The intramolecular 5-: Exo, 7- endo -dig transition metal-free cyclization sequence of (2-alkynylphenyl) benzyl ethers: Synthesis of seven-membered fused benzo [b] furans

Article abstract of DOI:10.1039/c6gc02423h

Base-promoted cyclization of (2-alkynylphenyl) benzyl ethers was studied in detail. The effects of the solvent, base, temperature, reaction time and amount of base on the efficacy of the cyclization reaction were analyzed and a new base-solvent system (tert-BuOK/DMSO) for effective cyclization of (2-alkynylphenyl) benzyl ethers was reported. The results showed that the cyclization reactions proceeded cleanly and smoothly under mild reaction conditions, employing tert-BuOK as a base, and DMSO as a solvent, at room temperature in a short reaction time (1 h). Under these conditions, a number of different substituted (2-alkynylphenyl) benzyl ethers were cyclized to the corresponding fused heterocycle cyclohepta[b]furans. This one-pot, two-step procedure occurred regioselectively giving only the cyclohepta[b]furans as the unique regioisomers via an initial intramolecular 5-exo-dig mode followed by an intramolecular 7-endo-dig mode. The cyclohepta[b]furan derivatives absorbed in the UV region (300-350 nm range) with molar absorptivity coefficient values attributed to spin and symmetry allowed π-π? electronic transitions. An emission located in the purple region (380-440 nm range), with a Stokes shift between 65-100 nm is probably associated with the charge transfer character of the excited state. The electrochemical analysis (CV) of the cyclohepta[b]furans showed an oxidation and reduction process, probably due to the presence of the selenium atom and π-anion radical species.

Full text of DOI:10.1039/c6gc02423h

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Intramolecular 5-exo, 7-endo-dig Transition Metal-Free Cyclization
Sequence of (2-Alkynylphenyl) Benzyl Ethers: Synthesis of Seven-
Membered Fused Benzo[b]furans
Received 00th
Accepted 00th
DOI: 10.1039/x0xx00000x
www.rsc.org/
Rafaela Gai,a Roberto do Carmo Pinheiro,a José S. S. Neto,a Bernardo A. Iglesias,b Thiago V.
Acunha,b Davi F. Backb and Gilson Zeni*,a
Base-promoted cyclization of (2-alkynylphenyl) benzyl ethers was studied in details. The effects of solvent, base,
temperature, reaction time and amount of base on the efficacy of the cyclization reaction was analyzed and a new base-
solvent system (tert-BuOK/DMSO) for effective cyclization of (2-alkynylphenyl) benzyl ethers was reported. The results
showed that the cyclization reactions proceeded cleanly and smoothly under mild reaction conditions, employing a tert-
BuOK as base, DMSO as solvent, at room temperature in a short reaction time (1 h). Under these conditions, a number of
different substituted (2-alkynylphenyl) benzyl ethers were cyclized to the corresponding fused heterocycle
cyclohepta[b]furans. This one-pot, two-steps procedure occurred regioselectively giving only the cyclohepta[b]furans as
the unique regioisomer via an initial intramolecular 5-exo-dig mode followed by an intramolecular 7-endo-dig mode. The
cyclohepta[b]furan derivatives absorbed in the UV region (300-350 nm range) with molar absorptivity coefficient values
attributed to spin and symmetry allowed π-π* electronic transitions. An emission located in the purple region (380-440
nm range), with a Stokes shift between 65-100 nm is probably associated to the charge transfer character of the excited
state. The electrochemical analysis (CV) of the cyclohepta[b]furans showed an oxidation and reduction process, probably
due to the presence of the selenium atom and π-anion radical species.
cyclohepta[b]furans are interesting building blocks and important
synthetic intermediates. For example, studies have shown that
they have been used as substrate for [8+2] cycloaddition
Introduction
reactions.11 These higher order conjugate additions have been
extensively used to directly entry to a large number of fused-
polycyclic compounds, which are part of numerous natural and non-
natural compounds. Cyclohepta[b]furans have multi-π-bonds and
the structural rigidity that leads to fast multistep electron transfer
as well as to physicochemical features, such as radical spin-trapping
therapeutic agents,12 near-infrared dark quenchers,13 color-tags for
the chromophore-supported purification technique14 and
The derivatives of fused heterocycles are valued not only for their
rich and varied chemistry but also for many important biological
properties.1 In contrast to the numerous studies developed for the
chemistry and preparation of fused five- and six-membered
heterocycles, the preparation of seven-membered derivatives is
limited and generally involves a multistep synthesis.2 However, the
discovery of several new families of cyclohepta[b]furan ring
containing different biological activities has generated an interest in
the development of new methodologies for the synthesis of these
heterocycles.3 Representative examples of different biological
activities include antimicrobial,4 cytotoxic,5 antiulcer,6 and anti-
inflammatory activities.7 Cyclohepta[b]furans isolated from natural
sources also have a broad spectrum of biological activities, for
example, interleukin-8 receptor antagonist,8 inhibitory activity
against PI3K9 and neuroprotective effects.10 Besides, substituted
electrochromic materials.15
Up to now, the most useful
methodology described to the preparation of these heterocycles is
the transition-metal-mediated cycloaddition reactions. In spite of
these methods, the cycloaddition reactions,16 ring expansion
reactions,17 ring-closing metathesis18 and domino cyclization
reactions19 have emerged as powerful tools to the preparation of
wide range of seven-membered heterocycles. Recently, there has
been enormous interest in the development of new methods
avoiding the use of transition metals.20 A green alternative to
transition metals in intramolecular cyclization is the base-promoted
annulations of unsaturated substrates.21 This methodology has
significant advantages over others, particularly in terms of
functional group tolerance, high levels of chemo-, regio-, and
stereoselectivity. In addition, the base-promoted annulation has
emerged as a powerful tool in organic synthesis due to the
aLaboratório de Síntese, ꢀeaꢁꢂidade, Aꢂaliação Farmacológica e Toxicológica de
Organocalcogênios CCNE, UFSM, Santa Maria, ꢀio Grande do Sul, Brazil 97105-900.
E-mail: gzeni@ufsm.br; Fax: (+55)55-3220-8978; Tel: (+55)55-3220-9611.
bLaboratório de Materiais Inorgânicos, Departamento de Química, UFSM, Santa
Maria, ꢀio Grande do Sul, Brazil 97105-900.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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reduction of generation of chemical wastes, reaction time, solvent,
and energy, demonstrating the clear economic impacts and
environmental benefits. In this paper, our aim was to develop
conditions for the base promoted annulation of (2-alkynylphenyl)
benzyl ethers 1, bearing a nucleophilic center an appropriate
distance to the alkyne, for the selective synthesis of naphtha
chromenes 3 (Scheme 1). These cascade annulation reactions
generally proceed through double intramolecular endo-dig
cyclization mode.22 However, after initial reactions to determine
the feasibility of this project, we found that the product obtained
was the cyclohepta[b]furans 2. The reactions probably proceed via
an intramolecular exo-dig/endo-dig sequence (Scheme 1). Thus, in
order to develop a versatile method for the preparation of
cyclohepta[b]furans 2, we performed a systematic study of the
base-promoted cyclization reaction of (2-alkynylphenyl) benzyl
ethers 1 varying different reaction parameters and these results will
presented below.
.
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DOI: 10.1039/C6GC02423H
Scheme 2
Due to the fact that the acidity of the t-BuOH is similar to that of
DMSO,23 the system DMSO/tert-BuOK would facilitate the
formation and stabilization of the anion intermediates. For this
reason, we began our investigation using tert-BuOK as base and
DMSO as solvent. The results show that the use of a catalytic
amount of tert-BuOK did not convert the (2-alkynylphenyl) benzyl
ether 1a in the desired product even under extended reaction time
(24 h) and high temperature (100 oC) (Table 1, entries 1 and 2). The
increase of tert-BuOK amount to 2.0 equiv led to a significant
increase of 2a yield, reaching 88%, in a short reaction time (Table 1,
entry 3). We subsequently examined the effect of solvent on the
cyclization of (2-alkynylphenyl) benzyl ether 1a. The type of solvent
had significant effect and almost all of the solvents tested, except
DMF, did not afford the product (Table 1, entries 5-10). The use of
protic solvent would quench the anions preventing the conversion
of the (2-alkynylphenyl) benzyl ether 1a. To check this hypothesis
we carried out an experiment using tert-BuOH as solvent. With this
reaction conditions, there was no formation of cyclohepta[b]furan
2a and the (2-alkynylphenyl) benzyl ether 1a was completely
recovered (Table 1, entry 11). This is also assumed by us as an
additional evidence for the anionic pathway (see mechanism
discussion). It was found that various bases, such as Cs2CO3, NaOH,
DBU, NaH, and KOH, were not effective to mediate the cyclization
of 2-alkynylphenyl) benzyl ether 1a, although KOH gave moderated
yield of cyclohepta[b]furan 2a at a high temperature (Table 1,
entries 12-16). The amount of base was then optimized; the yields
were not significantly changed by decreasing from 2.0 to 0.5 equiv
amount (Table 1, entries 17 and 18). For economic reason, 0.5
equiv of tert-BuOK was adopted for further studies. At various
interval times, during the optimization reactions, samples of the
reaction mixture were analyzed by TLC, which showed that 1 h was
the reaction time necessary to the complete consume of starting
material. In accordance with these results, we concluded that the
optimum set of conditions for the cyclization reaction of (2-
alkynylphenyl) benzyl ether 1a were the addition of tert-BuOK (50
mol%) to a solution of (2-alkynylphenyl) benzyl ether 1a (0.25
mmol) in DMSO (2.0 mL) at room temperature for 1 h. To
demonstrate the generality of the methodology, various (2-
alkynylphenyl) benzyl ethers 1 were cyclized using the optimized
reaction conditions and the results are listed in Table 2.
Scheme 1
Results and Discussion
General Conditions
The starting material (2-alkynylphenyl) benzyl ethers
1 was
prepared by Sonogashira reaction involving terminal alkynes 4
reacting with aryl bromides 5 (Scheme 2).24 The terminal alkynes 4
were synthesized by the reaction of 2-bromophenol with
corresponding benzyl bromides followed by Sonogashira25 and
retro-Favorskii26 reactions, respectively. The aryl bromides 5 were
prepared reacting 2-bromoiodo-benzene with terminal alkynes via
Sonogashira reaction.27
In order to optimize the reaction
conditions, we initiated our study by using (2-alkynylphenyl) benzyl
ether 1a (0.25 mmol), screening the action of bases, solvents,
temperature and reaction time and the results are summarized in
Table 1.
2 | J. Name., 2012, 00, 1-3
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observed. The cyclization conditions also worked well with
View Article Online
DOI: 10.1039/C6GC02423H
electron-withdrawing groups at the aromatic rings of benzyloxy
Table 1. Effect of different reaction parameters on the preparation of
cyclohepta[b]furan 2aa
affording the corresponding products 2f and 2g in 65 and 87%
yields, respectively.
We also studied the introduction of
substituents on the alkyne terminus. We observed that both
electron-rich and electron-deficient aryl groups directly bonded to
alkyne afforded the products in high yields, even though the aryl
containing a CF3, a strong electron-withdrawing substituent, gave
only moderated 54% yield (Table 2, cyclohepta[b]furans 2h-2p).
Furthermore, the experiments showed that the cyclization reactions
were not influenced by effects of adding substituents on the two
aromatic systems given that the expected products were obtained
in similar good yields (Table 1, cyclohepta[b]furans 2q-2t). An
exception to the other results was observed for the case of (2-
alkynylphenyl) benzyl ether having a 1-naphthyl group bonded to
alkyne. The reaction of this substrate with standard conditions
gave a mixture of cyclohepta[b]furan 2u and the product formed via
a double exo-dig cyclization 2u'. In this case, the formation of 2u'
may be attributed to the steric hindrance offered by the 1-naphthyl
substituent to the nucleophilic attack at the C1 of alkynes.
Concerning the substrate having an alkyl group attached to the
carbon-carbon triple bond, we did not observe the formation of
cyclohepta[b]furan 2v. In this case, only the starting material was
recovered even under various reaction conditions (Table 2,
cyclohepta[b]furan 2v). This lower reactivity is probably due to the
absence of pi (π) bonds next to the alkyne, which becomes the
carbon-carbon triple bond less reactive towards nucleophilic attack.
entry
1
base (equiv)
tert-BuOK (0.2)
tert-BuOK (0.2)
tert -BuOK (2)
tert -BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
tert-BuOK (2)
Cs2CO3 (2)
solvent
DMSO
DMSO
DMSO
DMF
time (h)
24
24
1
yield (%)b
N.R.c
N.R.c,d
88
2
3
4
1
83
5
THF
24
24
24
24
24
24
24
24
24
24
24
11
1
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
45d
6
dioxane
CH2Cl2
CH3CN
toluene
DMA
7
8
9
10
11
12
13
14
15
16
17
18
tert-BuOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
NaOH (2)
DBU (2)
NaH (2)
KOH (4)
Mechanism Proposal
tert-BuOK (1)
89
We assumed that the cyclization proceeds through; a) the
tert-BuOK (0.5)
1
90
[a]The reaction was performed by the addition of tert-BuOK to a solution of
formation of benzyl anion I via abstraction of benzylic hydrogen
(2-alkynylphenyl) benzyl ether 1a (0.25 mmol) in DMSO (2.0 mL) under from (2-alkynylphenyl) benzyl ethers 1 by tert-BuOK; b) the
argon atmosphere, at room temperature for the time indicated.
intramolecular anionic addition to the carbon-carbon triple bond
[b]Yields of purified products.
gives the vinyl anion II, via a 5-exo-dig mode; c) protonation of the
[c]The substrate 1a was not consumed.
[d]The reaction was performed at 100 °C.
vinyl anion by tert-BuOH, generated in situ, affords the benzofuran
intermediary III that upon further deprotonation gives IV. Next, in
the second cyclization step, the 6-exo-dig mode competes with 7-
Scope of the Reaction
endo-dig mode, therefore a mixture of cyclohepta[b]furans 2 and
dihydrobenzo-naphthofuran 2' would be produced (Scheme 3). The
nucleophilic attack of benzyl anion at the carbon-carbon bonds of
alkyne produces the anion V. The protonation/deprotonation
sequence gives the cyclized cyclohepta[b]furans 2. There is no way
to isolate any intermediates, such as bezofuran II and IV; however,
we presented herein some results of the experiments performed to
support this hypothesis. When (2-alkynylphenyl) benzyl ether 1a
reacted under optimized reaction, in the dark, to prevent the light-
induced formation of the radical, or in the presence of TEMPO a
radical inhibitor, the cyclohepta[b]furan 2a was obtained in 85%
and 89% yields, respectively (Schemes 4 and 5). This indicates that
the pathway does not follow the typical radical mechanism. When
the same reaction was carried out using hydrated THF or a protic
solvent instead of anhydrous THF, no cyclohepta[b]furan 2a was
detected and the (2-alkynylphenyl) benzyl ether 1a was completely
Because the yields varied with both electronic and steric effects,
any clear relationship between the structure of the (2-
alkynylphenyl) benzyl ether 1a and the reaction yield could not be
established. However, some results deserve a detailed analysis; for
example, in respect to the effect of the substituent on the
benzyloxy function we observed that the aryl group having no
substitution gave the highest yield for cyclohepta[b]furan 2a. The
electron-donating groups in the aromatic rings of benzyloxy
function were compatible with the reaction conditions, giving the
corresponding cyclohepta[b]furans 2c-2f in moderated to good
yields, although additional reaction time and an increase in
temperature were required. An exception to this behavior was
observed for cyclohepta[b]furan 2b, which was not obtained, even
though we made several modifications in the standard reaction
conditions. In this example, only unreacted starting material was
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recovered. This suggests that water and protic solvent may quench
the anions formed, hindering the reaction. In this context, our
cyclization methodology showed to be regioselective, providing the
desired cyclohepta[b]furan 2 via an intramolecular 5-exo-dig mode
followed by a 7-endo-dig mode.
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DOI: 10.1039/C6GC02423H
Table 2. Synthesis of cyclohepta[b]furans 2a
Scheme 4
Ph
tert-BuOK (0.5 equiv)
DMSO (2 mL), r.t., 1 h
O
2
R1
O
1
R1
R2
R2
1) radical scavenger (1.0 eq)
2) t-BuOK (0.5 eq)
O
Ph
Ph
DMSO, rt, 1 h
O
Ph
O
2a - 89%
O
O
1a
O
Me
Ph
O
Ph
Ph
Ph
Ph
Ph
Me
MeO
Me
2b ( - )
2c (70 %)b,c
2d (55 %)b
2e (81 %)b
2a (90 %)
Scheme 5
The formation of six-membered ring via intramolecular 6-endo-dig
mode, in the first cyclization, or six-membered ring via a 6-exo-dig
process, in the second cyclization, was not observed in any case.
This high regioselectivity can be explained by the stability of the
new sigma-bond system formed, the formation of the more stable
vinyl carbanion from original alkyl anion and due to the carbon, the
nucleophilic cyclization normally goes on via 5-exo-dig over 6-endo
closure in the substrate with these interatomic distances.28 In the
second cyclization step, the 7-endo-dig mode was preferred over 6-
exo-dig, albeit the both processes are acceptable according to the
Baldwin rule.28 It is reasonable to assume that steric and electronic
factors over the competitive cyclization modes are involved in this
reaction.29
O
O
O
O
O
Me
Ph
Ph
Ph
Ph
Ph
Me
F
Cl
Me
2f (65 %)c
2h (70 %)b,c
2i (80 %)b,c
2j (90 %)b
2g (87 %)
O
O
O
O
O
OMe
Ph
Ph
Ph
Ph
Ph
MeO
OMe
F
Cl
2k (79 %)c
2l (70 %)b,c
2m (82 %)c
2n (83 %)b
2o (88 %)
O
O
O
O
Ph
O
Ph
Ph
MeO
S
F3C
F
OMe
2q (75 %)c
OMe
2r (60 %)c
2p (54 %)b,c
2s (75 %)b,c
2t (90 %)b
Characterization of Cyclohepta[b]furan Derivatives
O
O
Ph
Ph
+
O
Ph Bu
H
In our methodology, except for the reaction of (2-alkynylphenyl)
benzyl ether having a 2-naphthyl group bonded to alkyne, which
gave a mixture of isomer derivatives, only the product resulting
from 5-exo-dig/7-endo-dig intramolecular sequence was obtained.
The presence of a unique isomer was confirmed by spectral 13C
NMR data from crude reaction mixture to avoid error in the
2v ( - )
2u
2u'
78 % (2u:2u' / 5:1)
[a]The reaction was performed in the presence of (2-alkynylphenyl) benzyl
ethers 1 (0.25 mmol) and tert-BuOK (50 mol%) in DMSO (2.0 mL) under an
argon atmosphere at room temperature for 1 h.
[b]The reaction was performed with tert-BuOK (1.0 equiv).
[c]The reaction was performed at 100 oC.
1
detection isomer peaks by H NMR. The structures of all products 2
were unambiguously elucidated by their NMR data and confirmed
by single crystal X-ray diffraction for compound 2f (Figure 1, CCDC
1485830 ), 2g (CCDC 1485827, Figure S1 Supporting Information)
and 2m (CCDC 1485825, Figure S1 Supporting Information).
Figure 1. The molecular structure with the atom-labeling scheme of the
compound 2f with 50% thermal ellipsoids (using ORTEP software) (CCDC
1485830)
Scheme 3
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UV-Vis and Emission Fluorescence Analysis of Cyclohepta[b]furan
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DOI: 10.1039/C6GC02423H
Derivatives 2a-2t
The comparative absorption spectra of compounds 2a-2t, using
CHCl3 as solvent, are shown in Figure 2 and the optical properties
are listed in Table 3. The cyclohepta[b]furan derivatives showed
absorption maxima located around 250-400 nm range, at the UV
region. The values for the molar absorptivity coefficient (ε) for
these compounds indicate that spin and symmetry allowed
electronic transitions, which could be related to π-π* and n→π*
transitions (Figure 2). We did not observe significant changes on
the absorption maxima location associated with different
substituent groups in the cyclohepta[b]furan compounds. The
fluorescence emission spectra of some cyclohepta[b]furans are
illustrated in Figure 3. The emission curves were obtained exciting
the compounds at the absorption maxima wavelength at λexc = 350
nm. Cyclohepta[b]furan compounds presented fluorescence
emission in the purple region (380-450 nm range). As already
observed in the ground state, they presented comparable location
to the emission maxima, which indicates that the different organic
Figure 2. Comparative electronic UV-Vis absorption spectra of
cyclohepta[b]furan compounds 2a-2t, containing different substituted
groups in chloroform solution
moieties in the cyclohepta[b]heterocycles did not play
a
fundamental role on the excited state of these compounds. In
addition, the fluorescent emission of cyclohepta[b]furans
containing methoxyl substituent (2k and 2q) can be attributed to
the electronic nature of this electron donor group (Figure 3). These
results probably can be attributed to the nature of the π-π*
electronic transition, indicating that these compounds allow better
electronic delocalization in the excited state. The Stokes shifts
observed in the excited state can indicate that cyclohepta[b]furans
present some charge separation, in special compounds 2e and 2k
(both with CH3O group). These results could be assigned to an
intramolecular charge transfer character in the excited state (Table
3). Moreover, they showed good fluorescence quantum yields if
compared to that of the DPA standard or cyclohepta[b]furan
compounds with donating substituents in meta or ortho position
(Table 3). This suggests that the presence of both oxygen atoms
and electronic donating groups enhance significantly the
fluorescent emission in these cyclohepta[b]furan derivatives.
Evidence also was found to correlate the higher fluorescence
quantum yields with the heterocyclic ring planarities.
Figure 3. Emission fluorescence spectra of compounds 2a-2t, in CHCl3
solution
The oxidation peaks observed in these compounds can be assigned
to the cation radical species of cyclohepta[b]furans in solution.
Analyzing the donor/acceptor groups in these derivatives, we
observed that they did not influence the changes in the redox
potential (Supplementary Information, Figure S2 and S3). An
exception was the derivatives 2q and 2r, which had lower oxidation
potentials when to compare to those of the other compounds
(Table 4). This may be related to the electronic properties of the
molecule.
Cyclic Voltammetry Analysis of Cyclohepta[b]furans 2a-2t
In order to better evaluate the redox properties of
cyclohepta[b]furans CV experiments were performed to verify the
redox potential values of compounds, in dry dichloromethane
solutions (Table 4). In general, at -2.00 to +2.00 V potential range,
the cyclic voltammograms of cyclofuran-derivatives displayed one
reversible reduction peak (Epc) between -0.90 V to -1.30 V versus
SHE redox couple (Figure 4). This reduction process can be
attributed to a C-O bond cleavage located in the furan unit, which
form an anion radical type species. Moving to the positive region,
all derivatives exhibit irreversible oxidation waves in the anodic
range (Epa) at +1.20 V to +1.80 V (Table 4).
Figure 4. Comparative cyclic voltammogram of compounds 2a, 2h, 2k, 2n, 2s
and 2t, in dichloromethane containing 0.1 M TBAPF6, as support electrolyte,
using scan rate at 100 mV/s, respectively.
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Table 3. UV-vis and emission data analysis of cyclohepta[b]furans 2a-2t
UV-vis, nm (ε; M-1cm-1)a
272 (3.469); 360 (1.435)
272 (5.437); 358 (1.485)
269 (7.513); 352 (2.891)
273 (6.940); 359 (1.064)
270 (6.956); 358 (1.067)
271 (4.373); 358 (1.784)
274 (6.333); 359 (1.040)
271 (3.633); 359 (1.507)
248 (6.954); 357 (1.323)
280 (4.487); 358 (2.079)
269 (5.988); 358 (1.226)
253 (4.195); 355 (2.018)
274 (9.871); 358 (2.787)
270 (4.007); 359 (1.605)
270 (7.955); 357 (2.143)
280 (3.122); 357 (1.287)
281 (3.177); 357 (1.461)
276 (3.053); 358 (1.136)
267 (6.507); 358 (2.169)
emission (nm)b
391
φfl
Stokes shifts (nm)d
E0-0 (eV)e
3.444
3.445
3.271
3.229
3.387
3.171
3.378
3.324
3.289
3.155
3.342
3.246
3.406
3.342
3.425
3.333
3.246
3.406
3.425
c
compound
2a
2c
2d
2e
2f
0.135
0.230
0.321
0.308
0.129
0.275
0.290
0.143
0.100
0.187
0.247
0.214
0.060
0.059
0.046
0.255
0.115
0.079
0.144
31
37
69
100
56
97
43
66
75
102
73
80
42
94
37
52
93
45
46
395
421
459
415
2g
2h
2i
455
402
425
2j
432
2k
2l
460
431
2m
2n
2o
2p
2q
2r
435
400
453
394
409
450
2s
403
2t
404
[a]Measured in CHCl3. [b]Measured in CHCl3 solution at 298K (λexc. = 350 nm). [c]9,10-Diphenylanthracene (DPA) in CHCl3 as standard (φfl = 0.65). [d]Stokes Shift
equation: Δλ´= λem - λabs (Δλ´ = 1/λabs – 1/λem x 107 cm-1). [e]E0-0 = 1240 / λ (in eV).
Table 4. Electrochemical data of cyclohepta[b]furans 2a-2t
a
a
b
compound
E1
E2
E3
HOMO (eV)c
-6.277
-5.986
-5.950
-6.179
-6.289
-6.256
-6.268
-5.937
-5.964
-6.234
-6.232
-6.360
-6.292
-6.160
-6.256
LUMO (eV)d
-2.833
-2.541
-2.679
-2.950
-2.902
-3.085
-2.890
-2.613
-2.675
-3.079
-2.890
-3.114
-2.886
-2.818
-2.831
ΔE (eV)
3.444
3.445
3.271
3.229
3.387
3.171
3.378
3.324
3.289
3.155
3.342
3.246
3.406
3.342
3.425
2a
2c
2d
2e
2f
+1.477 V
+1.186 V
+1.150 V
+1.379 V
+1.489 V
+1.456 V
+1.468 V
+1.137 V
+1.164 V
+1.434 V
+1.432 V
+1.560 V
+1.492 V
+1.360 V
+1.456 V
-----
-1.045 V
-0.994 V
-1.022 V
-1.148 V
-1.023 V
-1.048 V
-1.062 V
-1.041 V
-1.022 V
-1.026 V
-1.200 V
-1.126 V
-1.007 V
-1.099 V
-1.171 V
+1.489 V
+1.471 V
+1.661 V
+1.769 V
+1.739 V
-----
2g
2h
2i
+1.481 V
+1.453 V
-----
2j
2k
2l
+1.675 V
-----
2m
2n
2o
2p
+1.768 V
+1.654 V
+1.761 V
This journal is © The Royal Society of Chemistry 2016
J. Name., 2013, 00, 1-3 | 6
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Green Chemistry
Journal Name
ARTICLE
2q
2r
2s
2t
+0.698 V
+0.675 V
+1.338 V
+1.469 V
+1.155 V
-0.309 V
-----
-1.054 V
-0.913 V
-1.228 V
-5.498
-2.165
-2.229
-2.732
-2.844
3.333
View Article Online
DOI: 10.1039/C6GC02423H
-5.475
3.246
-6.138
3.406
+1.704 V
-1.046 V
-6.269
3.425
[a]
[b]
E
[c]
E
[d]
E
= Anodic peak (versus SHE).
= Cathodic peak (versus SHE).
= -[4.8 + E1ox (versus SHE)]eV.
E
LUMO
= [EHOMO + E0-0]. [e]ΔE = ELUMO - EHOMO
.
pa
pc
HOMO
using Gel GF254, 0.25 mm thickness. For visualization, TLC plates
were either placed under ultraviolet light, or stained with iodine
vapor, or acidic vanillin. Most reactions were monitored by TLC for
disappearance of starting material. The following solvents were
dried and purified by distillation from the reagents indicated:
tetrahydrofuran from sodium with a benzophenone ketyl indicator.
All other solvents were ACS or HPLC grade unless otherwise noted.
Air- and moisture-sensitive reactions were conducted in flame-dried
or oven dried glassware equipped with tightly fitted rubber septa
and under a positive atmosphere of dry nitrogen or argon.
Reagents and solvents were handled using standard syringe
techniques. Spectroscopic grade solvents (Sigma-Aldrich) were
used for fluorescence and UV-Vis measurements. UV-Vis electronic
absorption spectra in solution were performed on a UV-2600
Conclusions
To summarize, we showed that the (2-alkynylphenyl) benzyl ethers
1 react with tert-BuOK in DMSO to give the corresponding
cyclohepta[b]furans 2, via a sequential regioselective 5-exo-dig
mode followed by a 7-endo-dig mode. A systematic study to
determine the best reaction conditions of the cyclization system
revealed that the amount of base and solvent played an essential
role in this reaction. The reaction afforded cyclohepta[b]furans in
moderate to good yields and various functional groups were readily
accommodated in the final structure. We consider that this method
has significant advantages, such as a short reaction time, the
reactions were carried out under room temperature and given that
tert-BuOK is easily available commercially, less expensive and
relative non-toxic, our method could be considered an economic
and eco-friendly protocol. Another feature of this protocol is the
atom economy because two new carbon-carbon bonds were
formed in a one-pot procedure, which is an important concept of
green chemistry philosophy. The cyclohepta[b]furans 2 was
identified by their NMR data and the structures were confirmed by
single crystal X-ray diffraction. Furthermore, the cyclohepta[b]furan
derivatives absorbed the UV region (π-πꢀ and nꢁπꢀ transiꢂons)
and present fluorescence emission in the purple region (380-450
nm range) as well as redox potentials which can be attributed to the
anion/cation radical species.
spectrophotometer at a concentration of 1.0 x 10-4 - 1.0 x 10-5
M
range. Steady state fluorescence spectra were taken with an Cary
Eclipse spectrofluorometer. The maximum absorption wavelength
was used as excitation wavelength for fluorescence measurements.
The quantum yield of fluorescence (φF) was measured at 25 oC
using spectroscopic grade solvents within solutions with
absorbance intensity lower than A = 0.2. 9,10-Diphenylanthracene
(DPA, Aldrich) in CHCl3 was used as fluorescence quantum yield
standard (φF = 0.65). Cyclic voltammograms were recorded on
potenciostat/galvanostat system at room temperature under argon
atmosphere, using dry dichloromethane solution (Sigma-Aldrich).
Electrochemical grade tetrabutylammonium hexafluorophosphate
(TBAPF6, Sigma-Aldrich) was used as supporting electrolyte. These
experiments were carried out by employing a standard three
component system: a glassy carbon working electrode; a platinum
wire auxiliary electrode and a platinum wire pseudo-reference
electrode. To monitor the reference electrode, the Fc/Fc+ couple
was used as an internal reference. All measurements were
performed at room temperature (25 oC).
Experimental Section
General Methods
Proton nuclear magnetic resonance spectra (1H NMR) were
obtained on a NMR spectrometer at 400 MHz. Spectra were
recorded in CDCl3 solutions. Chemical shifts are reported in ppm,
referenced to the solvent peak of CDCl3 or tetramethylsilane (TMS)
as the external reference. Data are reported as follows: chemical
shift (δ), multiplicity, coupling constant (J) in Hertz and integrated
intensity. Carbon-13 nuclear magnetic resonance spectra (13C NMR)
were obtained on a 400 NMR spectrometer at 100 MHz. Spectra
were recorded in CDCl3 solutions. Chemical shifts are reported in
ppm, referenced to the solvent peak of CDCl3. Abbreviations to
denote the multiplicity of a particular signal are s (singlet), d
(doublet), t (triplet), q (quartet), quint (quintet), sex (sextet), dt
(double triplet), td (triple doublet) and m (multiplet). High
resolution mass spectra were recorded on a mass spectrometer
using electrospray ionization (ESI). Column chromatography was
performed using Silica Gel (230-400 mesh) following the methods
described by Still. Thin layer chromatography (TLC) was performed
General Procedure
General
Procedure
for
the
Preparation
of
H-
benzo[4,5]cyclohepta[1,2-b]benzofurans Derivatives 2a-u
To a tube, under argon, containing the substrate 1 (0.25 mmol) and
DMSO (2 mL), was added t-BuOK. The reaction mixture was
allowed to stir for 1 h. After this time, the mixture was diluted with
ethyl acetate (20 mL) and washed saturated solution of NH4Cl (2 x
20 mL). The organic phase was separated, dried over MgSO4 and
concentrated under vacuum. The residue was purified by column
chromatography on silica gel.
This journal is © The Royal Society of Chemistry 2016
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Green Chemistry
Page 8 of 12
ARTICLE
Journal Name
Characterization
(4). HRMS (ESI-TOF) m/z calcd for C30H23O2 [M + H]+: 415.1698.
View Article Online
DOI: 10.1039/C6GC02423H
Found: 415.1704.
6-diphenyl-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
(2a):
Isolated by column chromatography (hexane as eluent) as a white 5a-(4-chlorophenyl)-6-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
yellow solid. Yield: 0.086 g (90 %), mp 76-79 °C. 1H NMR (CDCl3, 400 b]benzofuran (2f): Isolated by column chromatography (hexane as
MHz): δ 7.52-7.50 (m, 1H), 7.48-7.40 (m, 2H), 7.30-7.23 (m, 7H), eluent) as a white yellow solid. Yield: 0.068 g (65 %), mp 174-176 °C.
7.20 (s, 1H), 7.17-7.02 (m, 6H), 6.93-6.90 (m, 2H), 6.71 (d, J = 8.0 Hz, 1H NMR (CDCl3, 400 MHz): δ 7.54 (ddd, J = 7.6 Hz, J = 1.3 Hz, J = 0.6
1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.3, 142.6, 140.9, 140.6, Hz, 1H), 7.46-7.40 (m, 2H), 7.38-7.11 (m, 11H), 7.03 (d, J = 9.0 Hz,
140.4, 135.0, 134.1, 131.3, 130.6, 129.9, 129.4, 129.3, 128.1, 127.9, 2H), 6.98-6.92 (m, 2H), 6.77-6.72 (m, 1H). 13C{1H} NMR (CDCl3, 100
127.5, 127.3, 126.8, 126.2, 126.1, 126.0, 121.0, 120.7, 116.5, 110.5, MHz): δ 161.1, 142.3, 140.6, 140.3, 139.1, 134.9, 134.0, 133.9,
91.5. MS (EI, 70 eV; m/z (relative intensity)): 385 ([M + 1], 8), 384 131.3, 130.8, 130.0, 129.5, 129.3, 128.1, 127.8, 127.6, 127.4, 127.0,
(28), 307 (100), 276 (10), 205 (3), 169 (3), 153 (11), 138 (4). HRMS 126.4, 125.9, 121.2, 120.8, 116.7, 110.5, 90.8. MS (EI, 70 eV; m/z
(ESI-TOF) m/z calcd for C29H21O [M + H]+: 385.1592. Found: (relative intensity)): 420 ([M + 2], 13), 419 ([M + 1], 13), 418 (38),
385.1602.
383 (3), 341 (72), 307 (100), 276 (22), 207 (8), 152 (16). HRMS (ESI-
TOF) m/z calcd for C29H20ClO [M + H]+: 419.1203. Found: 419.1210.
6-phenyl-5a-(m-tolyl)-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
(2c): Isolated by column chromatography (hexane as eluent) as a 5a-(4-fluorophenyl)-6-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
1
white yellow viscous oil. Yield: 0.069 g (70 %). H NMR (CDCl3, 400 b]benzofuran (2g): Isolated by column chromatography (hexane as
MHz): δ 7.56-7.52 (m, 1H), 7.49-7.42 (m, 2H), 7.36-7.25 (m, 5H), eluent) as a white yellow solid. Yield: 0.087 g (87 %), mp 183-185 °C.
7.22 (s, 1H), 7.20-7.07 (m, 5H), 6.99-6.91 (m, 3H), 6.90-6.86 (m, 1H), 1H NMR (CDCl3, 400 MHz): δ 7.54 (ddd, J = 7.6 Hz, J = 1.3 Hz, J = 0.5
6.74 (d, J = 8.0 Hz, 1H), 2.12 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): Hz, 1H), 7.47-7.42 (m, 2H), 7.36-7.25 (m, 7H), 7.23 (s, 1H), 7.21-7.11
δ 161.3, 142.6, 140.9, 140.7, 140.3, 137.5, 135.1, 134.2, 131.2, (m, 3H), 6.97-6.92 (m, 2H), 6.78-6.69 (m, 3H). 13C{1H} NMR (CDCl3,
130.6, 129.9, 129.4, 129.3, 128.9, 127.7, 127.5, 127.2, 126.9, 126.7, 100 MHz): δ 162.3 (d, J = 247.0 Hz), 161.0, 142.5, 140.7, 140.3,
126.2, 126.1, 123.4, 121.0, 120.7, 116.4, 110.5, 91.5, 21.4. MS (EI, 136.3 (d, J = 3.0 Hz), 134.8, 134.0, 131.2, 130.7, 129.8, 129.4, 129.3,
70 eV; m/z (relative intensity)): 400 ([M + 2], 3), 399 ([M + 1], 19), 128.2 (d, J = 8.0 Hz), 127.6, 127.4, 126.9, 126.3, 125.8, 121.1, 120.7,
398 (60), 383 (4), 321 (68), 307 (100), 276 (11), 205 (4), 160 (10), 116.5, 114.7 (d, J = 21.0 Hz), 110.5, 90.8. MS (EI, 70 eV; m/z (relative
138 (4). HRMS (ESI-TOF) m/z calcd for C30H23O [M + H]+: 399.1749. intensity)): 403 ([M + 1], 20), 402 (61), 325 (100), 307 (95), 276 (12),
Found: 399.1752.
205 (5), 162 (11), 153 (12). HRMS (ESI-TOF) m/z calcd for C29H20FO
[M + H]+: 403.1498. Found: 403.1503.
6-phenyl-5a-(o-tolyl)-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
(2d): Isolated by column chromatography (hexane as eluent) as a 5a-phenyl-6-(p-tolyl)-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
yellow viscous oil. Yield: 0.054 g (55 %). 1H NMR (CDCl3, 400 MHz): δ (2h): Isolated by column chromatography (hexane as eluent) as a
1
7.51-7.42 (m, 4H), 7.35-7.21 (m, 5H), 7.20-7.02 (m, 4H), 6.99-6.87 white yellow solid. Yield: 0.069 g (70 %), mp 170-173 °C. H NMR
(m, 4H), 6.85-6.79 (m, 1H), 6.65 (d, J = 8.0 Hz, 1H), 2.19 (s, 3H). (CDCl3, 400 MHz): δ 7.56 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H),
13C{1H} NMR (CDCl3, 100 MHz): δ 161.9, 141.8, 141.7, 139.9, 138.2, 7.33-7.24 (m, 4H), 7.23 (s, 1H), 7.21-7.01 (m, 8H), 6.99-6.90 (m, 2H),
135.3, 135.2, 134.3, 132.2, 130.6, 130.2, 129.4, 129.1, 129.0, 128.7, 6.75 (d, J = 8.0 Hz, 1H), 2.36 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz):
128.2, 127.5, 127.2, 126.4, 126.3, 125.8, 124.6, 121.1, 120.5, 114.6, δ 161.3, 142.5, 140.7, 140.4, 137.8, 137.0, 135.0, 134.0, 131.2,
109.9, 92.7, 21.7. MS (EI, 70 eV; m/z (relative intensity)): 400 ([M + 130.5, 129.8, 129.2, 128.9, 128.2, 128.0, 127.8, 126.6, 126.2, 126.1,
2], 3), 399 ([M + 1], 33), 398 (100), 383 (7), 321 (24), 307 (67), 276 120.9, 120.6, 116.5, 110.5, 91.5, 21.1. MS (EI, 70 eV; m/z (relative
(17), 205 (11), 176 (12). HRMS (ESI-TOF) m/z calcd for C30H23O [M + intensity)): 399 ([M+1], 10), 398 (47), 321 (100), 307 (72), 276 (14),
H]+: 399.1749. Found: 399.1755.
253 (16), 207 (15), 177 (9). HRMS (ESI-TOF) m/z calcd for C30H23O
[M + H]+: 399.1749. Found: 399.1758.
5a-(3-methoxyphenyl)-6-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
b]benzofuran (2e): Isolated by column chromatography (hexane as 5a-phenyl-6-(m-tolyl)-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
1
eluent) as a white yellow viscous oil. Yield: 0.083 g (81 %). H NMR (2i): Isolated by column chromatography (hexane as eluent) as a
1
(CDCl3, 400 MHz): δ 7.52 (ddd, J = 7.6 Hz, J = 1.3 Hz, J = 0.5 Hz, 1H), white yellow viscous oil. Yield: 0.080 g (80 %). H NMR (CDCl3, 400
7.48-7.42 (m, 2H), 7.35-7.26 (m, 5H), 7.21 (s, 1H), 7.20-7.11 (m, 3H), MHz): δ 7.57-7.47 (m, 1H), 7.36-6.99 (m, 15H), 6.97-6.89 (m, 2H),
6.99 (t, J = 8.0 Hz, 1H), 6.96-6.92 (m, 2H), 6.90 (ddd, J = 7.8 Hz, J = 6.77-6.71 (m, 1H), 2.33 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ
1.7 Hz, J = 1.1 Hz, 1H), 6.86-6.83 (m, 1H), 6.77-6.73 (m, 1H), 6.62 161.3, 142.7, 140.9, 140.5, 140.4, 137.1, 135.0, 134.1, 131.2, 130.6,
(ddd, J = 8.0 Hz, J = 3.0 Hz, J = 1.0 Hz, 1H), 3.52 (s, 3H). 13C{1H} NMR 129.9, 129.8, 129.2, 128.1, 128.0, 127.9, 127.4, 126.7, 126.6, 126.3,
(CDCl3. 100 MHz): δ 161.2, 159.2, 142.3, 142.2, 140.9, 140.7, 135.0, 126.1, 126.0, 121.0, 120.7, 116.4, 110.5, 91.5, 21.4. MS (EI, 70 eV;
134.1, 131.3, 130.6, 130.0, 129.5, 129.3, 128.9, 127.5, 127.3, 126.8, m/z (relative intensity)): 399 ([M + 1], 13), 398 (47), 321 (100), 307
126.2, 126.0, 121.0, 120.8, 118.5, 116.6, 113.6, 112.1, 110.5, 91.2, (83), 276 (15), 207 (11), 163 (6), 153 (8). HRMS (ESI-TOF) m/z calcd
55.0. MS (EI, 70 eV; m/z (relative intensity)): 415 ([M + 1], 14), 414 for C30H23O [M + H]+: 399.1749. Found: 399.1755.
(42), 337 (58), 321 (10), 307 (100), 276 (10), 207 (4), 163 (6), 138
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2016
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Page 9 of 12
Green Chemistry
Journal Name
5a-phenyl-6-(o-tolyl)-5aH-benzo[4,5]cyclohepta[1,2-b]benzofuran
ARTICLE
6-(4-chlorophenyl)-5a-phenyl-5aH-benzo[4,5]cycloheVpietwa[A1rt,i2cl-e Online
DOI: 10.1039/C6GC02423H
(2j): Isolated by column chromatography (hexane as eluent) as a b]benzofuran (2n): Isolated by column chromatography (hexane as
1
1
white yellow viscous oil. Yield: 0.089 g (90 %). H NMR (CDCl3, 400 eluent) as a white yellow viscous oil. Yield: 0.086 g (83 %). H NMR
MHz): δ 7.53 (d, J = 7.6 Hz, 1H), 7.40-7.10 (m, 12H), 7.09-6.98 (m, (CDCl3, 400 MHz): δ 7.55-7.51 (m, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.34-
3H), 6.91 (td, J = 7.6 Hz, J = 0.7 Hz, 1H), 6.74-6.67 (m, 2H), 1.96 (s, 7.23 (m, 6H), 7.22-7.00 (m, 7H), 6.94 (td, J = 7.5 Hz, J = 0.9 Hz, 1H),
3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.5, 142.0, 140.9, 140.5, 6.91 (s, 1H), 6.77-6.72 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ
140.0, 137.1, 134.8, 134.4, 131.3, 130.7, 130.2, 129.8, 129.5, 128.9, 161.1, 142.5, 140.2, 139.5, 138.9, 134.7, 134.1, 133.3, 131.3, 130.7,
127.9, 127.8, 127.2, 126.9, 126.3, 126.1, 125.9, 124.9, 121.0, 120.8, 130.6, 129.9, 129.6, 128.2, 128.0, 127.7, 127.0, 126.3, 126.1, 126.0,
117.0, 110.5, 91.7, 20.2. MS (EI, 70 eV; m/z (relative intensity)): 400 121.2, 120.8, 116.6, 110.5, 91.2. MS (EI, 70 eV; m/z (relative
([M + 2], 3), 399 ([M + 1], 19), 398 (59), 321 (100), 307 (39), 276 intensity)): 420 ([M + 2], 18), 419 ([M + 1], 18), 418 (56), 341 (100),
(10), 205 (3), 169 (6), 138 (4). HRMS (ESI-TOF) m/z calcd for C30H23O 307 (85), 276 (27), 205 (9), 176 (12), 153 (25). HRMS (ESI-TOF) m/z
[M + H]+: 399.1749. Found: 399.1753.
calcd for C29H20ClO [M + H]+: 419.1203. Found: 419.1225.
6-(4-methoxyphenyl)-5a-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
6-(4-fluorophenyl)-5a-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
b]benzofuran (2k): Isolated by column chromatography (hexane as b]benzofuran (2o): Isolated by column chromatography (hexane as
eluent) as a white yellow solid. Yield: 0.081 g (79 %), mp 163-166 °C. eluent) as a yellow viscous oil. Yield: 0.088 g (88 %). 1H NMR (CDCl3,
1H NMR (CDCl3, 400 MHz): δ 7.50 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 8.7 400 MHz): δ 7.53 (ddd, J = 7.6 Hz, J = 1.3 Hz, J = 0.6 Hz, 1H), 7.45-
Hz, 2H), 7.34-7.22 (m, 4H), 7.20 (s, 1H), 7.18-7.00 (m, 6H), 6.95-6.88 7.38 (m, 2H), 7.33-7.24 (m, 4H), 7.22 (s, 1H), 7.21-7.12 (m, 3H),
(m, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 3.76 (s, 3H). 7.11-7.04 (m, 3H), 7.03-6.91 (m, 3H), 6.91 (s, 1H), 6.75-6.72 (m, 1H).
13C{1H} NMR (CDCl3, 100 MHz): δ 161.2, 159.0, 142.4, 140.5, 140.3, 13C{1H} NMR (CDCl3, 100 MHz): δ 162.2 (d, J = 247.0 Hz), 161.1,
135.1, 134.0, 133.2, 131.2, 130.6, 130.5, 129.8, 128.5, 128.0, 127.9, 142.5, 140.2, 139.6, 136.5 (d, J = 3.0 Hz), 134.8, 134.1, 131.3, 131.0
126.5, 126.2, 126.1, 126.0, 121.0, 120.7, 116.5, 113.0, 110.4, 91.6, (d, J = 8.0 Hz), 130.7, 129.9, 129.3, 128.2, 128.0, 126.9, 126.2, 126.1,
55.2. MS (EI, 70 eV; m/z (relative intensity)): 415 ([M + 1], 15), 414 126.0, 121.1, 120.7, 116.6, 114.4 (d, J = 21.0 Hz), 110.4, 91.3. MS
(48), 337 (100), 307 (65), 293 (19), 276 (8), 207 (7), 163 (7). HRMS (EI, 70 eV; m/z (relative intensity)): 403 ([M + 1], 16), 402 (50), 325
(ESI-TOF) m/z calcd for C30H23O2 [M + H]+: 415.1698. Found: (100), 307 (58), 276 (8), 205 (5), 176 (4), 153 (13). HRMS (ESI-TOF)
415.1708.
m/z calcd for C29H20FO [M + H]+: 403.1498. Found: 403.1503.
6-(3-methoxyphenyl)-5a-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
5a-phenyl-6-(3-(trifluoromethyl)phenyl)-5aH-
b]benzofuran (2l): Isolated by column chromatography (hexane as benzo[4,5]cyclohepta[1,2-b]benzofuran (2p): Isolated by column
eluent) as a yellow viscous oil. Yield: 0.072 g (70 %). 1H NMR (CDCl3, chromatography (hexane as eluent) as a white yellow solid. Yield:
1
400 MHz): δ 7.56-7.50 (m, 1H), 7.34-7.02 (m, 13H), 7.00-6.97 (m, 0.061 g (54 %), mp 59-61 °C. H NMR (CDCl3, 400 MHz): δ 7.71 (s,
1H), 6.96-6.90 (m, 2H), 6.85 (ddd, J = 8.2 Hz, J = 2.6 Hz, J = 1.0 Hz, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.56 (d, J = 7.5 Hz, 2H), 7.46-7.37 (m,
1H), 6.75 (d, J = 8.0 Hz, 1H), 3.73 (s, 3H). 13C{1H} NMR (CDCl3, 100 1H), 7.36-7.02 (m, 11H), 7.01-6.90 (m, 2H), 6.73 (d, J = 8.0 Hz, 1H).
MHz): δ 161.3, 159.0, 142.7, 142.1, 140.8, 140.5, 134.9, 134.3, 13C{1H} NMR (CDCl3, 100 MHz): δ 161.1, 142.8, 141.3, 140.2, 139.5,
131.4, 130.7, 130.0, 129.4, 128.5, 128.1, 128.0, 126.9, 126.3, 126.2, 134.7, 134.5, 132.9, 131.4, 130.9, 130.3 (quart, J = 32.0 Hz), 130.2,
126.1, 122.1, 121.1, 120.8, 116.6, 115.1, 113.1, 110.6, 91.5, 55.3. 130.0, 128.3, 128.0, 127.9, 127.2, 126.3, 126.2 (2C), 126.0, 124.3
MS (EI, 70 eV; m/z (relative intensity)): 415 ([M + 1], 18), 414 (65), (quart, J = 272.0 Hz), 124.0 (quart, J = 4.0 Hz), 121.3, 120.8, 116.7,
337 (99), 307 (100), 293 (17), 276 (11), 207 (13), 163 (9). HRMS (ESI- 110.6, 91.2. MS (EI, 70 eV; m/z (relative intensity)): 453 ([M + 1],
TOF) m/z calcd for C30H23O2 [M + H]+: 415.1698. Found: 415.1703.
14), 452 (45), 375 (100), 307 (69), 276 (11), 205 (5), 176 (5), 153
(20). HRMS (ESI-TOF) m/z calcd for C30H20F3O [M + H]+: 453.1466.
Found: 453.1471.
6-(2-methoxyphenyl)-5a-phenyl-5aH-benzo[4,5]cyclohepta[1,2-
b]benzofuran (2m): Isolated by column chromatography (hexane as
1
eluent) as a white solid. Yield: 0.084 g (82 %), mp 138-140 °C. H 5a-(3-methoxyphenyl)-6-(4-methoxyphenyl)-5aH-
NMR (CDCl3, 400 MHz): δ 7.57 (d, J = 7.3 Hz, 1H), 7.42 (sl, 1H), 7.36- benzo[4,5]cyclohepta[1,2-b]benzofuran (2q): Isolated by column
7.23 (m, 5H), 7.21 (d, J = 7.5 Hz, 1H), 7.18-6.88 (m, 8H), 6.79 (s, 1H), chromatography (hexane as eluent) as a yellow solid. Yield: 0.083 g
1
6.74 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H), 3.19 (s, 3H). 13C{1H} (75 %), mp 156-159 °C. H NMR (CDCl3, 400 MHz): δ 7.52 (ddd, J =
NMR (CDCl3, 100 MHz): δ 162.4, 157.8, 142.9, 139.9, 139.2, 134.8, 7.6 Hz, J = 1.3 Hz, J = 0.6 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7.35-7.26
134.7, 130.7, 130.6, 130.5, 130.3, 129.7, 128.8, 128.2, 127.6, 127.5, (m, 2H), 7.21 (s, 1H), 7.20-7.10 (m, 3H), 7.02-6.96 (m, 1H), 6.95-6.89
126.4, 126.3, 125.8, 120.6, 120.4, 120.1, 115.9, 110.1, 109.8, 91.4, (m, 3H), 6.88-6.82 (m, 3H), 6.78-6.74 (m, 1H), 6.62 (ddd, J = 8.0 Hz, J
54.6. MS (EI, 70 eV; m/z (relative intensity)): 416 ([M + 2], 4), 415 = 2.6 Hz, J = 1.0 Hz, 1H), 3.80 (s, 3H), 3.53 (s, 3H). 13C{1H} NMR
([M + 1], 23), 414 (69), 337 (100), 321 (52), 307 (60), 292 (8), 276 (CDCl3, 100 MHz): δ 161.2, 159.1, 159.0, 142.2, 142.1, 140.4, 135.1,
(8), 207 (6), 168 (9). HRMS (ESI-TOF) m/z calcd for C30H23O2 [M + 134.0, 133.3, 131.3, 130.6, 130.5, 129.9, 128.9, 128.6, 126.6, 126.2,
H]+: 415.1698. Found: 415.1700.
126.1, 121.0, 120.7, 118.6, 116.6, 113.5, 113.0, 112.2, 110.4, 91.4,
55.2, 55.0. MS (EI, 70 eV; m/z (relative intensity)): 446 ([M + 2], 2),
445 ([M + 1], 16), 444 (50), 429 (2), 413 (3), 337 (100), 321 (6), 293
This journal is © The Royal Society of Chemistry 2016
J. Name., 2013, 00, 1-3 | 9
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Green Chemistry
Page 10 of 12
ARTICLE
Journal Name
(15), 265 (4), 163 (4). HRMS (ESI-TOF) m/z calcd for C31H25O3 [M + 1H), 7.52-6.84 (m, 20.7H), 6.67-6.62 (m, 0.2H), 6.39-6.33 (m, 1H).
View Article Online
13
1
H]+: 445.1804. Found: 445.1810.
DOI: 10.1039/C6GC02423H
C{ H} NMR (CDCl3, 100 MHz): δ 161.5, 161.0, 142.1, 140.4, 139.7,
139.3, 139.0, 138.5, 138.1, 134.8, 134.7, 134.5, 133.9, 133.3, 132.9,
132.6, 131.3, 131.1, 130.7, 130.6, 130.3, 130.2, 130.1, 130.0, 128.6,
128.3, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.1, 127.0, 126.9,
126.8, 126.7, 126.4, 126.2, 126.1, 126.0, 125.9, 125.8, 125.4, 125.3,
124.9, 124.6, 121.1, 121.0, 120.9, 120.7, 117.1, 116.8, 110.6, 110.5,
91.8. MS (EI, 70 eV; m/z (relative intensity)): 436 ([M + 2], 4), 435
([M + 1], 26), 434 (75), 357 (100), 326 (11), 307 (35), 217 (3), 178
(13), 163 (10). HRMS (ESI-TOF) m/z calcd for C33H23O [M + H]+:
435.1749. Found: 435.1760.
5a-(4-fluorophenyl)-6-(4-methoxyphenyl)-5aH-
benzo[4,5]cyclohepta[1,2-b]benzofuran (2r): Isolated by column
chromatography (hexane as eluent) as a white yellow solid. Yield:
0.064 g (60 %), mp 75-78 °C. 1H NMR (CDCl3, 400 MHz): δ 7.53 (ddd,
J = 7.6 Hz, J = 1.3 Hz, J = 0.5 Hz, 1H), 7.40 (d, J = 8.9 Hz, 2H), 7.35-
7.09 (m, 8H), 6.94 (td, J = 7.6 Hz, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.86 (d,
J = 8.9 Hz, 2H), 6.78-6.70 (m, 3H), 3.81 (s, 3H). 13C{1H} NMR (CDCl3,
100 MHz): δ 162. 3 (d, J = 247. 0 Hz), 161.1, 159.1, 142.5, 140.3,
136.4 (d, J = 3.0 Hz), 135.0, 133.9, 133.0, 131.2, 130.7, 130.6, 129.8,
128.5, 128.2 (d, J = 8.0 Hz), 126.7, 126.2, 125.9, 121.1, 120.7, 116.5,
114.7 (d, J = 22.0 Hz), 113.0, 110.5, 91.0, 55.2. MS (EI, 70 eV; m/z
(relative intensity)): 434 ([M + 2], 4), 433 ([M + 1], 30), 432 (96), 417
(3), 401 (3), 337 (100), 325 (99), 294 (20), 276 (4), 168 (11). HRMS
(ESI-TOF) m/z calcd for C30H22FO2 [M + H]+: 433.1604. Found:
433.1609.
Acknowledgements
We are grateful to FAPERGS, CAPES and CNPq for financial support.
CNPq and CAPES are also acknowledged for the fellowships (R.G.
and G. Z.).
5a-phenyl-6-(thiophen-3-yl)-5aH-benzo[4,5]cyclohepta[1,2-
Notes and references
b]benzofuran (2s): Isolated by column chromatography (hexane as
1
eluent) as a white yellow viscous oil. Yield: 0.073 g (75 %). H NMR
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MHz): δ 161.0, 142.2, 141.1, 140.2, 135.5, 134.8, 134.3, 131.2,
130.7, 129.8, 129.2, 128.1, 128.0, 127.9, 126.7, 126.3, 126.2, 126.1,
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1
eluent) as a white yellow viscous oil. Yield: 0.097 g (90 %). H NMR
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(s, 1H), 7.19-7.06 (m, 6H), 7.05 (s, 1H), 6.93 (td, J = 7.6 Hz, J = 0.9 Hz,
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Found: 435.1758.
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10 | J. Name., 2012, 00, 1-3
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Green Chemistry
Journal Name
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Green Chemistry
Page 12 of 12
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DOI: 10.1039/C6GC02423H
Table of Contents
We present the results on the intramolecular transition metal-free cyclization of (2-
alkynylphenyl) benzyl ethers promoted by sodium tert-butoxide.