Bronsted acid-catalyzed cycloisomerization of but-2-yne-1,4-diols with or without 1,3-dicarbonyl compounds to tri- and tetrasubstituted furans

Article abstract of DOI:10.1021/jo301093f

A Bronsted acid-catalyzed method to prepare tri- and tetrasubstituted furans efficiently from cycloisomerization of but-2-yne-1,4-diols with or without 1,3-dicarbonyl compounds is described. By taking advantage of the orthogonal modes of reactivity of the alcoholic substrate through slight modification of the reaction conditions, a divergence in product selectivity was observed. At room temperature, p-TsOH?H ₂O-mediated tandem alkylation/cycloisomerization of the propargylic 1,4-diol with the β-dicarbonyl compound was found to selectively occur to provide the tetrasubstituted furan product. On the other hand, increasing the reaction temperature to 80 °C was discovered to result in preferential p-TsOH?H₂O-catalyzed dehydrative rearrangement of the unsaturated alcohol and formation of the 2,3,5-trisubstituted furan adduct.

Full text of DOI:10.1021/jo301093f

Article
pubs.acs.org/joc
Brønsted Acid-Catalyzed Cycloisomerization of But-2-yne-1,4-diols
with or without 1,3-Dicarbonyl Compounds to Tri- and
Tetrasubstituted Furans
Srinivasa Reddy Mothe, Sherman Jun Liang Lauw, Prasath Kothandaraman, and Philip Wai Hong Chan*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: A Brønsted acid-catalyzed method to prepare tri- and tetrasubstituted furans efficiently from cycloisomerization of
but-2-yne-1,4-diols with or without 1,3-dicarbonyl compounds is described. By taking advantage of the orthogonal modes of
reactivity of the alcoholic substrate through slight modification of the reaction conditions, a divergence in product selectivity was
observed. At room temperature, p-TsOH·H2O-mediated tandem alkylation/cycloisomerization of the propargylic 1,4-diol with
the β-dicarbonyl compound was found to selectively occur to provide the tetrasubstituted furan product. On the other hand,
increasing the reaction temperature to 80 °C was discovered to result in preferential p-TsOH·H2O-catalyzed dehydrative
rearrangement of the unsaturated alcohol and formation of the 2,3,5-trisubstituted furan adduct.
Scheme 1. Design of Propargylic 1,4-Diol-Based Approaches
for the Synthesis of Furan Derivatives
INTRODUCTION
■
Furans occupy an important place in the heterocyclic family of
compounds because of their prevalence as a key structural
component in a myriad of natural and pharmaceutical products
and ability to serve as a versatile building block in organic
synthesis.1,2 While this has led to a myriad of impressive ap-
proaches for furan synthesis being developed over the years,1−3
there remains a need for new methods for their construction
with selective control substitution of patterns from starting
materials and a catalytic system that are readily accessible,
atom-economical, and low cost.
Over the past decade, the use of unsaturated alcohols in
Brønsted acid-catalyzed synthetic strategies directed toward
the assembly of carbocyclic and heterocyclic compounds has
received an increasing amount of attention.4−7 For example, we
recently reported a method for the synthesis of 3-halohydro-
furans that relied on TfOH-mediated hydroxylation/halocycli-
zation of cyclopropyl methanols with H2O and N-halosuccin-
imide (NXS, X = I, Br, Cl) or Selectfluor.5a Further exploration
of this field led us to examine the potential Brønsted acid-
catalyzed reactivity of readily available propargylic 1,4-diols 1
(Scheme 1). Thus far, the cycloisomerization chemistry of this
class of compounds has been reported only in electrophilic
halocyclizations in the presence of a stoichiometric amount of a
halogen source, such as I2, to give 3,4-dihalodihydrofurans
Received: June 1, 2012
Published: July 12, 2012
© 2012 American Chemical Society
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(Scheme 1, eq 1).7 In contrast, a catalytic rearrangement pro-
cess involving Brønsted acid-induced ionization of a propargylic
1,4-diol, which results in the formation the aromatic oxygen
heterocycle is not known. As part of effects to develop this type
of reaction, we report herein that p-TsOH·H2O can mediate
tandem alkylation/cycloisomerization of but-2-yne-1,4-diols 1
with 1,3-dicarbonyl compounds 2 (Scheme 1, eq 2). This pro-
cess provides a convenient synthetic route to tetrasubstituted
furans 3 in 42−94% yield for a wide variety of substrates under
mild conditions at room temperature. In the course of this
study, our discovery that a synthetic route to 2,3,5-trisubsti-
tuted furans 4 in 60−85% yield from p-TsOH·H2O-catalyzed
dehydrative rearrangement of the starting 1,4-diol under slightly
modified reaction conditions is also presented (Scheme 1, eq 3).
A notable observation we have made for this latter furan forming
process is that it occurs via the in situ formed allenyl ketone
intermediate 5, the cycloisomerization chemistry of which has
been extensively studied under transition metal catalysis.8
subjecting 1a (1 equiv) and 2a (2 equiv) in MeNO2 with 10 mol %
of p-TsOH·H2O at room temperature for 6 h gave the best re-
sult (entry 1). Under these conditions, (4-(2,2-diphenylvinyl)-
2,5-diphenylfuran-3-yl)(phenyl)methanone 3a was afforded in
92% yield. The structure of the furan product was determined
1
by H NMR measurements and comparison with the X-ray
crystal structure analysis of three closely related adducts (vide
infra). Lower product yields of 68 and 85% were obtained on
decreasing the catalyst loading from 10 to 5 mol % or in the
absence of a nitrogen atmosphere (entries 2 and 3). Similarly,
lower product yields were found on repeating the reaction with
TFA, TfOH or Tf2NH in place of p-TsOH·H2O as the catalyst
or employing CH2Cl2 in place of MeNO2 as the solvent
(entries 4−6 and 8). Changing the catalyst from p-TsOH·H2O
to HCl or solvent from MeNO2 to 1,4-dioxane were the only
instances in which either recovery of the starting material in
near quantitative yield or decomposition was found (entries 7
and 9). Unexpectedly, 2,3,5-triphenylfuran 4a was afforded in
53% yield when MeNO2 was replaced by toluene as the solvent
at 80 °C for 1 h because of the heterogeneity of the reaction
mixture at room temperature (entry 10). The unprecedented
formation of 4a via a mechanistically intriguing dehydrative
rearrangement of 1a prompted us to additionally examine this
transformation more closely to establish a second set of re-
action conditions to this class of substituted furans (entries 11−16).
This initially showed that a comparable yield of the tri-
substituted furan was found on repeating the reaction in the
absence of the 1,3-dicarbonyl compound (entry 11). Our
studies subsequently showed changing the solvent from toluene
to 1,2-dichloroethane gave 4a in 80% yield (entry 12). In
contrast, lower product yields were obtained in the absence of a
nitrogen atmosphere, or on replacing 1,2-dichloroethane with
MeCN or MeNO2 as the solvent, or reducing the reaction time
from 1 h to 30 min (entries 13−16). Reactions with MeCN as
solvent or conducted for 30 min also afforded the allenyl
ketone byproduct 5a in 44 and 54% yield, respectively (entries
14 and 16).8 On the basis of the above results, reaction of 1a
with 2a in the presence of 10 mol % of p-TsOH·H2O in
MeNO2 at room temperature for 6 h provided the optimum
conditions to the tetrasubstituted furan. On the other hand,
reaction of 1a with 10 mol % of p-TsOH·H2O in 1,2-dichlo-
roethane at 80 °C for 1 h gave the best conditions to the tri-
substituted product.
With the two optimized conditions to access tetra- and tri-
substituted furans in hand, we first turned to assessing the
scope of the bimolecular reaction for a series of 1,3-dicarbonyl
compounds and propargylic 1,4-diols (Table 2). These
experiments showed that with p-TsOH·H2O as the catalyst
and MeNO2 as the solvent, the conditions proved to be broad,
and a variety of tetrasubstituted furans could be furnished in
good to excellent yields from the corresponding substrates 1b−
r and 2a−d. Reactions of starting 1,4-diols 1b−g, containing
para-substituted electron-withdrawing or electron-donating aryl
groups at R1 and R2, with 2a gave 3b−g in excellent yields of
78−86%. The presence of a second alkyne moiety at R1 was
found to have no influence on the course of the reaction, with
3h afforded in 82% yield. Likewise, replacing the phenyl
substituent at R3 with derivatives of the aromatic structure
containing an electron-withdrawing (1j,k) or electron-donating
(1l) group at the para position of the ring afforded the
corresponding furan products 3j−l in excellent yields of 89−
91%. Similarly, the tetrasubstituted furans 3n−r with a pendant
alkyl, cyclohexyl, 1-napthyl or 2-thiophene functional group
RESULTS AND DISCUSSION
■
All the but-2-yne-1,4-diols examined in this work were prepared
from reaction of the corresponding aldehyde and substituted
prop-2-yn-1-ol pretreated with LDA following literature
procedures.9 With 1,1,4-triphenylbut-2-yne-1,4-diol 1a and
1,3-diphenylpropane-1,3-dione 2a as the model substrates in
hand, we then began by focusing on a variety of Brønsted acid
catalysts to test our hypothesis (Table 1). This revealed that
a
Table 1. Optimization of the Reaction Conditions
yield (%)
conditions
entry
1
catalyst
solvent
(°C)/(h)
3a
4a
5a
p-TsOH·H2O MeNO2
p-TsOH·H2O MeNO2
p-TsOH·H2O MeNO2
TfOH
TFA
rt/6
92
68
85
20
72
25
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
54
−
44
b
2
rt/6
c
3
rt/6
4
MeNO2
MeNO2
MeNO2
MeNO2
rt/6
5
rt/6
6
Tf2NH
HCl
rt/6
−
−
d
7
rt/6
−
8
p-TsOH·H2O CH2Cl2
p-TsOH·H2O 1,4-dioxane
p-TsOH·H2O PhMe
rt/6
20
−
−
e
9
rt/6
−
10
80/1
80/1
80/1
80/1
80/0.5
80/1
80/1
−
−
−
−
−
−
−
53
58
80
70
30
55
20
f
11
p-TsOH·H2O PhMe
f
12
cf
,
p-TsOH·H2O (CH2Cl)2
p-TsOH·H2O (CH2Cl)2
p-TsOH·H2O (CH2Cl)2
p-TsOH·H2O MeNO2
p-TsOH·H2O CH3CN
13
14
15
16
f
f
f
a
All reactions were performed with 1a:2a ratio = 1:2 and 10 mol % of
b
c
catalyst. Reaction performed with 5 mol % of catalyst. Reaction
d
performed without the exclusion of air. Mixture of unknown
decomposition products obtained on the basis of TLC and 1H
e
NMR analysis of the reaction mixture. No reaction observed on the
f
basis of TLC and 1H NMR analysis of the reaction mixture. Reaction
performed in the absence of 2a.
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a
Table 2. Tandem Cycloisomerizations of 1b−r with 2a−d Catalyzed by p-TsOH·H2O
a
b
All reactions were performed with 1:2 ratio = 1:2 and 10 mol % of p-TsOH·H2O in MeNO2 at rt for 6 h. Product obtained as a 1.3:1 mixture of
c
d
e
E/Z isomers. Product obtained as a 1.1:1 mixture of E/Z isomers. Product obtained as a 1:1 mixture of E/Z isomers. Product obtained as a 1:2
mixture of E/Z isomers.
a
Table 3. Tandem Cycloisomerizations of 1b−r Catalyzed by p-TsOH·H2O
a
b
All reactions were performed at the 0.16 mmol scale with 10 mol % of p-TsOH·H2O in 1,2-dichloroethane at 80 °C for 1 h. Product obtained as
c
d
an inseparable 2.5:1 mixture of regioisomers. Product obtained as an inseparable 3.3:1 mixture of regioisomers. Mixture of decomposition products
obtained that could not be identified by H NMR analysis or mass spectrometry.
1
at R3 were obtained in 72−86% yield from the corresponding
reactions of starting alcohols 1n−r with 2a. This contrasted to the
analogous reactions where the phenyl substituent at R1 was
replaced with a t-Bu group (1i) or both carbinol carbon centers
are secondary alcohols (1m) with 2a. Reaction of the former was
the only example found to give the corresponding furan 3i in a
lower yield of 42%. Moreover, reaction of the latter was found to
furnish the tetrasubstituted furan regiosiomer 6m in 45% yield.
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On the other hand, reactions of 1,3-dicabonyl compounds bearing
a methyl or Ar group (2b−d) with 1a were found to proceed well
and provide 3s−u in excellent yields. For reactions in which R1 ≠
R2, the tetrasubstituted furan products were also obtained as a
mixture of E/Z isomers in a ratio of up to 2:1 based on 1H NMR
measurements of the respective crude mixtures. The structure of
the furan products were also determined on the basis of X-ray
crystallographic analysis of 3d, 3q, 3r, and 6m.10
This leads to the protonated analogue I, which undergoes
dehydration to give the alkynyl substituted carbocation II and
its allenic resonance form III. At room temperature,
nucleophilic attack at the acetylenic carbon center in II or
allenic carbon center in III by 2 would then to give the
alkylated adduct IV (Scheme 2, path 1). Subsequent isomer-
ization to its enolate form and protonation of the remaining
hydroxyl moiety by p-TsOH·H2O would provide cationic
tautomer V. Intramolecular nucleophilic substitution of the
enolic oxygen onto the carbon center of the protonated
hydroxyl group of this newly formed species followed by
aromatization of the resulting hydrofuran VI obtained would
then deliver the tetrasubstituted furan 3. In these reactions,
trapping at the sterically less hindered carbon center of the
putative ionized species II or III could be one possible reason
for the obtained product regioselectivities.12 Such a pathway
would limit any unfavorable steric interactions between the sub-
stituents of the tertiary carbocationic center and the incoming
carbon nucleophile. The selective formation of 3s could be due
to attack of the more nucleophilic and less sterically bulky
methyl ketone over that of the phenyl ketone in intermediate V.
The regioisomer 6m from 1m could be due to the direct alkyl-
ation by 2a of a presumably more reactive carbocationic species
of II generated from the secondary 1,4-diol 1m (Scheme 2,
path 2).13 This would give the propargylic adduct VII, which
can isomerize to its enolate form and protonation at the
remaining hydroxyl moiety by p-TsOH·H2O to form cationic
tautomer VIII. Cyclization of this cationic intermediate
involving nucleophilic substitution of the enolic oxygen onto
the carbon center of the protonated hydroxyl group would give
IX, which can undergo aromatization via X to afford 6m.
At 80 °C, it is thought that deprotonation of II preferentially
occurs at the secondary carbinol carbon center to give the
cumenol XI that readily isomerizes to the allenyl ketone 5
(Scheme 3).14 In a manner similar to that reported for the
analogous metal-catalyzed allenoate/allenyl ketone cycliza-
tions,8 this is followed by intramolecular addition of the
carbonyl oxygen onto the allene moiety of the adduct triggered
by the Brønsted acidic conditions (Scheme 3, route a). A [1,2]-
aryl shift of the resultant cyclic oxonium intermediate XII
would give XIII, which then aromatizes to provide the 2,3,5-
trisubstituted furan 4. Alternatively, the allenyl ketone 5 could
isomerize to the corresponding vinyl cationic species XV via
XIV, which would then undergo a [1,2]-aryl shift to give the
disubstituted variant XVI (Scheme 3, route b). Cycloaddition
involving attack of the enolic hydroxyl group onto the
carbocationic carbon center of this species followed by
deprotonation would then give 4.
We next sought to define the scope of the intramolecular
reaction with the same set of propargylic 1,4-diols compounds
1b−r, and the results are summarized in Table 3. Overall, this led
us to find the cyclization reactions to proceed well on applying
the p-TsOH·H2O-catalyzed conditions in 1,2-dichloroethane
described in Table 1, entry 12. Under these conditions, the
corresponding 2,3,5-trisubstituted furans 4b−g, 4j−l, 4n, and
4p−r were afforded in 60−85% yield. For reactions of 1f and
1g, the corresponding 2,3,5-trisubstituted adducts were also
obtained as mixture of regioisomers in ratios of up to 3.3:1,
comparable to those reported for the metal-catalyzed cyclo-
isomerization of allenyl ketones.11 Reactions of 1h,i, 1m, and
1o were the only instances in which no product formation was
observed. In our hands, reactions of 1h,i and 1m were found to
give a mixture of decomposition products that could not be
1
identified by H NMR analysis or mass spectrometry. For 1o,
the allenyl ketone 5o was the only product obtained in 68%
yield, even on prolonging the reaction time to 5 h.
Tentative mechanisms for the present p-TsOH·H2O-catalyzed
tri- and tetrasubstituted furan forming reactions are outlined in
Schemes 2 and 3. For the formation of the tetrasubstituted
Scheme 2. Tentative Mechanism for p-TsOH·H2O-Catalyzed
Cycloisomerization of 1 in the Presence of 2
To demonstrate that the allenyl ketone 5 is the actual
intermediate that leads to the formation of the trisubstituted
adduct, we first examined the reaction of 5a with 10 mol % of
p-TsOH·H2O in 1,2-dichloroethane at 80 °C for 1 h (Scheme 4,
eq 1). This afforded 4a in 86% yield, comparable to that
directly obtained from 1a as described in Table 1, entry 12. The
mechanistic premise put forward in Scheme 3 for the formation
of the allenyl ketone 5 via the cumenol XI was also supported
by the following deuterium labeling experiments (Scheme 4, eq
2−4). Exposing a solution of 1a-d6 in 1,2-dichloroethane with
p-TsOH·H2O (10 mol %) under the conditions shown in
Scheme 4, eq 2, gave 4a-d5 in 72% yield but with no retention
1
of D content at C3 in the product, as determined by both H
oxygen heterocycle, this could involve protonation of 1 by the
Brønsted acid at the tertiary carbinol oxygen center (Scheme 2).
NMR analysis and GC−MS measurements. In contrast,
repeating the reactions of 1a-d6 and 1a with 10 equiv of D2O
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Scheme 3. Tentative Mechanism for Cycloisomerization of 1 Catalyzed by p-TsOH·H2O
Scheme 4. Control Experiments with 1a, 1a-d6 and 5a
Catalyzed by p-TsOH·H2O
present reactions are currently underway and will be reported
in due course.
EXPERIMENTAL SECTION
■
General Remarks. All reactions were performed under a nitrogen
atmosphere. Unless specified, all reagents and starting materials were
purchased from commercial sources and used as received. Solvents
were purified following standard literature procedures. Analytical thin
layer chromatography (TLC) was performed using precoated silica gel
plate. Visualization was achieved by UV light (254 nm). Flash
chromatography was performed using silica gel and a gradient solvent
system (n-hexane/EtOAc as eluent). H and 13C NMR spectra were
1
measured on 300, 400, and 500 MHz spectrometers. Chemical shifts
(ppm) were recorded with tetramethylsilane (TMS) as the internal
reference standard. Multiplicities are given as follows: s (singlet), bs
(broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet).
The number of protons (n) for a given resonance is indicated by nH
and coupling constants are reported as a J value in Hz. Infrared spectra
were recorded on a FTIR spectrometer. Solid samples were examined
as a thin film between NaCl salt plates. High resolution mass spectra
(HRMS) were obtained using a LC/HRMS TOF spectrometer using
simultaneous electrospray (ESI).
Experimental Procedure for Preparation of Substituted But-
2-yne-1,4-diols (1a)−(1r).9,15 To a solution of the appropriate
aldehyde or ketone (2.7 mmol) in THF (5 mL) was added dropwise
ethynylmagnesium bromide (0.5 M THF solution; 2.9 mL; 3.5 mmol)
at room temperature. The resulting solution was stirred for a further
1−10 h at the same temperature. On completion, the reaction mixture
was quenched by adding saturated NH4Cl (50 mL) and extracted with
EtOAc (2 × 25 mL). The combined organic layers were washed with
water (25 mL), brine (25 mL), dried over Na2SO4 and concentrated
under reduced pressure. Purification by flash column chromatography
on silica gel (eluent: n-hexane/EtOAc = 9:1) gave the propargylic
alcohol intermediate 7. To a solution of diisopropylamine (0.47 g,
4.6 mmol) in anhydrous THF (5 mL) was added butyl lithium (1.6 M
hexane solution; 2.9 mL; 4.6 mmol) at −78 °C in a dropwise manner.
The resulting solution was stirred for 1 h prior to slow addition of 7
(1.3 mmol) in THF at −78 °C. The resulting mixture was stirred at
the same temperature for 1 h. The appropriate aldehyde (2.0 mmol) in
THF (2 mL) was added to the reaction mixture and allowed to stir for
a further 1 h at the same temperature. On completion, the reaction
mixture was quenched by adding saturated NH4Cl (50 mL) and
extracted with EtOAc (2 × 25 mL). The combined organic layers were
washed with water (25 mL), brine (25 mL), dried over Na2SO4 and
concentrated under reduced pressure. Purification by flash column
chromatography on silica gel (eluent: n-hexane/EtOAc = 4:1) gave the
title compound.
afforded 4a-d6 and 4a-d1 in 61 and 64% yield and with a D
content of 92%, incorporated at C3 of the adduct on the basis
1
of H NMR analysis and GC−MS measurements (Scheme 4,
eq 3 and 4).
CONCLUSION
■
In summary, an efficient Brønsted acid-catalyzed synthetic
route to tetrasubstituted furans from but-2-yne-1,4-diols and
1,3-dicarbonyl compounds under mild conditions at room
temperature has been reported. The intriguing reactivities of
the propargylic 1,4-diol at an elevated reaction temperature of
80 °C was also discovered and exploited to prepare the 2,3,5-
trisubstituted class of furans. By judiciously applying one of
these two reaction temperatures and solvent medium, our
studies showed that a divergence in product selectivity was
possible. Efforts to explore the synthetic applications of the
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General Procedure for Optimizing the Brønsted Acid-
Catalyzed Reactions of (1a) with (2a). The Brønsted acid catalyst
(8−16 μmol) was added to the respective solvent (2 mL) at room
temperature prior to adding the starting materials. A solution of 1a
(0.16 mmol) and 2a (0.32 mmol) in 2 mL of the same solvent was
then added dropwise to the solution of the Brønsted acid at room
temperature. The resulting mixture was stirred at for 6 h at the same
temperature. On completion, the reaction mixture was concentrated
under reduced pressure and purified by flash column chromatography
on silica gel (eluent: n-hexane/EtOAc = 9:1) to give 3a.
General Procedure for Optimizing the Brønsted Acid-
Catalyzed Reactions of (1a). To a solution of p-TsOH·H2O
(16 μmol) in the respective solvent (2 mL) was added a solution of 1a
(0.16 mmol) in the same solvent at room temperature. The resulting
mixture was then stirred at 80 °C for 1 h. On completion, the reaction
mixture was cooled down to room temperature and concentrated
under reduced pressure. Purification by flash column chromatography
on silica gel (eluent: n-hexane/EtOAc = 9:1) gave 4a and/or 5a.
Representative Procedure for Brønsted Acid-Catalyzed
Intermolecular Reactions of (1) with (2). To a solution of
p-TsOH·H2O (16 μmol) in MeNO2 (2 mL) at room temperature was
added dropwise the propargylic 1,4-diol 1 (0.16 mmol) and 1,3-
dicarbonyl compound 2 (0.32 mmol) dissolved in MeNO2 (2 mL).
The resulting mixture was stirred at room temperature for 6 h and
monitored by TLC analysis. The solvent was concentrated under
reduced pressure. Purification by flash column chromatography on
silica gel (eluent: n-hexane/EtOAc = 9:1) gave the tetrasubstituted
furan 3.
140.9, 140.5, 129.3, 129.2, 128.5, 128.3, 127.8, 127.7, 126.5, 115.3,
115.09, 115.05, 114.8, 114.6, 88.7, 87.0, 73.0, 64.0; IR (neat, cm−1)
3442, 3018, 2399, 1645, 1602, 1521, 1473, 1423, 1338, 1215, 1097,
1014, 927, 758, 669, 624; HRMS (ESI) calcd for C22H17O2F2
[M + H]+ 351.1197, found 351.1214.
1,1-bis(4-Chlorophenyl)-4-phenylbut-2-yne-1,4-diol (1c).
Yield 75%; wt 0.10 g; white solid: mp 120−122 °C; 1H NMR
(CDCl3, 400 MHz) δ 7.45−7.42 (m, 6H), 7.37−7.32 (m, 3H), 7.25−
7.22 (m, 4H), 5.50 (s, 1H), 3.47 (bs, 1H), 2.82 (bs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 142.84, 142.82, 139.9, 133.9, 128.8, 128.7, 128.5,
127.3, 126.6, 88.4, 87.5, 73.5, 64.6; IR (neat, cm−1) 3446, 3018, 2399,
1489, 1404, 1215, 1093, 1014, 927, 775, 669; HRMS (ESI) calcd for
C22H17O2Cl2 [M + H]+ 383.0606, found 383.0594.
1,1-bis(4-Bromophenyl)-4-phenylbut-2-yne-1,4-diol (1d).
Yield 78%; wt 0.10 g; white solid: mp 133−135 °C; 1H NMR
(CDCl3, 400 MHz) δ 7.41−7.23 (m, 13H), 5.44 (s, 1H), 3.86 (bs,
1H), 3.20 (bs, 1H); 13C NMR (CDCl3, 100 MHz) δ 143.34, 143.31,
139.8, 131.5, 128.8, 128.7, 128.5, 127.7, 127.67, 126.6, 125.6, 122.1,
88.3, 87.4, 73.6, 64.5; IR (neat, cm−1) 3419, 3018, 2399, 2088, 1635,
1516, 1417, 1215, 1010, 927, 771, 669; HRMS (ESI) calcd for
C22H17O2Br2 [M + H]+ 470.9595, found 470.9602.
4-Phenyl-1,1-di-p-tolylbut-2-yne-1,4-diol (1e). Yield 81%; wt
0.11 g; light brown solid: mp 140−142 °C; 1H NMR (CDCl3, 400 MHz)
δ 7.54−7.52 (m, 2H), 7.47 (d, 4H, J = 8.2 Hz), 7.39−7.33 (m, 3H), 7.12
(d, 4H, J = 8.0), 5.56 (s, 1H), 3.04 (bs, 1H), 2.61 (bs, 1H), 2.32 (s, 6H);
13C NMR (CDCl3, 100 MHz) δ 142.0, 140.3, 137.4, 128.9, 128.6, 128.4,
126.7, 125.9, 89.6, 86.6, 74.2, 64.7, 21.0; IR (neat, cm−1) 3419, 3018, 2399,
2088, 1637, 1560, 1516, 1473, 1419, 1215, 927, 771, 669; HRMS (ESI)
calcd for C24H23O2 [M + H]+ 343.1698, found 343.1690.
Representative Procedure for Brønsted Acid-Catalyzed
Intramolecular Reactions of (1). To a solution of p-TsOH·H2O
(16 μmol) in 1,2-dichloroethane (2 mL) at room temperature was
added dropwise the propargylic 1,4-diol 1 (0.16 mmol) dissolved in
1,2-dichloroethane (2 mL). The resulting mixture was stirred at 80 °C
for 1 h and monitored by TLC analysis. On completion, the reaction
mixture was cooled down to room temperature and concentrated
under reduced pressure. Purification by flash column chromatography
on silica gel (eluent: n-hexane/EtOAc = 9:1) gave the trisubstituted
furan 4.
1-(4-Bromophenyl)-1,4-diphenylbut-2-yne-1,4-diol (1f). Yield
1
76%; wt 0.10 g; yellow solid: mp 109−111 °C; dr ratio = 1:1; H
NMR (CDCl3, 400 MHz) δ 7.53−7.24 (m, 14H), 5.50 (s, 1H,
diastereomer A or B), 5.49 (s, 1H, diastereomer A or B), 3.40
(bs, 1H), 2.80 (bs, 1H); 13C NMR (CDCl3, 100 MHz) δ 144.2, 143.8,
140.0, 131.3, 128.7, 128.6, 128.4, 128.0, 127.8, 126.6, 125.9, 121.8,
88.8, 87.2, 74.0, 64.6; IR (neat, cm−1) 3446, 3018, 2399, 1635, 1521,
1473, 1419, 1215, 1010, 927, 756, 669; HRMS (ESI) calcd for
C22H18O2Br [M + H]+ 393.0490, found 393.0481.
Procedure for Brønsted Acid-Catalyzed Reaction of (5a). To
a solution of p-TsOH·H2O (16 μmol) in 1,2-dichloroethane (2 mL) at
room temperature was added dropwise 5 (0.16 mmol) dissolved in
1,2-dichloroethane (2 mL). The resulting mixture was stirred at 80 °C
for 1 h. On completion, the reaction mixture was cooled down to
room temperature and concentrated under reduced pressure.
Purification by flash column chromatography on silica gel (eluent:
n-hexane/EtOAc = 9:1) gave 4a.
1,4-Diphenyl-1-p-tolylbut-2-yne-1,4-diol (1g). Yield 75%; wt
0.11 g; white solid: mp 123−125 °C; H NMR (CDCl3, 300 MHz)
1
δ 7.56−7.23 (m, 12H), 7.10 (d, 2H, J = 7.7 Hz), 5.52 (s, 1H), 3.13 (bs,
1H), 2.65 (bs, 1H), 2.29 (s, 3H); 13C NMR (CDCl3, 100 MHz)
δ 144.8, 141.9, 140.3, 137.5, 129.0, 128.6, 128.4, 128.2, 127.7, 126.7,
126.0, 89.5, 86.8, 74.3, 64.6, 21.0; IR (neat, cm−1) 3439, 3018, 2088,
1637, 1508, 1419, 1215, 1016, 927, 758, 669; HRMS (ESI) calcd for
C23H21O2 [M + H]+ 329.1542, found 329.1541.
Representative Procedure for Brønsted Acid-Catalyzed
Reactions of (1a) and (1a-d6) in the Presence of D2O. To a
solution of p-TsOH·H2O (16 μmol) in 1,2-dichloroethane (2 mL) at
room temperature was added dropwise the propargylic 1,4-diol 1
(0.16 mmol) dissolved in 1,2-dichloroethane (2 mL) followed by the
addition of D2O (1.6 mmol). The resulting mixture was stirred at
80 °C for 1 h and monitored by TLC analysis. On completion, the
reaction mixture was cooled down to room temperature and
concentrated under reduced pressure. Purification by flash column
chromatography on silica gel (eluent: n-hexane/EtOAc = 9:1) gave 4a-
1,4,6-Triphenylhexa-2,5-diyne-1,4-diol (1h). Yield 82%; wt
0.11 g; light brown solid: mp 129−131 °C; 1H NMR
(CDCl3+CD3OD, 500 MHz) δ 7.86−7.84 (m, 2H), 7.56−7.29
(m, 13H), 5.53 (s, 1H, diastereomer A or B), 5.52 (s, 1H, diastereomer
A or B), 3.32 (bs, 2H); 13C NMR (CDCl3+CD3OD, 125 MHz) δ
142.0, 140.3, 131.5, 128.5, 128.3, 128.2, 128.1, 128.0, 126.6, 126.5,
125.7, 122.0, 89.2, 86.3, 84.5, 84.3, 84.2, 64.8, 63.8, 63.7; IR (neat,
cm−1) 3018, 2399, 1516, 1419, 1215, 927, 769, 669; HRMS (ESI)
calcd for C24H19O2 [M + H]+ 339.1385, found 339.1387.
5,5-Dimethyl-1,4-diphenylhex-2-yne-1,4-diol (1i). Yield 79%;
wt 0.12 g; colorless oil: inseparable mixture with benzylic alcohol (1:1
ratio); 1H NMR (CDCl3, 400 MHz) δ 7.57−7.51 (m, 4H), 7.37−7.23
(m, 6H, (4H, benzylic)), 5.50 (s, 1H), 4.60 (s, 2H, (benzylic)), 2.83
(bs, 1H), 2.75 (bs, 1H), 0.99 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ
141.9, 140.8, 140.6, 128.6, 128.5, 128.3, 127.6, 127.4, 127.1, 127.0,
126.6, 89.8, 85.5, 78.9, 65.2, 64.6, 39.5, 25.4; IR (neat, cm−1) 3383,
3014, 2972, 2401, 1953, 1726, 1600, 1492, 1454, 1392, 1215, 1136,
1078, 1001, 906, 756, 700, 667; HRMS (ESI) calcd for C20H23O2
[M + H]+ 295.1698, found 295.1686.
1
d1 or 4a-d6 with a D content incorporated at C3 on the basis of H
NMR analysis and GC−MS measurements or 4a-d5 when D = 0%.
1,1,4-Triphenylbut-2-yne-1,4-diol (1a). Yield 85%; wt 0.25 g;
white solid: mp 139−141 °C; 1H NMR (CD3OD, 300 MHz) δ 7.61−
7.55 (m, 6H), 7.36−7.15 (m, 9H), 5.57 (s, 1H); 13C NMR (CD3OD,
75 MHz) δ 145.7, 141.3, 128.1, 127.7, 127.6, 127.0, 126.5, 125.8, 88.8,
86.7, 73.7, 63.7; IR (neat, cm−1) 3419, 3018, 2399, 1635, 1556, 1419,
1215, 1004, 927, 771, 669; HRMS (ESI) calcd for C22H19O2 [M + H]+
315.1385, found 315.1378.
1,1-bis(4-Fluorophenyl)-4-phenylbut-2-yne-1,4-diol (1b).
Yield 69%; wt 0.098 g; light brown solid: mp 131−133 °C; 1H
NMR (CDCl3+CD3OD, 400 MHz) δ 7.54−7.50 (m, 5H), 7.38−7.28
(m, 3H), 7.21−7.17 (m, 1H), 6.99−6.94 (m, 4H), 5.53 (s, 1H), 2.68
(bs, 2H); 13C NMR (CDCl3+CD3OD, 100 MHz) δ 163.5, 160.9,
4-(4-Fluorophenyl)-1,1-diphenylbut-2-yne-1,4-diol (1j). Yield
71%; wt 0.22 g; white solid: mp 113−115 °C; 1H NMR (CDCl3, 500
MHz) δ 7.53−7.51 (m, 4H), 7.41−7.38 (m, 2H), 7.29−7.21 (m, 6H),
6.97 (t, 2H, J = 8.6 Hz), 5.42 (s, 1H), 3.54 (bs, 1H), 3.19 (bs, 1H); 13C
NMR (CDCl3, 125 MHz) δ 163.8, 161.8, 144.7 (d, 1C, JC−F = 10.1 Hz),
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Article
136.2 (d, 1C, JC−F = 11.4 Hz), 128.78, 128.71, 128.5, 128.0, 126.1,
115.7, 115.5, 89.7, 86.8, 74.6, 64.0; IR (neat, cm−1) 3421, 3018, 2399,
1635, 1508, 1419, 1215, 1014, 927, 771, 669; HRMS (ESI) calcd for
C22H18O2F [M + H]+ 333.1291, found 333.1279.
3689, 3018, 2962, 2397, 1521, 1419, 1215, 1004, 927, 769, 667;
HRMS (ESI) calcd for C20H23O2 [M + H]+ 295.1698, found 295.1706.
1,1,-Triphenylbut-2-yne-1,4-diol (1a-d6). Yield 81%; wt 0.12 g;
white solid: mp 141−143 °C; 1H NMR (CDCl3+CD3OD, 400 MHz)
δ 7.59 (d, 4H, J = 7.6 Hz), 7.30−7.20 (m, 6H), 3.2 (bs, 2H); 13C
NMR (CDCl3+CD3OD, 100 MHz) δ 145.18, 145.12, 140.4, 128.0,
127.4, 125.96, 125.94, 89.0, 86.6, 77.3, 73.9; IR (neat, cm−1) 3446,
3018, 2399, 1635, 1521, 1423, 1215, 1029, 927, 771, 669; HRMS
4-(4-Bromophenyl)-1,1-diphenylbut-2-yne-1,4-diol (1k).
1
Yield 73%; wt 0.27 g; light brown solid: mp 166−168 °C; H NMR
(CDCl3+CD3OD, 500 MHz) δ 7.58−7.55 (m, 4H), 7.48−7.40 (m,
4H), 7.31−7.19 (m, 6H), 5.49 (s, 1H); 13C NMR (CDCl3+CD3OD,
125 MHz) δ 145.15, 145.10, 139.9, 131.6, 131.58, 131.55, 128.6, 128.5,
128.3, 128.2, 127.8, 127.6, 126.0, 125.97, 125.95, 122.1, 89.4, 86.3,
74.0, 63.4; IR (neat, cm−1) 3419, 3018, 2399, 2088, 1635, 1521, 1419,
1215, 1010, 927, 771, 669; HRMS (ESI) calcd for C22H18O2Br [M + H]+
393.0490, found 393.0487.
1
(ESI) calcd for C22 H14 2H5O2 [M + H]+ 320.1699, found 320.1686.
(4-(2,2-Diphenylvinyl)-2,5-diphenylfuran-3-yl)(phenyl)-
1
methanone (3a). Wt 0.073 g; yellow solid: mp 124−126 °C; H
NMR (CDCl3, 400 MHz) δ 7.89−7.87 (m, 2H), 7.55−7.20 (m, 16H),
7.10−6.90 (m, 7H), 6.74 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
191.1, 152.3, 149.6, 146.6, 142.8, 138.8, 137.1, 132.7, 130.66, 130.61,
129.8, 129.5, 128.79, 128.71, 128.5, 128.3, 128.2, 128.0, 127.95,
127.90, 127.8, 127.7, 127.1, 127.0, 125.5, 122.7, 121.0, 118.1; IR (neat,
cm−1) 3018, 1734, 1653, 1597, 1483, 1446, 1327, 1215, 1074, 1026,
898, 758, 669; HRMS (ESI) calcd for C37H26O2Na [M + Na]+
525.1831, found 525.1830.
4-(4-tert-Butylphenyl)-1,1-diphenylbut-2-yne-1,4-diol (1l).
Yield 78%; wt 0.27 g; white solid: mp 162−164 °C; 1H NMR
(CDCl3+CD3OD, 400 MHz) δ 7.59 (d, 4H, J = 7.3 Hz), 7.46 (d, 2H,
J = 7.8 Hz), 7.38 (d, 2H, J = 7.8 Hz) 7.29−7.21 (m, 6H) 5.50 (s, 1H),
1.30 (s, 9H); 13C NMR (CDCl3+CD3OD, 100 MHz) δ 151.2, 145.2,
145.1, 137.6, 128.1, 127.4, 126.5, 126.02, 126.00, 125.4, 89.0, 86.8,
74.0, 63.8, 34.5, 31.2; IR (neat, cm−1) 3439, 3018, 2399, 1635, 1419,
1215, 927, 771, 669; HRMS (ESI) calcd for C26H27O2 [M + H]+
371.2011, found 371.2013.
1,4-Diphenylbut-2-yne-1,4-diol (1m). Yield 87%; wt 0.15 g;
light brown solid: mp 117−119 °C; 1H NMR (CDCl3+CD3OD,
400 MHz) δ 7.52 (d, 4H, J = 7.2 Hz), 7.35−7.26 (m, 6H), 5.47 (s, 2H),
3.32 (bs, 2H); 13C NMR (CDCl3+CD3OD, 100 MHz) δ 140.6, 128.4,
128.1, 126.63, 126.62, 86.1, 86.0, 63.9; IR (neat, cm−1) 3585, 3018,
2399, 1653, 1521, 1456, 1419, 1338, 1217, 1122, 1014, 927, 771, 698,
669; HRMS (ESI) calcd for C16H15O2 [M + H]+ 239.1072, found
239.1082.
4-(Naphthalen-1-yl)-1,1-diphenylbut-2-yne-1,4-diol (1n).
Yield 71%; wt 0.12 g; white solid: mp 121−123 °C; 1H NMR
(CDCl3, 500 MHz) δ 8.22−7.82 (m, 2H), 7.80 (d, 1H, J = 8.2 Hz),
7.74 (d, 1H, J = 7.0 Hz), 7.56−7.46 (m, 6H), 7.37 (t, 1H, J = 7.6 Hz),
7.25−7.18 (m, 6H), 6.12 (s, 1H); 13C NMR (CDCl3, 125 MHz) δ
144.6, 144.5, 135.2, 133.9, 130.4, 129.3, 128.6, 128.2, 127.6, 126.3,
125.9, 125.8, 125.1, 124.6, 123.9, 89.8, 86.8, 74.4, 62.9; IR (neat, cm−1)
3439, 3018, 2399, 2088, 1633, 1519, 1423, 1215, 1014, 927, 771, 669;
HRMS (ESI) calcd for C26H21O2 [M + H]+ 365.1542, found 365.1545.
1,1-Diphenyl-4-(thiophen-2-yl)but-2-yne-1,4-diol (1o). Yield
82%; wt 0.12 g; pale yellow solid: mp 156−158 °C; 1H NMR
(CDCl3+CD3OD, 500 MHz) δ 7.62−7.58 (m, 4H), 7.31−7.21 (m,
7H), 7.14 (bd, 1H, J = 3.4 Hz), 6.95−6.94 (m, 1H), 5.73 (s, 1H), 3.04
(bs, 2H); 13C NMR (CDCl3+CD3OD, 125 MHz) δ 145.1, 145.0,
144.8, 128.2, 127.6, 126.8, 126.1, 126.0, 125.8, 125.5, 88.4, 86.1, 74.0,
59.8; IR (neat, cm−1) 3441, 3018, 2399, 2088, 1635, 1516, 1419, 1215,
1014, 927, 771, 669; HRMS (ESI) calcd for C20H17O2S [M + H]+
321.0949, found 321.0965.
4-Cyclohexyl-1,1-diphenylbut-2-yne-1,4-diol (1p). Yield 86%;
wt 0.13 g; white solid: mp 141−143 °C; 1H NMR (CDCl3, 400 MHz)
δ 7.58 (d, 4H, J = 7.6 Hz), 7.32−7.22 (m, 6H), 4.26 (d, 1H, J = 5.9 Hz),
3.18 (bs, 1H), 2.19 (bs, 1H), 1.86−1.58 (m, 5H), 1.28−1.01 (m, 6H);
13C NMR (CDCl3, 100 MHz) δ 144.9, 128.2, 127.6, 125.9, 88.3, 87.4,
74.4, 67.2, 44.1, 28.6, 28.1, 26.4, 25.87, 25.84; IR (neat, cm−1) 3446,
3018, 2399, 1647, 1521, 1419, 1338, 1215, 1016, 927, 771, 669; HRMS
(ESI) calcd for C22H25O2 [M + H]+ 321.1855, found 321.1870.
1,1-Diphenylpent-2-yne-1,4-diol (1q). Yield 80%; wt 0.09 g;
white solid: mp 109−111 °C; 1H NMR (CDCl3, 400 MHz) δ 7.55 (d,
4H, J = 7.1 Hz), 7.30−7.20 (m, 6H), 4.56 (q, 1H, J = 6.6 Hz), 3.47
(bs, 1H), 2.92 (bs, 1H), 1.44 (d, 3H, J = 6.6 Hz); 13C NMR (CDCl3,
100 MHz) δ 144.8, 128.2, 127.7, 126.01, 126.00, 89.0, 86.7, 74.2, 58.4,
24.0; IR (neat, cm−1) 3419, 3018, 2397, 1645, 1489, 1448, 1328, 1215,
1020, 925, 758, 669; HRMS (ESI) calcd for C17H17O2 [M + H]+
253.1229, found 253.1227.
(4-(2,2-bis(4-Fluorophenyl)vinyl)-2,5-diphenylfuran-3-yl)-
(phenyl)methanone (3b). Wt 0.059 g; yellow solid: mp 173−
175 °C; 1H NMR (CDCl3, 400 MHz) δ 7.86−7.84 (m, 2H), 7.54−6.84
(m, 20H), 6.75 (s, 1H), 6.62 (t, 1H, J = 8.7 Hz); 13C NMR (CDCl3,
100 MHz) δ 191.1, 163.8, 163.4, 161.4, 161.0, 152.4, 152.3, 149.8,
149.7, 145.5 (d, 1C, JC−F = 14.2 Hz), 142.6, 138.9, (d, 1C, JC−F
=
12.2 Hz), 138.6, 137.1, 136.7, 134.8, 132.9, 132.7, 132.4, 132.3, 130.58
(d, 1C, JC−F = 24.6 Hz), 129.9, 129.8, 129.7, 129.49, 129.41, 128.84,
128.83, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0, 127.96, 127.93
(d, 1C, JC−F = 10.0 Hz), 127.2, 127.1, 125.5, 122.6, 122.5, 120.8, 118.1,
118.0, 115.0, 114.9, 114.8, 114.7; IR (neat, cm−1) 3392, 3018, 2397,
1647, 1506, 1444, 1328, 1215, 898, 756; HRMS (ESI) calcd for
C37H24O2F2Na [M + Na]+ 561.1642, found 561.1631.
(4-(2,2-bis(4-Chlorophenyl)vinyl)-2,5-diphenylfuran-3-yl)-
(phenyl)methanone (3c). Wt 0.061 g; pale yellow solid: mp 195−
1
197 °C; H NMR (CDCl3, 400 MHz) δ 7.82 (d, 2H, J = 7.4 Hz),
7.49−7.17 (m, 15H), 7.08 (d, 2H, J = 8.4 Hz), 6.87 (d, 2H, J =
8.4 Hz), 6.81 (d, 2H, J = 8.4 Hz), 6.77 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 191.0, 152.4, 150.1, 144.1, 140.7, 137.0, 136.4, 134.0,
133.8, 132.9, 131.8, 130.3, 129.6, 129.5, 129.2, 128.8, 128.6, 128.39,
128.31, 128.25, 128.1, 128.0, 127.1, 125.5, 122.3, 120.5, 118.9; IR
(neat, cm−1) 3442, 3018, 2399, 1647, 1506, 1490, 1417, 1338, 1215,
1091, 1014, 927, 777, 669; HRMS (ESI) calcd for C37H25O2Cl2 [M + H]+
571.1232, found 571.1252.
(4-(2,2-bis(4-Bromophenyl)vinyl)-2,5-diphenylfuran-3-yl)-
(phenyl)methanone (3d). Wt 0.060 g; pale yellow solid: mp 209−
1
211 °C; H NMR (CDCl3, 400 MHz) δ 7.82 (d, 2H, J = 7.6 Hz),
7.80−7.17 (m, 15H), 7.01 (dd, 4H, J1 = 6.5, J2 = 8.0 Hz), 6.79 (s, 1H),
6.75 (d, 2H, J = 8.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 191.0, 152.4,
150.1, 144.2, 141.1, 137.4, 136.4, 132.9, 132.1, 131.3, 131.1, 130.3,
129.8, 129.5, 129.2, 128.8, 128.6, 128.3, 128.17, 128.10, 127.2, 125.5,
122.3, 122.2, 120.4, 119.0; IR (neat, cm−1) 3680, 3018, 2399, 1653,
1597, 1521, 1489, 1419, 1328, 1215, 1070, 1010, 929, 908, 756, 667;
HRMS (ESI) calcd for C37H25O2Br2 [M + H]+ 659.0221, found
659.0221.
(4-(2,2-di-p-Tolylvinyl)-2,5-diphenylfuran-3-yl)(phenyl)-
methanone (3e). Wt 0.061 g; pale yellow solid: mp 176−178 °C; 1H
NMR (CDCl3, 500 MHz) δ 7.91 (d, 2H, J = 7.4 Hz), 7.51−7.37
(m, 7H), 7.34 (t, 1H, J = 7.4 Hz), 7.22−7.18 (m, 5H), 7.07 (dd, 4H,
J1 = 8.1, J2 = 17.7 Hz), 6.81 (d, 2H, J = 8.0 Hz), 6.74 (d, 2H, J = 7.9
Hz), 6.70 (s, 1H), 2.35 (s, 3H), 2.13 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 191.0, 152.0, 149.7, 146.4, 140.2, 137.5, 137.2, 136.9, 136.0,
132.4, 130.7, 130.6, 129.8, 129.6, 128.79, 128.72, 128.5, 128.4, 128.29,
128.25, 127.8, 127.7, 127.2, 127.1, 125.4, 122.7, 121.4, 116.8, 21.2,
21.1; IR (neat, cm−1) 3018, 2399, 1653, 1598, 1516, 1419, 1336, 1215,
1026, 929, 771, 669; HRMS (ESI) calcd for C39H31O2 [M + H]+
531.2324, found 531.2321.
5,5-Dimethyl-1,1-diphenylhex-2-yne-1,4-diol (1r). Yield 82%;
1
wt 0.11 g; white solid: mp 163−165 °C; H NMR (CDCl3+CD3OD,
(4-(2-(4-Bromophenyl)-2-phenylvinyl)-2,5-diphenylfuran-3-
400 MHz) δ 7.58−7.22 (m, 10H), 4.10 (s, 1H), 3.63 (bs, 2H), 1.01
(s, 9H); 13C NMR (CDCl3+CD3OD, 100 MHz) δ 145.4, 145.3, 127.9,
127.3, 126.5, 125.89, 125.87, 88.1, 86.6, 73.9, 70.8, 35.9, 25.2; IR (neat, cm−1)
yl)(phenyl)methanone (3f). Wt 0.061 g; pale yellow solid: mp 155−
1
157 °C; E/Z ratio = 1.3:1; H NMR (CDCl3, 400 MHz) δ 7.86 (d,
2H, J = 8.2 Hz), 7.53−7.31 (m, 9H), 7.29−7.16 (m, 8H), 7.05−6.76
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(m, 5H), 6.71 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 191.1 (1C, E
or Z isomer), 191.0 (1C, E or Z isomer), 152.5, 152.3, 150.0, 149.7,
145.49, 145.40, 142.2, 141.7, 138.2, 137.9, 137.0, 136.4, 132.8, 132.7,
132.2, 131.1, 131.0, 130.5, 130.4, 129.8, 129.6, 129.4, 129.3, 128.8,
128.6, 128.5, 128.2, 128.1, 128.08, 128.02, 127.9, 127.16, 127.11,
125.5, 121.98, 121.95, 120.75, 120.72, 118.6, 118.4; IR (neat, cm−1)
3442, 3018, 2399, 1653, 1521, 1419, 1338, 1215, 1026, 927, 769, 669;
HRMS (ESI) calcd for C37H25O2BrNa [M + Na]+ 603.0936, found
603.0942.
(2,5-Diphenyl-4-(2-phenyl-2-(p-tolyl)vinyl)furan-3-yl)-
(phenyl)methanone (3g). Wt 0.066 g; pale yellow solid: mp 161−
163 °C; E/Z ratio = 1.1:1; 1H NMR (CDCl3, 400 MHz) δ 7.89−7.37
(m, 9H), 7.35−7.12 (m, 9H), 7.06−6.95 (m, 3H), 6.90 (d, 1H, J =
6.9 Hz), 6.79 (d, 1H, J = 8.0 Hz), 6.72 (s, 1H), 6.70 (d, 1H, J = 5.0 Hz).
2.32 (s, 3H, E or Z isomer), 2.10 (s, 3H, E or Z isomer); 13C NMR
(CDCl3, 100 MHz) δ 191.1 (1C, E or Z isomer), 191.0 (1C, E or
Z isomer), 152.2, 152.1, 149.8, 149.5, 146.58, 146.52, 143.07, 143.05,
138.9, 137.6, 137.3, 137.2, 136.8, 135.9, 132.6, 130.67, 130.61, 129.88,
129.83, 129.5, 128.78, 128.73, 128.57, 128.50, 128.4, 128.3, 128.26,
128.23, 128.21, 127.99, 127.94, 127.8, 127.76, 127.74, 127.1, 127.0,
125.5, 122.8, 122.6, 121.3, 121.0, 117.5, 117.3; IR (neat, cm−1) 3419,
3018, 2399, 1647, 1506, 1338, 1215, 927, 771, 669; HRMS (ESI) calcd
for C38H28O2Na [M + Na]+ 539.1987, found 539.1994.
(neat, cm−1) 3446, 3018, 2399, 1653, 1521, 1479, 1419, 1215, 1008,
927, 771, 669; HRMS (ESI) calcd for C37H26O2Br [M + H]+
581.1116, found 581.1128.
(5-(4-(tert-Butyl)phenyl)-4-(2,2-diphenylvinyl)-2-phenylfur-
1
an-3-yl)(phenyl)methanone (3l). Wt 0.067 g; yellow oil: H NMR
(CDCl3, 300 MHz) δ 7.81 (d, 2H, J = 8.5 Hz), 7.53−7.36 (m, 7H),
7.24−7.18 (m, 8H), 7.09−6.88 (m, 7H), 6.72 (s, 1H), 1.34 (s, 9H);
13C NMR (CDCl3, 75 MHz) δ 191.1, 152.0, 151.1, 149.9, 146.3, 142.9,
138.8, 137.1, 132.6, 130.6, 129.8, 129.6, 128.4, 128.28, 128.23, 127.9,
127.8, 127.77, 127.70, 127.0, 125.7, 125.3, 122.6, 120.4, 118.3, 34.7,
31.2; IR (neat, cm−1) 3441, 3018, 2399, 1653, 106, 1417, 1338, 1215,
927, 771, 669; HRMS (ESI) calcd for C41H35O2 [M + H]+ 559.2637,
found 559.2644.
(4-(2,2-Diphenylvinyl)-5-(naphthalen-1-yl)-2-phenylfuran-3-
yl)(phenyl)methanone (3n). Wt 0.054 g; brown oil: 1H NMR
(CDCl3, 400 MHz) δ 8.06−8.03 (m, 1H), 7.83−7.79 (m, 4H), 7.53−
7.6.79 (m, 20H), 6.66 (s, 1H), 6.61−6.59 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ 192.0, 152.8, 150.2, 146.3, 142.8, 139.2, 137.1, 133.8,
133.1, 131.0, 130.1, 130.0, 129.7, 129.5, 129.2, 128.7, 128.4, 128.3,
128.27, 128.23, 128.0, 127.8, 127.7, 127.6, 127.5, 127.4, 127.2, 126.9,
126.3, 126.0, 125.9, 125.1, 122.8, 122.4, 117.2; IR (neat, cm−1) 3439,
3018, 2399, 1651, 1489, 1446, 1323, 1215, 1132, 1074, 898, 756, 696,
669; HRMS (ESI) calcd for C41H29O2 [M + H]+ 553. 2168, found
553.2161.
(4-(2,2-Diphenylvinyl)-2-phenyl-5-(thiophen-2-yl)furan-3-
yl)(phenyl)methanone (3o). Wt 0.064 g; yellow oil: 1H NMR
(CDCl3, 400 MHz) δ 7.87 (d, 2H, J = 7.5 Hz), 7.48−7.27 (m, 13H),
7.22 (d, 1H, J = 5.0 Hz), 7.13−6.91 (m, 6H), 6.87 (d, 2H, J = 7.3 Hz);
13C NMR (CDCl3, 100 MHz) δ 193.6, 150.4, 148.5, 142.7, 142.2,
141.0, 137.2, 133.7, 132.1, 129.8, 129.6, 128.8, 128.5, 128.4, 128.3,
128.2, 128.0, 127.8, 127.6, 127.4, 127.3, 126.2, 125.7, 121.7, 121.0,
112.9; IR (neat, cm−1) 3394, 3018, 2399, 1654, 1597, 1490, 1446,
1215, 929, 906, 767, 669; HRMS (ESI) calcd for C35H25O2S [M + H]+
509.1575, found 509.1594.
(5-Cyclohexyl-4-(2,2-diphenylvinyl)-2-phenylfuran-3-yl)-
(phenyl)methanone (3p). Wt 0.067 g; yellow oil: 1H NMR (CDCl3,
400 MHz) δ 7.70 (d, 2H, J = 7.5 Hz), 7.40−7.02 (m, 18H), 6.60
(s, 1H), 2.53−2.46 (m, 1H), 1.74−1.47 (m, 7H), 1.25−1.13 (m, 3H);
13C NMR (CDCl3, 100 MHz) δ 192.3, 156.4, 151.4, 145.2, 143.1,
(4-(2,4-Diphenylbut-1-en-3-yn-1-yl)-2,5-diphenylfuran-3-yl)-
(phenyl)methanone (3h). Wt 0.063 g; yellow solid: mp 118−120
1
°C; E/Z ratio = 1:1; H NMR (CDCl3, 400 MHz) δ 7.85−7.73 (m,
4H), 7.53−7.16 (m, 19H), 7.06−6.94 (m, 3H); 13C NMR (CDCl3,
100 MHz) δ 192.1 (1C, E or Z isomer), 190.9 (1C, E or Z isomer),
153.3, 152.7, 149.9, 149.7, 138.4, 137.9, 136.7, 136.4, 132.8, 132.7,
131.67, 131.61, 130.6, 130.2, 129.9, 129.6, 129.3, 129.0, 128.85,
128.81, 128.7, 128.6, 128.39, 128.34, 128.29, 128.24, 128.21, 128.1,
128.09, 128.03, 128.00, 127.9, 127.8, 127.4, 127.2, 127.1, 126.3, 126.2,
125.9, 125.1, 123.2, 122.9, 122.4, 119.9, 119.3, 98.0, 91.2, 89.9, 87.7; IR
(neat, cm−1) 3442, 3018, 2399, 1653, 1489, 1215, 1026, 927, 773, 669;
HRMS (ESI) calcd for C39H27O2 [M + H]+ 527.2011, found 527.2006.
(4-(3,3-Dimethyl-2-phenylbut-1-en-1-yl)-2,5-diphenylfuran-
3-yl)(phenyl)methanone (3i). Wt 0.034 g; pale yellow solid: mp
145−147 °C; E/Z ratio = 1:2; 1H NMR (CDCl3, 400 MHz) δ 7.84 (d,
1H, J = 7.4 Hz), 7.76 (d, 2H, J = 7.4 Hz), 7.67 (d, 1H, J = 7.2 Hz),
7.45−7.02 (m, 25H), 6.81 (d, 2H, J = 6.9 Hz), 6.50 (s, 1H, E or Z
isomer), 6.11 (s, 1H, E or Z isomer), 1.35 (s, 9H, E or Z isomer), 1.14
(s, 9H, E or Z isomer); 13C NMR (CDCl3, 100 MHz) δ 193.9 (1C, E
or Z isomer), 193.7 (1C, E or Z isomer), 156.2, 152.3, 151.3, 150.4,
147.8, 146.9, 145.9, 141.3, 137.39, 137.35, 133.4, 133.3, 132.0, 131.9,
129.8, 129.78, 129.71, 129.5, 129.4, 129.2, 129.1, 128.6, 128.5, 128.4,
128.32, 128.30, 128.2, 128.0, 127.9, 127.8, 127.5, 127.24, 127.21,
126.8, 126.3, 126.2, 125.8, 122.3, 121.6, 116.0, 110.6, 37.1, 36.0, 30.9,
29.7; IR (neat, cm−1) 3414, 3018, 2399, 1653, 1521, 1419, 1325, 1215,
1020, 927, 779, 669; HRMS (ESI) calcd for C35H31O2 [M + H]+
483.2324, found 483.2326.
139.8, 137.3, 132.8, 130.8, 129.9, 128.2, 128.1, 128.0, 127.9, 127.5,
127.3, 126.7, 121.6, 118.3, 117.8, 36.6, 30.9, 26.3, 25.8; IR (neat, cm−1)
3446, 3018, 2399, 2308, 1647, 1506, 1338, 1215, 927, 767, 669;
HRMS (ESI) calcd for C37H33O2 [M + H]+ 509.2481, found 509.2474.
(4-(2,2-Diphenylvinyl)-5-methyl-2-phenylfuran-3-yl)-
(phenyl)methanone (3q). Wt 0.064 g; pale yellow solid: mp 143−
1
145 °C; H NMR (CDCl3, 400 MHz) δ 7.75 (d, 2H, J = 7.1 Hz),
7.43−7.37 (m, 3H), 7.29−7.07 (m, 15H), 6.56 (s, 1H), 1.91 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 192.4, 151.6, 148.9, 145.4, 143.0,
140.0, 137.3, 132.9, 130.6, 129.9, 129.7, 128.2, 128.19, 128.17, 128.0,
127.9, 127.5, 127.2, 126.6, 121.8, 120.0, 117.7, 12.5; IR (neat, cm−1)
3018, 2399, 1653, 1597, 1489, 1215, 1074, 1022, 929, 771, 669;
HRMS (ESI) calcd for C32H25O2 [M + H]+ 441.1855, found 441.1855.
(5-(tert-Butyl)-4-(2,2-diphenylvinyl)-2-phenylfuran-3-yl)-
(phenyl)methanone (3r). Wt 0.070 g; pale yellow solid: mp 125−
(4-(2,2-Diphenylvinyl)-5-(4-fluorophenyl)-2-phenylfuran-3-
yl)(phenyl)methanone (3j). Wt 0.069 g; pale yellow solid: mp 143−
145 °C; 1H NMR (CDCl3, 400 MHz) δ 7.81 (dd, 2H, J1 = 5.4, J2 = 8.5
Hz), 7.56 (d, 2H, J = 7.7 Hz), 7.50−7.48 (m, 2H), 7.40 (t, 1H, J = 7.2
Hz), 7.25−6.96 (m, 15H), 6.89 (d, 2H, J = 7.3 Hz), 6.69 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ 191.1, 163.6, 161.1, 152.2, 148.7, 146.9,
142.7, 138.8, 137.0, 132.7, 130.5, 129.8, 129.4, 128.5, 128.0 (d, 1C,
JC−F = 26.1 Hz), 128.00, 127.86, 127.81, 127.7, 127.4, 127.3, 127.0,
126.9 (d, 1C, JC−F = 16.8 Hz), 126, 122.7, 120.6, 117.7, 115.9, 115.7;
IR (neat, cm−1) 3419, 3018, 2399, 1653, 1516, 1417, 1328, 1215, 927,
769, 669; HRMS (ESI) calcd for C37H26O2F [M + H]+ 521.1917,
found 521.1916.
(5-(4-Bromophenyl)-4-(2,2-diphenylvinyl)-2-phenylfuran-3-
yl)(phenyl)methanone (3k). Wt 0.067 g; pale yellow solid: mp
181−183 °C; 1H NMR (CDCl3, 400 MHz) δ 7.72 (d, 2H, J = 8.5 Hz),
7.56−7.49 (m, 7H), 7.41 (t, 1H, J = 7.3 Hz), 7.27−7.20 (m, 7H),
7.11−6.97 (m, 5H), 6.89 (d, 2H, J = 7.0 Hz), 6.69 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 191.0, 152.5, 148.5, 147.1, 142.6, 138.7, 137.0,
132.8, 131.9, 130.5, 129.8, 129.4, 129.3, 128.6, 128.3, 128.2, 128.08,
128.01, 127.9, 127.8, 127.0, 126.9, 122.8, 121.8, 121.5, 117.5; IR
1
127 °C; H NMR (CDCl3, 500 MHz) δ 7.47 (d, 2H, J = 7.1 Hz),
7.39−7.33 (m, 3H), 7.23−7.11 (m, 8H), 7.04−6.92 (m, 7H), 6.69
(s, 1H), 1.44 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 191.5, 158.4,
150.8, 144.6, 143.3, 139.1, 137.4, 132.3, 130.8, 129.9, 129.7, 128.2,
128.1, 128.0, 127.9, 127.8, 127.6, 127.46, 127.42, 126.9, 122.2, 119.1,
117.9, 34.3, 29.3; IR (neat, cm−1) 3419, 3016, 2972, 2432, 2399, 1651,
1598, 1519, 1489, 1423, 1319, 1215, 1074, 1028, 927, 781, 667;
HRMS (ESI) calcd for C35H31O2 [M + H]+ 483.2324, found 483.2324.
(4-(2,2-Diphenylvinyl)-2-methyl-5-phenylfuran-3-yl)-
(phenyl)methanone (3s). Wt 0.058 g; yellow solid: mp 108−
110 °C; 1H NMR (CDCl3, 400 MHz) δ 7.77 (d, 2H, J = 7.2 Hz), 7.47−
7.22 (m, 11H), 7.10−7.01 (m, 5H), 6.83 (d, 2H, J = 7.0 Hz), 6.75 (s,
1H), 2.20 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 190.6, 154.7,
148.8, 145.8, 142.9, 139.0, 137.9, 132.3, 130.8, 129.77, 129.74, 128.7,
128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 125.3, 122.8, 119.2,
118.4, 31.6; IR (neat, cm−1) 3018, 2399, 1647, 1521, 1419, 1215, 927,
6944
dx.doi.org/10.1021/jo301093f | J. Org. Chem. 2012, 77, 6937−6947

The Journal of Organic Chemistry
Article
771, 669; HRMS (ESI) calcd for C32H25O2 [M + H]+ 441.1855, found
441.1866.
100 MHz) δ 152.8, 148.1, 146.7, 134.0, 133.2, 131.8, 131.5, 130.8,
130.3, 129.9, 128.8, 128.7, 128.6, 128.5, 127.79, 127.75, 127.70, 127.5,
127.4, 126.2, 125.1, 123.88, 123.85, 121.3, 109.6, 108.9; IR (neat,
cm−1) 3444, 3018, 2399, 1716, 1506, 1417, 1338, 1215, 929, 771, 669;
HRMS (ESI) calcd for C22H16OBr [M + H]+ 375.0385, found
375.0383.
3,5-Diphenyl-2-(p-tolyl)furan (4g). Wt 0.038 g; brown solid: mp
142−144 °C; regioisomeric ratio = 3.3:1; 1H NMR (CDCl3, 400
MHz) δ 7.76 (d, 2H, J = 7.9 Hz), 7.62 (d, 1H, J = 7.7 Hz), 7.50−7.45
(m, 1H), 7.40 (t, 2H, J = 7.6 Hz), 7.36 (d, 2H, J = 7.9 Hz), 7.32−7.18
(m, 6H), 7.12 (d, 1H, J = 8.0 Hz, A or B isomer), 6.80 (s, 1H,
regioisomer of 4j′ or 4j″), 6.79 (s, 1H, regioisomer of 4j′ or 4j″), 2.39
(s, 1H, regioisomer of 4j′ or 4j″), 2.34 (s, 1H, regioisomer of 4j′ or
4j″); 13C NMR (CDCl3, 100 MHz) δ 152.4, 147.7, 137.0, 131.3,
131.2, 130.6, 129.4, 129.1, 128.7, 128.68, 128.64, 128.5, 128.3, 127.4,
127.3, 126.1, 126.0, 124.5, 123.8, 123.7, 109.5, 109.3, 21.2; IR (neat,
cm−1) 3676, 3018, 1602, 1512, 1489, 1419, 1261, 1215, 1097, 1020,
929, 756, 669; HRMS (ESI) calcd for C23H19O [M + H]+ 311.1436,
found 311.1425.
5-(4-Fluorophenyl)-2,3-diphenylfuran (4j). Wt 0.038 g; pale
yellow oil: 1H NMR (CDCl3, 500 MHz) δ 7.75−7.71 (m, 2H), 7.60−
7.59 (m, 2H), 7.47−7.24 (m, 8H), 7.14−7.09 (m, 2H), 6.75 (s, 1H);
13C NMR (CDCl3, 125 MHz) δ 163.4, 161.4, 151.9, 148.1, 134.3,
131.2, 128.9, 128.8, 128.6, 127.7, 127.5, 127.1 (d, 1C, JC−F = 13.1 Hz),
126.3, 125.8, 125.7, 124.7, 116.1, 115.9, 109.3; IR (neat, cm−1) 3419,
3018, 2962, 2399, 1653, 1604, 1498, 1442, 1261, 1215, 1157, 1097,
1012, 952, 933, 837, 756, 696, 669; HRMS (ESI) calcd for C22H16OF
[M + H]+ 315.1185, found 315.1180.
(4-(2,2-Diphenylvinyl)-2-(4-methoxyphenyl)-5-phenylfuran-
3-yl)(4-methoxyphenyl)methanone (3t). Wt 0.084 g; yellow oil:
1H NMR (CDCl3, 400 MHz) δ 7.83 (d, 2H, J = 7.2 Hz), 7.53−7.45
(m, 4H), 7.38 (t, 2H, J = 7.6 Hz), 7.30−7.13 (m, 6H), 7.01−6.88 (m,
5H), 6.75 (s, 1H), 6.74−6.69 (m, 4H), 3.80 (s, 3H), 3.73 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 189.9, 163.2, 159.7, 152.0, 149.0, 146.4,
142.9, 138.9, 132.2, 130.8, 130.6, 130.2, 128.7, 128.5, 128.3, 128.0,
127.7, 127.6, 125.4, 122.5, 121.7, 120.9, 118.2, 113.7, 113.2, 55.4, 55.2;
IR (neat, cm−1) 3680, 3441, 3018, 2839, 2399, 1645, 1598, 1500, 1419,
1334, 1255, 1215, 1170, 1136, 1029, 927, 900, 767, 669; HRMS (ESI)
calcd for C39H31O4 [M + H]+ 563.2222, found 563.2226.
1-(4-(2,2-Diphenylvinyl)-2-methyl-5-phenylfuran-3-yl)-
1
ethanone (3u). Wt 0.051 g; pale yellow oil: H NMR (CDCl3, 400
MHz) δ 7.60 (d, 2H, J = 7.3 Hz), 7.39−7.19 (m, 8H), 7.14−7.05 (m,
3H), 6.92 (s, 1H), 6.91−6.89 (m, 2H), 2.48 (s, 3H), 2.29 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 195.2, 156.4, 148.1, 146.2, 142.6, 139.1,
130.6, 130.0, 128.4, 128.3, 128.2, 127.9, 127.7, 127.49, 127.40, 125.5,
124.2, 118.9, 117.8, 30.5, 14.4; IR (neat, cm−1) 3442, 3018, 2399,
1668, 1516, 1444, 1361, 1215, 1118, 927, 771, 669; HRMS (ESI) calcd
for C27H23O2 [M + H]+ 379.1698, found 379.1697.
2,3,5-Triphenylfuran (4a). Wt 0.037 g; pale yellow solid: mp 91−
93 °C; 1H NMR (CDCl3, 400 MHz) δ 7.77 (d, 2H, J = 7.8 Hz), 7.61
(d, 2H, J = 8.0 Hz), 7.47−7.24 (m, 11H), 6.81 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 152.5, 147.9, 134.3, 131.1, 130.5, 128.76, 128.72,
128.6, 128.4, 127.54, 127.51, 127.3, 126.1, 124.5, 123.8, 109.4; IR
(neat, cm−1) 3439, 3018, 2962, 2399, 1635, 1556, 1419, 1261, 1215,
1097, 1014, 929, 775, 698, 669; HRMS (ESI) calcd for C22H17O [M +
H]+ 297.1279, found 297.1291.
5-(4-Bromophenyl)-2,3-diphenylfuran (4k). Wt 0.039 g; pale
1
yellow oil: H NMR (CDCl3, 400 MHz) δ 7.62−7.57 (m, 4H), 7.53
2,3-bis(4-Fluorophenyl)-5-phenylfuran (4b). Wt 0.037 g; pale
(d, 2H, J = 8.4 Hz), 7.45 (d, 2H, J = 7.2 Hz), 7.40−7.23 (m, 6H), 6.81
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 151.4, 148.2, 134.0, 131.9,
130.8, 129.4, 128.7, 128.6, 128.4, 127.7, 127.4, 126.1, 125.2, 124.6,
121.2, 110.0; IR (neat, cm−1) 3439, 3018, 2962, 2399, 2088, 1637,
1521, 1485, 1419, 1261, 1215, 1097, 1008, 929, 779, 669; HRMS
(ESI) calcd for C22H16OBr [M + H]+ 375.0385, found 375.0385.
5-(4-tert-Butylphenyl)-2,3-diphenylfuran (4l). Wt 0.040 g;
1
yellow oil: H NMR (CDCl3, 400 MHz) δ 7.75 (d, 2H, J = 7.6 Hz),
7.55−7.37 (m, 6H), 7.29 (t, 1H, J = 7.4 Hz), 7.08 (t, 2H, J = 8.6 Hz),
7.01 (t, 2H, J = 8.7 Hz), 6.76 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
163.4, 160.9, 152.6, 147.0, 130.3, 130.2, 128.7, 127.9 (d, 1C, JC−F
=
31.8 Hz), 127.6, 123.8, 123.2, 115.8, 115.6, 115.4, 109.2; IR (neat,
cm−1) 3442, 3018, 2399, 1653, 1521, 1473, 1419, 1338, 1217, 1014,
927, 958, 669; HRMS (ESI) calcd for C22H15OF2 [M + H]+ 333.1091,
found 333.1085.
1
yellow solid: mp 104−106 °C; H NMR (CDCl3, 300 MHz) δ 7.70
(d, 2H, J = 8.4 Hz), 7.61−7.59 (m, 2H), 7.48−7.23 (m, 10H), 6.76
(s, 1H), 1.35 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 152.8, 150.6,
147.5, 134.4, 131.2, 128.7, 128.6, 128.3, 127.8, 127.3, 127.2, 126.0,
125.6, 124.4, 123.6, 108.9, 34.6, 31.2; IR (neat, cm−1) 3419, 3018,
2399, 1647, 1506, 1456, 1338, 1215, 927, 771, 669; HRMS (ESI) calcd
for C26H25O [M + H]+ 353.1905, found 353.1900.
2,3-bis(4-Chlorophenyl)-5-phenylfuran (4c). Wt 0.038 g;
1
yellow solid: mp 128−130 °C; H NMR (CDCl3, 400 MHz) δ 7.74
(d, 2H, J = 7.4 Hz), 7.51 (d, 2H, J = 8.6 Hz), 7.42 (t, 2H, J = 7.6 Hz),
7.36 (s, 4H), 7.32−7.25 (m, 3H), 6.76 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 153.0, 146.9, 133.46, 133.43, 132.4, 130.1, 129.9, 129.2,
129.0, 128.8, 128.7, 127.8, 127.3, 123.8, 123.7, 109.1; IR (neat, cm−1)
3018, 2854, 2399, 1489, 1261, 1215, 1093, 1014, 952, 931, 831, 775,
669; HRMS (ESI) calcd for C22H15OCl2 [M + H]+ 365.0500, found
365.0512.
5-(Naphthalen-1-yl)-2,3-diphenylfuran (4n). Wt 0.028 g; pale
1
yellow oil: H NMR (CDCl3, 500 MHz) δ 8.58 (d, 1H, J = 8.4 Hz),
7.91 (d, 1H, J = 7.5 Hz), 7.87−7.85 (m, 2H), 7.66 (d, 2H, J = 7.3 Hz),
7.58−7.51 (m, 5H), 7.41 (t, 2H, J = 7.4 Hz), 7.36−7.24 (m, 4H), 6.90
(s, 1H); 13C NMR (CDCl3, 125 MHz) δ 152.2, 148.3, 134.3, 134.0,
131.1, 130.2, 128.8, 128.75, 128.70, 128.6, 128.4, 128.1, 127.5, 127.3,
126.7, 126.2, 126.09, 126.01, 125.5, 125.3, 124.2, 113.7; IR (neat,
cm−1) 3018, 2399, 1600, 1502, 1442, 1215, 1097, 1016, 923, 777, 696,
669; HRMS (ESI) calcd for C26H19O [M + H]+ 347.1436, found
347.1432.
2,3-bis(4-Chlorophenyl)-5-phenylfuran (4d). Wt 0.038 g;
1
yellow solid: mp 154−156 °C; H NMR (CDCl3, 400 MHz) δ 7.74
(d, 2H, J = 7.4 Hz), 7.52 (d, 2H, J = 8.3 Hz), 7.43−7.40 (m, 6H),
7.32−7.28 (m, 3H), 6.76 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
153.1, 146.9, 132.9, 132.0, 131.7, 130.2, 130.1, 129.6, 128.8, 127.9,
127.5, 123.9, 121.6, 121.5, 109.1; IR (neat, cm−1) 3439, 3018, 2399,
2104, 1635, 1516, 1419, 1215, 1010, 927, 754, 669; HRMS (ESI) calcd
for C22H14OBr2Na [M + Na]+ 474.9309, found 474.9297.
5-Cyclohexyl-2,3-diphenylfuran (4p). Wt 0.034 g; pale yellow
1
oil: H NMR (CDCl3, 400 MHz) δ 7.52−7.40 (m, 4H), 7.35−7.24
5-Phenyl-2,3-di-p-tolylfuran (4e). Wt 0.037 g; pale yellow oil:
1H NMR (CDCl3, 500 MHz) δ 7.75 (d, 2H, J = 7.2 Hz), 7.51 (d, 2H,
J = 8.2 Hz), 7.40 (t, 2H, J = 7.7 Hz), 7.35 (d, 2H, J = 8.0 Hz), 7.28
(d, 1H, J = 7.4 Hz), 7.19 (d, 2H, J = 7.8 Hz), 7.12 (d, 2H, J = 8.0 Hz),
6.78 (s, 1H), 2.39 (s, 3H), 2.34 (s, 3H); 13C NMR (CDCl3, 125 MHz)
δ 152.1, 148.0, 137.3, 136.8, 131.4, 130.8, 130.6, 129.3, 129.0, 128.7,
128.5, 127.3, 126.0, 123.8, 123.7, 109.4, 21.3, 21.2; IR (neat, cm−1)
3676, 3018, 1602, 1512, 1472, 1419, 1252, 1215, 1097, 1017, 929, 757,
669; HRMS (ESI) calcd for C24H21O [M + H]+ 325.1592, found
325.1579.
(m, 5H), 7.21−7.17 (m, 1H), 6.13 (s, 1H), 2.73−2.66 (m, 1H), 2.13−
1.71 (m, 5H), 1.52−1.25 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ
160.0, 146.2, 134.9, 131.6, 128.6, 128.5, 128.2, 126.9, 126.8, 125.9,
122.7, 107.4, 37.2, 31.5, 26.1, 25.9; IR (neat, cm−1) 3446, 3018, 2399,
1647, 1516, 1417, 1338, 1215, 1014, 927, 775, 669; HRMS (ESI) calcd
for C22H23O [M + H]+ 303.1749, found 303.1736.
5-Methyl-2,3-diphenylfuran (4q). Wt 0.028 g; pale yellow oil:
1H NMR (CDCl3, 400 MHz) δ 7.50 (d, 2H, J = 7.5 Hz), 7.40−7.19
(m, 8H), 6.15 (s, 1H), 2.38 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
151.3, 146.7, 134.7, 131.4, 128.58, 128.55, 128.3, 127.0, 126.9, 125.9,
123.1, 110.1, 13.5; IR (neat, cm−1) 3419, 3018, 2343, 1637, 1521,
1419, 1328, 1215, 925, 771, 669; HRMS (ESI) calcd for C17H15O [M
+ H]+ 235.1123, found 235.1118.
2-(4-Bromophenyl)-3,5-diphenylfuran (4f). Wt 0.039 g; yellow
1
oil: regioisomeric ratio = 2.5:1; H NMR (CDCl3, 400 MHz) δ 7.76
(d, 2H, J = 7.9 Hz), 7.60−7.27 (m, 12H), 6.80 (s, 1H, regioisomer of
4i′ or 4i″), 6.78 (s, 1H, regioisomer of 4i′ or 4i″); 13C NMR (CDCl3,
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Article
5-(tert-Butyl)-2,3-diphenylfuran (4r). Wt 0.038 g; pale yellow
oil: H NMR (CDCl3, 400 MHz) δ 7.52 (d, 2H, J = 7.4 Hz), 7.42
AUTHOR INFORMATION
■
1
Corresponding Author
*E-mail: waihong@ntu.edu.sg.
Notes
(d, 2H, J = 7.2 Hz), 7.33 (bt, 2H, J = 7.2 Hz), 7.26, (bt, 3H, J = 7.8 Hz),
7.19 (d, 1H, J = 7.0 Hz), 6.12 (s, 1H), 1.36 (s, 9H); 13C NMR (CDCl3,
100 MHz) δ 163.2, 146.2, 134.9, 131.7, 128.6, 128.5, 128.2, 126.9, 126.8,
125.9, 122.6, 106.6, 32.7, 29.1 IR (neat, cm−1) 3419, 3018, 2399, 1647,
1521, 1419, 1338, 1215, 927, 771, 669; HRMS (ESI) calcd for C20H21O
[M + H]+ 277.1592, found 277.1602.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
2,3,5-Triphenylfuran (4a-d1). Wt 0.029 g; yellow solid: mp 94−
96 °C; 1H NMR (CDCl3, 400 MHz) δ 7.78 (d, 2H, J = 7.7 Hz), 7.62
(d, 2H, J = 7.4 Hz), 7.48−7.25 (m, 11H); 13C NMR (CDCl3, 125
MHz) δ 152.5, 147.9, 134.3, 131.1, 130.5, 128.76, 128.71, 128.6, 128.4,
127.53, 127.51, 127.3, 126.1, 124.4, 123.8, 109.4; IR (neat, cm−1)
3439, 3018, 2962, 2399, 1635, 1556, 1419, 1261, 1215, 1097, 1014,
This work is supported by a College of Science Start-Up Grant
from Nanyang Technological University (NTU) and a Science
and Engineering Research Council Grant (092 101 0053) from
A*STAR, Singapore. An Undergraduate Research Experience
on Campus stipend (to S.J.L.L.) from NTU is also acknowl-
edged. We thank Dr. Yongxin Li of this Division for providing
the X-ray crystallographic data reported in this work as well as
the Editor and referees for helpful comments and suggestions.
1
929, 775, 698, 669; HRMS (ESI) calcd for C22 H16 2HO [M + H]+
298.1342, found 298.1332.
2,3,5-Triphenylfuran (4a-d5). Wt 0.033 g; yellow solid: mp 91−
93 °C; 1H NMR (CDCl3, 500 MHz) δ 7.61−746 (m, 4H), 7.38
(t, 2H, J = 7.4 Hz), 7.34−7.24 (m, 4H), 6.81 (s, 1H); 13C NMR
(CDCl3, 125 MHz) δ 152.5, 147.8, 134.3, 131.1, 130.3, 128.7, 128.6,
128.4, 128.2, 128.0, 127.5, 127.3, 126.1, 124.5, 123.6, 114.6, 109.4; IR
(neat, cm−1) 3446, 3018, 2399, 1602, 1516, 1419, 1215, 1022, 927,
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1
775, 669; HRMS (ESI) calcd for C22 H12 2H5O [M + H]+ 302.1593,
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1
2,3,5-Triphenylfuran (4a-d6). Wt 0.028 g; pale yellow oil: H
NMR (CDCl3, 500 MHz) δ 7.62−7.46 (m, 4H), 7.40−7.23 (m, 6H);
13C NMR (CDCl3, 75 MHz) δ 147.8, 134.3, 131.1, 130.3, 128.7, 128.6,
128.4, 128.2, 127.9, 127.4, 127.3, 126.1, 124.4, 123.4, 123.0, 109.4; IR
(neat, cm−1) 3421, 3018, 2926, 2399, 1602, 1502, 1477, 1442, 1379,
1
1213, 1099, 1022, 954, 779, 694, 669; HRMS (ESI) calcd for C22 H11
2H6O [M + H]+ 303.1656, found 303.1659.
1,4,4-Triphenylbuta-2,3-dien-1-one (5a). Wt 0.040 g; brown
1
color oil: H NMR (CDCl3, 400 MHz) δ 7.82 (d, 2H, J = 7.7 Hz),
7.50 (t, 1H, J = 7.3 Hz), 7.39−7.25 (m, 12H), 6.80 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 216.1, 191.5, 137.4, 134.2, 132.7, 128.76, 128.72,
128.6, 128.34, 128.33, 113.7, 96.5; IR (neat, cm−1) 3439, 3018, 2399,
1635, 1521, 1419, 1259, 1215, 1097, 1016, 927, 848, 771, 669; HRMS
(ESI) calcd for C22H17O [M + H]+ 297.1279, found 297.1292.
4,4-Diphenyl-1-(thiophen-2-yl)buta-2,3-dien-1-one (5o). Wt
0.032 g; brown color oil: 1H NMR (CDCl3, 400 MHz) δ 7.799−7.790
(m, 1H), 7.60 (bd, 1H, J = 4.9 Hz), 7.40−7.34 (m, 10H), 7.05 (bt, 1H,
J = 4.3 Hz), 6.77 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 214.8,
181.9, 143.0, 134.0, 133.8, 132.6, 128.7, 128.6, 128.4, 127.9, 127.1,
114.5, 96.8; IR (neat, cm−1) 3439, 3018, 2399, 1625, 1521, 1416, 1242,
1215, 1095, 1011, 927, 771, 669; HRMS (ESI) calcd for C20H15OS
[M + H]+ 303.0844, found 303.0856.
(2,4-Diphenyl-5-styrylfuran-3-yl)(phenyl)methanone (6m).
1
Wt 0.04 g; pale yellow solid: mp 146−148 °C; E/Z ratio = 1:1; H
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all starting materials and products,
GC−MS spectra of 4a-d1, 4a-d5, 4a-d6, and CIF files of 3d, 3q,
3r, and 6m. This material is available free of charge via the
Internet at http://pubs.acs.org.
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