Modular Assembly of Furotropones and Benzofurotropones, and Study of Their Physicochemical Properties

Article abstract of DOI:10.1021/acs.joc.5b00226

A rapid and straightforward synthesis of a novel series of furo[2,3-d]tropones (or cyclohepta[b]furan-6-ones) has been developed starting from readily and commercially available materials. Directed α-lithiation of furan-3-carboxaldehydes and subsequent re

Full text of DOI:10.1021/acs.joc.5b00226

Article
pubs.acs.org/joc
Modular Assembly of Furotropones and Benzofurotropones, and
Study of Their Physicochemical Properties
Rajendra P. Shirke and S. S. V. Ramasastry*
Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, SAS Nagar,
Manuali, Punjab 140 306, India
S
* Supporting Information
ABSTRACT: A rapid and straightforward synthesis of a novel
series of furo[2,3-d]tropones (or cyclohepta[b]furan-6-ones)
has been developed starting from readily and commercially
available materials. Directed α-lithiation of furan-3-carbox-
aldehydes and subsequent reaction with a variety of aldehydes
efficiently provide, in one step, access to 3-formyl-2-
furylcarbinols, which are otherwise only accessible with
difficulty. The 3-formyl-2-furylcarbinols are further elaborated
in two steps to the synthesis of furo[2,3-d]tropones in good
yields via sequential bismuth(III)chloride-catalyzed furfuryla-
tion and an unusual base promoted cyclization strategy. Thus,
diverse polysubstituted furotropones and benzofurotropones can be rapidly assembled. This methodology thereby offers a
potential approach for the synthesis of several bioactive natural products containing cyclohepta[b]furan core and also for the
buildup of complex molecular architectures through higher order cycloaddition reactions of tropones. Further, the new
chromophores have been found to possess promising fluorescence properties. Selective fluorogenic sensing behavior of
furotropones toward Fe3+ ions has also been elucidated.
starting compounds, (ii) harsh reaction conditions, (iii) poor
yields, (iv) limited substrate scope (that hinders diversifica-
tion). Herein we describe general synthesis of a variety of furo-
and benzofuro[2,3-d]tropones, study of their physicochemical
properties, and especially their ability in cation sensing.
INTRODUCTION
■
Among nonbenzenoid aromatics, tropones have been studied in
great detail from synthetic and theoretical standpoint.1
Occurrence of several troponoid natural products possessing
interesting biological activities spurred several studies directed
toward understanding structure activity relationships as well as
their physicochemical properties.2 Tropones traditionally have
been employed in several higher order cycloaddition reactions3
and quite often as synthons in natural product synthesis.4
Among annulated tropone derivatives, aryl-annulated tropones
are well-studied, while heteroaryl-annulated tropones are
mostly unfamiliar.5 A detailed literature review exposes lack
of synthetically flexible methods for the synthesis of heteroaryl-
annulated tropones and also a general understanding about
their physical and biological properties is particularly missing.
Toward this, we have initiated research to establish a short,
efficient and scalable approach for the synthesis of previously
unknown furo[2,3-d]tropones from readily available starting
materials. Known methods for the synthesis of furo[2,3-
d]tropones are depicted in Scheme 1.6 The key step in El-Borai
and Shafiee’s approach (method-1, Scheme 1) for tropones
involved the cyclocondensation of furan or benzofuran-2,3-
dicarboxaldehydes I and ketones II under strong basic
conditions.6a,b On the other hand, Takeshita’s Claisen
rearrangement of (E/Z)-4-(3-chloro-2-propenyloxy)tropones
III under thermal conditions furnished furo[2,3-d]tropones
(method-2, Scheme 1).6c Evidently, these methods are
associated with the drawbacks such as (i) difficult-to-access
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Tropones. A general
approach toward the synthesis of furotropones is depicted in
Scheme 2. To begin with, commercially available 3-
furancarboxaldehydes of the type A are converted to 3-
formyl-2-furylcarbinols B in a single step via regioselective
directed α-lithiation-alkylation strategy published earlier by our
research group.7 Following this strategy, aldehyde functionality
in 3-furancarboxaldehydes A can be masked by treatment with
lithium N-methylpiperazide [LNMP, obtained by the reaction
of N-methylpiperazine (NMP) and n-BuLi]. Chelation
controlled lithiation of the resulting adduct at the C-2 position
with n-BuLi generates 2-lithiofurans in highly selective manner.
Reaction of 2-lithiofurans with aldehydes (or ketones) and
subsequent hydrolysis generates conveniently 3-formyl-2-
furylcarbinols B. Bismuth(III) catalyzed reaction of furylcarbi-
nols B and 1,3-dicarbonyls C generate the tricarbonyls D in
very good yields via intermolecular Friedel−Crafts-type
reaction.8 Base mediated intramolecular aldol condensation of
Received: January 31, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 1. Known Methods for the Synthesis of Furo[2,3-d]tropones
Scheme 2. One-Step Synthesis of 3-Formyl-2-furyl Carbinols (B) and a Two-Step Synthesis of Furotropones and
Benzofurotropones (E)
diketoaldehydes D delivers furotropones E in good to excellent
yields via cyclization of the dienolates F on to the appropriately
positioned aldehyde functionality and subsequent aerobic
oxidative aromatization of G.7 This method thus constitutes a
general, short, efficient and straightforward approach for the
synthesis of cyclohepta[b]furan-6-ones (commonly referred to
as furotropones). Some advantages of furan-based strategies are
the ready availability of starting materials, ease of manipulation
and high degree of synthetic flexibility.
Since the general synthetic approach described in Scheme 2
permits diversity across the aldehydes A and H, and the
dicarbonyls C, a variety of highly functionalized furotropones
and benzofurotropones (3a−3n) could be rapidly synthesized,
Table 1. All the new compounds were fully characterized by
comprehensive spectroscopic data. All of these heteroaryl-
annulated tropones exhibited good solubility profiles in
common organic solvents such as toluene, DCM, THF,
DMSO, DMF, ethanol, ACN, etc., at room temperature itself.
Most of the tropones were isolated as colorless to pale yellow
solids.
Tropones possessing both aliphatic and aromatic β-ketone
functionality (at C-7) could be accessed efficiently via this
methodology (Table 1, entries 1−9), in addition to a diverse
range of aryls and heteroaryls at C-8. More interestingly,
tropones with β,β′-diketones are of particular interest from
synthesis point of view (Table 1, entries 10−12). This novel
class of tropones can be accessed by the reaction of triketones
such as 2d and 3-formyl-2-furylcarbinols under standard
conditions. This methodology is found to be particularly
efficient in establishing a short and scalable method for the
synthesis of new benzofurotropones in good yields (Table 1,
entries 13 and 14).
By virtue of the inherent restrictions the mechanism involves,
there exist certain structural limitations for 1,3-dicarbonyls. For
B
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 1. Scope of Various Aldehydes and 1,3-Dicarbonyls for the Synthesis of a Variety of Furotropones and Benzofurotropones
example, cyclic diketones (such as 1,3-cyclohexanedione 2f or
the β-ketoester 2g) cannot form tropones obviously because of
the inaccessibility of dienolate intermediates toward the
aldehydic carbonyl, even otherwise also would lead to highly
energetic bridged structures. Likewise, the diketones of the type
1,3-diphenyl-1,3-propanedione 2h (not possessing α-acidic
protons and thus dienolate formation is hindered) or 2i cannot
generate tropones. Indeed we prepared respective tricarbonyls
with the general structure D with aforementioned dicarbonyls,
attempted base mediated intramolecular aldol reaction was
unsuccessful and yielded no meaningful product. In addition,
step-III failed to deliver tropones in cases where R1 is aliphatic.
Interestingly, reaction of 3-formyl-2-furylcarbinols 3a1 and
3c1, and 3-methylpentane-2,4-dione 2e under bismuth(III)
C
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 3. Synthesis of C-7 and C-8 Disubstituted Furotropones via Retro-Claisen Condensation
Scheme 4. Synthesis of Mono (C-8) Substituted Furotropones via in Situ Ethoxy Decarbonylation
Scheme 5. Synthesis of 2,3′-Bifuran Derivatives
catalysis generated expectedly the diketoaldehyde 3o2 and 3p2.
Reaction of 3o2 and 3p2 under base mediated reaction
furnished, surprisingly, 7,8-disubstituted furotropones 3o and
3p, respectively, in good yields, presumably via a retro-Claisen-
aromatization sequence as shown in Scheme 3. After the initial
aldol condensation, in order to attain aromaticity, the 7,7,8-
trisubstituted cyclohepta[b]furan-6-ones 3o3 and 3p3 undergo
base-mediated retro-Claisen cleavage followed by aromatization
to form furotropones 3o and 3p, respectively.
presence of a catalytic amount of bismuth(III)chloride, under
standard reaction conditions not only furnished the β-
ketoesters 3q3, 3r3 and 3s3, but subsequently underwent in
situ ethoxy decarbonylation, generating mono (C-8) sub-
stituted furotropones 3q, 3r and 3s, respectively, in good yields,
Scheme 4. However, the reaction can be interrupted
prematurely to isolate the β-ketoesters, but the case of
furotropone 3i may be an exception where formation of ethoxy
decarbonylation product was not observed even after prolonged
reaction times.
Further, reaction of the tricarbonyls 3q2, 3r2 and 3s2, which
were obtained by the reaction of 3-formyl-2-furylcarbinols 3a1,
3c1 and 3s1, and ethyl acetoacetate 2c, respectively, in the
Of particular interest, reaction of the diketoaldehyde 3t2,
possessing a pendent alkyne functionality, under standard base
D
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
mediated conditions failed to generate the expected furotro-
pone 3t; however, to our surprise, it yielded a 2,3′-bifuran
derivative 4 in 78% yield in a mechanism described in Scheme
5. Subtle variations across the alkynes and/or diketones can
potentially generate an array of functionalized 2,3′-bifuran
derivatives.9 This method thus can be a general approach for
the synthesis of otherwise difficult to access, functionalized and
highly substituted bifuran derivatives.
Several natural products possessing cyclohepta[b]furan core
are known in the literature, some of the representative examples
are depicted in Figure 1. This methodology can be very much
Figure 1. Some natural products possessing cyclohepta[b]furan core.
convenient for developing short synthesis of several of these
bioactive compounds. For example, frondosin B, liphagal and
other natural products are synthetic challenges with their wide
structural diversity and stereochemical features coupled with
their interesting biological activity profiles.10
Crystal Structure of the Furotropone 3j. Molecular
structure of the tropone 3j was confirmed by single crystal X-
ray diffraction analysis and the molecular packing arrangement
in the solid state were further analyzed (see Supporting
Information for details), Figure 2.
Photophysical Properties. In order to better understand
the photophysical properties of the newly synthesized
furotropones in detail, initially UV−vis absorption spectra of
the furotropone 3q under various solvent systems were
recorded and the results are summarized in Figure 3a. A
Figure 3. (a) UV−vis absorption spectra of 3q (10 μM) in different
solvents, and (b) fluorescence emission spectra of 3q (10 μM) in
different solvents.
striking impact of solvents on the UV absorption pattern was
witnessed. Among the solvents screened, a nonpolar solvent
such as toluene at 10 μM concentration exhibited an absorption
maximum at 332 nm (due to n−π* transition) while in a polar
solvent DMSO at the same concentration, 3q displayed an
absorption maximum at 338 nm, essentially indicating a
bathochromic shift (red shift) of about 6 nm. On the other
hand, a hypsochromic shift (blue shift) of about 18 nm was
observed in case of π−π* transitions for furotropone 3q from
toluene to DMSO. Further, UV−vis absorption spectra of few
other di- and triketofurotropones (3b, 3c, 3e, 3g, 3h, 3j, 3k)
were also recorded (see Supporting Information for details).
Subsequently, the fluorescence emission spectra of furo-
tropne 3q were also recorded in different solvents at 10 μM
concentration and the results are summarized in Figure 3b and
Table 2. Fluorescence emission patterns were found to be
strongly solvent dependent. Solvent effect was more
pronounced in n−π* transition when excited the molecule at
340 nm. Interestingly, maximum Stokes shift (97 nm) was
observed in DMSO and also in ethanol (94 nm) while
minimum Stokes shift was realized in acetone (41 nm).
Fluorescence life expectancy (τf) was found to be maximum in
THF (5.89 ns) and it was found to be least in ethanol (1.34
ns). These results perhaps indicate inherently rigid electronic
nature and thus least solvent polarity dependency of
Figure 2. ORTEP diagram of 3j (CCDC 1046548) with 50%
ellipsoidal probability.
E
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 2. Photophysical Data of 3q in Different Solvents
a
b
c
d
solvent
λabs (nm)
ε
log ε
λemi (nm)
Δλstokes (nm)
τf (ns)
Φf
THF
ACN
256, 330
260, 334
284, 332
266, 338
210, 334
256, 332
244, 337
10.84
8.722
4.17
5.09
8.34
7.9
1.0350
0.940
0.620
0.7067
0.921
0.8976
0.977
402
410
406
435
375
376
431
72
76
74
97
41
44
94
5.89
3.13
2.38
3.31
1.41
1.47
1.34
0.0048
0.0145
0.0011
0.0017
0.0036
0.0083
0.0081
toluene
DMSO
acetone
EtOAc
ethanol
9.485
a
b
c
THF: tetrahydrofuran; ACN: acetonitrile; DMSO: dimethyl sulfoxide; EtOAc: ethyl acetate. π−π* and n−π* absorption maxima. Stokes shift =
d
abs
emi
λmax − λmax
. Fluorescent lifetime.
furotropones. These results further point to their strong
nonpolar character and also possible absence of push−pull
electronic effects in the excited state. From Table 2, it can also
be noted that the molar absorptivity (ε) for 3q in toluene
solution is found to be minimum (4.17) and in THF solvent, it
is maximum (10.84). Fluorescence emission spectra of few
other furotropones (3b, 3c, 3e, 3g, 3h, 3j, 3k) were recorded
and their fluorescence lifetimes were also measured in ethanol,
which indicated that the lifetimes lie within 1.08 to 1.44 ns (see
Supporting Information for details).
Interesting electronic and spectroscopic properties, along
with the presence of the 1,3- di- and 1,3,5-triketo groups in
unique molecular environment inspired us to explore the
application of furotropones as fluorescent chemosensors for
cations with the potential to coordinate to these functionalities.
Furotropone 3b was chosen as a model substrate and exposed
to the aqueous solutions of different metal salts11 in ethanol.
Almost no change in the fluorescence intensity was observed
when solutions of other metal ions such as Hg2+, Pb2+, Cr2+,
Cd2+, Ag+, Zn2+, Cu2+, Co2+, Fe2+, Ni2+ were tested.
Furotropone 3b was found to exhibit an interesting and highly
selective fluorescent molecular sensing property for Fe3+, Figure
4.12 We surmised that the 1,3-dicarbonyl moiety in 3b could
prefer interaction with the soft π-surfaces. Decreasing the metal
ion concentration (up to 10 μM), significant influence on the
fluorescence intensity was observed. From this study we have
realized that furotropone 3b (and potentially other analogues)
could function as a probe for the detection of Fe3+ up to 10 μM
concentration.
CONCLUSIONS
■
In summary, we have developed a modular approach to rapidly
access functionalized and polysubstituted furotropones and
benzofurotropones starting from readily accessible materials.
The three-step protocol features directed α-alkylation of 3-
furancarboxaldehydes, Bi(III)-mediated furfurylation and an
unusual base-mediated intramolecular aldol condensation
reaction. Mono substituted (C-8) furotropones could be
accessed via in situ alkoxy decarbonylation of furotropone β-
ketoesters, disubstituted (C-7 and 8) furotropones could be
synthesized in a retro-Claisen-aromatization strategy, and
trisubstituted (C-5, 7 and 8) furotropones were conveniently
prepared by means of a base-mediated intramolecular aldol
reaction of 1,3,5-triketones. Moreover, studies directed at
understanding the physicochemical properties of furotropones
yielded interesting results. We have identified that these new
chromophores, with their unique structural features, have
potential to be highly sensitive and selective sensors for the
detection of hard cations such as Fe3+, and the detection limit
could be as low as 10 μM. We believe that our results could
provide guidance for the design and synthesis of new tropone-
based polycyclic aromatic heterocycles. Further synthetic
modifications of furotropones for chemosensor applications
are planned.
EXPERIMENTAL SECTION
■
General Experimental Methods. n-BuLi, 3-methyl benzofuran,
all the aldehydes, N-methylpiperazine, N,O-dimethylhydroxylamine
hydrochloride and solvents were purchased from commercial sources
and were used without further purification. For thin-layer chromatog-
raphy (TLC), silica aluminum foils with a fluorescent indicator (254
nm) were used and compounds were visualized by irradiation with UV
light and/or by treatment with a solution of p-anisaldehyde (23 mL),
concentrated H2SO4 (35 mL), and acetic acid (10 mL) in ethanol (900
mL) followed by heating. Column chromatography was performed
using silica gel 100−200 mesh (approximately 15−20 g per 1 g of the
crude product). Dry THF was obtained by distillation over sodium
and stored over sodium wire. IR spectra were recorded on a FT-IR
system as thin films or KBr pellets, as indicated, with νmax values given
in reciprocal centimeters. Melting points were recorded on a digital
melting point apparatus and were uncorrected. 1H NMR and 13C
NMR spectra were recorded on a 400 MHz FT-NMR spectrometer.
NMR shifts are reported as delta (δ) units in parts per million (ppm),
and coupling constants (J) are reported in hertz (Hz). The following
abbreviations are utilized to describe peak patterns when appropriate:
Figure 4. Selective sensing of Fe3+ by 3b in ethanol solvent with
different concentrations of Fe3+.
serve as a suitable bidentate ligand for Fe3+ while the fused ring
system could enhance the structural rigidity and change the π-
electron distribution. In other words, the hard cation such as
Fe3+ interacts with the hard oxygen atoms of the carbonyls
present in the furoptopone 3b. The possibility of cation-π
interactions are less favored since the hard cations will not
F
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
br = broad, s = singlet, d = doublet, t = triplet, q = quartet, and m =
multiplet. Proton chemical shifts are given in δ relative to
tetramethylsilane (δ 0.00 ppm) in CDCl3. Carbon chemical shifts
are internally referenced to the deuterated solvent signals in CDCl3 (δ
77.1 ppm). High-resolution mass spectra were recorded on a Q-TOF
mass spectrometer.
General Procedure for Step-II, Scheme 2 (Reaction of 3-
Formyl-2-furylcarbinols with Various 1,3-Dicarbonyls). To a
solution of furfuryl alcohol (0.1 mmol, 1 equiv) in nitromethane (1
mL), were added acetylacetone (0.11 mmol, 1.1 equiv) followed by
BiCl3 (0.02 mmol, 0.2 equiv) at room temperature. The reaction was
stirred at room temperature until the alcohol was consumed as
monitored by TLC, and the reaction mixture was quenched with
aqueous saturated sodium bicarbonate solution (1−2 mL). The
reaction mixture was diluted with ethyl acetate (1−2 mL), and the
layers were separated. The aqueous layer was further extracted with
ethyl acetate (1−2 mL). The organic layers were combined, dried over
Na2SO4, concentrated, and purified by silica gel column chromatog-
raphy (ethyl acetate−hexanes) to afford 1,3-dicarbonyl adducts in 60−
95% yields.
General Procedure for Step-I, Scheme 2 (Synthesis of 3-
Formyl-2-furylcarbinols Starting from 3-Furancarboxalde-
hyes). To a solution of N-methylpiperazine (NMP, 0.07 mL, 0.66
mmol) in THF (2 mL) at −78 °C was added n-BuLi (2 M in
cyclohexane, 0.33 mL, 0.66 mmol). After 15 min, 3-furaldehyde (50
mg, 0.045 mL, 0.52 mmol) was added, and then the reaction mixture
was stirred for an additional 30 min. A cyclohexane solution of n-BuLi
(0.66 mL, 1.32 mmol) was added, and the mixture was stirred for an
additional 15 min, and then the mixture was warmed to −30 °C in 2 h.
The solution was again cooled to −78 °C and an aldehyde (1.02
mmol) was added dropwise over 5 min. The mixture was warmed to
room temperature over 30 min. The reaction progress was monitored
by TLC. Reaction mixture was quenched with saturated aq.
ammonium chloride solution and extracted with ethyl acetate. The
organic extracts were combined, dried (Na2SO4), filtered, and
concentrated. The crude product was purified by column chromatog-
raphy on silica gel (ethyl acetate−hexanes) to afford 3-formyl-2-
furylcarbinols in 60−80% yields.
Spectral Data of 1,3-Dicarbonyl Adducts. Some of the 1,3-
dicarbonyl adducts prepared during study are already known in the
literature.7,8 Complete characterization data of newly synthesized
compounds is given below.
2-(2-Benzoyl-3-oxo-1-phenylbutyl)furan-3-carbaldehyde (3b2).
This compound was isolated as colorless liquid starting from 40 mg
of 3a1 and obtained 66 mg in 97% yield: Rf = 0.4 (EtOAc/Hexane =
3/7); IR (thin film, neat) νmax/cm−1 2925, 1722, 1673, 1600, 1546,
1443, 1325, 752; 1H NMR (400 MHz, CDCl3) δ 10.10 (s, 1H), 8.05−
8.02 (m, 2H), 7.62 (tt, J = 7.4 and 1.7 Hz, 1H), 7.52−7.47 (m, 4H),
7.38−7.35 (m, 2H), 7.31−7.27 (m, 1H), 7.18 (d, J = 1.9 Hz, 1H), 6.59
(d, J = 2.0 Hz, 1H), 5.78 (d, J = 11.5 Hz, 1H), 5.63 (d, J = 11.6 Hz,
1H), 2.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 200.9, 193.1,
184.7, 161.9, 142.4, 137.1, 135.9, 134.1, 129.2 (2CH), 128.9 (2CH),
128.8 (2CH), 128.4 (2CH), 128.1, 122.3, 108.7, 66.3, 43.6, 29.1;
HRMS (ESI) m/z calcd for C22H18O4Na (M + Na)+ 369.1103, found
369.1104.
Spectral Data of Newly Synthesized Alcohols. Some of the 3-
formyl-2-furylcarbinols prepared during this study are already known
in the literature.7,8 Complete characterization data of newly
synthesized compounds is given below.
2-(Hydroxy(thiophen-2-yl)methyl)furan-3-carbaldehyde (3g1).
This compound was isolated as colorless liquid: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 3372, 2872, 1672, 1580,
1
1516, 1422, 1237, 1127, 1024, 805; H NMR (400 MHz, CDCl3) δ
2-(2-Acetyl-1-(4-ethylphenyl)-3-oxobutyl)furan-3-carbaldehyde
(3c2). This compound was isolated as colorless liquid starting from 50
mg of 3c1 and obtained 67 mg in 95% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax/cm−1 2965, 1733, 1702, 1681, 1574,
1514, 1471, 1358, 1124, 746. 1H NMR (400 MHz, CDCl3) δ 10.05 (s,
1H), 7.34 (d, J = 2.0 Hz, 1H), 7.27 (m, 2H), 7.15 (d, J = 8.3 Hz, 2H),
6.68 (d, J = 2.0 Hz, 1H), 5.38 (d, J = 11.8 Hz, 1H), 4.92 (d, J = 12.0
Hz, 1H), 2.60 (q, J = 7.0 Hz, 2H), 2.17 (s, 3H), 2.03 (s, 3H), 1.20 (t, J
= 7.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.1, 200.9, 184.7,
161.9, 144.0, 142.5, 134.2, 128.7 (2CH), 128.0 (2CH), 122.0, 109.7,
71.7, 42.8, 30.2, 29.4, 28.3, 15.2; HRMS (ESI) m/z calcd for
C19H20O4Li (M + Li)+ 319.1522, found 319.1565.
2-(2-Benzoyl-1-(4-ethylphenyl)-3-oxobutyl)furan-3-carbaldehyde
(3d2). This compound was isolated as colorless liquid starting from 50
mg of 3c1 and obtained 76 mg in 94% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax /cm−1 2922, 1725, 1680, 1448, 1358,
1267, 1125, 1023, 748; 1H NMR (400 MHz, CDCl3) δ 10.12 (s, 1H),
8.03 (dd, J = 8.5 and 1.3 Hz, 2H), 7.62 (tt, J = 7.4 and 1.3 Hz, 1H),
7.51−7.48 (m, 2H), 7.39 (tt, J = 10.1 and 1.7 Hz, 2H), 7.20−7.147 (m,
3H), 6.58 (d, J = 2.0 Hz, 1H), 5.76 (d, J = 11.5 Hz, 1H), 5.60 (d, J =
11.5 Hz, 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.04 (s, 3H), 1.22 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 201.1, 193.2, 184.7, 162.3,
144.1, 142.3, 135.9, 134.1, 134.0, 128.9 (2CH), 128.8 (2CH), 128.7
(2CH), 128.3 (2CH), 122.2, 66.4, 43.2, 29.0, 28.4, 18.6, 15.3; HRMS
(ESI) m/z calcd for C24H22O4Na (M + Na)+ 397.1416, found
397.1432.
9.98 (s, 1H), 7.42 (d, J = 1.9 Hz, 1H), 7.32 (m, 1H), 6.98 (m, 2H),
6.83 (d, J = 1.9 Hz, 1H), 6.30 (d, J = 7.0 Hz, 1H), 4.69 (d, J = 7.0 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 187.0, 162.1, 143.7, 142.5,
126.9, 126.1, 125.2, 122.5, 110.2, 66.6; HRMS (ESI) m/z calcd for
C10H9O3S (M + H)+ 209.0272, found 209.0277.
2-([1,1′-Biphenyl]-4-yl(hydroxy)methyl)furan-3-carbaldehyde
(3i1). This compound was isolated as colorless liquid: Rf = 0.4
(EtOAc/Hexane = 3/7); IR (thin film, neat) νmax/cm−1 3370, 2870,
1670, 1578, 1514, 1418, 1235, 1022, 703; 1H NMR (400 MHz,
CDCl3) δ 10.0 (s, 1H), 7.63−7.58 (m, 4H), 7.51−7.44 (m, 4H), 7.42
(d, J = 2.0 Hz, 1H), 7.37 (tt, J = 8.5 and 1.2 Hz, 1H), 6.83 (d, J = 2.0
Hz, 1H), 6.15 (d, J = 7.3 Hz, 1H), 4.49 (d, J = 7.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 187.2, 163.2, 142.4, 141.3, 140.5, 139.1, 128.8
(2CH), 127.5 (2CH), 127.3, 127.1 (2CH), 126.6 (2CH), 122.6, 110.2,
70.3; HRMS (ESI) m/z calcd for C18H15O3 (M + H)+ 279.1021, found
279.1026.
2-(Hydroxy(phenyl)methyl)benzofuran-3-carbaldehyde (3m1).
This compound was isolated as colorless liquid: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 3313, 3031, 1661, 1575,
1
1495, 1479, 1452, 1176, 1011, 748; H NMR (400 MHz, CDCl3) δ
10.48 (s, 1H), 8.12 (dd, J = 6.8 and 3.3 Hz, 1H), 7.53−7.51 (m, 3H),
7.43−7.36 (m, 5H), 6.29 (d, J = 5.5 Hz, 1H), 4.03 (d, J = 5.6 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 186.6, 166.7, 139.6, 128.9 (2CH),
128.7, 126.4 (2CH), 125.8, 125.0, 124.8, 121.4, 117.5, 111.5, 101.9,
65.4; HRMS (ESI) m/z calcd for C16H13O3 (M + H)+ 253.0865, found
253.0839.
2-(2-Benzoyl-1-(furan-2-yl)-3-oxobutyl)furan-3-carbaldehyde
(3e2). This compound isolated as colorless liquid starting from 40 mg
of 3e1 and obtained 49 mg in 71% yield: Rf = 0.4 (EtOAc/Hexane =
3/7); IR (thin film, neat) νmax/cm−1 2922, 1725, 1680, 1594, 1417,
1269, 1012, 744; 1H NMR (400 MHz, CDCl3) δ 10.11 (s, 1H), 8.05−
8.02 (m, 2H), 7.54−7.47 (m, 4H), 7.40 (d, J = 2.0 Hz, 1H), 7.16 (dd, J
= 1.8 and 0.7 Hz, 1H), 6.75 (d, J = 2.0 Hz, 1H), 6.14 (dd, J = 3.0 and
1.8 Hz, 1H), 6.11 (d, J = 3.2 Hz, 1H), 5.81 (d, J = 10.3 Hz, 1H), 2.11
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 199.7, 192.9, 184.8, 159.6,
149.7, 142.8, 142.4, 136.1, 134.1, 128.9 (2CH), 128.8 (2CH), 122.9,
110.6, 108.9, 108.0, 63.2, 37.3, 29.0; HRMS (ESI) m/z calcd for
C20H16O5Na (M + Na)+ 359.0895, found 359.0898.
2-((3-Fluorophenyl)(hydroxy)methyl)furan-3-carbaldehyde (3s1).
This compound was isolated as colorless liquid: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 3363, 2927, 1673, 1615,
1592, 1488, 1451, 1250, 1129, 1024, 787; 1H NMR (400 MHz,
CDCl3) δ 9.96 (s, 1H), 7.41 (d, J = 1.8 Hz, 1H), 7.37−7.34 (m, 1H),
7.18 (dd, J = 13.2 and 8.9, 2H), 7.02 (td, J = 8.4 and 2.5 Hz, 1H), 6.82
(d, J = 2.0 Hz, 1H), 6.08 (d, J = 5.3 Hz, 1H), 4.73 (d, J = 6.8 Hz,1H);
13C NMR (100 MHz, CDCl3) δ 187.3, 162.9 (d, J = 245.06 Hz),
162.6, 142.6, 142.5, 130.1 (d, J = 8.05 Hz), 122.6, 121.7, 115.2 (d, J =
20.9 Hz), 113.2 (d, J = 22.51 Hz), 110.4, 69.8; 19F NMR (376.4 MHz,
CDCl3) δ −112.15; HRMS (ESI) m/z calcd for C12H8FO2 (M −
OH)+ 203.0509, found 203.0498.
G
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2-(2-Benzoyl-1-(5-methylfuran-2-yl)-3-oxobutyl)furan-3-carbal-
dehyde (3f2). This compound was isolated as colorless liquid starting
from 40 mg of 3f1 and obtained 50 mg in 74% yield: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 2922, 1725, 1680, 1448,
1597, 1448, 1274, 1250, 1181, 1013, 742; 1H NMR (400 MHz,
CDCl3) δ 10.10 (s, 1H), 8.07−8.05 (m, 2H), 7.82−7.80 (m, 2H),
7.55−7.53 (m, 2H), 7.51−7.50 (m, 2H), 7.45 (s, 1H), 7.49−7.47 (m,
2H), 7.43−7.43 (m, 1H), 7.37 (dd, J = 1.7 and 0.6 Hz, 1H), 7.24 (d, J
= 1.9 Hz, 1H), 6.67 (d, J = 1.9 Hz, 1H), 6.36 (d, J = 3.1 Hz, 1H),
6.30−6.28 (m, 1H), 5.79 (d, J = 11.4 Hz, 1H), 5.60 (d, J = 11.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 193.0, 190.5, 184.8, 182.1,
159.9, 156.2, 149.7, 143.0, 142.7, 142.6, 134.1, 132.9, 129.0, 128.95,
128.91 (2CH), 128.7 (2CH), 127.1 (2CH), 122.7, 110.8, 108.4, 107.8,
96.2, 60.2, 37.9; HRMS (ESI) m/z calcd for C27H20O6Na (M + Na)+
463.1168, found 463.1158.
1
1358, 1267, 1125, 1023, 748, 695; H NMR (400 MHz, CDCl3) δ
10.11 (s, 1H), 8.06−8.04 (m, 2H), 7.54−7.47 (m, 4H), 7.39 (d, J = 1.9
Hz, 1H), 6.75 (d, J = 2.0 Hz, 1H), 5.97 (d, J = 11.3 Hz, 1H), 5.94 (d, J
= 3.0 Hz, 1H), 5.79 (d, J = 11.3 Hz, 1H), 2.12 (s, 3H), 2.04 (d, J = 0.8
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 192.7, 184.8, 159.8,
152.5, 147.7, 142.6, 136.6, 134.1, 128.9 (2CH), 128.8 (2CH), 122.8,
109.1, 108.8, 106.7, 64.3, 37.3, 28.4, 13.5; HRMS (ESI) m/z calcd for
C21H18O5Na (M + Na)+ 373.1052, found 373.1073.
2-(1-([1,1′-Biphenyl]-4-yl)-2-benzoyl-3,5-dioxo-5-phenylpentyl)-
furan-3-carbaldehyde (3l2). This compound was isolated as colorless
liquid starting from 40 mg of 3i1 and obtained 52 mg in 70% yield: Rf
= 0.4 (EtOAc/Hexane = 3/7); IR (thin film, neat) νmax /cm−1 2925,
2-(2-Acetyl-3-oxo-1-(thiophen-2-yl)butyl)furan-3-carbaldehyde
(3g2). This compound was isolated as colorless liquid starting from 40
mg of 3g1 and obtained 42 mg in 75% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax/cm−1 2997, 2866, 1721, 1698, 1680,
1
2853, 1734, 1681, 1597, 1487, 1448, 1123, 1077, 821, 738; H NMR
1
1610, 1512, 1394, 1360, 1250, 1182, 1088, 1045, 744; H NMR (400
(400 MHz, CDCl3) δ 10.18 (s, 1H), 8.07−8.05 (m, 2H), 7.82−7.80
(m, 2H), 7.51−7.47 (m, 7H), 7.45−7.43 (m, 6H), 7.37−7.36 (m, 1H),
7.24 (d, J = 1.9 Hz, 1H), 6.67 (d, J = 2.0 Hz, 1H), 6.35 (d, J = 3.6 Hz,
1H), 6.31 (s, 1H), 6.30−6.29 (m, 1H), 6.20 (d, J = 3.6 Hz, 1H), 5.60
(d, J = 11.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 193.0, 190.5,
184.9, 182.1, 159.8, 149.7, 142.7, 142.3, 135.7, 135.7, 134.0, 134.6,
134.0, 133.5, 132.9, 129.0 (2CH), 128.9 (2CH), 128.8 (3CH), 128.7
(3CH), 128.1, 127.1 (2CH), 122.7, 110.8, 108.6, 108.4, 96.2, 60.2,
37.9; HRMS (ESI) m/z calcd for C35H26O5Na (M + Na)+ 549.1678,
found 549.1661.
2-(2-Acetyl-3-oxo-1-phenylbutyl)benzofuran-3-carbaldehyde
(3m2). This compound was isolated as colorless liquid starting from
30 mg of 3m1 and obtained 23 mg in 60% yield: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 2947, 2868, 1720, 1697,
1681, 1487, 1451, 1124, 760; 1H NMR (400 MHz, CDCl3) δ 10.45 (s,
1H), 8.11−8.09 (m, 1H), 7.52−7.49 (m, 1H), 7.46−7.44 (m, 2H),
7.40 (d, J = 4.8 Hz, 1H), 7.37−7.33 (m, 3H), 5.55 (d, J = 11.8 Hz,
1H), 5.10 (q, J = 11.8 Hz, 2H), 2.23 (s, 3H), 2.08 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 200.9, 200.3, 184.7, 166.0, 153.8, 136.6, 129.4
(2CH), 128.6, 128.2 (2CH), 125.6, 124.9, 124.6, 121.9, 117.1, 111.0,
71.2, 43.2, 30.3, 29.7; HRMS (ESI) m/z calcd for C21H18O4Na (M +
Na)+ 357.1103, found 357.1103.
2-(2-Benzoyl-3-oxo-1-phenylbutyl)benzofuran-3-carbaldehyde
(3n2). This compound was isolated as colorless liquid starting from 45
mg of 3m1 and obtained 45 mg in 65% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax/cm−1 2962, 2929, 1738, 1704, 1681,
1575, 1487, 1125, 765, 747; 1H NMR (400 MHz, CDCl3) δ 10.49 (s,
1H), 8.06−8.04 (m, 2H), 7.97−7.95 (m, 2H), 7.49−7.45 (m, 2H),
7.42−7.40 (m, 3H), 7.38−7.35 (m, 3H), 7.22−7.18 (m, 2H), 5.97 (d, J
= 11.5 Hz, 1H), 5.80 (d, J = 11.3 Hz, 1H), 2.18 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 200.0, 193.1, 184.8, 166.7, 153.9, 137.0, 134.1,
129.0 (2CH), 128.9 (2CH), 128.8 (2CH), 128.5, 128.3 (2CH), 127.0,
125.5, 124.9, 124.6, 122.07, 117.2, 110.0, 65.3, 43.7, 29.3; HRMS
(ESI) m/z calcd for C26H20O4Na (M + Na)+ 419.1259, found
419.1250.
MHz, CDCl3) δ 10.07 (s, 1H), 7.36 (d, J = 2.0 Hz, 1H), 7.22 (dd, J =
5.2 and 1.0 Hz, 1H), 7.01 (dd, J = 3.5 and 0.6 Hz, 1H), 6.94−6.92 (m,
1H), 6.70 (d, J = 2.0 Hz, 1H), 5.75 (d, J = 5.8 Hz, 1H), 4.91 (d, J = 5.8
Hz, 1H), 2.16 (s, 3H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
200.7, 200.2, 184.7, 160.2, 142.6, 139.3, 127.1, 126.5, 125.7, 122.1,
109.1, 72.3, 38.1, 30.1, 29.4; HRMS (ESI) m/z calcd for C15H14O4SNa
(M + Na)+ 313.0510, found 313.0520.
2-(2-Benzoyl-3-oxo-1-(thiophen-2-yl)butyl)furan-3-carbaldehyde
(3h2). This compound was isolated as colorless liquid starting from 40
mg of 3g1 and obtained 63 mg in 94% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax/cm−1 2956, 2870, 1721, 1698, 1682,
1
1573, 1519, 1418, 1366, 1124, 759; H NMR (400 MHz, CDCl3) δ
10.13 (s, 1H), 8.01 (dd, J = 0.9 Hz, 3H), 7.51−7.47 (m, 2H), 7.43 (d, J
= 2.0 Hz, 1H), 7.07 (d, J = 1.0 Hz, 1H), 6.95−6.93 (m, 1H), 6.79−
6.77 (m, 1H), 6.74 (d, J = 2.0 Hz, 1H), 6.02 (d, J = 11.3 Hz, 1H), 5.79
(d, J = 11.3 Hz, 1H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
199.9, 192.7, 184.7, 160.8, 142.7, 139.6, 136.4, 134.1, 128.9 (2CH),
128.8 (2CH), 126.9, 126.6, 125.3, 122.3, 109.1, 66.6, 38.6, 28.8;
HRMS (ESI) m/z calcd for C20H16O4SNa (M + Na)+ 375.0667, found
375.0663.
Ethyl 2-([1,1′-biphenyl]-4-yl(3-formylfuran-2-yl)methyl)-3-oxobu-
tanoate (3i2). This compound was isolated as colorless liquid starting
from 55 mg of 3i1 and obtained 61 mg in 80% yield: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax/cm−1 2957, 2870, 1722, 1697,
1680, 1570, 1514, 1413, 1370, 1124, 766; 1H NMR (400 MHz,
CDCl3) δ 10.11 (s, 1H), 7.62−7.61 (m, 1H), 7.54−7.53 (m, 3H),
7.44−7.42 (m, 4H), 7.39 (d, J = 2.0 Hz, 1H), 7.36−7.35 (m, 1H), 6.71
(d, J = 2.0 Hz, 1H), 5.38 (d, J = 5.3 Hz, 1H), 4.76 (d, J = 3.3 Hz, 1H),
4.04 (qd, J = 7.1 and 1.8 Hz, 2H), 2.29 (s, 3H), 1.06 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 200.0, 184.5, 166.7, 161.9,
142.6, 140.7, 140.2, 139.8, 136.4, 128.8 (2CH), 128.7 (2CH), 127.7
(2CH), 127.5 (2CH), 127.3, 109.6, 64.1, 63.1, 61.9, 42.3, 29.0; HRMS
(ESI) m/z calcd for C24H22O5Na (M + Na)+ 413.1365, found
413.1373.
2-(2-Benzoyl-3,5-dioxo-1,5-diphenylpentyl)furan-3-carbaldehyde
(3j2). This compound was isolated as colorless liquid starting from 40
mg of 3a1 and obtained 70 mg in 73% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax /cm−1 2924, 2852, 1681, 1597, 1493,
2-(2-Acetyl-2-methyl-3-oxo-1-phenylbutyl)furan-3-carbaldehyde
(3o2). This compound was isolated as colorless liquid starting from 30
mg of 3a1 and obtained 35 mg in 80% yield: Rf = 0.4 (EtOAc/Hexane
= 3/7); IR (thin film, neat) νmax/cm−1 2925, 1738, 1716, 1682, 1580,
1494, 1454, 1369, 1246, 1145, 1045, 758; 1H NMR (400 MHz,
CDCl3) δ 10.0 (s, 1H), 7.40 (d, J = 1.9 Hz, 1H), 7.29−7.27 (m, 5H),
6.7 (d, J = 1.9 Hz, 1H), 5.98 (s, 1H), 2.05 (s, 3H), 2.06 (s, 3H), 1.74
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 205.2, 204.0, 185.0, 162.2,
142.2, 136.8, 129.8 (2CH), 128.6 (2CH), 127.8, 122.9, 108.8, 71.4,
45.5, 27.2, 26.5, 16.5; HRMS (ESI) m/z calcd for C18H19O4 (M + H)+
299.1283, found 299.1249.
2-(2-Acetyl-1-(4-ethylphenyl)-2-methyl-3-oxobutyl)furan-3-car-
baldehyde (3p2). This compound was isolated as colorless liquid
starting from 47 mg of 3c1 and obtained 59 mg in 90% yield: Rf = 0.4
(EtOAc/Hexane = 3/7); IR (thin film, neat) νmax/cm−1 3363, 1673,
1583, 1503, 1418, 1274, 1145, 1128, 1012; 1H NMR (400 MHz,
CDCl3) δ 9.99 (s, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.20 (d, J = 8.2 Hz,
2H), 7.11 (d, J = 8.2 Hz, 2H), 6.72 (d, J = 1.9 Hz, 1H), 5.90 (s, 1H),
2.60 (q, J = 7.6 Hz, 2H), 2.04 (s, 3H), 2.01 (s, 3H), 1.73 (s, 3H), 1.20
1
1448, 1278, 1026, 744, 695; H NMR (400 MHz, CDCl3) δ 10.10 (s,
1H), 8.03−8.00 (m, 2H), 7.80−7.78 (m, 1H), 7.63−7.62 (m, 1H),
7.61−7.60 (m, 2H), 7.54−7.53 (m, 1H), 7.52−7.51 (m, 1H), 7.50−
7.49 (m, 2H), 7.48−7.47 (m, 2H), 7.34−7.32 (m, 1H), 7.21 (s, 2H),
7.17−7.16 (m, 1H), 7.13−7.11 (m, 1H), 6.38−6.36 (m, 1H), 5.65 (d, J
= 11.5 Hz, 1H), 5.55 (d, J = 11.5 Hz, 1H), 5.03 (dd, J = 10.7 and 4.7
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 193.6, 193.6, 193.0, 182.0,
159.0, 142.4, 137.9, 137.3, 135.9, 133.9, 133.5, 132.4, 129.3 (2CH),
128.9 (2CH), 128.8 (2CH), 128.7 (2CH), 128.1 (2CH), 127.1
(2CH), 122.2, 112.6, 62.3, 53.4, 44.4; HRMS (ESI) m/z calcd for
C29H22O5Na (M + Na)+ 473.1365, found 473.1384.
2-(2-Benzoyl-1-(furan-2-yl)-3,5-dioxo-5-phenylpentyl)furan-3-
carbaldehyde (3k2). This compound isolated as colorless liquid
starting from 45 mg of 3e1 and obtained 77 mg in 75% yield: Rf = 0.4
(EtOAc/Hexane = 3/7); IR (thin film, neat) νmax /cm−1 2926, 1682,
H
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 205.2, 204.2,
185.1, 162.5, 143.8, 142.5, 133.9, 129.7 (2CH), 128.1 (2CH), 122.9,
108.7, 71.5, 45.2, 28.3, 27.2, 26.6, 16.5, 15.2; HRMS (ESI) m/z calcd
for C20H22O4Na (M + Na)+ 349.1416, found 349.1417.
7-Acetyl-8-(4-ethylphenyl)-6H-cyclohepta[b]furan-6-one (3c).
This compound was isolated as a pale yellow solid (28 mg, 74%):
mp = 250−253 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 2963, 2925, 2854, 1711, 1621, 1578, 1538, 1496,
1454, 1340, 1136, 1091, 816; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J
= 1.8 Hz, 1H), 7.55 (d, J = 11.8 Hz, 1H), 7.28 (m, 4H), 7.10 (d, J =
11.8 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 2.73 (q, J = 7.6 Hz, 2H), 2.10
(s, 3H), 1.30 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
203.2, 185.1, 153.7, 146.3, 145.7, 145.2, 137.5, 136.8, 131.6, 131.0,
129.2 (2CH), 128.3, 127.8 (2CH), 113.0, 31.0, 28.6, 15.1; HRMS
(ESI) m/z calcd for C19H17O3 (M + H)+ 293.1178, found 293.1176.
7-Benzoyl-8-(4-ethylphenyl)-6H-cyclohepta[b]furan-6-one (3d).
This compound was isolated as a pale yellow solid (23 mg, 62%):
mp = 260−262 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
Ethyl 2-((4-ethylphenyl)(3-formylfuran-2-yl)methyl)-3-oxobuta-
noate (3r2) major. This compound was isolated as colorless liquid
starting from 20 mg of 3c1 and obtained 19 mg in 65% yield: Rf = 0.4
(EtOAc/Hexane = 3/7); IR (thin film, neat) νmax /cm−1 2966, 1743,
1
1720, 1681, 1514, 1245, 1124, 750; H NMR (400 MHz, CDCl3) δ
10.01 (s, 1H), 7.36 (d, J = 2.0 Hz, 1H), 7.30−7.28 (m, 2H), 7.16−7.14
(m, 2H), 6.69 (d, J = 2.0 Hz, 1H), 5.32 (d, J = 4.0 Hz, 1H), 4.70 (d, J
= 3.7 Hz, 1H), 4.10−4.07 (m, 2H), 2.60 (q, J = 7.5 Hz, 2H), 2.26 (s,
3H), 1.20 (td, J = 7.6 and 2.6 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 200.5, 184.7, 166.6, 162.5, 143.9, 142.5,
134.6, 128.6 (2CH), 128.3 (2CH), 122.1, 108.8, 82.6, 61.9, 42.2, 29.4,
28.4, 15.4, 13.7; HRMS (ESI) m/z calcd for C20H22O5Na (M + Na)+
365.1365, found 365.1356.
Ethyl 2-((3-fluorophenyl)(3-formylfuran-2-yl)methyl)-3-oxobuta-
noate (3s2). This compound was isolated as colorless liquid starting
from 30 mg of 3s1 and obtained 31 mg in 69% yield: Rf = 0.4 (EtOAc/
Hexane = 3/7); IR (thin film, neat) νmax /cm−1 2958, 2927, 1733,
1681, 1521, 1418, 1359, 1131, 1046, 888; 1H NMR (400 MHz,
CDCl3) δ 10.07 (s, 1H), 7.35 (d, J = 2.0 Hz, 1H), 7.19−7.16 (m, 2H),
6.99−6.94 (m, 2H), 6.70 (d, J = 2.0 Hz, 1H), 5.37 (d, J = 6.3 Hz, 1H),
5.34 (d, J = 6.3 Hz, 1H), 4.00−4.10 (m, 2H), 2.28 (s, 3H), 1.14 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 184.6, 166.4,
162.8 (d, J = 245.86 Hz), 161.4, 142.7, 139.8 (d, J = 7.00 Hz), 130.6
(d, J = 8.15 Hz), 124.1, 122.5, 115.3 (d, J = 22.23 Hz), 115.0 (d, J =
20.7 Hz), 109.2, 62.9, 62.1, 42.2, 30.9, 13.9; 19F NMR (376.4 MHz,
CDCl3) δ −111.8; HRMS (ESI) m/z calcd for C18H17O5FNa (M +
Na)+ 355.0958, found 355.0967.
1
neat) νmax /cm−1 2960, 2926, 1671, 1636, 1536, 1494, 813; H NMR
(400 MHz, CDCl3) δ 7.72 (dd, J = 6.4 and 1.3 Hz, 2H), 7.63 (d, J =
2.0 Hz, 1H), 7.61 (d, J = 11.8, 1H), 7.46 (tt, J = 8.6, 2.4, and 1.2 Hz,
1H), 7.32 (t, J = 7.8 Hz, 2H), 7.14 (d, J = 11.8 Hz, 2H), 7.08 (brs,
3H), 6.90 (d, J = 2.0 Hz, 1H), 2.60 (q, J = 7.5 Hz, 2H), 1.19 (t, J = 7.7
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 195.5, 185.6, 153.7, 145.7,
145.7, 144.7, 144.2, 138.7, 137.4, 136.8, 132.9, 131.5, 130.9, 128.7
(2CH), 128.6, 128.3 (2CH), 127.4, 127.3, 127.3, 113.0, 28.5, 15.0;
HRMS (ESI) m/z calcd for C24H19O3 (M + H)+ 355.1334, found
355.1337.
7-Benzoyl-8-(furan-2-yl)-6H-cyclohepta[b]furan-6-one (3e). This
compound was isolated as a pale yellow solid (34 mg, 91%): mp =
252−255 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film, neat)
νmax/cm−1 3145, 2924, 2853, 1675, 1574, 1544, 1498, 1449, 1336,
1
1255, 831, 693; H NMR (400 MHz, CDCl3) δ 7.90−7.87 (m, 2H),
7.75 (d, J = 1.9 Hz, 1H), 7.55−7.49 (m, 2H), 7.42−7.38 (m, 2H), 7.32
(dd, J = 1.7 and 0.7, 1H), 7.05 (d, J = 11.7 Hz, 1H), 6.93 (dd, J = 3.4
and 0.6 Hz, 1H), 6.90 (d, J = 1.9 Hz, 1H). 6.42 (q, J = 1.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 195.3, 185.5, 151.8, 145.4, 145.2,
2-(1-Phenyloct-2-yn-1-yl)furan-3-carbaldehyde (3t2). This com-
pound was isolated as a colorless liquid starting from 30 mg of 3t1 and
obtained 42 mg in 85% yield: Rf = 0.4 (EtOAc/Hexane = 3/7); IR
(thin film, neat) νmax/cm−1 3363, 2123, 1705, 1673, 1583, 1503, 1418,
144.2, 142.5, 137.2, 136.7, 132.9, 131.1, 128.7, 128.6 (2CH), 128.4
(2CH), 127.4, 116.8, 113.1, 111.8; HRMS (ESI) m/z calcd for
C20H13O4 (M + H)+ 317.0814, found 317.0823.
1
1274, 1145, 1128, 1012, 896, 785; H NMR (400 MHz, CDCl3) δ
10.20 (s, 1H), 7.94 (dd, J = 8.5 and 1.3 Hz, 2H), 7.60 (m, 3H), 7.23
(dd, J = 2.0 and 0.5 Hz, 1H), 6.62 (d, J = 2.0 Hz, 1H), 5.40 (d, J = 10.4
Hz, 1H), 5.23 (td, J = 10.4 and 2.3 Hz, 1H), 2.35 (s, 3H) 2.19 (td, J =
7.2 and 1.8 Hz, 2H), 1.35−1.29 (m, 4H), 1.11−1.06 (s, 2H), 0.77 (t, J
= 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.0, 192.3, 184.4,
158.6, 142.7, 135.6, 134.2, 129.1 (2CH), 128.9 (2CH), 122.8, 108.3,
86.6, 74.4, 66.3, 30.9, 29.9, 28.3, 28.0, 22.1, 18.6, 13.9; HRMS (ESI)
m/z calcd for C23H25O4 (M + H)+ 365.1753, found 365.1755.
General Procedure for Step-III, Scheme 2 (Base Mediated
Intramolecular Aldol Condensation of the 1,3-Dicarbonyl
Adducts for the Synthesis of Furotropones). To a solution of
the 1,3-dicarbonyl adduct (0.06 mmol, 1 equiv) in 1 mL DMF, sodium
carbonate (5 mg, 1 equiv) was added under nitrogen atmosphere. The
flask was placed in an oil bath (80 °C) and stirring was continued for 3
h. The reaction mixture was washed with water and extracted with
ethyl acetate. The organic extracts were combined, dried (Na2SO4),
filtered, and concentrated. The crude product was purified by column
chromatography on silica gel (ethyl acetate−hexanes) to afford
furotropone.
Spectral Data of Furotropones. Some of the furotropones
prepared during study are already known in the literature.7,8 Complete
characterization data of newly synthesized compounds is given below.
7-Benzoyl-8-phenyl-6H-cyclohepta[b]furan-6-one (3b). This
compound was isolated as a pale yellow solid (22 mg, 75%): mp =
266−269 °C; Rf = 0.4 (EtOAc/Hexane= 2/3); IR (thin film, neat)
νmax/cm−1 2923, 1711, 1673, 1535, 1497, 1454, 1343, 1260, 1096, 734;
1H NMR (400 MHz, CDCl3) δ 7.73−7.70 (m, 2H), 7.62 (d, J = 11.8
7-Benzoyl-8-(5-methylfuran-2-yl)-6H-cyclohepta[b]furan-6-one
(3f). This compound was isolated as a pale yellow solid (30 mg, 74%):
mp = 255−258 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 2923, 2852, 1678, 1623, 1535, 1497, 1448, 1361,
1249, 1096, 833; 1H NMR (400 MHz, CDCl3) δ 7.95−7.92 (m, 2H),
7.74 (d, J = 1.9 Hz, 1H), 7.53−7.49 (m, 2H), 7.44−7.40 (m, 2H),
7.04−7.00 (m, 2H), 6.88 (d, J = 1.9 Hz, 1H), 6.06−6.04 (m, 1H), 1.96
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 195.6, 185.8, 155.0, 151.5,
144.9, 143.7, 141.1, 137.3, 137.2, 132.6, 130.8, 128.5 (3CH), 128.3
(2CH), 127.2, 119.0, 113.1, 108.6, 13.1; HRMS (ESI) m/z calcd for
C21H15O4 (M + H)+ 331.0970, found 331.0953.
7-Acetyl-8-(thiophen-2-yl)-6H-cyclohepta[b]furan-6-one (3g).
This compound was isolated as a pale yellow solid (13 mg, 70%):
mp = 250−253 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 3132, 2922, 1708, 1616, 1573, 1537, 1496, 1452,
1325, 1165, 1089, 830, 794; 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J
= 1.9 Hz, 1H), 7.57 (dd, J = 4.9 and 1.4 Hz, 1H), 7.57 (d, J = 11.8 Hz,
1H), 7.14 (m, 2H), 7.08 (d, J = 11.8 Hz, 1H), 6.87 (d, J = 1.9 Hz, 1H),
2.17 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 202.7, 184.6, 147.2,
145.6, 137.4, 137.1, 132.9, 131.6, 131.3, 130.1, 128.5, 128.1, 127.0,
113.1, 30.6; HRMS (ESI) m/z calcd for C15H11O3S (M + H)+
271.0429, found 271.0440.
7-Benzoyl-8-(thiophen-2-yl)-6H-cyclohepta[b]furan-6-one (3h).
This compound was isolated as a pale yellow solid (18 mg, 95%):
mp = 260−263 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 3112, 2954, 2853, 1673, 1537, 1494, 1452, 1356,
1328, 1258, 1092, 823; 1H NMR (400 MHz, CDCl3) δ 7.77−7.76 (m,
2H), 7.68 (d, J = 1.9 Hz, 1H), 7.59 (d, J = 11.8 Hz, 1H), 7.48 (tt, J =
7.4 and 1.7 Hz, 1H), 7.35 (m, 3H), 7.11 (d, J = 11.8 Hz, 1H), 7.01
(dd, J = 3.6 and 1.2 Hz, 1H), 6.91 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 195.0, 185.1, 153.2, 145.7, 145.2, 137.3, 136.3, 133.2, 133.1,
132.1, 131.5, 131.2, 128.8 (2CH), 128.5, 128.4 (2CH), 128.41, 126.5,
113.2. HRMS (ESI) m/z calcd for C20H13O3S (M + H)+ 333.0585,
found 333.0598.
Hz, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.46 (tt, J = 7.3 and 1.2 Hz, 1H),
7.34−7.30 (m, 3H), 7.30−7.20 (m, 4H), 7.14 (d, J = 11.8 Hz, 1H),
6.90 (d, J = 1.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 195.3, 185.6,
153.6, 145.8, 144.1, 138.4, 137.4, 136.7, 133.7, 133.0, 131.5, 129.4,
129.3, 129.3, 128.7 (2CH), 128.7, 128.6, 128.3 (2CH), 127.8, 113.0;
HRMS (ESI) m/z calcd for C22H15O3 (M + H)+ 327.1000, found
327.0990.
I
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
Ethyl 8-([1,1′-biphenyl]-4-yl)-6-oxo-6H-cyclohepta[b]furan-7-car-
boxylate (3i). This compound was isolated as a pale yellow solid (21
mg, 75%): mp = 273−276 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR
(thin film, neat) νmax/cm−1 3031, 2925, 2854, 1730, 1620, 1590, 1539,
1496, 1043, 758; 1H NMR (400 MHz, CDCl3) δ 7.73 (tt, J = 5.3 and
1.9 Hz, 1H), 7.69 (t, J = 1.9 Hz, 1H), 7.67−7.66 (m, 1H), 7.65−7.64
(m, 2H), 7.55 (d, J = 11.9 Hz, 1H), 7.51−7.48 (m, 4H), 7.43−7.39
(m, 1H), 7.15 (d, J = 11.9 Hz, 1H), 6.87 (d, J = 1.8 Hz, 1H), 4.05 (q, J
= 7.1 Hz, 2H), 0.97 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 183.8, 166.6, 146.0, 141.8, 140.2, 137.4, 133.4, 131.3, 129.6, 129.4
(2CH), 128.9 (2CH), 128.8 (2CH), 127.7, 127.2, 127.17 (2CH),
127.11, 126.7, 113.1, 61.3, 13.6; HRMS (ESI) m/z calcd for C24H19O4
(M + H)+ 371.1283, found 371.1287.
6-Oxo-8-phenyl-6H-cyclohepta[b]furan-5,7-diyl)bis-
(phenylmethanone) (3j). This compound was isolated as a pale yellow
solid (15 mg, 76%): mp = 290−293 °C; Rf = 0.4 (EtOAc/Hexane = 2/
3); IR (thin film, neat) νmax/cm−1 3060, 2924, 2853, 1674, 1597, 1540,
1448, 1286, 1208, 872; 1H NMR (400 MHz, CDCl3) δ 7.94−7.93 (m,
1H), 7.92 (t, J = 4.0 and 2.0 Hz, 2H), 7.71 (m, 1H), 7.69 (t, J = 4.0 Hz,
2H), 7.54 (tt, J = 8.0 and 4.0 Hz, 1H), 7.46−7.40 (m, 3H), 7.32−7.26
(m, 7H), 6.98 (d, J = 4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
195.8, 194.7, 183.9, 154.0, 146.6, 146.2, 145.3, 138.4, 136.7, 135.8,
133.4, 133.2, 133.2, 131.7, 129.3, 129.2 (2CH), 128.9 (2CH), 128.8
(2CH), 128.5 (2CH), 128.3 (2CH), 128.0 (2CH), 127.7, 113.7;
HRMS (ESI) m/z calcd for C29H19O4 (M + H)+ 431.1283, found
431.1267.
8-(Furan-2-yl)-6-oxo-6H-cyclohepta[b]furan-5,7-diyl)bis-
(phenylmethanone) (3k). This compound was isolated as a pale
yellow solid (23 mg, 70%): mp = 285−288 °C; Rf = 0.4 (EtOAc/
Hexane = 2/3); IR (thin film, neat) νmax/cm−1 2923, 2853, 1690, 1674,
1542, 1498, 1261, 835; 1H NMR (400 MHz, CDCl3) δ 7.89−7.86 (m,
4H), 7.83 (d, J = 2.0 Hz, 1H), 7.50 (tt, J = 8.0 and 1.2 Hz, 2H), 7.42−
7.37 (m, 4H), 7.35 (dd, J = 2.0 and 0.8 Hz, 1H), 7.07 (dd, J = 3.6 and
0.6 Hz, 2H), 6.99 (d, J = 2.0 Hz, 1H), 6.47 (dd, J = 2.0 and 1.3 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 195.4, 184.0, 180.5, 152.1,
146.3, 145.5, 144.6, 143.1, 136.9, 135.7, 133.3, 133.0, 131.2, 129.2
(2CH), 128.7 (2CH), 128.56, 128.54 (2CH), 128.50, 128.4 (2CH),
127.6, 117.5, 113.8, 112.1; HRMS (ESI) m/z calcd for C27H17O5 (M +
H)+ 421.1076, found 421.1072.
1281, 883, 819; H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 11.8 Hz,
1H), 7.99−7.97 (m, 1H), 7.74−7.71 (m, 2H), 7.54−7.51 (m, 1H),
7.50−7.45 (m, 4H), 7.35 (t, J = 1.5 Hz, 1H), 7.33−7.28 (m, 6H); 13C
NMR (100 MHz, CDCl3) δ 195.1, 185.4, 155.1, 154.5, 147.6, 147.3,
146.3, 139.0, 137.5, 136.5, 133.7, 133.1, 129.1, 128.7 (2CH), 128.6,
128.5, 128.4 (2CH), 127.9, 127.9, 125.9, 124.5, 123.7, 120.1, 112.3;
HRMS (ESI) m/z calcd for C26H17O3 (M + H)+ 377.1178, found
377.1179.
7-Methyl-8-phenyl-6H-cyclohepta[b]furan-6-one (3o). This com-
pound was isolated as a pale yellow solid (14 mg, 60%): mp = 261−
263 °C; Rf = 0.4 (EtOAc/Hexane = 1/1); IR (thin film, neat) νmax
/
cm−1 2928, 1710, 1620, 1575, 1536, 1452, 1356, 1352, 1326, 830, 716;
1H NMR (400 MHz, CDCl3) δ 7.55−7.47 (m, 5H), 7.26−7.24 (m,
2H), 7.10 (d, J = 11.9 Hz, 1H), 6.79 (d, J = 1.9 Hz, 1H), 2.03 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 187.3, 154.2, 144.3, 142.3, 139.1,
138.3, 134.5, 129.8, 128.5 (2CH), 128.2 (2CH), 127.9, 126.6, 112.0,
19.5; HRMS (ESI) m/z calcd for C16H13O2 (M + H)+ 237.0900, found
237.0909.
7-Benzoyl-8-(4-ethylphenyl)-6H-cyclohepta[b]furan-6-one (3p).
This compound was isolated as a pale yellow solid (14 mg, 62%):
mp = 268−271 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 2900, 1715, 1690, 1620, 1470, 1430, 1356, 1351,
1
1315, 1270, 830; H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 1.9 Hz,
1H), 7.47 (d, J = 11.8 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.17 (d, J =
8.0 Hz, 2H), 7.09 (d, J = 11.8 Hz, 1H), 6.78 (d, J = 1.9 Hz, 1H), 2.78
(q, J = 7.6 Hz, 2H), 2.04 (s, 3H), 1.34 (t, J = 7.6 Hz, 3H) .13C NMR
(100 MHz, CDCl3) δ 187.3, 144.3, 143.8, 142.9, 139.3, 135.5, 134.5,
130.2, 129.8, 128.1 (2CH), 128.0 (2CH), 126.5, 112.0, 28.6, 19.6,
15.3; HRMS (ESI) m/z calcd for C18H17O2 (M + H)+ 265.1229, found
265.1227.
8-(4-Ethylphenyl)-6H-cyclohepta[b]furan-6-one (3r). This com-
pound was isolated as a pale yellow liquid (12 mg, 60%): Rf = 0.4
(EtOAc/Hexane = 1/1); IR (thin film, neat) νmax/cm−1 2963, 2926,
2854, 1710, 1620, 1590, 1540, 1496, 1460, 1350, 1090, 847; 1H NMR
(400 MHz, CDCl3) δ 7.64 (d, J = 2.0 Hz, 1H), 7.52−7.48 (m, 3H),
7.36−7.33 (m, 2H), 7.06−7.02 (m, 2H), 6.85 (d, J = 1.8 Hz, 1H), 2.76
(q, J = 7.7 Hz, 2H), 1.33 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 186.9, 153.4, 145.5, 144.6, 140.7, 136.3, 136.0, 134.8, 131.4,
129.1 (2CH), 128.4, 127.9 (2CH), 113.0, 28.6, 15.3; HRMS (ESI) m/
z calcd for C17H15O2 (M + H)+ 251.1072, found 251.1071.
8-(3-Fluorophenyl)-6H-cyclohepta[b]furan-6-one (3s). This com-
pound was isolated as a pale yellow liquid (12 mg, 55%): Rf = 0.4
(EtOAc/Hexane = 1/1); IR (thin film, neat) νmax/cm−1 2924, 2853,
8-([1,1′-Biphenyl]-4-yl)-6-oxo-6H-cyclohepta[b]furan-5,7-diyl)bis-
(phenylmethanone) (3l). This compound was isolated as a pale yellow
solid (32 mg, 84%): mp = 297−300 °C; Rf = 0.4 (EtOAc/Hexane = 2/
3); IR (thin film, neat) νmax/cm−1 3059, 2925, 1673, 1597, 1579, 1538,
1
1
1494, 1337, 1286, 1006; H NMR (400 MHz, CDCl3) δ 7.95 (d, J =
1730, 1621, 1545, 1498, 1455, 1343, 1259, 1092, 1041, 867, 789; H
1.0 Hz, 1H), 7.93−7.92 (m, 2H), 7.73 (d, J = 1.0 Hz, 1H), 7.72−7.71
(m, 2H), 7.57−7.55 (m, 1H), 7.54 (s, 2H), 7.52 (t, J = 1.2 Hz, 1H),
7.50 (s, 1H), 7.45 (d, J = 1.8 Hz, 1H), 7.44−7.43 (m, 2H), 7.42−7.41
(m, 2H), 7.38 (t, J = 1.2 Hz, 1H), 7.36 (t, J = 2.2 Hz, 1H), 7.35 (t, J =
1.2 Hz, 1H), 7.32 (s, 1H), 7.30 (s, 1H), 6.99 (d, J = 1.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 195.8, 194.8, 183.9, 154.0, 146.7, 146.2,
145.4, 141.6, 140.0, 138.2, 136.8, 135.8, 133.4, 133.2, 132.1, 131.7,
129.8, 129.8, 129.2 (2CH), 128.9 (2CH), 128.8 (2CH), 128.6 (2CH),
128.3 (2CH), 127.78, 127.74, 127.1 (2CH), 126.6 (2CH), 113.7;
HRMS (ESI) m/z calcd for C35H23O4 (M + H)+ 507.1596, found
507.1608.
NMR (400 MHz, CDCl3) δ 7.65 (d, J = 2.0 Hz, 1H), 7.53 (d, J = 11.5
Hz, 1H), 7.49−7.45 (m, 1H), 7.34−7.29 (m, 2H), 7.21 (dt, J = 8.4 and
1.9, 1H), 7.04 (dd, J = 11.7 and 2.3 Hz, 2H), 6.87 (d, J = 2.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 186.7, 156.2 (d, J = 226.96 Hz),
144.8, 139.4, 136.5, 136.1, 131.5, 130.9, 130.0 (d, J = 8.16 Hz), 128.6,
126.3, 124.8, 116.4 (d, J = 22.77 Hz), 116.1 (d, J = 20.71 Hz), 113.1;
19F NMR (376.4 MHz, CDCl3) δ −112.6; HRMS (ESI) m/z calcd for
C15H10FO2 (M + H)+ 241.0665, found 241.0667.
4′-Acetyl-2′-hexyl-5′-methyl-[2,3′-bifuran]-3-carbaldehyde (4).
This compound was isolated as a colorless liquid (27 mg, 78%): Rf
= 0.3 (EtOAc/Hexane = 1/5); IR (thin film, neat) νmax/cm−1 3059,
2925, 1673, 1597, 1579, 1538, 1494, 1337, 1286, 1006, 739; 1H NMR
(400 MHz, CDCl3) δ 9.74 (s, 1H), 7.66−7.64 (m, 2H), 7.46 (tt, J =
7.4 and 1.2 Hz, 1H), 7.34−7.30 (m, 2H), 7.23 (dd, J = 2.0 and 0.5 Hz,
1H), 6.63 (d, J = 2.0 Hz, 1H), 2.67 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H),
1.71−1.66 (m, 2H), 1.32−1.26 (m, 6H), 0.87 (t, J = 6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 191.0, 184.9, 156.6, 155.8, 155.0, 143.2,
138.2, 132.5, 128.8 (2CH), 128.2 (2CH), 124.1, 121.3, 109.8, 108.0,
31.3, 28.7, 27.9, 26.7, 22.4, 14.0, 13.8; HRMS (ESI) m/z calcd for
C23H25O4 (M + H)+ 365.1753, found 365.1766.
7-Acetyl-6-phenyl-8H-cyclohepta[b]benzofuran-8-one (3m). This
compound was isolated as a pale yellow solid (12 mg, 61%): mp =
201−202 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film, neat)
1
νmax/cm−1 2919, 2852, 1716, 1668, 1635, 1480, 1385, 1284, 819; H
NMR (400 MHz, CDCl3) δ 7.98 (d, J = 11.9 Hz, 1H), 7.96−7.94 (m,
1H), 7.53−7.50 (m, 3H), 7.49−7.47 (m, 2H), 7.47−7.39 (m, 2H),
7.28 (d, J = 7.4 Hz, 1H), 6.70 (s, 1H), 2.14 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 202.8, 185.0, 154.5, 149.2, 137.6, 133.8, 129.4 (2CH),
129.3, 129.1, 128.5, 128.4, 128.4 (2CH), 125.8, 124.5, 123.5, 120.1,
116.1, 112.3, 30.9; HRMS (ESI) m/z calcd for C21H15O3 (M + H)+
315.1021, found 315.1026.
7-Benzoyl-6-phenyl-8H-cyclohepta[b]benzofuran-8-one (3n).
This compound was isolated as a pale yellow solid (15 mg, 65%):
mp = 207−210 °C; Rf = 0.4 (EtOAc/Hexane = 2/3); IR (thin film,
neat) νmax/cm−1 2922, 2852, 1709, 1668, 1635, 1557, 1480, 1446,
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Figures giving H and 13C NMR of all new compounds, some
physicochemical data and figures, tables, and CIF files giving
J
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(8) Dhiman, S.; Ramasastry, S. S. V. Org. Biomol. Chem. 2013, 11,
4299.
single crystal X-ray diffraction analysis data of compound 3j.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b00226.
(9) 2,3′-Bifurans traditionally have been synthesized by employing
typical Pd-mediated coupling strategy. Few miscellaneous methods,
though not general in nature, are reported. For example, see:
(a) Pennanen, S. I. J. Heterocycl. Chem. 1977, 14, 745. (b) Liu, Z.;
Yu, W.; Yang, L.; Liu, Z.-L. Tetrahedron Lett. 2007, 48, 5321.
(c) Kumar, T.; Mobin, S. M.; Namboothiri, I. N. N. Tetrahedron 2013,
69, 4964.
AUTHOR INFORMATION
■
Corresponding Author
*Tel: (+91) 172 2293169. Fax: (+91) 172 2240266. E-mail:
ramsastry@iisermohali.ac.in.
(10) For frondosin B, see: (a) Patil, A. D.; Freyer, A. J.; Kilmer, L.;
Offen, P.; Carte, B.; Jurewicz, A. J.; Johnson, R. K. Tetrahedron 1997,
53, 5047. For liphagal, see: (b) Marion, F.; Williams, D. E.; Patrick, B.
O.; Hollander, I.; Mallon, R.; Kim, S. C.; Roll, D. M.; Feldberg, L.;
Soest, R. V.; Andersen, R. J. Org. Lett. 2006, 8, 321. For
salvixalapoxide, see: (c) Esquivel, B.; Tello, R.; Sanchez, A. A. J. Nat.
Prod. 2005, 68, 787. For languidulane, see: (d) Maldonado, E.;
Ortega, A. Phytochemistry 1997, 45, 1461. For spiniferin-2, see:
(e) Fontana, A.; Trivellone, E.; Mollo, E.; Cimino, G. J. Nat. Prod.
1994, 57, 510. For gnididione, see: (f) Jacobi, P. A.; Selnick, H. G. J.
Org. Chem. 1990, 55, 202.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Department of Science and Technology (DST),
New Delhi for financial support through Fast Track Scheme
(SR/FT/CS-156/2011) and Indian Institute of Science
Education and Research (IISER) Mohali for funding. We
thank NMR and X-ray facilities of IISER-Mohali. We thank
DCS colleagues for their help in recording and analyzing UV−
vis and fluorescence data. R.S. thanks IISER-Mohali for a
research fellowship.
(11) Test solutions containing Zn2+, Mg2+, Ni2+, Cu2+, Hg2+, Sn2+,
Co2+, In2+, Sn2+, Cd2+, Cr2+, Fe2+ were prepared by using their halides,
and Pb2+ solution was prepared by using its nitrate.
(12) Sahoo, S. K.; Sharma, D.; Bera, R. K.; Crisponi, G.; Callan, J. F.
Chem. Soc. Rev. 2012, 41, 7195.
REFERENCES
■
(1) (a) Pauson, P. L. Chem. Rev. 1955, 55, 9. (b) Pietra, F. Chem. Rev.
1973, 73, 293. (c) Pietra, F. Acc. Chem. Res. 1979, 12, 132. (d) Asao,
T.; Ito, S.; Murata, I. Eur. J. Org. Chem. 2004, 899. (e) Liu, N.; Song,
W.; Schienebeck, C. M.; Zhang, M.; Tang, W. Tetrahedron 2014, 70,
9281.
(2) (a) Funk, R. L.; Bolton, G. L. J. Org. Chem. 1987, 52, 3173.
(b) Feldman, K. S.; Come, J. H.; Kosmider, B. J.; Smith, P. M.; Rotella,
D. P.; Wu, M. J. J. Org. Chem. 1989, 54, 592. (c) Feldman, K. S.; Wu,
M. J.; Rotella, D. P. J. Am. Chem. Soc. 1989, 111, 6457. (d) Rigby, J. H.;
Ateeq, H. S. J. Am. Chem. Soc. 1990, 112, 6442. (e) Graening, T.;
Bette, V.; Neudorfl, J.; Lex, J.; Schmalz, H.-G. Org. Lett. 2005, 7, 4317.
̈
(f) Li, P.; Yamamoto, H. Chem. Commun. 2010, 46, 6294.
(3) Several inspiring studies were reported in this field, some selected
references: (a) Nair, V.; Poonoth, M.; Vellalath, S.; Suresh, E.;
Thirumalai, R. J. Org. Chem. 2006, 71, 8964. (b) Nair, V.; Abhilash, K.
G. Top. Heterocycl. Chem. 2008, 13, 173. (c) Thangaraj, M.; Bhojgude,
S. S.; Bisht, R. H.; Gonnade, R. G.; Biju, A. T. J. Org. Chem. 2014, 79,
4757. (d) Kumar, P.; Thakur, A.; Hong, X.; Houk, K. N.; Louie, J. J.
Am. Chem. Soc. 2014, 136, 17844. (e) Liu, H.; Wu, Y.; Zhao, Y.; Li, Z.;
Zhang, L.; Yang, W.; Jiang, H.; Jing, C.; Yu, H.; Wang, B.; Xiao, Y.;
Guo, H. J. Am. Chem. Soc. 2014, 136, 2625 and references cited
therein.
(4) (a) Boye, O.; Brossi, A. In The Alkaloids; Brossi, A., Cordell, G.
A., Eds.; Academic Press: San Diego, 1992; Vol. 41, p 125. (b) Le
Hello, C. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San
Diego, 2000; Vol. 53, Chapter 5. (c) Nozoe, T. Bull. Chem. Soc. Jpn.
1936, 11, 295. (d) Teng, H.-L.; Yao, L.; Wang, C.-J. J. Am. Chem. Soc.
2014, 136, 4075.
(5) For aryl-annulated tropones, see: (a) Kudoh, M.; Satoh, T.;
Ikeda, H.; Nakazawa, T.; Miyashi, T.; Katagiri, S.; Sudoh, S. Bull.
Chem. Soc. Jpn. 2009, 82, 70. (b) Ohkita, M.; Nishida, S.; Tsuji, T. J.
Am. Chem. Soc. 1999, 121, 4589. (c) Arican, D.; Bruckner, R. Org. Lett.
2013, 15, 2582. For heteroaryl-annulated tropones, see: (d) Etaiw, S.
H.; El-Borai, M.; Ismail, M. I. Can. J. Chem. 1980, 58, 2358. (e) Kudoh,
M.; Sudoh, S.; Katagiri, S.; Nakazawa, T.; Ishihara, M.; Jinguji, M.;
Higashi, M.; Yamaguchi, H.; Miyatake, R.; Sugihara, Y.; Kabuto, C.
Bull. Chem. Soc. Jpn. 2006, 79, 1240.
(6) (a) El-Borai, M.; Guilard, R.; Fournari, P. Bull. Soc. Chim. Fr.
1974, 7, 1383. (b) Shafiee, A. J. Heterocycl. Chem. 1975, 12, 177.
(c) Nakamura, A.; Kubo, K.; Ikeda, Y.; Mori, A.; Takeshita, H. Bull.
Chem. Soc. Jpn. 1994, 67, 2803.
(7) Dhiman, S.; Ramasastry, S. S. V. Indian J. Chem., Sect. A 2013, 52,
1103.
K
DOI: 10.1021/acs.joc.5b00226
J. Org. Chem. XXXX, XXX, XXX−XXX