Gold-Catalyzed Synthesis of 1-(Furan-3-yl)-1,2-diones

Article abstract of DOI:10.1021/acs.joc.7b01997

A gold-catalyzed synthesis of an important building block, 1-(furan-3-yl)-1,2-diones, from easily available starting materials under mild reaction conditions was reported. Preliminary mechanistic investigation indicated that water was involved as a reacta

Full text of DOI:10.1021/acs.joc.7b01997

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Gold-Catalyzed Synthesis of 1-(Furan-3-yl)-1,2-diones
Bing Zhang, Tao Wang, and Zunting Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01997 • Publication Date (Web): 02 Oct 2017
Downloaded from http://pubs.acs.org on October 2, 2017
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The Journal of Organic Chemistry
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Gold-Catalyzed Synthesis of 1-(Furan-3-yl)-1,2-diones
Bing Zhang, Tao Wang,* Zunting Zhang
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Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry
and Chemical Engineering, Shaanxi Normal University, No.620 West Chang'an Avenue, Xi’an 710119,
China.
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Eꢀmail: chemtao@snnu.edu.cn.
TOC Graphic
ABSTRACT: A goldꢀcatalyzed synthesis of an important building block, 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones,
from easily available starting materials under mild reaction conditions was reported. Preliminary mechꢀ
anistic investigation indicated that water was involved as a reactant in the reaction serving as an oxygen
source.
1,2ꢀDiketones are found in pharmaceutically important natural products. For examples Chaetogline
H, Homofascaplysin B and Hyrtiosin B are some of the representative natural products possessing 1,2ꢀ
diketones in their structures. 1 In addition, 1,2ꢀdiketones are useful building blocks for the synthesis of a
large array of heterocycles including quinoxalines, imidazoles, oxazoles, thiazoles and 1,2,5ꢀthiadiazole
1,1ꢀdioxides (Figure 1). Considering the importance of heterocycles in pharmaceuticals and material
Figure 1. Applications of 1,2-diketones in the synthesis of heterocycles
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science, the preparation of structurally diverse 1,2ꢀdiketones are of interest. 2 In the past few years, the
explosive development of homogeneous gold catalysis3 has enabled the synthesis of structurally diverse
3ꢀfunctionalized furans including 3ꢀhalofurans,4 3ꢀalkynylfurans,5,6 3ꢀalkoxyfurans,7 3ꢀacyloxylfurans,8
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3ꢀacylfurans
and furanꢀ3ꢀcarboxylates.10 Although structurally diverse 3ꢀfunctionalized furans were
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accessible via gold catalysis, the synthesis of 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones was not reported. The existing
patent method for the preparation of such kind of 1,2ꢀdiketones starts from 3ꢀformyl furans via multiꢀ
step synthesis (Scheme 1).12 However, preꢀsynthesized 3ꢀformyl furans are required, which are not readꢀ
ily accessible. To continue our efforts in gold catalysis,13 we herein want to report an in situ strategy, in
which 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones are prepared under gold catalysis from 1,4ꢀdiynꢀ3ꢀol derivatives
(Scheme 1).14 The starting material is easily prepared via a twoꢀstep reaction starting from terminal alꢀ
kyne and methyl 2ꢀhydroxypropanoate.
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Scheme 1. Synthesis of 1-(furan-3-yl)-1,2-diones
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The formation of 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdione 3a was initially observed when 2a was treated with AuCl3
in dichloromethane at room temperature. The starting material 2a was fully consumed after 24 h deliverꢀ
ing a 1,2ꢀdione product 3a, which was confirmed by NMR and MS spectra and was further confirmed
by an Xꢀray diffraction single crystal structure analysis via a oneꢀpot transformation to quinoxaline.16
The decomposition of compounds was also observed from TLC analysis. The formation of 3a was quite
interesting because an unprecedented oxidation reaction seemed to be involved in the reaction cascade.
Encouraged by the result, we started to optimize the reaction conditions (Table 1). When AuBr317 was
added in place of AuCl3, 3a was obtained in 26% isolated yield (entry 2). An often used gold(III) comꢀ
pound, dichloro(2ꢀpyridinecarboxylato)gold (PicAuCl2),18 was also examined but failed to catalyze this
reaction (entry 3). Further investigation revealed that gold(I) complexes showed almost no activity to
this reaction (entries 4ꢀ6). During the optimization, we found that the decomposition of compounds was
observed only when 3a was formed. If the reaction did not occur, the TLC was clean with no decompoꢀ
sition observed. This observation indicated the decomposition of 3a might account for its low isolated
yield. The crude NMR investigation also supported this hypothesis. To keep 3a from decomposition, the
silica gel was treated with triethylamine before a column chromatography. To our delight, the isolated
yield of 3a was increased from 32% (entry 1) to 52% (entry 7) when AuCl3 was used as a catalyst. To
further optimize the reaction, silver salts were added to active the gold catalyst by chloride abstraction
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(entries 8ꢀ10).19 The addition of AgNTf2 (entry 8) and AgOTf (entry 9) improved the reaction by giving
3a with better yields, respectively. Toluene was found the most suitable solvent (entry 14) for this transꢀ
formation in a solvent screen (entries 11ꢀ15). When the reaction was carried out in toluene, the use of
AuCl3 (5 mol %) / AgNTf2 (15 mol %) as catalyst gave the best result (88% yield, entry 15). The addiꢀ
tion of 5 mol % of 1,10ꢀphenanthroline totally inhibited the reaction (entry 16). Decreasing the catalyst
loading to 3 mol % led to a lower yield and a longer reaction time (entry 17). It was found that the addiꢀ
tion of molecular sieve fully inhibited the reaction (entry 18). This result indicated that water was reꢀ
quired for this transformation. However, further investigation showed that the presence of too much waꢀ
ter also inhibited the reaction (entries 18ꢀ22). A reasonable explanation is that gold catalyst was extractꢀ
ed by water from toluene, which resulted in a longer reaction time and a lower yield.
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Table 1. Reaction Optimizationa
Entry
1
Catalyst (5 mol %)
AuCl3
Solvent
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
time
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
40 min
30 min
24 h
4 h
Yieldb
32c
26c
2
AuBr3
3
PicAuCl2
trace
NR
trace
NR
52d
65d
69d
51d
4
AuCl
5
Ph3PAuCl /AgNTf2
IPrAuCl / AgNTf2
AuCl3
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7
8
AuCl3 / AgNTf2
AuCl3 / AgOTf
AuCl3 / AgSbF6
AuCl3 / AgOTf
AuCl3 / AgOTf
AuCl3 / AgOTf
AuCl3 / AgOTf
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10
11
12
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14
15
16e
17
45d
62d
CH3CN
DCE
50d
80d
88d
NR
80d
toluene
toluene
toluene
toluene
AuCl3 / AgNTf2
AuCl3 / AgNTf2
AuCl3 (3 mol %) /
AgNTf2 (9 mol %)
18f
19g
20h
21i
22j
AuCl3 / AgNTf2
AuCl3 / AgNTf2
AuCl3 / AgNTf2
AuCl3 / AgNTf2
AuCl3 / AgNTf2
toluene
(anhydrous)
40 min
40 min
40 min
1.5 h
NR
86d
86d
82d
56d
toluene
(anhydrous)
toluene
(anhydrous)
toluene
(anhydrous)
toluene
8 h
(anhydrous)
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aAll the reactions were carried out on a 0.3 mmol scale in 3 mL of solvent at room temperature by the use of 5 mol % of gold salt and 15
mol % of silver salt (if addd) as catalyst; commercial solvents were used without further drying. b Isolated yield after silica gel chromatogꢀ
raphy. c The decomposition of 2a or 3a was observed. d Isolated yield after silica gel chromatography (petroleum ether : ethyl acetate :
triethylamine = 30 : 1 : 0.1); the silica gel was pretreated with triethylamine before the column chromatography. e 5 mol % of 1,10ꢀ
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phenanthroline was added as an additive. f 4 Å MS was added. g 1 equivalent of water was added. h 2 equivalents of water was added. 3
equivalents of water was added. j 4 equivalents of water was added.
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Having established optimized reaction conditions, the scope of the substrates was explored (Scheme
2). The substrates with a substituted phenyl group on the alkyne terminal were examined firstly. The
substituents in the benzene ring did not affect the yield of the products dramatically, no matter if the
substituents were electronꢀwithdrawing groups or electronꢀdonating groups (3aꢀ3g). Substrates with
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Sheme 2. Reaction scope for the synthesis of 1,2-dionesa
a
The reactions were carried out on 0.3 mmol scale by the use of commercial grade toluene as solvent; the yields given are isolated
yields.
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heteroaromatic groups also worked well, delivering the corresponding products in moderate yields (3h
and 3i). αꢀNaphthꢀ1ꢀylꢀ1,2ꢀdione 3j was also obtained in 65% yield. In addition, the substrates with aliꢀ
phatic groups on the alkyne terminal also worked smoothly affording the corresponding 1,2ꢀdiones (3k
and 3l). When an unsymmetric starting material was subjected to the standard reaction conditions, the
reaction suffered from a low regioselectivity to afford 3m and 3m’ in 25% and 36% yields, respectively.
When R3 substituent was a ethyl group, 1,2ꢀdione 3n was also obtained in 78% yield. When R3 was
phenyl and substituted phenyl groups, the reactions worked well under standard condition, delivering
corresponding products in excellent yields (3oꢀ3q, 84%ꢀ92%).
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The strategy for the synthesis of 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones was also used in a oneꢀpot synthesis of 2ꢀ
(furanꢀ3ꢀyl)quinoxalines. The results are summarized in Scheme 3. Benzeneꢀ1,2ꢀdiamine was added into
the reaction mixture after the starting materials 2 were fully consumed. The oneꢀpot reaction gave a vaꢀ
riety of 2ꢀ(furanꢀ3ꢀyl)ꢀquinoxalines in good yields.
Sheme 3. Reaction scope of one-pot synthesis of 2-(furan-3-yl)quinoxalinesa
a
The reactions were carried out on 0.3 mmol scale by the use of commercial grade toluene as solvent; the yields given are isolated
yields.
Control reactions indicated that the gold catalyst added in the reaction not only catalyze the formation
of 1,2ꢀdiones, but also promoted the subsequent condensation reaction. The reaction was dramatically
accelerated when gold and silver salts were added, affording 4a in a better yield (eq 1 and eq 2).
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To gain insight into the reaction, several control experiments were carried out. The reaction worked
smoothly to afford 18O labeled product when 18O water was added (eq 3). It was found that most of the
oxygen in the furan ring and the carbonyl oxygen close to the furan were labeled. Because oxygen exꢀ
change occurred between water and carbonyl groups, we carried out additional two control experiments
to get further insight. When unlabeled 1,2ꢀdione 3a was subjected to 18Oꢀwater under the standard conꢀ
ditions, after 0.5 hours 3a remained unlabeled (eq 4). In a further investigation, the reaction was
quenched when 50% of 2a was consumed. The recovered 2a remained unlabeled while 3a was labeled
with 18O (eq 5).These results suggested that water was involved as a reactant in the reaction, serving as
an oxygen source. When D2O was added, 25% of 3a was deuterated at the furan ring (eq 6).
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Based on the control experiments, a plausible reaction mechanism was proposed (Scheme 4). The coꢀ
ordination of triple bond to the gold catalyst facilitates the 5ꢀendoꢀdig cyclization of 2a, affording vinylꢀ
gold intermediate A.20 The nucleophilic attack of water to intermediate A gives intermediate B, which
undergoes a protonꢀtransfer and a protonation of the AuꢀC(sp2) bond forming intermediate C.21 Under
acidic condition, D is formed via a protonꢀcatalyzed process, which further converts to E via the ketoꢀ
enol tautomerization. After dehydration of E under acidic condition, F is formed. A 5ꢀendoꢀdig cyclizaꢀ
tion of F in the presence of a gold catalyst affords furylꢀgold intermediate G, which further delivers I in
the presence of water via a nucleophilic attack by water and a protonation of the AuꢀC(sp2) bond.22 An
oxidation of intermediate I under air finally affords 3a as a product.23
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Scheme 4. Proposed mechanism
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In conclusion, we have developed an efficient method to prepare 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones under mild
reaction conditions. This method provides an efficient way to get structurally diverse 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀ
diones from easily available starting materials. To the best of our knowledge, there is no convenient
method to prepare 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones until this report. In addition, a oneꢀpot synthesis of 2ꢀ
(furanꢀ3ꢀyl)quinoxalines was also developed based on the 1,2ꢀdione synthesis. Considering 1,2ꢀdione is
an important building block in synthesis, this method shows great potential in both the natural products
synthesis and material science.
Experiment Section
General Information. NMR spectra were recorded on a Bruker AM 400 or AM 600 spectrometers.
Chemical shifts were referenced to residual signals from CHCl3, δ = 7.26 ppm and δ = 77.16 ppm as
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internal references for H and C chemical shifts, respectively. Signal multiplicity as follows: s (sinꢀ
glet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad). High resolution mass spectrometry
(HRMS) was recorded using electronspray ionization quadrupole timeꢀofꢀflight (ESIꢀQꢀTOF) technique.
IR spectra were recorded on a Nicollet 170SX FTꢀIR spectrophotometer with KBr pellets.
General procedure for synthesis of 1a-1l, 1n-1q.
nꢀButyllithium (15 mmol, 6 mL, 2.5 M in hexane) was added slowly to a solution of alkyne (15
mmol) in THF (30 mL) at ꢀ78 oC. The solution was stirred for 30 minutes at this temperature. After that
methyl 2ꢀhydroxypropanoate (520 mg, 5 mmol) was added at the same temperature. The resulting soluꢀ
o
tion was then allowed to stir 2 hours at ꢀ40 C. The reaction was quenched by addition of aqueous satuꢀ
rated NH4Cl (30 mL); the phases were separated and the aqueous phase was extracted with EtOAc (2 x
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20 mL). The combined organics were washed with brine (30 mL), dried over Na2SO4, concentrated and
purified by flash chromatography on silica gel (petroleum ether / ethyl acetate = 30 : 1) to afford the
product.
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5ꢀPhenylꢀ3ꢀ(phenylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1a). 795.0 mg, 55% yield, yellow solid; m.p. 113.2ꢀ
114.2 oC; 1H NMR (400 MHz, CDCl3): δ = 7.50ꢀ7.45 (m, 4 H), 7.29ꢀ7.27 (m, 6 H), 4.12 (d, 1 H, J = 4.9
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Hz), 3.84 (s, 1 H), 2.97 (s, 1 H), 1.52 (d, 3 H, J = 6.3 Hz); C NMR (100 MHz, CDCl3): δ = 132.1,
132.0, 128.9, 128.4, 121.9, 121.8, 87.2, 86.1, 85.6, 85.0, 74.6, 68.8, 17.9 ppm; IR (KBr): ṽ = 3379,
3223, 2225 cmꢀ1; HRMS (ESI): calculated for C19H16O2Na [M+Na]+: 299.1048, found 299.1060.
5ꢀ(4ꢀFluorophenyl)ꢀ3ꢀ((4ꢀfluorophenyl)ethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1b). 795.6 mg, 51% yield, yellow
o
solid; m.p. 69.1ꢀ70.8 C 1H NMR (400 MHz, CDCl3): δ = 7.49ꢀ7.44 (m, 4 H), 7.03ꢀ6.98 (m, 4 H), 4.09
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(m, 1 H), 3.44 (sbr, 1 H), 2.65 (sbr, 1 H), 1.51 (d, 3 H, J = 6.0 Hz); C NMR (100 MHz, CDCl3): δ =
163.1 (JFꢀC = 250.9 Hz), 134.1 (JFꢀC = 6.6 Hz), 134.0 (JFꢀC = 5.9 Hz), 118.0 (JFꢀC = 3.7 Hz), 117.9 (JFꢀC
=
3.9 Hz), 115.8 (JFꢀC = 22.0 Hz), 115.7 (JFꢀC = 22.1 Hz), 86.8, 85.8, 84.7, 81.2, 74.6, 68.8, 17.9 ppm; IR
(KBr): ṽ = 2925, 2227, 1566, 1485 cmꢀ1; HRMS (ESI): calculated for C19H14O2F2Na [M+Na]+:
335.0860, found 335.0872.
5ꢀ(4ꢀChlorophenyl)ꢀ3ꢀ((4ꢀchlorophenyl)ethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1c). 842.8 mg, 49% yield, yellow
o
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solid; m.p. 121.7ꢀ122.7 C H NMR (400 MHz, CDCl3): δ = 7.44ꢀ7.40 (m, 4 H), 7.32ꢀ7.29 (m, 4 H),
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4.10ꢀ4.06 (m, 1 H), 3.21 (sbr, 1 H), 2.46 (sbr, 1 H), 1.50 (d, 3 H, J = 6.2 Hz); C NMR (100 MHz,
CDCl3): δ = 135.2, 133.3, 133.2, 129.3, 128.8, 120.3, 120.2, 87.9, 86.9, 84.6, 84.1, 74.5, 68.8, 17.9
ppm; IR (KBr): ṽ = 2925, 2227, 1566, 1485 cmꢀ1; HRMS (ESI): calculated for C19H14O2Cl2Na
[M+Na]+: 367.0269, found 367.0283.
5ꢀ(4ꢀBromophenyl)ꢀ3ꢀ((4ꢀbromophenyl)ethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1d). 1041.6 mg, 48% yield, yellow
solid; m.p. 124.2ꢀ125.7 oC; 1H NMR (400 MHz, CDCl3): δ = 7.45 (d, 4 H, J = 8.4 Hz), 7.34 (d, 4 H, J =
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8.4 Hz), 4.11ꢀ4.06 (m, 1 H), 3.40 (sbr, 1 H), 2.58 (sbr, 1 H), 1.50 (d, 3 H, J = 6.1 Hz); C NMR (100
MHz, CDCl3): δ = 133.5, 133.4, 131.8, 131.7, 128.5, 123.5, 120.8, 120.7, 88.0, 87.0, 84.7, 84.2, 74.5,
68.8, 17.9 ppm; IR (KBr): ṽ = 3388, 2983, 2231 1598, 1508 cmꢀ1; HRMS (ESI): calculated for
C19H14O2Br2Na [M+Na]+: 456.9238, found 456.9257.
5ꢀ(Pꢀtolyl)ꢀ3ꢀ(pꢀtolylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1e). 790.4 mg, 52% yield, yellow solid; m.p. 93.6ꢀ94.6
oC 1H NMR (400 MHz, CDCl3): δ = 7.40ꢀ7.36 (m, 4 H), 7.14 (d, 4 H, J = 7.8 Hz), 4.09ꢀ4.07 (m, 1 H),
3.21 (sbr, 1 H), 2.50 (sbr, 1 H); 2.35 (s, 6 H), 1.52 (d, 3 H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3): δ
= 139.3, 139.2, 132.0, 131.9, 129.2, 118.9, 118.8, 86.5, 85.8, 85.4, 85.3, 74.7, 69.0, 21.7, 17.9 ppm; IR
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(KBr): ṽ = 3219, 2985, 1600, 1508 cmꢀ1; HRMS (ESI): calculated for C21H20O2Na [M+Na]+: 327.1361,
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found 327.1374.
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5ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ((4ꢀmethoxyphenyl)ethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1f). 1142.4 mg, 68% yield,
yellow solid; m.p. 106.6ꢀ107.6 oC; 1H NMR (400 MHz, CDCl3): δ = 7.42 (m, 4 H), 6.83 (m, 4 H), 4.08ꢀ
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MHz, CDCl3): δ = 160.1, 133.6, 133.5, 114.1, 86.0, 85.6, 85.1, 84.9, 74.7, 69.0, 55.4, 17.9 ppm; IR
(KBr): ṽ = 3176, 2989, 2225, 1602, 1504, 1245 cmꢀ1; HRMS (ESI): calculated for C21H20O4Na
[M+Na]+: 359.1259, found 359.1253.
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5ꢀ(Mꢀtolyl)ꢀ3ꢀ(mꢀtolylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1g). 1140.0 mg, 75% yield, reddish brown oil; H
NMR (400 MHz, CDCl3): δ = 7.35ꢀ7.29 (m, 4 H), 7.21ꢀ7.13 (m, 4 H), 4.17ꢀ4.13 (m, 1 H), 3.93 (sbr, 1
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H), 3.06 (sbr, 1 H), 2.32 (s, 6 H), 1.56 (d, 3 H, J = 6.3 Hz); C NMR (100 MHz, CDCl3): δ = 138.0,
132.6, 132.5, 129.8, 129.8, 129.1, 129.0, 128.2, 121.7, 121.7, 86.9, 85.8, 85.7, 85.1, 74.6, 68.8, 21.2,
17.8 ppm; IR (KBr): ṽ = 3388, 2985, 2229, 1602, 1483 cmꢀ1; HRMS (ESI): calculated for C21H20O2Na
[M+Na]+: 327.1361, found 327.1375.
5ꢀ(Thiophenꢀ2ꢀyl)ꢀ3ꢀ(thiophenꢀ2ꢀylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1h). 892.8 mg, 62% yield, brown solid;
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m.p. 138.1ꢀ139.1 C; H NMR (400 MHz, CDCl3): δ = 7.30ꢀ7.28 (m, 4 H), 6.99ꢀ6.97 (m, 2 H), 4.11ꢀ
4.07 (m, 1 H), 3.36 (s, 1 H), 2.57 (sbr, 1 H)，1.50 (d, 3 H, J = 6.3 Hz); 13C NMR (100 MHz, CDCl3): δ
= 133.4, 133.3, 128.2, 128.1, 127.2, 121.7, 121.6, 90.5, 89.6, 79.4, 78.9, 74.5, 69.2, 17.9 ppm; IR (KBr):
ṽ = 3383, 3192, 2225, 1620, 1502 cmꢀ1; HRMS (ESI): calculated for C15H12O2S2Na [M+Na]+: 311.0176,
found 311.0190.
5ꢀ(Thiophenꢀ3ꢀyl)ꢀ3ꢀ(thiophenꢀ3ꢀylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1i). 907.2 mg, 63% yield, yellow solid;
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m.p. 145.2ꢀ146.2 C; H NMR (400 MHz, CDCl3): δ = 7.56ꢀ7.54 (m, 2 H), 7.29ꢀ7.27 (m, 2 H), 7.18ꢀ
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7.15 (m, 2 H), 4.10ꢀ4.08 (m, 1 H), 3.36 (s, 1 H), 2.60 (sbr, 1 H), 1.52 (d, 3 H, J = 6.2 Hz); C NMR
(100 MHz, CDCl3): δ = 130.2, 130.1, 130.1, 130.0, 125.6, 125.6, 120.9, 120.9, 86.7, 85.7, 81.0, 80.5,
74.5, 69.0, 17.9 ppm; IR (KBr): ṽ = 3386, 3199, 2233, 1620, 1450 cmꢀ1; HRMS (ESI): calculated for
C15H12O2S2Na [M+Na]+: 311.0176, found 311.0177.
5ꢀ(Naphthalenꢀ1ꢀyl)ꢀ3ꢀ(naphthalenꢀ1ꢀylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1j). 770.8 mg, 41% yield, yellow
oil; 1H NMR (400 MHz, CDCl3): δ = 8.45ꢀ8.38 (m, 2 H), 7.86 (d, 4 H, J = 8.3 Hz), 7.79ꢀ7.77 (m, 2 H),
7.60ꢀ7.51 (m, 4 H), 7.45ꢀ7.41 (m, 2 H), 4.34ꢀ4.32 (m, 1 H), 3.64 (sbr, 1 H), 2.83 (sbr, 1 H), 1.70 (d, 3 H,
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J = 6.5 Hz); C NMR (100 MHz, CDCl3): δ = 133.6, 133.5, 133.2, 131.2, 131.1, 129.6, 129.6, 128.5,
128.4, 127.3, 126.7, 126.1, 126.0, 125.2, 119.5, 119.5, 92.2, 91.2, 84.1, 83.6, 74.7, 69.4, 18.2 ppm; IR
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(KBr): ṽ = 3388, 2983, 2221, 1585, 1506 cmꢀ1; HRMS (ESI): calculated for C27H20O2Na [M+Na]+:
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399.1361, found 399.1343.
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5ꢀCyclopropylꢀ3ꢀ(cyclopropylethynyl)pentꢀ4ꢀyneꢀ2,3ꢀdiol (1k). 489.6 mg, 48% yield, pale yellow solid;
m.p. 54.7ꢀ55.7 oC; 1H NMR (400 MHz, CDCl3): δ = 3.80ꢀ3.74 (m, 1 H), 2.86 (sbr, 1 H), 2.33 (sbr, 1 H),
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1.32ꢀ1.23 (m, 5 H), 0.79ꢀ0.69 (m, 8 H); C NMR (100 MHz, CDCl3): δ = 89.2, 88.7, 74.6, 74.0, 72.9,
68.1, 17.6, 8.5 8.4, ꢀ0.4, ꢀ0.5 ppm; IR (KBr): ṽ = 3406, 3234, 2233 cmꢀ1; HRMS (ESI): calculated for
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C13H16O2Na [M+Na]+: 227.1048, found 227.1059.
3ꢀ(Hexꢀ1ꢀynꢀ1ꢀyl)nonꢀ4ꢀyneꢀ2,3ꢀdiol (1l). 580.8 mg, 44% yield, pale yellow liquid; 1H NMR (400 MHz,
CDCl3): δ = 3.83ꢀ3.79 (m, 1 H), 3.00 (s, 1 H), 2.40 (s, 1 H), 2.25ꢀ2.20 (m, 4 H), 1.54ꢀ1.44 (m, 4 H),
1.42ꢀ1.37 (m, 4 H), 1.34 (d, 3 H, J = 6.2 Hz), 0.89 (t, 6 H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3): δ
= 86.1, 85.7, 79.0, 77.9, 76.8, 74.5, 68.1, 30.6, 30.5, 22.1, 22.0, 18.5, 18.5, 17.6, 13.7 ppm; IR (KBr): ṽ
= 3417, 2960, 2235 cmꢀ1; HRMS (ESI): calculated for C15H24O2Na [M+Na]+: 259.1674, found
259.1684.
Procedures for the synthesis of 1m
Step 1. Synthesis of 4-(tert-butyldimethylsilyloxy)-1-phenylpent-1-yn-3-ol: To a 100ꢀmL schlenk
flask was placed phenylacetylene (1.25 g, 12 mmol) in anhydrous THF (0.5 M, 24 mL). A solution of nꢀ
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BuLi (2.5 M in hexane, 4.8 mL, 12 mmol) in hexane was added dropwise at ꢀ78 C and the reaction
mixture was stirred 2 h at the same temperature. A solution of 2ꢀ(tertꢀbutyldimethylsilyloxy)propanal
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(1.52 g, 8 mmol) in anhydrous THF (0.5 M, 16 mL) was added to the reaction mixture at ꢀ78 C. After
having been stirred for 2 h, the reaction was quenched with sat. aqueous NH4Cl (10 mL). The resulting
mixture was extracted with EtOAc (10 mL × 3). The combined organic layer was dried (MgSO4), filꢀ
tered, and concentrated to give 4ꢀ(tertꢀbutyldimethylsilyloxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀol (1.6 g, 81% yield)
as product.
4ꢀ((Tertꢀbutyldimethylsilyl)oxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀol: 1.6 g, 81% yield, yellow solid; m.p. 41.8ꢀ42.8
oC; 1H NMR (400 MHz, CDCl3): δ = 7.46ꢀ7.43 (m, 2 H), 7.31ꢀ7.29 (m, 3 H), 4.50ꢀ4.47 (m, 1 H), 4.05ꢀ
4.00 (m, 1 H), 2.51 (sbr, 1H), 1.31 (d, 3 H, J = 6.2 Hz), 0.93 (s, 9 H), 0.13 (s, 6 H); 13C NMR (100
MHz, CDCl3): δ = 131.9, 128.5, 128.4, 122.8, 87.3, 86.1, 71.3, 67.7, 25.9, 18.5, 18.2, ꢀ4.3, ꢀ4.7. IR
(KBr): ṽ = 3180, 2241, 1598 cmꢀ1; HRMS (ESI): calculated for C17H26O2SiNa [M+Na]+: 313.1600,
found 313.1594.
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Step 2. Synthesis of 4-((tert-butyldimethylsilyl)oxy)-1-phenylpent-1-yn-3-one:To a 50ꢀmL schlenk
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flask was placed freshly distilled DMSO (1.1 mL, 14.9 mmol) and anhydrous NEt3 (3.0 mL, 22 mmol)
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in CH2Cl2 (10 mL). Oxalyl chloride (3.7 mL, 7.4 mmol) was added dropwise at ꢀ78 C for 15 min. A
solution of the 4ꢀ((tertꢀbutyldimethylsilyl)oxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀol (1.6 g, 5.5 mmol) in CH2Cl2 (11
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mL) was added to the reaction mixture at ꢀ78 C. After having been stirred for 2 h, the reaction was
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quenched with sat. aqueous NaHCO3 solution (30 mL). The resulting mixture was extracted with
CH2Cl2 (10 mL× 3). The combined organic layer was dried (MgSO4), filtered, and concentrated to give
intermediate C (1.1 g, 85% yield)
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4ꢀ((Tertꢀbutyldimethylsilyl)oxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀone. 1.1 g, 85% yield, yellow oil; H NMR (400
MHz, CDCl3): δ = 7.59 (m, 2 H), 7.48ꢀ7.44 (m, 1 H), 7.40ꢀ7.36 (m, 2 H), 4.37ꢀ4.31 (m, 1 H), 1.45 (d, 3
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H, J = 6.7 Hz), 0.95 (s, 9 H,), 0.15 (s, 3 H), 0.12 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 190.7,
133.2. 130.9, 128.8, 120.3, 94.3, 86.6, 75.2, 25.9, 20.8, 18.4, ꢀ4.6, ꢀ4.8. IR (KBr): ṽ = 2198, 1676, 1467
cmꢀ1; HRMS (ESI): calculated for C17H24O2SiNa [M+Na]+: 311.1443, found 311.1440.
Step 3. Synthesis of 3-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1-phenylnona-1,4-diyn-3-ol: To a 100ꢀ
mL schlenk flask was placed phenylacetylene (1.25 g, 12 mmol) in anhydrous THF (24 mL). A solution
of nꢀBuLi (2.5 M in hexane, 4.8 mL, 12 mmol) was added dropwise at ꢀ78 oC. The reaction mixture was
stirred at ꢀ78 oC for 0.5 h. After that a solution of 4ꢀ((tertꢀbutyldimethylsilyl)oxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀ
one (1.52 g, 8 mmol) in anhydrous THF (16 mL) was added to the reaction mixture at ꢀ78 oC. After havꢀ
ing been stirred for 2 h, the reaction was quenched with sat. aqueous NH4Cl (10 mL). The resulting mixꢀ
ture was extracted with EtOAc (10 mL× 3). The combined organic layer was dried (MgSO4), filtered,
and concentrated to give 3ꢀ(1ꢀ((tertꢀbutyldimethylsilyl)oxy)ethyl)ꢀ1ꢀphenylnonaꢀ1,4ꢀdiynꢀ3ꢀol (2.2 g,
80% yield) as product.
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3ꢀ(1ꢀ((Tertꢀbutyldimethylsilyl)oxy)ethyl)ꢀ1ꢀphenylnonaꢀ1,4ꢀdiynꢀ3ꢀol. 2.2 g, 80% yield yellow oil; H
NMR (400 MHz, CDCl3): δ = 7.46ꢀ7.43 (m, 2 H), 7.32ꢀ7.27 (m, 3 H), 4.08ꢀ4.03 (m, 1 H), 3.15 (s, 1 H),
2.27 (t, 2 H, J = 7.0 Hz), 1.56ꢀ1.48 (m, 2 H), 1.47ꢀ1.41 (m, 2 H), 1.39 (d, 3 H, J = 6.1 Hz), 0.93 (m, 12
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H), 0.15 (s, 6 H); C NMR (100 MHz, CDCl3): δ = 131.9, 128.5, 128.3, 122.6, 89.2, 86.1, 83.2, 78.1,
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75.3, 68.2, 30.5, 25.9, 22.0, 18.8, 18.6, 18.1, 13.7, ꢀ4.2, ꢀ4.6. IR (KBr): ṽ = 3232, 2239, 1600 cmꢀ1;
HRMS (ESI): calculated for C23H34O2SiNa [M+Na]+: 393.2226, found 393.2221.
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Step 4. Synthesis of 1m:Tetrabutylammonium fluoride (1 M in THF, 3.6 mL, 3.6 mmol) was added at 0
°C to a solution of 3ꢀ(1ꢀ((tertꢀbutyldimethylsilyl)oxy)ethyl)ꢀ1ꢀphenylnonaꢀ1,4ꢀdiynꢀ3ꢀol (1.1 g, 3.0
mmol) in THF. The reaction mixture was stirred for 2 h at rt and then quenched with water and extractꢀ
ed with ether (30 mL x 3). The combined organic layers were dried over anhydrous Na2SO4 and concenꢀ
trated under reduced pressure. The crude product was subjected to column chromatography (petroleum
ether / ethyl acetate = 10 : 1) to afford 1m (626.4 mg, 90% yield) as a white solid.
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3ꢀ(Phenylethynyl)nonꢀ4ꢀyneꢀ2,3ꢀdiol (1m). 626.4 mg, 90% yield, yellow solid; m.p. 49.7.5ꢀ50.7 C; H
NMR (400 MHz, CDCl3): δ = 7.49ꢀ7.44 (m, 2 H), 7.34ꢀ7.28 (m, 3 H), 3.99ꢀ3.96 (m, 1 H), 3.11 (s, 1 H),
2.45 (d, 2H, J = 5.4 Hz), 2.28 (t, 2 H, J = 7.2 Hz), 1.58ꢀ1.41 (m, 2 H), 1.46ꢀ1.40 (m, 5 H), 0.92 (t, 3 H, J
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= 7.3 Hz); C NMR (100 MHz, CDCl3): δ = 132.0, 128.9, 128.4, 122.0, 87.7, 87.0, 84.5, 77.3, 74.5,
68.6, 30.6, 22.1, 18.6, 17.8, 13.7. IR (KBr): ṽ = 3440, 2931, 2231, 1635, 1444 cmꢀ1; HRMS (ESI):
calculated for C17H20O2Na [M+Na]+: 279.1363, found 279.1358.
1ꢀPhenylꢀ3ꢀ(phenylethynyl)hexꢀ1ꢀyneꢀ3,4ꢀdiol (1n). 768.6 mg, 53% yield, yellow solid; m.p. 111.6ꢀ
112.6 oC; 1H NMR (400 MHz, CDCl3): δ = 7.51ꢀ7.48 (m, 4 H), 7.38ꢀ7.30 (m, 6 H), 3.82ꢀ3.77 (m, 1 H),
3.28ꢀ3.25 (m, 1 H), 2.39ꢀ2.37 (m, 1 H), 2.13ꢀ2.05 (m, 1 H), 1.77ꢀ1.69 (m, 1 H), 1.15 (t, 3 H, J = 7.4 Hz);
13C NMR (100 MHz, CDCl3): δ = 132.1, 132.0, 129.1, 129.0, 128.4, 122.0, 121.9, 87.2, 86.3, 85.6, 85.2,
80.1, 68.6, 25.3, 11.0 ppm; IR (KBr): ṽ = 3502, 3438, 2226, 1614, 1514, 1442 cmꢀ1; HRMS (ESI):
calculated for C20H18O2Na [M+Na]+: 313.1204, found 313.1204.
1,4ꢀDiphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀyneꢀ1,2ꢀdiol (1o). 1081.6 mg, 64% yield, white solid; m.p. 160.6ꢀ
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161.6 C; H NMR (400 MHz, CDCl3): δ = 7.69ꢀ7.67 (m, 2 H), 7.45ꢀ7.30 (m, 13 H), 5.05 (d, 1 H, J =
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3.0 Hz), 3.17 (sbr, 1 H), 3.11 (d, 1 H, J = 3.0 Hz); C NMR (100 MHz, CDCl3): δ = 137.5, 132.0,
131.9, 129.1, 129.0, 128.8, 128.4, 128.4, 128.3, 127.8, 121.9, 121.9, 86.9, 86.5, 86.3, 86.2, 80.3, 69.1
ppm; IR (KBr): ṽ = 3503, 3435, 2264, 1597, 1487, 1323 cmꢀ1; HRMS (ESI): calculated for C24H18O2Na
[M+Na]+: 361.1199, found 361.1199.
1ꢀ(4ꢀMethoxyphenyl)ꢀ4ꢀphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀyneꢀ1,2ꢀdiol (1p). 1049.0 mg, 57% yield, white
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solid; m.p. 144.8ꢀ145.8 C; H NMR (400 MHz, CDCl3): δ = 7.61ꢀ7.59 (m, 2 H), 7.46ꢀ7.43 (m, 4 H),
7.36ꢀ7.29 (m, 6 H), 6.93ꢀ6.90 (m, 2 H), 5.01 (s, 1 H), 3.81 (s, 3 H), 3.39 (d, 1 H, J = 14.3 Hz), 3.21 (d, 1
H, J = 8.1 Hz); 13C NMR (100 MHz, CDCl3): δ = 159.9, 132.0, 131.9, 129.7, 129.0, 129.0, 128.4, 122.0,
121.9, 113.3, 87.0, 86.4, 86.3, 86.1, 79.9, 69.1, 55.4 ppm; IR (KBr): ṽ = 3356, 2924, 2226, 1609, 1512
1021 cmꢀ1; HRMS (ESI): calculated for C25H20O3Na [M+Na]+: 391.1305, found 391.1304.
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1ꢀ(4ꢀChlorophenyl)ꢀ4ꢀphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀyneꢀ1,2ꢀdiol (1q). 1190.4 mg, 64% yield, white
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solid; m.p. 145.4ꢀ146.4 C; H NMR (400 MHz, CDCl3): δ = 7.62ꢀ7.60 (m, 2 H), 7.44ꢀ7.42 (m, 4 H),
7.36ꢀ7.30 (m, 8 H), 5.02 (s, 1 H), 3.31 (s, 1 H), 3.27 (s, 1 H); 13C NMR (100 MHz, CDCl3): δ = 136.0,
134.6, 132.0, 131.9, 129.7, 129.2, 129.2, 128.5, 128.4, 127.9, 121.7, 121.6, 86.7, 86.6, 86.5, 85.9, 79.6,
68.9 ppm; IR (KBr): ṽ = 3368, 2230, 1595, 1487 cmꢀ1; HRMS (ESI): calculated for C24H17O2ClNa
[M+Na]+: 395.0809, found 395.0807.
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General procedure for the synthesis of 2a-2e and 2g-2n.
To a schlenk flask was placed freshly distilled DMSO (0.5 mL, 6.8 mmol) and anhydrous NEt3 (1.4 mL,
10 mmol) in CH2Cl2 (10 mL). Oxalyl chloride (1.7 mL, 3.4 mmol) was added dropwise at ꢀ78 oC for 15
min. After that a solution of the compounds 1 (2.5 mmol) in CH2Cl2 (5 mL) was added to the reaction
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mixture at ꢀ78 C. After having been stirred for 2 h, the reaction was quenched with sat. aqueous Naꢀ
HCO3 solution (30 mL). The resulting mixture was extracted with CH2Cl2 (10 mL× 3). The combined
organic layer was dried (Na2SO4), filtered, and concentrated to give the crude product.
General procedure for the synthesis of 2f and 2o-2q. A solution of 1,1,1ꢀtrialkanoyloxyꢀ1,1ꢀdihydroꢀ
1,2ꢀbenziodoxolꢀ3(1H)ꢀone (1.5 g, 3.6 mmol) was added to the solution of compounds 1 (3 mmol) in
anhydrous CH2Cl2 (30 mL) under nitrogen at room temperature. The reaction was monitored by TLC.
When the conversion is complete, the reaction is quenched with an aqueous solution of Naꢀ
HCO3/Na2S2O3 and stirred for 10 minutes. After that the solvent was removed and the crude product
was purified via column chromatography on silica gel (petroleum ether / ethyl acetate = 50 : 1) to afford
the target product.
3ꢀHydroxyꢀ5ꢀphenylꢀ3ꢀ(phenylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2a). 520.6 mg, 76% yield, yellow solid; m.p.
86.1ꢀ87.1 oC; 1H NMR (400 MHz, CDCl3): δ = 7.52ꢀ7.49 (m, 4 H), 7.39ꢀ7.41 (m, 6 H), 4.68 (sbr, 1 H),
2.72 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 199.3, 132.0, 129.3, 128.4, 121.3, 85.7, 84.8, 68.6, 23.2
ppm; IR (KBr): ṽ = 3452, 2227, 1730, 1598, 1490 cmꢀ1; HRMS (ESI): calculated for C19H14O2Na
[M+Na]+: 297.0891, found 297.0904.
5ꢀ(4ꢀFluorophenyl)ꢀ3ꢀ((4ꢀfluorophenyl)ethynyl)ꢀ3ꢀhydroxypentꢀ4ꢀynꢀ2ꢀone (2b). 395.3 mg, 51% yield,
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yellow solid; m.p. 86.3ꢀ87.3 C; 1H NMR (400 MHz, CDCl3): δ = 7.50ꢀ7.46 (m, 4 H), 7.04 (t, 4 H, J =
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8.6 Hz), 4.57 (s, 1 H), 2.69 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 199.2, 163.3 (JFꢀC = 252.1 Hz),
134.1(JFꢀC = 8.7 Hz), 117.5 (JFꢀC = 3.4 Hz), 115.9 (JFꢀC = 22.2 Hz), 84.8, 84.6, 68.7, 22.3 ppm; IR (KBr):
ṽ = 3423, 2227, 1724, 1487 cmꢀ1; HRMS (ESI): calculated for C19H12O2F2Na [M+Na]+: 333.0703,
found 333.0717.
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5ꢀ(4ꢀChlorophenyl)ꢀ3ꢀ((4ꢀchlorophenyl)ethynyl)ꢀ3ꢀhydroxypentꢀ4ꢀynꢀ2ꢀone (2c). 427.5 mg, 50% yield,
yellow solid; m.p. 107.9ꢀ108.7 oC; 1H NMR (400 MHz, CDCl3): δ = 7.42 (d, 4 H, J = 8.2 Hz), 7.33ꢀ7.30
(m, 4 H), 4.59 (s, 1 H), 2.68 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 198.9, 135.7, 133.3, 128.9,
119.8, 85.6, 84.8, 68.7, 23.3 ppm; IR (KBr): ṽ = 3425, 2231, 1728, 1490 cmꢀ1; HRMS (ESI): calculated
for C19H12O2Cl2Na [M+Na]+: 365.0112, found 365.0125.
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5ꢀ(4ꢀBromophenyl)ꢀ3ꢀ((4ꢀbromophenyl)ethynyl)ꢀ3ꢀhydroxypentꢀ4ꢀynꢀ2ꢀone (2d). 517.2 mg, 48% yield,
o
yellow solid; m.p. 86.3ꢀ87.3 C; 1H NMR (400 MHz, CDCl3): δ = 7.49ꢀ7.47 (m, 4 H), 7.35 (d, 4 H, J=
8.4 Hz), 4.60 (s, 1 H), 2.68 (s, 3 H,); 13C NMR (100 MHz, CDCl3): δ = 198.8, 133.5, 131.9, 124.0,
120.3, 85.6, 84.8, 68.7, 23.3 ppm; IR (KBr): ṽ = 3419, 2231, 1728, 1598, 1487 cmꢀ1; HRMS (ESI):
calculated for C19H12O2Br2Na [M+Na]+: 454.9081, found 454.9101.
3ꢀHydroxyꢀ5ꢀ(pꢀtolyl)ꢀ3ꢀ(pꢀtolylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2e). 317.1 mg, 42% yield, yellow solid; m.p.
59.2ꢀ60.2 oC; 1H NMR (400 MHz, CDCl3): δ = 7.39 (d, 4 H, J = 8.1 Hz), 7.14 (d, 4 H, J = 8.1 Hz), 4.58
(s, 1 H), 2.70 (s, 3 H), 2.36 (s, 6 H); 13C NMR (100 MHz, CDCl3): δ = 199.6, 139.6, 132.0, 129.2,
118.4, 85.9, 84.4, 68.7, 23.2, 21.6 ppm; IR (KBr): ṽ = 3429, 2225, 1726, 1568, 1485 cmꢀ1; HRMS (ESI):
calculated for C21H18O2Na [M+Na]+: 325.1204, found 325.1217.
3ꢀHydroxyꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀ((4ꢀmethoxyphenyl)ethynyl)pentꢀ4ꢀynꢀ2ꢀone (2f). 380.8 mg, 38%
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yield, yellow solid; m.p.96.8ꢀ97.8 C; H NMR (400 MHz, CDCl3): δ = 7.43 (d, 4 H, J = 8.7 Hz), 6.85
(d, 4 H, J = 8.7 Hz), 4.56 (s, 1 H), 3.82 (s, 6 H), 2.68 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 199.8,
160.5, 133.7, 114.2, 113.6, 85.8, 83.9, 68.8, 55.5, 23.3 ppm; IR (KBr): ṽ = 3429, 2225, 1730, 1602,
1510 cmꢀ1; HRMS (ESI): calculated for C21H18O4Na [M+Na]+: 357.1103, found 357.1087.
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3ꢀHydroxyꢀ5ꢀ(mꢀtolyl)ꢀ3ꢀ(mꢀtolylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2g). 588.9 mg, 78% yield, yellow oil; H
NMR (400 MHz, CDCl3): δ = 7.33ꢀ7.30 (m, 4 H), 7.25ꢀ7.17 (m, 4 H), 4.61 (sbr, 1 H), 2.71 (s, 3 H),
13
2.34 (s, 6 H); C NMR (100 MHz, CDCl3): δ = 199.5, 138.2, 132.6, 130.3, 129.1, 128.4, 121.3, 85.9,
84.6, 68.7, 23.2, 21.3 ppm; IR (KBr): ṽ = 3444, 2223, 1735, 1600, 1483 cmꢀ1; HRMS (ESI):
calculated for C21H18O2Na [M+Na]+: 325.1204, found 325.1215.
3ꢀHydroxyꢀ5ꢀ(thiophenꢀ2ꢀyl)ꢀ3ꢀ(thiophenꢀ2ꢀylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2h). 286.0 mg, 40% yield,
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brown oil; H NMR (400 MHz, CDCl3): δ = 7.32 (t, 4 H, J = 5.4 Hz), 7.00 (t, 2 H, J = 5.4 Hz), 4.61
(sbr, 1 H), 2.68 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 198.8, 133.8, 128.7, 127.2, 121.1, 88.3, 79.6,
68.9, 23.4 ppm; IR (KBr): ṽ = 2991, 2362, 1735 cmꢀ1; HRMS (ESI): calculated for C15H10O2S2Na
[M+Na]+: 309.0020, found 309.0033.
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3ꢀHydroxyꢀ5ꢀ(thiophenꢀ3ꢀyl)ꢀ3ꢀ(thiophenꢀ3ꢀylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2i). 336.1 mg, 47% yield, brown
oil; 1H NMR (400 MHz, CDCl3): δ = 7.55 (d, 2 H, J = 4.7 Hz), 7.29 (t, 2 H, J = 4.7 Hz), 7.15 (d, 2 H, J
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= 4.7 Hz), 4.58 (s, 1 H), 2.68 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 199.3, 130.6, 129.9, 125.8,
120.5, 84.5, 81.1, 68.7, 23.3 ppm; IR (KBr): ṽ = 3431, 2231, 1732 cmꢀ1; HRMS (ESI): calculated for
C15H10O2S2Na [M+Na]+: 309.0020, found 309.0033.
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3ꢀHydroxyꢀ5ꢀ(naphthalenꢀ1ꢀyl)ꢀ3ꢀ(naphthalenꢀ1ꢀylethynyl)pentꢀ4ꢀynꢀ2ꢀone (2j). 598.4 mg, 64% yield,
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yellow oil; H NMR (400 MHz, CDCl3): δ = 8.39 (d, 2 H, J = 8.3 Hz), 7.89 (t, 4 H, J = 6.2 Hz), 7.80ꢀ
7.78 (m, 2 H), 7.63ꢀ7.53 (m, 4 H), 7.48ꢀ7.45 (m, 2 H), 4.84 (s, 1 H), 2.88 (s, 3 H); 13C NMR (100 MHz,
CDCl3): δ = 199.4, 133.5, 133.2, 131.4, 130.0, 128.6, 127.4, 126.8, 125.9, 125.2, 119.0, 89.8, 84.4, 69.2,
23.6 ppm; IR (KBr): ṽ = 3440, 2318, 1733, 1506 cmꢀ1; HRMS (ESI): calculated for C27H18O2Na
[M+Na]+: 397.1204, found 397.1193.
5ꢀCyclopropylꢀ3ꢀ(cyclopropylethynyl)ꢀ3ꢀhydroxypentꢀ4ꢀynꢀ2ꢀone (2k). 257.6 mg, 51% yield, yellow oil;
1H NMR (400 MHz, CDCl3): δ = 4.25 (s, 1 H), 2.48 (s, 3 H), 1.31ꢀ1.22 (m, 2 H), 0.79ꢀ0.71 (m, 8 H);
13C NMR (100 MHz, CDCl3): δ = 200.3, 89.5, 82.1, 71.9, 67.9, 22.9, 15.8, 8.4, 8.4, ꢀ0.43 ppm; IR
(KBr): ṽ = 3460, 2243, 1733 cmꢀ1; HRMS (ESI): calculated for C13H14O2Na [M+Na]+: 225.0891, found
225.0901.
3ꢀ(Hexꢀ1ꢀynꢀ1ꢀyl)ꢀ3ꢀhydroxynonꢀ4ꢀynꢀ2ꢀone (2l). 235.8 mg, 36% yield, pale liquid; 1H NMR (400 MHz,
CDCl3): δ = 4.28 (s, 1 H), 2.50 (s, 3 H), 2.22 (t, 4 H, J = 7.2 Hz), 1.52ꢀ1.45 (m, 4 H), 1.42ꢀ1.33 (m, 4
H), 0.88 (t, 6 H, J = 7.3 Hz); 13C NMR (100 MHz, CDCl3): δ =200.5, 86.6, 77.0, 67.9, 30.3, 22.8, 22.0,
18.5, 13.6 ppm; IR (KBr): ṽ = 3456, 2239, 1733 cmꢀ1; HRMS (ESI): calculated for C15H22O2Na
[M+Na]+: 257.1517, found 257.1510.
1
3ꢀHydroxyꢀ3ꢀ(phenylethynyl)nonꢀ4ꢀynꢀ2ꢀone (2m). 393.7 mg, 62% yield; yellow oil; H NMR (400
MHz, CDCl3): δ = 7.48ꢀ7.44 (m, 2 H), 7.37ꢀ7.29 (m, 3 H), 4.46 (s, 1 H), 2.61 (s, 3 H), 2.28 (t, 2H, J =
7.1 Hz), 1.57ꢀ1.50 (m, 2 H), 1.46ꢀ1.37 (m, 2 H), 0.92 (t, 3 H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3):
δ = 199.9, 132.0, 129.2, 128.4, 121.6, 87.4, 85.4, 85.1, 76.5, 68.3, 30.2, 23.1, 22.1, 18.6, 13.6. IR (KBr):
ṽ = 3427, 2237, 1733, 1616, 1490 cmꢀ1; HRMS (ESI): calculated for C17H18O2Na [M+Na]+: 277.1204,
found 277.1201.
4ꢀHydroxyꢀ6ꢀphenylꢀ4ꢀ(phenylethynyl)hexꢀ5ꢀynꢀ3ꢀone (2n). 489.6 mg, 68% yield, yellow solid; m.p.
62.7ꢀ63.7 oC; 1H NMR (400 MHz, CDCl3): δ = 7.51ꢀ7.49 (m, 4 H), 7.37ꢀ7.34 (m, 6 H), 4.69 (sbr, 1 H),
13
3.21ꢀ3.15 (m, 2 H), 1.30 (t, 3 H, J = 7.3 Hz); C NMR (100 MHz, CDCl3): δ = 202.8, 132.0, 129.3,
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128.5, 121.5, 85.5, 85.2, 68.4, 29.3, 8.8 ppm; IR (KBr): ṽ = 3394, 2098, 1676, 1512, 1423 cmꢀ1; HRMS
(ESI): calculated for C20H16O2Na [M+Na]+: 311.1048, found 311.1051.
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2ꢀHydroxyꢀ1,4ꢀdiphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀynꢀ1ꢀone (2o). 302.4 mg, 30% yield, yellow oil; H
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NMR (400 MHz, CDCl3): δ = 8.58ꢀ8.56 (m, 2 H), 7.68ꢀ7.64 (m, 1 H), 7.55ꢀ7.51 (m, 2 H), 7.41ꢀ7.38 (m,
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4 H), 7.35ꢀ7.25 (m, 6 H), 5.22 (sbr, 1 H); C NMR (100 MHz, CDCl3): δ = 190.9, 134.8, 131.9, 131.5,
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130.5, 129.3, 128.4, 128.3, 121.6, 87.2, 86.5, 66.0 ppm; IR (KBr): ṽ = 3408, 2226, 1693, 1595, 1489
cmꢀ1; HRMS (ESI): calculated for C24H16O2Na [M+Na]+: 359.1043, found 359.1037.
2ꢀHydroxyꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀynꢀ1ꢀone (2p). 340.4 mg, 31% yield,
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yellow solid; m.p. 96.9ꢀ97.9 C; H NMR (400 MHz, CDCl3): δ = 8.57ꢀ8.55 (m, 2 H), 7.42ꢀ7.40 (m, 4
H), 7.35ꢀ7.27 (m, 6 H), 7.02ꢀ6.98 (m, 2 H), 5.37 (sbr, 1 H), 3.91 (s, 3 H); 13C NMR (100 MHz, CDCl3):
δ = 189.3, 164.9, 134.1, 131.9, 129.2, 128.4, 123.2, 121.8, 113.8, 86.9, 86.8, 65.5, 55.8 ppm; IR (KBr):
ṽ = 3393, 2266, 1678, 1593, 1502 cmꢀ1; HRMS (ESI): calculated for C25H18O3Na [M+Na]+: 389.1148,
found 389.1146.
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀhydroxyꢀ4ꢀphenylꢀ2ꢀ(phenylethynyl)butꢀ3ꢀynꢀ1ꢀone (2q). 310.8 mg, 28% yield,
yellow solid; m.p. 120.8ꢀ121.8 oC; 1H NMR (400 MHz, CDCl3): δ = 8.54ꢀ8.51 (m, 2 H), 7.52ꢀ7.50 (m, 2
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H), 7.42ꢀ7.39 (m, 4 H), 7.37ꢀ7.28 (m, 6 H), 5.15 (sbr, 1 H); C NMR (100 MHz, CDCl3): δ = 189.8,
141.5, 132.8, 131.9, 129.4, 128.8, 128.5, 121.4, 87.5, 86.1, 65.9 ppm; IR (KBr): ṽ = 3383, 2228, 1688,
1583, 1485 cmꢀ1; HRMS (ESI): calculated for C24H15O2ClNa [M+Na]+: 393.0653, found 393.0649.
General procedure for the synthesis of 1-(furan-3-yl)-1,2-diones.
AgNTf2 (17.5 mg, 0.045 mmol) and AuCl3 (4.5 mg, 0.015 mmol) were dissolved in 2 mL of commerꢀ
cial grade toluene and was stirred at rt for 15 min. After that a solution of 2 (0.3 mmol) in 1 mL of toluꢀ
ene was added. The resulting mixture was continually stirred at room temperature for 0.5 h. After that
the solvent was removed and the crude product was purified via column chromatography on silica gel
(petroleum ether / ethyl acetate / triethylamine, 300 : 10 : 1) to afford 1ꢀ(furanꢀ3ꢀyl)ꢀ1,2ꢀdiones.
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1ꢀ(2ꢀMethylꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3a). 76.6 mg, 88% yield, yellow oil; H
NMR (400 MHz, CDCl3): δ = 8.04 (d, 2 H, J = 7.6 Hz), 7.69ꢀ7.63 (m, 3 H), 7.55ꢀ7.51 (m, 2 H), 7.40ꢀ
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7.37 (m, 2 H), 7.31ꢀ7.27 (m, 1 H), 6.91 (s, 1 H), 2.68 (s, 3 H); C NMR (100 MHz, CDCl3): = 193.5,
189.3, 161.4, 153.0, 134.9, 132.7, 130.2, 129.5, 129.1, 128.9, 128.3, 124.1, 120.3, 104.9, 14.9 ppm; IR
(KBr): ṽ = 1670, 1554, 1448, 1199 cmꢀ1; HRMS (ESI): calculated for C19H14O3Na [M+Na]+: 313.0841,
found 313.0833.
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1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀ(5ꢀ(4ꢀfluorophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3b). 73.4 mg, 75%
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yield, yellow solid; m.p. 136.7ꢀ137.7 C; H NMR (400 MHz, CDCl3): δ = 8.09ꢀ8.06 (m, 2 H), 7.62ꢀ
7.59 (m 2 H), 7.22ꢀ7.18 (m, 2 H), 7.10ꢀ7.16 (m, 2 H), 6.82 (s, 1 H), 2.67 (s, 3 H); 13C NMR (100 MHz,
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CDCl3): δ = 191.6, 188.6, 166.7 (JFꢀC = 258.2 Hz), 162.8 (JFꢀC = 248.7 Hz), 161.7, 152.2, 133.1 (JFꢀC
9.6 Hz), 129.1 (JFꢀC = 2.8 Hz), 125.9 (JFꢀC = 8.2 Hz), 125.9, 120.2, 116.5 (JFꢀC = 22.6 Hz), 116.1(JFꢀC
=
=
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22.3 Hz), 104.6, 14.9 ppm; IR (KBr): ṽ = 1724, 1595, 1500, 1413, 1226, 1093 cmꢀ1; HRMS (ESI):
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calculated for C19H12O3F2Na [M+Na]+: 349.0652, found 349.0668.
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀ(5ꢀ(4ꢀchlorophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3c). 90.2 mg, 84%
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yield, yellow solid; m.p. 164.1ꢀ165.3 C; H NMR (400 MHz, CDCl3): δ = 7.98 (d, 2 H, J = 8.1Hz),
7.55 (d, 2 H, J = 8.6 Hz), 7.50 (d, 2 H, J = 8.6 Hz), 7.35 (d, 2 H, J = 8.6 Hz), 6.69 (s, 1 H), 2.68 (s, 3 H);
13C NMR (100 MHz, CDCl3): δ = 191.7, 188.3, 162.0, 151.9, 141.8, 134.1, 131.6, 131.0, 129.5, 129.2,
128.0, 125.2, 120.1, 105.4, 14.9 ppm; IR (KBr): ṽ = 1658, 1568, 1485, 1402, 1130 cmꢀ1; HRMS(ESI):
calculated for C19H12O3Cl2Na [M+Na]+: 381.0061, found 381.0048.
1ꢀ(4ꢀBromophenyl)ꢀ2ꢀ(5ꢀ(4ꢀbromophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3d). 110.2 mg, 82%
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yield, yellow solid; m.p. 169.8ꢀ170.8 C; H NMR (400 MHz, CDCl3): δ = 7.90 (d, 2 H, J = 8.4 Hz),
7.68 (d, 2 H, J = 8.4 Hz), 7.53ꢀ7.48 (m, 4 H), 6.90 (s, 1 H), 2.68 (s, 3 H); 13C NMR (100 MHz, CDCl3):
δ = 192.0, 188.2, 162.1, 152.0, 132.6, 132.2, 131.7, 131.4, 131.4, 130.6, 128.4, 125.5, 122.3, 120.2,
105.5, 15.0 ppm; IR (KBr): ṽ = 1658, 1577, 1201 cmꢀ1; HRMS (ESI): calculated for C19H12O3Br2Na
[M+Na]+: 470.9030, found 470.9046.
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1ꢀ(2ꢀMethylꢀ5ꢀ(pꢀtolyl)furanꢀ3ꢀyl)ꢀ2ꢀ(pꢀtolyl)ethaneꢀ1,2ꢀdione (3e). 83.9 mg, 87% yield, brown oil; H
NMR (400 MHz, CDCl3): δ = 7.93 (d, 2 H, J = 8.0 Hz), 7.53 (d, 2 H, J = 7.8 Hz), 7.32 (d, 2 H, J = 7.8
13
Hz), 7.19 (d, 2 H, J = 8.0 Hz), 6.84 (s, 1 H), 2.66 (s, 3 H), 2.45 (s, 3 H), 2.36 (s, 3 H); C NMR (100
MHz, CDCl3): δ = 193.3, 189.6, 161.0, 153.2, 146.2, 138.2, 130.3, 130.2, 129.8, 129.6, 126.9, 124.0,
120.3, 104.1, 22.0, 21.4, 14.8 ppm; IR (KBr): ṽ = 1660, 1564, 1413, 1174 cmꢀ1; HRMS (ESI): calculated
for C21H18O3Na [M+Na]+: 341.1154, found 341.1168.
1ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀ(5ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3f). 92.4 mg, 78%
yield, yellow solid, m.p. 81.4ꢀ82.4 oC; 1H NMR (400 MHz, CDCl3): δ = 7.99 (d, 2 H, J = 8.8 Hz), 7.55
(d, 2 H, J = 8.8 Hz), 6.98 (d, 2 H, J = 8.8 Hz), 6.90 (d, 2 H, J = 8.8 Hz), 6.75 (s, 1 H), 3.88 (s, 3 H), 3.82
(s, 3 H), 2.63 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 192.3, 189.9, 165.0, 160.7, 159.7, 153.0,
132.7, 125.7, 125.5, 122.6, 120.5, 114.6, 114.3, 103.2, 55.8, 55.4, 14.8 ppm; IR (KBr): ṽ = 1664, 1504,
1425, 1253, 1174 cmꢀ1; HRMS (ESI): calculated for C21H18O5Na [M+Na]+: 373.1052, found 373.1042.
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1
1ꢀ(2ꢀMethylꢀ5ꢀ(mꢀtolyl)furanꢀ3ꢀyl)ꢀ2ꢀ(mꢀtolyl)ethaneꢀ1,2ꢀdione (3g). 76.3 mg, 80% yield, brown oil; H
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NMR (400 MHz, CDCl3): δ = 7.83ꢀ7.81 (m, 2 H), 7.47ꢀ7.38 (m, 4 H), 7.30ꢀ7.27 (m, 1 H), 7.13ꢀ7.11 (m,
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1 H), 6.86 (s, 1 H), 2.66 (s, 3 H), 2.42 (s, 3 H), 2.36 (s 3 H); C NMR (100 MHz, CDCl3): δ = 193.8,
189.5, 161.2, 153.1, 139.1, 138.6, 135.8, 132.7, 130.5, 129.4, 129.1, 129.0, 128.8, 127.5, 124.6, 121.2,
120.3, 104.7, 21.5, 21.4, 14.9 ppm; IR (KBr): ṽ = 1722, 1658, 1554, 1467, 1163 cmꢀ1; HRMS (ESI):
calculated for C21H18O3Na [M+Na]+: 341.1154, found 341.1168.
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1ꢀ(2ꢀMethylꢀ5ꢀ(thiophenꢀ2ꢀyl)furanꢀ3ꢀyl)ꢀ2ꢀ(thiophenꢀ2ꢀyl)ethaneꢀ1,2ꢀdione (3h). 47.0 mg, 52% yield,
brown oil; 1H NMR (400 MHz, CDCl3): δ = 7.98ꢀ7.97 (dd, 1 H, J = 4.9, 1.0 Hz), 7.84ꢀ7.83 (dd, 1 H, J =
4.9, 1.0 Hz), 7.28ꢀ7.26 (m, 2 H), 7.22ꢀ7.20 (m, 1 H), 7.05ꢀ7.03 (m, 1 H), 6.93 (s, 1 H), 2.70 (s, 3 H); 13C
NMR (100MHz, CDCl3): δ = 186.4, 184.1, 162.1, 148.2, 139.0, 137.3, 137.0, 132.3, 128.8, 127.9,
125.2, 123.7, 119.5, 105.3, 15.0 ppm; IR(KBr): ṽ = 1726, 1639, 1460, 1261 cmꢀ1; HRMS (ESI):
calculated for C15H10O3S2Na [M+Na]+: 324.9969, found 324.9980.
1ꢀ(2ꢀMethylꢀ5ꢀ(thiophenꢀ3ꢀyl)furanꢀ3ꢀyl)ꢀ2ꢀ(thiophenꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3i). 43.5 mg, 48% yield,
yellow oil; 1H NMR (400 MHz, CDCl3): δ = 8.36ꢀ8.35 (m, 1 H), 7.70ꢀ7.68 (m 1 H), 7.51ꢀ7.49 (m, 1 H),
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7.41ꢀ7.39 (m, 1 H), 7.36ꢀ7.33 (m, 1 H), 7.28ꢀ7.27 (m, 1 H), 6.81 (s, 1 H), 2.68 (s, 3 H); C NMR (100
MHz, CDCl3): δ = 187.9, 186.1, 161.5, 149.8, 137.6, 137.4, 131.3, 127.7, 127.1, 126.7, 124.6, 120.1,
119.5, 104.9, 15.0 ppm; IR (KBr): ṽ = 1737, 1604, 1188, 1087 cmꢀ1; HRMS (ESI): calculated for
C15H10O3S2Na [M+Na]+: 324.9969, found 324.9954.
1ꢀ(Naphthalenꢀ1ꢀyl)ꢀ2ꢀ(5ꢀ(naphthalenꢀ1ꢀyl)furanꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3j). 78.4 mg, 65% yield,
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yellow solid, m.p. 77.2ꢀ79.3 C; 1H NMR (400 MHz, CDCl3): δ = 9.25 (d, 1 H, J = 8.6 Hz), 8.32 (m, 1
H), 8.15 (d, H, J = 8.2 Hz), 8.07ꢀ8.05 (m, 1 H), 7.97 (d, 1 H, J = 8.6 Hz), 7.90ꢀ7.86 (m, 2 H), 7.77ꢀ7.72
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(m, 2 H), 7.65ꢀ7.61 (m, 1 H), 7.58ꢀ7.49 (m, 4 H), 7.06 (s, 1 H), 2.74 (s, 3 H); C NMR (100 MHz,
CDCl3): δ = 196.2, 189.8, 161.7, 152.4, 136.0, 134.9, 134.3, 134.0, 131.4, 130.3, 129.5, 129.5, 129.0,
128.8, 128.5, 127.2, 127.2, 127.1, 126.9, 126.6, 126.3, 126.0, 125.4, 125.2, 124.6, 120.6, 109.3, 15.0
ppm; IR (KBr): ṽ = 1658, 1508, 1257, 1174, 1099 cmꢀ1; HRMS (ESI): calculated for C27H18O3Na
[M+Na]+: 413.1154, found 413.1142.
1ꢀCyclopropylꢀ2ꢀ(5ꢀcyclopropylꢀ2ꢀmethylfuranꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (3k). 28.1 mg, 43% yield, yellow
liquid; 1H NMR (400 MHz, CDCl3): δ = 6.37 (s, 1 H), 2.67ꢀ2.60 (m, 1 H), 2.55 (s, 1 H), 1.84ꢀ1.78 (m, 1
H), 1.22ꢀ1.78 (m, 2 H), 1.13ꢀ1.09 (m, 2 H), 0.89ꢀ0.84 (m, 2 H), 0.75ꢀ0.71(m, 2 H); 13C NMR (100 MHz,
CDCl3): δ = 201.8, 186.3, 161.3, 156.2, 117.5, 104.6, 17.0, 14.8, 13.2, 8.3, 6.6 ppm; IR (KBr): ṽ = 1706,
1581, 1427, 1218, 1078 cmꢀ1; HRMS (ESI): calculated for C13H14O3Na [M+Na]+: 241.0841, found
241.0849.
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1ꢀ(5ꢀButylꢀ2ꢀmethylfuranꢀ3ꢀyl)hexaneꢀ1,2ꢀdione (3l). 27.8 mg, 37% yield, brown liquid; H NMR (400
MHz, CDCl3): δ = 6.41 (s, 1 H), 2.82 (t, 2 H, J = 7.2 Hz), 2.54ꢀ2.58 (m, 5 H), 1.66ꢀ1.56 (m, 4 H), 1.42ꢀ
1.32 (m, 4 H), 0.95ꢀ0.90 (m, 6 H); 13C NMR (100 MHz, CDCl3): δ = 202.9, 186.9. 161.5, 155.3, 117.3,
105.7, 37.4, 29.9, 27.4, 25.3, 22.5, 22.3, 14.9, 13.9, 13.9 ppm; IR (KBr): ṽ = 1660, 1462, 1234 cmꢀ1;
HRMS (ESI): calculated for C15H22O3Na [M+Na]+: 273.1467, found 273.1453.
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1ꢀ(2ꢀMethylꢀ5ꢀphenylfuranꢀ3ꢀyl)hexaneꢀ1,2ꢀdione (3m). 29.2 mg, 36% yield, yellow oil; H NMR (400
MHz, CDCl3): δ = 7.98 (m, 2 H), 7.64 (m, 1 H), 7.51ꢀ7.49 (m, 2 H), 6.25 (s, 1 H), 2.56 (m, 5 H), 1.59
(m, 2 H), 1.40ꢀ1.31 (m, 2 H), 0.91 (t, 3H, J = 7.3 Hz). 13C NMR (100 MHz, CDCl3): δ = 193.8, 189.5,
160.6, 155.8, 134.8, 132.8, 130.2, 129.0, 119.1, 105.0, 29.8, 27.4, 22.3, 14.7, 13.9 ppm; IR (KBr): ṽ =
1658, 1450, 1166 cmꢀ1; HRMS (ESI): calculated for C17H18O3Na [M+Na]+: 293.1154, found 293.1151.
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1ꢀ(5ꢀButylꢀ2ꢀmethylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3m’). 20.3 mg, 25% yield, yellow oil; H
NMR (400 MHz, CDCl3): δ = 7.65 (m, 2 H), 7.39 (m, 2 H), 7.31ꢀ7.27 (m, 1 H), 7.12 (s, 1 H), 2.88 (t,
2H, J = 7.3 Hz), 2.69 (s, 3 H), 1.70ꢀ1.62 (m, 2 H), 1.45ꢀ1.36 (m, 2 H), 0.95 (t, 3H, J = 7.3 Hz). 13C NMR
(100 MHz, CDCl3): δ = 202.5, 186.3, 162.5, 152.4, 129.8, 128.9, 128.1, 123.9, 118.5, 105.7, 37.3, 25.3,
22.5, 15.1, 14.0 ppm; IR (KBr): ṽ = 1714, 1552, 1400, 1157 cmꢀ1; HRMS (ESI): calculated for
C17H18O3Na [M+Na]+: 293.1154, found 293.1147.
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1ꢀ(2ꢀEthylꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3n). 71.1 mg, 78% yield, yellow oil; H
NMR (400 MHz, CDCl3): δ = 8.04ꢀ8.02 (m, 2 H), 7.69ꢀ7.63 (m, 3 H), 7.55ꢀ7.51 (m, 2 H), 7.41ꢀ7.37 (m,
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2 H), 7.31ꢀ7.28 (m, 1 H), 6.90 (s, 1 H), 3.11ꢀ3.05 (m, 2 H), 1.35 (t, 3H, J = 7.5 Hz); C NMR (100
MHz, CDCl3): = 193.5, 189.3, 166.3, 152.9, 134.9, 132.7, 130.2, 129.6, 129.1, 128.9, 128.2, 124.0,
119.4, 104.9, 22.3, 12.1 ppm; IR (KBr): ṽ = 1670, 1654, 1445, 1197 cmꢀ1; HRMS (ESI): calculated for
C20H16O3Na [M+Na]+: 327.0997, found 327.0996.
1ꢀ(2,5ꢀDiphenylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3o). 95.0 mg, 90% yield, yellow solid; m.p.
138.6ꢀ139.6 oC; 1H NMR (400 MHz, CDCl3): δ = 8.10ꢀ8.07 (m, 2 H), 7.98ꢀ7.96 (m, 2 H), 7.71ꢀ7.69 (m,
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2 H), 7.65ꢀ7.61 (m, 1 H), 7.50ꢀ7.39 (m, 7 H), 7.33ꢀ7.29 (m, 1 H), 7.01 (s, 1 H); C NMR (100 MHz,
CDCl3): = 193.4, 189.1, 159.0, 153.5, 134.8, 132.8, 130.6, 130.2, 129.3, 129.3, 129.1, 129.0, 128.7,
128.6, 128.5, 124.3, 120.1, 107.4 ppm; IR (KBr): ṽ = 1622, 1553, 1489, 1109 cmꢀ1; HRMS (ESI):
calculated for C24H16O3Na [M+Na]+: 375.0992, found 375.0989.
1ꢀ(2ꢀ(4ꢀMethoxyphenyl)ꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3p). 105.4 mg, 92% yield,
yellow solid; m.p. 129.8ꢀ130.8 oC; 1H NMR (400 MHz, CDCl3): δ = 8.16ꢀ8.14 (m, 2 H), 8.00ꢀ7.98 (m, 2
H), 7.71ꢀ7.63 (m, 3 H), 7.52ꢀ7.48 (m, 2 H), 7.42ꢀ7.39 (m, 2 H), 7.33ꢀ7.30 (m, 1 H), 7.00ꢀ6.96 (m, 3 H),
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3.89 (s, 3 H); C NMR (100 MHz, CDCl3): = 193.8, 189.0, 161.6, 159.4, 152.8, 134.8, 132.9, 130.5,
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130.2, 129.5, 129.1, 129.0, 128.5, 124.3, 122.0, 118.9, 114.0, 107.4, 55.6 ppm; IR (KBr): ṽ = 1663,
1589, 1495, 1177 cmꢀ1; HRMS (ESI): calculated for C25H18O4Na [M+Na]+: 405.1097, found 405.1099.
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1ꢀ(2ꢀ(4ꢀChlorophenyl)ꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (3q). 97.3 mg, 84% yield, yellow
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solid; m.p. 132.5ꢀ133.5 C; H NMR (400 MHz, CDCl3): δ = 8.15ꢀ8.12 (m, 2 H), 8.00ꢀ7.98 (m, 2 H),
7.71ꢀ7.65 (m, 3 H), 7.54ꢀ7.50 (m, 2 H), 7.46ꢀ7.40 (m, 4 H), 7.36ꢀ7.32 (m, 1 H), 6.99 (s, 1 H); 13C NMR
(100 MHz, CDCl3): = 193.3, 189.0, 157.5, 153.7, 136.7, 135.0, 133.5, 132.7, 131.3, 130.2, 129.9, 129.2,
129.1, 128.9, 127.8, 124.4, 120.2, 107.7 ppm; IR (KBr): ṽ = 1666, 1481, 1171, 1096 cmꢀ1; HRMS (ESI):
calculated for C24H15O3ClNa [M+Na]+: 409.0602, found 409.0603.
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General procedure for the synthesis of quinoxalines.
AgNTf2 (17.5 mg, 0.045 mmol) and AuCl3 (4.5 mg, 0.015 mmol) were dissolved in 2 mL of toluene and
was stirred at rt for 15 min. After that substrate 2 (0.3 mmol) in 1 mL of toluene was added. The resultꢀ
ing mixture was continually stirred at room temperature for 0.5 h. After that the benzeneꢀ1,2ꢀdiamine in
1 mL of toluene was added and the crude product was purified via column chromatography on silica gel
(petroleum ether / ethyl acetate, 20 : 1) to give quinoxalines.
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2ꢀ(2ꢀMethylꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ3ꢀphenylquinoxaline (4a). 71.7 mg, 66% yield, brown oil; H NMR
(400 MHz, CDCl3): δ = 8.20ꢀ8.15 (m, 2 H), 7.80ꢀ7.77 (m, 2 H), 7.71ꢀ7.69 (m, 2 H), 7.57 (d, 2 H, J = 7.4
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Hz), 7.46ꢀ7.44 (m, 3 H), 7.35ꢀ7.32 (m, 2 H), 7.27ꢀ7.23 (m, 1 H), 6.47 (s, 1 H), 2.31 (s, 3 H); C NMR
(100 MHz, CDCl3): δ = 153.8, 152.1, 151.8, 148.0, 141.4, 141.1, 139.1, 130.7, 130.1, 129.9, 129.6,
129.4, 129.2, 129.0, 128.8, 128.6, 127.3, 123.7, 121.6, 107.4, 13.4 ppm; IR (KBr): ṽ = 1613, 1573, 1120
cmꢀ1; HRMS (ESI): calculated for C25H18ON2Na [M+Na]+: 385.1317, found 385.1329.
2ꢀ(4ꢀFluorophenyl)ꢀ3ꢀ(5ꢀ(4ꢀfluorophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)quinoxaline (4b). 66.9 mg, 56% yield,
yellow solid; m.p. 134.1ꢀ135.1 oC; 1H NMR (400 MHz, CDCl3): δ = 8.16ꢀ8.11 (m, 2 H), 7.79ꢀ7.76 (m, 2
H), 7.72ꢀ7.68 (m, 2 H), 7.54 (m, 2 H), 7.13 (t, 2 H, J = 8.6 Hz), 7.06 (t, 2 H, J = 8.6 Hz), 76.4 (s, 1 H),
2.28 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 163.5 (JFꢀC = 249.6 Hz), 162.3(JFꢀC = 247.0 Hz), 152.6,
151.9, 151.3, 147.6, 141.4, 141.1, 135.2 (JFꢀC = 3.9 Hz), 131.6 (JFꢀC = 8.6 Hz), 130.2, 130.1, 129.3,
129.1, 126.9 (JFꢀC = 3.1 Hz), 125.5 (JFꢀC = 7.8 Hz), 121.6, 125.8 (JFꢀC = 22.3 Hz), 115.7 (JFꢀC = 21.6 Hz),
106.8, 13.3 ppm; IR (KBr): ṽ = 1600, 1500, 1431, 1089 cmꢀ1; HRMS (ESI): calculated for
C25H16ON2F2Na [M+Na]+: 421.1128, found 421.1144.
2ꢀ(4ꢀChlorophenyl)ꢀ3ꢀ(5ꢀ(4ꢀchlorophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)quinoxaline (4c). 87.7 mg, 68% yield,
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brown oil; H NMR (400 MHz, CDCl3): δ = 8.16ꢀ8.12 (m, 2 H), 7.80ꢀ7.75 (m, 2 H), 7.65 (d, 2 H, J =
8.7 Hz), 7.51 (d, 2 H, J = 8.2 Hz), 7.41(d, 2 H, J = 8.7 Hz), 7.33 (d, 2 H, J = 8.7 Hz), 6.50 (s, 1 H), 2.27
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(s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 152.4, 152.2, 151.2, 147.4, 141.4, 141.1,137.5, 135.5, 133.2,
131.0, 130.4, 130.2, 129.4, 129.1, 129.0, 128.9, 125.0, 121.7, 107.6, 13.4 ppm; IR (KBr): ṽ = 1735,
1483, 1188, 1087 cmꢀ1; HRMS (ESI): calculated for C25H16ON2Cl2Na [M+Na]+: 453.0537, found
453.0545.
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2ꢀ(4ꢀBromophenyl)ꢀ3ꢀ(5ꢀ(4ꢀbromophenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)quinoxaline (4d). 95.1 mg, 60% yield,
yellow oil; 1H NMR (400 MHz, CDCl3): δ = 8.15ꢀ8.12 (m, 2 H), 7.80ꢀ7.75 (m, 2 H), 7.60ꢀ7.55 (m, 4 H),
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7.50ꢀ7.43 (m, 4 H), 6.52 (s, 1 H), 2.26 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 152.4, 152.3, 151.2,
147.3, 141.4, 141.1, 137.9, 132.0, 131.8, 131.3, 130.4, 130.2, 129.4, 129.3, 129.0, 125.2, 123.8, 121.6,
121.3, 107.7, 13.4 ppm; IR (KBr): ṽ = 1679, 1516, 1342, 1261, 1047 cmꢀ1; HRMS (ESI): calculated for
C25H16ON2Br2Na [M+Na]+: 542.9507, found 542.9517.
2ꢀ(2ꢀMethylꢀ5ꢀ(pꢀtolyl)furanꢀ3ꢀyl)ꢀ3ꢀ(pꢀtolyl)quinoxaline (4e). 79.6 mg, 66% yield, orange oil; 1H NMR
(400 MHz, CDCl3): δ = 8.17ꢀ8.12 (m, 2 H), 7.76ꢀ7.73 (m, 2 H), 7.58 (d, 2 H, J = 8.4 Hz), 7.47 (d, 2 H, J
= 7.4 Hz), 7.22 (t, 2 H, J = 8.4 Hz), 7.15 (d, 2 H, J = 7.4 Hz), 6.48 (s, 1 H), 2.41 (s, 1 H), 2.36 (s, 3 H),
2.27 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 153.8, 152.0, 151.5, 148.1, 141.2, 141.1, 139.1, 137.1,
136.2, 129.8, 129.7, 129.5, 129.4, 129.3, 129.2, 129.0, 128.1, 123.6, 121.7, 106.7, 21.5, 21.4, 13.3, ppm;
IR (KBr): ṽ = 1612, 1502, 1419, 1220, 1124 cmꢀ1; HRMS (ESI): calculated for C27H22ON2Na [M+Na]+:
413.1630, found 413.1637.
2ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ(5ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀmethylfuranꢀ3ꢀyl)quinoxaline (4f). 77.2 mg, 61% yield,
yellow solid; m.p. 123.6ꢀ124.6 oC; 1H NMR (400 MHz, CDCl3): δ = 8.14ꢀ8.09 (m, 2 H), 7.75ꢀ7.70 (m, 2
H), 7.68 (d, 2 H, J = 8.8 Hz), 7.53 (d, 2 H, J = 8.8 Hz ), 6.95ꢀ6.89 (m, 4 H), 6.43 (s, 1 H), 3.84 (s, 3 H),
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3.82 (s, 3 H), 2.24 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 160.4, 159.1, 153.4, 152.0, 151.0, 148.0,
141.1, 141.1, 131.5, 131.1, 129.7, 129.7, 129.2, 128.9, 125.1, 123.8, 121.7, 114.2, 114.0, 105.8, 55.5,
55.4, 13.2, ppm; IR (KBr): ṽ = 1573, 1417, 1226, 1074 cmꢀ1; HRMS (ESI): calculated for
C27H22O3N2Na [M+Na]+: 445.1528, found 445.1520.
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2ꢀ(2ꢀMethylꢀ5ꢀ(mꢀtolyl)furanꢀ3ꢀyl)ꢀ3ꢀ(mꢀtolyl)quinoxaline (4g). 70.2 mg, 60% yield. brown oil; H
NMR (400 MHz, CDCl3): = 8.17ꢀ8.11 (m, 2 H), 7.76ꢀ7.72 (m, 2 H), 7.56 (s, 1 H), 7.40ꢀ7.33 (m, 2 H),
7.28ꢀ7.24 (m, 1 H), 7.23ꢀ7.21 (m, 3 H), 7.04 (d, 1 H, J = 7.4 Hz), 6.45 (s,1 H), 2.39 (s, 3 H), 2.36 (s, 3
H), 2.28 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 154.0, 152.0, 151.9, 148.1, 141.3, 141.0, 139.0,
138.3, 130.6, 130.1, 129.9, 129.9, 129.8, 129.3, 129.0, 128.7, 128.3, 128.1, 126.8, 124.3, 121.6, 120.9,
107.3, 21.6, 21.6, 13.4 ppm; IR (KBr): ṽ = 1533, 1353, 1261, 1091 cmꢀ1; HRMS (ESI): calculated for
C27H22ON2Na [M+Na]+: 413.1630, found 413.1642.
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2ꢀ(2ꢀMethylꢀ5ꢀ(thiophenꢀ2ꢀyl)furanꢀ3ꢀyl)ꢀ3ꢀ(thiophenꢀ2ꢀyl)quinoxaline (4h). 50.5 mg, 46% yield, yellow
oil; 1H NMR (400 MHz, CDCl3): δ = 8.14ꢀ8.09 (m, 2 H), 7.80ꢀ7.72 (m, 2 H), 7.49 (dd, 1 H, J = 5.1, 0.9
Hz), 7.44 (dd, 1 H, J = 5.1, 0.8 Hz), 7.30ꢀ7.26 (m, 2 H), 7.09ꢀ7.04 (m, 2 H), 6.67 (s, 1 H), 2.30 (s, 3 H);
13C NMR (100 MHz, CDCl3): δ = 151.0, 148.1, 147.5, 146.3, 142.3, 141.1, 140.8, 133.5, 130.3, 129.9,
129.6, 129.0, 129.0, 128.1, 127.8, 124.3, 122.8, 121.6, 107.1, 13.0 ppm; IR (KBr): ṽ = 1639, 1261, 1028
cmꢀ1; HRMS (ESI): calculated for C21H14ON2S2Na [M+Na]+: 397.0445, found 397.0426.
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2ꢀ(2ꢀMethylꢀ5ꢀ(thiophenꢀ3ꢀyl)furanꢀ3ꢀyl)ꢀ3ꢀ(thiophenꢀ3ꢀyl)quinoxaline (4i). 51.6 mg, 44% yield, yellow
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oil; H NMR (400 MHz, CDCl3): δ = 8.14ꢀ8.09 (m, 2 H), 7.75ꢀ7.73 (m, 3 H), 7.44 (m, 2 H), 7.35ꢀ7.32
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(m, 2 H), 7.27 (m, 2 H), 6.47 (s, 1 H), 2.24 (s, 3 H); C NMR (100 MHz, CDCl3): δ = 151.2, 149.3,
149.2, 147.8, 141.2, 141.1, 140.2, 132.4, 130.0, 129.9, 129.2, 129.0, 128.7, 127.4, 126.4, 125.7, 124.7,
121.3, 118.9, 107.0, 13.0 ppm; IR (KBr): ṽ = 1546 1323, 1224 cmꢀ1; HRMS (ESI): calculated for
C21H14ON2S2Na [M+Na]+: 397.0445, found 397.0430.
2ꢀ(2ꢀMethylꢀ5ꢀ(naphthalenꢀ1ꢀyl)furanꢀ3ꢀyl)ꢀ3ꢀ(naphthalenꢀ1ꢀyl)quinoxaline (4j). 70.7 mg, 51% yield,
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yellow oil; H NMR (400 MHz, CDCl3): δ = 8.26ꢀ8.20 (m, 2 H), 8.11ꢀ8.08 (m, 1 H), 7.98 (d, 1 H, J =
8.2 Hz), 7.88ꢀ7.81 (m, 2 H), 7.79ꢀ7.76 (m, 1 H), 7.70 (d, 1 H, J = 8.0 Hz), 7.68ꢀ7.59 (m, 3 H), 7.50ꢀ7.36
(m, 3 H), 7.42ꢀ7.36 (m, 2 H), 7.34ꢀ7.30 (m, 1 H), 7.23 (d, 1 H, J = 8.6 Hz), 5.80 (s, 1 H), 2.72 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 154.0, 153.7, 147.7, 149.4, 141.8, 140.8, 137.1, 133.9, 133.8, 131.8,
130.4, 130.0, 129.9, 129.5, 129.4, 129.2, 128.6, 128.4, 128.3, 128.1, 126.9, 126.5, 126.2, 125.9, 125.6,
125.6, 125.5, 125.3, 125.1, 120.8, 111.1, 13.8 ppm. IR (KBr): ṽ = 1606, 1508, 1257, 1101, 1016 cmꢀ1;
HRMS (ESI): calculated for C33H22ON2Na [M+Na]+: 485.1630, found 485.1613.
2ꢀ(2,5ꢀDiphenylfuranꢀ3ꢀyl)ꢀ3ꢀphenylquinoxaline (4k). 92.9 mg, 73% yield, yellow oil; 1H NMR (400
MHz, CDCl3): δ = 8.22ꢀ8.17 (m, 2 H), 7.82ꢀ7.80 (m, 2 H), 7.75ꢀ7.73 (m, 2 H), 7.44ꢀ7.37 (m, 4 H), 7.32ꢀ
7.30 (m, 1 H) 7.21ꢀ7.13 (m, 8 H), 6.93 (s, 1 H); 13C NMR (100 MHz, CDCl3): δ = 154.5, 153.3, 151.1,
148.5, 141.6, 141.4, 138.4, 130.5, 130.4, 130.3, 130.1, 129.5, 129.3, 129.2, 128.9, 128.7, 128.4, 128.1,
128.0, 127.9, 126.2, 124.1, 122.4, 109.3 ppm; IR (KBr): ṽ = 1622, 1553, 1489, 1109 cmꢀ1; HRMS (ESI):
calculated for C30H20ON2Na [M+Na]+: 447.1468, found 447.1465.
2ꢀ(2ꢀ(4ꢀMethoxyphenyl)ꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ3ꢀphenylquinoxaline (4l). 103.5 mg, 76% yield, yellow oil;
1H NMR (400 MHz, CDCl3): δ = 8.20ꢀ8.15 (m, 2 H), 7.82ꢀ7.78 (m, 2 H), 7.72ꢀ7.70 (m, 2 H), 7.42ꢀ7.39
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(m, 4 H), 7.32ꢀ7.27 (m, 1 H) 7.24ꢀ7.14 (m, 5 H), 6.88 (s, 1 H), 6.71ꢀ6.68 (m, 2 H), 3.78 (s, 3 H); C
NMR (100 MHz, CDCl3): δ = 159.7, 154.6, 152.8, 151.4, 148.7, 141.6, 141.4, 138.5, 130.5, 130.2,
130.1, 129.5, 129.3, 129.2, 128.9, 128.8, 128.0, 127.8, 127.7, 124.0, 123.5, 121.1, 113.9, 109.2, 55.5
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ppm; IR (KBr): ṽ = 1599, 1504, 1254, 1173, 1024 cmꢀ1; HRMS (ESI): calculated for C31H22O2N2Na
[M+Na]+: 477.1573, found 477.1573.
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2ꢀ(2ꢀ(4ꢀChlorophenyl)ꢀ5ꢀphenylfuranꢀ3ꢀyl)ꢀ3ꢀphenylquinoxaline (4m). 92.1 mg, 67% yield, brown oil;
1H NMR (400 MHz, CDCl3): δ = 8.21ꢀ8.15 (m, 2 H), 7.83ꢀ7.81 (m, 2 H), 7.73ꢀ7.71 (m, 2 H), 7.44ꢀ7.39
(m, 4 H), 7.33ꢀ7.12 (m, 8 H), 6.90 (s, 1 H); 13C NMR (100 MHz, CDCl3): δ = 154.3, 153.6, 149.9,
148.1, 141.7, 141.4, 138.3, 134.0, 130.5, 130.3, 130.2, 129.6, 129.3, 129.2, 128.9, 128.6, 128.1, 127.4,
124.2, 122.9, 109.5 ppm; IR (KBr): ṽ = 1622, 1485, 1402, 1254, 1088 cmꢀ1; HRMS (ESI): calculated for
C30H19ON2ClNa [M+Na]+: 481.1078, found 481.1071.
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ASSOCIATED CONTENT
Supporting Information
1
Copies of H and 13C NMR spectra of all new compounds (PDF) and Xꢀray crystallographic data of
compound 4f (cif).
The Supporting Information is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: chemtao@snnu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support by the National Natural Science Foundation of China (21502110, 21542002), the 111
Project (B14041) and the Fundamental Research Funds for the Central Universities (GK201703022) are
greatly appreciated.
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