Hz, 1H), 7.53
(dt, J = 7.5, 1.0 Hz, 1H), 7.37−7.45 (m, 3H), 7.23−7.24 (m, 2H), 7.13
(s, 1H), 6.51 (s, 1H), 3.96 (s, 3H), 3.57 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 195.3, 150.2, 149.0, 148.1, 145.8, 139.1, 136.3, 131.7, 131.4,
129.3, 128.9, 128.6, 128.43, 128.40, 127.8, 127.3, 114.3, 113.1, 100.1,
56.2, 55.8; IR (CHCl3, cm−1) ν 3020, 1669, 1516, 1262, 1216, 761;
HRMS (ESI) calcd for C23H18IO3 (M + H)+ 469.0295, found 469.0298.
3′-Iodo-3-methoxy-2′-phenyl-4′H-spiro[cyclohexa[2,5]diene-1,1′-
naphthalene]-4,4′-dione (3d). Eluent of column chromatography:
hexanes/ethyl acetate 5:1. This product was obtained as a white solid
1
(40.8 mg, 18% yield): mp 250.8−251.5 °C; H NMR (500 MHz,
CDCl3) δ 8.31 (dd, J = 7.9, 0.7 Hz, 1H), 7.59 (dt, J = 7.3, 1.1 Hz, 1H),
7.51 (t, J = 7.7 Hz, 1H), 7.32−7.34 (m, 3H), 7.29 (d, J = 7.8 Hz, 1H),
6.96−7.00 (m, 2H), 6.73 (dd, J = 9.8, 2.7 Hz, 1H), 6.33 (d, J = 9.8 Hz,
1H), 5.70 (d, J = 2.6 Hz, 1H), 3.62 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 179.9, 178.8, 161.6, 152.2, 147.9, 141.5, 139.8, 133.9, 130.1,
129.2, 129.1, 129.0, 128.3, 128.2, 128.1, 128.0, 127.5, 127.4, 116.0, 114.0,
55.4, 53.6; IR (CHCl3, cm−1) ν 3021, 1667, 1637, 1215, 760; HRMS
(ESI) calcd for C22H16IO3 (M + H)+ 455.0139, found 455.0138.
6-Iodo-8,9,10-trimethoxy-7-phenyldibenzocyclohepten-5-one
(2e). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as a yellow solid (223.7 mg, 90% yield): mp
1
172.4−173.6 °C; H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz,
1H), 7.65−7.68 (m, 1H), 7.49−7.51 (m, 2H), 7.31−7.34 (m, 2H),
7.24−7.28 (m, 3H), 6.85 (s, 1H), 3.94 (s, 3H), 3.74 (s, 3H), 3.05 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 197.0, 153.9, 152.1, 144.79,
144.76, 141.9, 140.8, 136.8, 134.4, 131.6, 129.0, 128.5, 128.4, 127.8,
127.7, 126.5, 123.2, 108.7, 98.4, 60.7, 59.5, 56.2; IR (CHCl3, cm−1) ν
3017, 2940, 2848, 1691, 1588, 1480, 1384, 1348, 1215, 1122, 1107, 759;
HRMS (ESI) calcd for C24H20IO4 (M + H)+ 499.0401, found 499.0403.
6-Iodo-9-methoxy-8,10-dimethyl-7-phenyldibenzocyclohepten-
5-one (2f). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as a yellow solid (93.9 mg, 40% yield):
mp 165.2−165.9 °C; 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz,
1H), 7.62 (dt, J = 7.5, 1.0 Hz, 1H), 7.48 (d, J = 7.5 Hz,1H), 7.43 (t, J = 7.4
Hz, 1H), 7.25−7.29 (m, 6H), 3.58 (s, 3H), 2.33 (s, 3H), 1.76 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 197.4, 156.9, 145.4, 142.8, 140.7, 137.3,
134.6, 134.0, 131.9, 131.5, 131.3, 131.0, 130.1, 128.4, 128.2, 127.9, 127.7,
126.3, 98.5, 60.0, 16.6, 15.9; IR (CHCl3, cm−1) ν 3019, 2963, 2934,
1694, 1592, 1471, 1444, 1254, 1202, 1117, 1072, 1003, 756; HRMS
(ESI) calcd for C24H20IO2 (M + H)+ 467.0502, found 467.0504.
3′-Iodo-3,5-dimethyl-2′-phenyl-4′H-spiro[cyclohexa[2,5]diene-
1,1′-naphthalene]-4,4′-dione (3f). Eluent of column chromatography:
hexanes/ethyl acetate 5:1. This product was obtained as a yellow crystal
1
(70.6 mg, 31% yield): mp 204.7−205.3 °C; H NMR (500 MHz,
CDCl3) δ 8.30 (dd, J = 8.0, 1.6 Hz, 1H), 7.57 (td, J = 7.5, 1.6 Hz, 1H),
7.49 (t, J = 7.6 Hz, 1H), 7.31−7.32 (m, 3H), 7.23 (d, J = 7.8 Hz, 1H),
6.92−6.94 (m, 2H), 6.48 (s, 2H), 1.81 (s, 6H); 13C NMR (125 MHz,
CDCl3) δ 185.9, 179.0, 162.1, 142.6, 141.7, 140.0, 136.9, 133.7, 129.0,
128.82, 128.80, 128.17, 128.14, 127.9, 127.3, 113.7, 53.3, 16.1; IR
(CHCl3, cm−1) ν 3009, 2921, 1659, 1641, 1596, 1450, 1297, 1241, 1122,
1038, 756; HRMS (ESI) calcd for C23H18IO2 (M + H)+ 453.0346, found
453.0345.
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Article
6-Iodo-3,9-dimethoxy-7-phenyl-5H-dibenzocyclohepten-5-one
(2g). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as a yellow crystal (18.7 mg, 8% yield): mp
174.2−175.1 °C; 1H NMR (500 MHz, CDCl3) δ 7.72 (d, J = 8.7 Hz,
1H), 7.59 (d, J = 8.8 Hz, 1H), 7.38−7.45 (m, 3H), 7.21−7.25 (m, 3H),
7.09 (d, J = 2.8 Hz, 1H), 6.96 (dd, J = 8.7, 2.6 Hz, 1H), 6.58 (d, J = 2.7
Hz, 1H), 3.92 (s, 3H), 3.64 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
195.5, 159.6, 158.0, 150.6, 145.9, 140.0, 135.1, 132.2, 130.6, 130.5, 129.4,
129.3, 128.7, 128.4, 119.6, 116.8, 115.0, 110.1, 102.1, 55.9, 55.4; IR
(CHCl3, cm−1) ν 3021, 2955, 2833, 1662, 1603, 1483, 1338, 1280, 1218,
1130, 1051, 1038, 755; HRMS (ESI) calcd for C23H18IO3 (M + H)+
469.0295, found 469.0296.
6-Iodo-8,10-dimethoxy-7-phenyldibenzocyclohepten-5-one (2l).
Three equivalents of I2 was used instead of ICl. Eluent of column
chromatography: hexanes/ethyl acetate 10:1. This product was obtained
as a yellow solid (114.0 mg, 49% yield): mp 180.5−181.4 °C; 1H NMR
(500 MHz, CDCl3) δ 7.89 (d, J = 7.9 Hz, 1H), 7.65−7.68 (m, 1H),
7.50−7.52 (m, 2H), 7.23−7.29 (m, 3H), 7.19−7.21 (m, 2H), 6.72 (d, J =
2.5 Hz, 1H), 6.37 (d, J = 2.5 Hz, 1H), 3.86 (s, 3H), 3.31 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 197.1, 160.4, 159.3, 145.0, 144.8, 140.9,
140.0, 136.8, 131.6, 128.9, 128.8, 128.7, 127.4, 127.2, 126.5, 118.7, 106.7,
99.6, 98.1, 55.73, 55.66; IR (CHCl3, cm−1) ν 3015, 2936, 2839, 1688,
1600, 1456, 1338, 1208, 1026, 758; HRMS (ESI) calcd for C23H18IO3
(M + H)+ 469.0295, found 469.0285.
3′-Iodo-6′-methoxy-2′-phenyl-4′H-spiro[cyclohexa[2,5]diene-
1,1′-naphthalene]-4,4′-dione (3g). Eluent of column chromatography:
hexanes/ethyl acetate 5:1. This product was obtained as a light yellow
solid (184.0 mg, 81% yield): mp 268.1−269.8 °C; 1H NMR (500 MHz,
CDCl3) δ 7.75 (d, J = 2.7 Hz, 1H), 7.32−7.37 (m, 3H), 7.14−7.20 (m,
2H), 6.99−7.01 (m, 2H), 6.68−6.71 (m, 2H), 6.27−6.30 (m, 2H), 3.90
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 184.7, 178.7, 160.7, 160.2,
148.0, 141.5, 130.4, 130.1, 129.7, 129.4, 129.1, 128.2, 127.4, 122.5, 114.5,
110.6, 55.9, 53.0; IR (CHCl3, cm−1) ν 3055, 3019, 2968, 1670, 1648,
1493, 1345, 1288, 1239, 1039, 863, 829; HRMS (ESI) calcd for
C22H16IO3 (M + H)+ 455.0139, found 455.0137.
6-Iodo-10,11-dimethoxy-7-phenyldibenzocyclohepten-5-one
(2m). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (207.3 mg, 89% yield): H
NMR (500 MHz, CDCl3) δ 8.05 (d, J = 7.9 Hz, 1H), 7.60 (t, J = 7.6 Hz,
1H), 7.50−7.55 (m, 2H), 7.37−7.42 (m, 3H), 7.22 (d, J = 6.3 Hz, 2H),
6.80 (q, J = 9.0 Hz, 2H), 3.87 (s, 3H), 3.34 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 196.5, 152.9, 149.8, 146.9, 145.1, 140.8, 132.3, 132.0,
130.3, 129.8, 129.4, 128.9, 128.7, 128.5, 128.3, 127.7, 125.8, 111.6, 99.7,
60.5, 56.1; IR (CHCl3, cm−1) ν 3017, 2939, 2838, 1679, 1590, 1486,
1289, 1218, 1132, 1018, 758, 702; HRMS (ESI) calcd for C23H18IO3 (M
+ H)+ 469.0295, found 469.0298.
6-Iodo-7-phenyldibenzocyclohepten-5-one (2h). Eluent of column
chromatography: hexanes/ethyl acetate 10:1. This product was obtained
as a yellow solid (183.7 mg, 90% yield): mp 131.5−132.2 °C; 1H NMR
(500 MHz, CDCl3) δ 7.86 (d, J = 7.9 Hz, 1H), 7.71 (ddd, J = 7.7, 7.4, 1.4
Hz, 2H), 7.63 (dd, J = 7.4, 1.4 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.40−
7.45 (m, 4H), 7.21−7.26 (m, 3H), 7.12 (dd, J = 8.1, 1.2 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ 195.6, 150.4, 145.6, 139.8, 137.6, 136.5,
134.6, 131.9, 131.8, 131.3, 129.4, 129.3, 128.8, 128.7, 128.6, 128.5, 127.8,
127.1, 102.1; IR (CHCl3, cm−1) ν 3061, 3019, 1676, 1595, 1441, 1217,
760; HRMS (ESI) calcd for C21H14IO (M + H)+ 409.0084, found
409.0085.
6-Iodo-10-methoxy-7-phenyldibenzocyclohepten-5-one (2i). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as an orange oil (191.5 mg, 87% yield); 1H NMR
(500 MHz, CDCl3) δ 7.85 (d, J = 7.7 Hz, 1H), 7.71 (dt, J = 7.6, 1.5 Hz,
1H), 7.63 (dd, J = 7.8, 1.4 Hz, 1H), 7.57 (t, J = 7.3 Hz, 1H), 7.39−7.44
(m, 3H), 7.22−7.23 (m, 2H), 7.17 (d, J = 2.6 Hz, 1H), 7.03 (d, J = 8.9
Hz, 1H), 6.77 (dd, J = 8.9, 2.7 Hz, 1H), 3.85 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 195.5, 159.2, 150.4, 145.9, 139.5, 139.2, 136.3, 134.0,
131.8, 129.4, 129.3, 129.0, 128.6, 128.4, 127.9, 127.3, 115.8, 113.9, 99.9,
55.7; IR (CHCl3, cm−1) ν 3009, 2840, 1671, 1602, 1490, 1338, 1282,
1232, 1071, 1037, 752, 701; HRMS (ESI) calcd for C22H16IO2 (M + H)+
439.0189, found 439.0191.
6-Iodo-10-methoxy-9-methyl-7-phenyldibenzocyclohepten-5-
one (2n). Eluent of column chromatography: hexanes/ethyl acetate
10:1. This product was obtained as a yellow solid (194.7 mg, 86% yield):
mp 172.2−173.1 °C; 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 7.9 Hz,
1H), 7.71 (td, J = 7.5, 1.5 Hz, 1H), 7.64 (dd, J = 7.4, 1.4 Hz, 1H), 7.55 (t,
J = 7.3 Hz, 1H), 7.40−7.45 (m, 3H), 7.23 (s, broad, 2H), 7.07 (s, 1H),
6.85 (s, 1H), 3.91 (s, 3H), 2.09 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
195.6, 157.7, 150.6, 145.9, 139.4, 136.9, 136.6, 134.1, 131.7, 129.4, 129.1,
128.64, 128.56, 128.3, 127.23, 127.21, 127.0, 111.7, 99.6, 55.7, 16.1; IR
(CHCl3, cm−1) ν 3019, 1669, 1606, 1503, 1339, 1251, 1216, 1142, 1026,
761; HRMS (ESI) calcd for C23H18IO2 (M + H)+ 453.0346, found
453.0349.
3-Fluoro-6-iodo-10-methoxy-7-phenyldibenzocyclohepten-5-one
(2o). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
1
This product was obtained as a yellow oil (201.7 mg, 88% yield): H
NMR (500 MHz, CDCl3) δ 7.83 (dd, J = 8.7, 5.1 Hz, 1H), 7.38−7.45
(m, 4H), 7.33 (dd, J = 8.3, 2.7 Hz, 1H), 7.20−7.21 (m, 2H), 7.12 (d, J =
2.6 Hz, 1H), 7.02 (d, J = 8.9 Hz, 1H), 6.76 (dd, J = 8.9, 2.7 Hz, 1H), 3.85
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 194.2, 164.9 (d, JC−F = 251.5
Hz), 159.3, 151.1, 145.8, 140.8 (d, JC−F = 6.7 Hz), 138.3, 134.1, 132.6 (d,
JC−F = 3.0 Hz), 131.6 (d, JC−F = 8.2 Hz), 129.3, 128.7, 128.5, 127.7, 119.1
(d, JC−F = 21.6 Hz), 115.8, 113.8 (d, JC−F = 3.0 Hz), 113.6, 98.9, 55.7; IR
(CHCl3, cm−1) ν 3013, 2938, 2846, 1675, 1607, 1492, 1273, 1228, 832,
752; HRMS (ESI) calcd for C22H15FIO2 (M + H)+ 457.0095, found
457.0096.
10-Fluoro-6-iodo-7-phenyldibenzocyclohepten-5-one (2j). Eluent
of column chromatography: hexanes/ethyl acetate 10:1. This product
was obtained as a yellow oil (191.9 mg, 90% yield): 1H NMR (500 MHz,
CDCl3) δ 7.83 (d, J = 7.9 Hz, 1H), 7.73 (t, J = 7.1 Hz, 1H), 7.58−7.64
(m, 2H), 7.38−7.45 (m, 4H), 7.22 (s, broad, 2H), 7.11 (dd, J = 8.9, 6.0
Hz, 1H), 6.90−6.94 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 195.3,
161.8 (d, JC−F = 252.5 Hz), 149.5, 145.4, 139.9 (d, JC−F = 8.4 Hz), 139.6,
6-Iodo-3,10-dimethoxy-7-phenyldibenzocyclohepten-5-one (2p).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow oil (224.9 mg, 96% yield): 1H NMR
(500 MHz, CDCl3) δ 7.77 (d, J = 8.8 Hz, 1H), 7.37−7.44 (m, 3H),
7.24−7.26 (m, 1H), 7.20 (d, J = 5.6 Hz, 2H), 7.12 (dd, J = 4.2, 2.8 Hz,
2H), 7.00 (d, J = 8.9 Hz, 1H), 6.72 (dd, J = 8.9, 2.5 Hz, 1H), 3.92 (s, 3H),
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 195.2, 160.2, 159.2, 150.8,
146.2, 140.3, 139.0, 134.1, 131.0, 129.3, 129.2, 128.6, 128.3, 127.4, 119.4,
115.3, 113.3, 110.2, 99.5, 55.9, 55.6; IR (CHCl3, cm−1) ν 3013, 2963,
2937, 2838, 1668, 1600, 1489, 1335, 1294, 1226, 1042, 757; HRMS
(ESI) calcd for C23H18IO3 (M + H)+ 469.0295, found 469.0297.
6-Iodo-7-(4-methoxyphenyl)dibenzocyclohepten-5-one (2q). Elu-
ent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow solid (191.2 mg, 87% yield): mp
135.3 (d, JC−F = 1.7 Hz), 134.5 (d, JC−F = 8.4 Hz), 132.0, 131.0 (d, JC−F
=
3.1 Hz), 129.43, 129.36, 129.2, 128.8, 128.6, 127.3, 117.4 (d, JC−F = 22.9
Hz), 115.2 (d, JC−F = 21.5 Hz), 101.5; IR (CHCl3, cm−1) ν 3063, 3020,
1675, 1609, 1588, 1487, 1440, 1217, 753, 700; HRMS (ESI) calcd for
C21H13FIO (M + H)+ 426.9990, found 426.9992.
6-Iodo-8,10-dimethyl-7-phenyldibenzocyclohepten-5-one (2k).
Eluent of column chromatography: hexanes/ethyl acetate 10:1. This
product was obtained as a yellow solid (196.3 mg, 90% yield): mp
218.0−219.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.9 Hz,
1H), 7.62 (dt, J = 7.4, 1.5 Hz, 1H), 7.49 (dt, J = 7.0, 1.8 Hz, 1H), 7.43 (dt,
J = 7.5, 1.3 Hz, 1H), 7.23−7.28 (m, 6H), 6.89 (d, J = 1.6 Hz, 1H), 2.33 (s,
3H), 1.77 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 197.4, 145.6, 142.8,
140.9, 138.5, 138.33, 138.30, 137.5, 132.1, 131.8, 131.5, 130.0, 129.1,
128.6, 128.2, 128.1, 127.7, 126.1, 98.5, 23.2, 21.3; IR (CHCl3, cm−1) ν
3019, 2947, 2922, 1690, 1591, 1444, 1277, 1216, 756; HRMS (ESI)
calcd for C23H18IO (M + H)+ 437.0397, found 437.0397.
1
132.9−133.8 °C; H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 7.7 Hz,
1H), 7.67−7.71 (m, 2H), 7.63 (d, J = 7.4 Hz, 1H), 7.55 (t, J = 7.3 Hz,
1H), 7.39 (t, J = 7.4 Hz, 1H), 7.17−7.22 (m, 3H), 7.12 (d, J = 7.8 Hz,
1H), 6.95 (d, J = 8.1 Hz, 2H), 3.84 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 195.7, 159.4, 150.0, 139.7, 137.8, 137.4, 136.3, 134.8, 132.0,
131.7, 131.1, 130.8, 129.2, 128.64, 128.59, 127.6, 126.9, 113.8, 101.7,
55.4; IR (CHCl3, cm−1) ν 3061, 3014, 2956, 2835, 1672, 1605, 1507,
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1296, 1248, 1174, 1031, 759; HRMS (ESI) calcd for C22H16IO2 (M +
H)+ 439.0189, found 439.0190.
award. We thank Dr. Cliff Soll at Hunter College and Dr. Chin H.
Lin at New York University for their help to record the mass
spectra for the new compounds.
9-Chloro-6-iodo-7-(4-methoxyphenyl)dibenzocyclohepten-5-one
(2r). Eluent of column chromatography: hexanes/ethyl acetate 10:1.
This product was obtained as a yellow solid (214.3 mg, 91% yield): mp
209.8−211.0 °C; 1H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz,
1H), 7.71 (dt, J = 7.2, 1.7 Hz, 1H), 7.59−7.62 (m, 2H), 7.56 (dt, J = 7.1,
0.9 Hz, 1H), 7.36 (dd, J = 8.5, 2.2 Hz, 1H), 7.15−7.16 (m, 2H), 7.08 (d, J
= 2.3 Hz, 1H), 6.95−6.97 (m, 2H), 3.87 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 195.5, 159.8, 148.7, 139.7, 137.1, 136.2, 136.1, 135.5, 133.6,
132.6, 131.9, 131.5, 130.9, 129.1, 129.0, 128.8, 127.1, 114.1, 103.1, 55.5;
IR (CHCl3, cm−1) ν 3013, 2958, 2931, 2838, 1678, 1606, 1507, 1475,
1294, 1248, 1175, 1107, 1031, 830, 752; HRMS (ESI) calcd for
C22H15ClIO2 (M + H)+ 472.9800, found 472.9801.
Methyl 4-(6-Iodo-10-methoxy-5-oxo-dibenzocyclohepten-7-yl)-
benzoate (2s). Eluent of column chromatography: hexanes/ethyl
acetate 5:1. This product was obtained as a yellow oil (234.7 mg, 95%
yield): 1H NMR (500 MHz, CDCl3) δ 8.10−8.12 (m, 2H), 7.85 (d, J =
7.9 Hz, 1H), 7.70−7.73 (m, 1H), 7.62 (dd, J = 7.6, 1.4 Hz, 1H), 7.57 (dt,
J = 7.5, 1.0 Hz, 1H), 7.31−7.32 (m, 2H), 7.18 (d, J = 2.8 Hz, 1H), 6.95
(d, J = 8.9 Hz, 1H), 6.76 (dd, J = 8.9, 2.7 Hz, 1H), 3.94 (s, 3H), 3.85 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 195.1, 166.8, 159.4, 150.1, 149.5,
139.41, 139.39, 136.2, 133.6, 131.9, 130.02, 129.99, 129.6, 129.4, 129.1,
127.32, 127.30, 116.1, 113.9, 100.0, 55.7, 52.5; IR (CHCl3, cm−1) ν
3016, 2951, 2840, 1723, 1675, 1607, 1436, 1281, 1112, 1018, 757, 706;
HRMS (ESI) calcd for C24H18IO4 (M + H)+ 497.0244, found 497.0231.
6-Iodo-10-methoxy-7-(thiophen-3-yl)dibenzocyclohepten-5-one
(2t). Three equivalents of I2 was used instead of ICl. Eluent of column
chromatography: hexanes/ethyl acetate 10:1. This product was obtained
as a yellow solid (206.1 mg, 93% yield): mp 155.0−156.4 °C; 1H NMR
(500 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 1H), 7.70 (t, J = 7.4 Hz, 1H),
7.61 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.37−7.38 (m, 1H),
7.31 (d, J = 1.5 Hz, 1H), 7.16 (d, J = 2.2 Hz, 1H), 7.06 (d, J = 8.9 Hz,
1H), 6.99 (d, J = 4.9 Hz, 1H), 6.79 (dd, J = 8.9, 2.3 Hz, 1H), 3.86 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 195.6, 159.2, 146.1, 145.3, 139.5, 138.9,
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136.2, 133.6, 131.8, 129.2, 128.96, 128.89, 127.8, 127.1, 125.7, 125.6,
115.7, 113.9, 99.9, 55.6; IR (CHCl3, cm−1) ν 3016, 2939, 2837, 1672,
1605, 1280, 1212, 758; HRMS (ESI) calcd for C20H14IO2S (M + H)+
444.9754, found 444.9758.
7-(Cyclohex-1-en-1-yl)-6-iododibenzocyclohepten-5-one (2u).
Three equivalents of I2 was used instead of ICl. Eluent of column
chromatography: hexanes/ethyl acetate 10:1. This product was obtained
as a yellow oil (173.7 mg, 79% yield); 1H NMR (500 MHz, CDCl3) δ
7.77 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 8.9 Hz, 1H), 7.65 (dt, J = 7.9, 1.4 Hz,
1H), 7.59 (dd, J = 7.6, 1.2 Hz, 1H), 7.52 (dt, J = 7.5, 0.8 Hz, 1H), 7.14 (d,
J = 2.8 Hz, 1H), 6.93 (dd, J = 8.8, 2.7 Hz, 1H), 5.84−5.86 (m, 1H), 3.88
(s, 3H), 2.27−2.29 (m, 2H), 1.88−1.90 (m, 2H), 1.68−1.69 (m, 4H);
13C NMR (125 MHz, CDCl3) δ 195.6, 159.2, 152.1, 142.8, 139.5, 139.4,
136.2, 132.3, 131.5, 130.5, 129.2, 128.8, 127.2, 125.5, 116.1, 114.2, 98.2,
55.7, 27.6, 25.2, 22.8, 22.0; IR (CHCl3, cm−1) ν 3015, 2933, 2835, 1670,
1603, 1486, 1281, 1254, 1214, 755; HRMS (ESI) calcd for C22H19IKO2
(M + K)+ 481.0061, found 481.0046.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H and 13C NMR spectra for the new compounds. This
material is available free of charge via the Internet at http://pubs.
acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yu.chen1@qc.cuny.edu.
■
Notes
(22) For selected examples on formation of iodonium intermediate,
see: (a) Arcadi, A.; Cacchi, S.; Di Giuseppe, S.; Fabrizi, G.; Marinelli, F.
Org. Lett. 2002, 4, 2409−2412. (b) Yao, T.; Larock, R. C. J. Org. Chem.
2003, 68, 5936−5942. (c) Crone, B.; Kirsch, S. F. J. Org. Chem. 2007, 72,
5435−5438. (d) Fischer, D.; Tomeba, H.; Pahadi, N. K.; Patil, N. T.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 4764−4766. (e) Xie, Y.-
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We appreciate the financial support in the form of a Queens
College Research Enhancement Award and the PSC−CUNY
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The Journal of Organic Chemistry
Article
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