Stereoselective synthesis of: E -3-(arylmethylidene)-5-(alkyl/aryl)-2(3 H)-furanones by sequential hydroacyloxylation-Mizoroki-Heck reactions of iodoalkynes

Article abstract of DOI:10.1039/c8ob02063a

A modular, stereoselective synthesis of E-3-(arylidene)-5-(alkyl/aryl)-2(3H)-furanones was developed. The methodology features regioselective addition of β-aryl acrylic acids to iodoacetylenes to furnish the Z-acyloxy iodoalkenes. A stereoselective 5-exo-trig Mizoroki-Heck reaction of the acyloxy iodoalkenes generates the target E-2(3H)-furanones. The approach was applied in a formal synthesis of the naturally occurring kinase inhibitor BE-23372M.

Full text of DOI:10.1039/c8ob02063a

Organic &
Biomolecular Chemistry
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PAPER
Stereoselective synthesis of E-3-(arylmethylidene)-
-(alkyl/aryl)-2(3H)-furanones by sequential
hydroacyloxylation-Mizoroki–Heck reactions of
iodoalkynes†
5
Cite this: Org. Biomol. Chem., 2018,
6, 7971
1
Gopinathan Muthusamy and Sunil V. Pansare
*
A modular, stereoselective synthesis of E-3-(arylidene)-5-(alkyl/aryl)-2(3H)-furanones was developed.
The methodology features regioselective addition of β-aryl acrylic acids to iodoacetylenes to furnish the
Z-acyloxy iodoalkenes. A stereoselective 5-exo-trig Mizoroki–Heck reaction of the acyloxy iodoalkenes
generates the target E-2(3H)-furanones. The approach was applied in a formal synthesis of the naturally
occurring kinase inhibitor BE-23372M.
Received 22nd August 2018,
Accepted 10th October 2018
DOI: 10.1039/c8ob02063a
rsc.li/obc
esting biological profile which includes antitubercular (inhi-
Introduction
7
bition of Mycobacterium sulfotransferase), antimalarial
8
9
The 3-(arylidene/alkylidene)-5-(aryl/alkyl) 2(3H)-furanone motif (selective inhibition of falcipain-2), analgesic and anti-
1
0
is encountered in several natural products and biologically inflammatory
activity. In addition, 2(3H)-furanones are
1
relevant molecules. Representative examples of such fura- useful starting materials for the synthesis of a variety of oxa-
2
11
12
nones are the protein kinase inhibitor BE-23372M (1, Fig. 1)
isolated from Rhizoctonia strain F23372, furanone 2 (Z isomer
cycles and azacycles.
Given their natural occurrence and biological activity, the
3
4
of 1) and ralfuranone I (3). The related 3-alkylidene 2(3H)-fura- synthesis of 3-(arylidene/alkylidene)-5-(aryl/alkyl) furanones is
none motif (unsubstituted at C5) also occurs as a component of interest, but only a handful of methods are currently avail-
5
of terpenoid natural products such as peronemin D
1
(4) and able. A summary of these strategies is provided in Fig. 2. The
6
guttoside (5). Other E-3-(arylidene/alkylidene)-5-(aryl/alkyl) classical approach involves use of γ-keto acids and aryl alde-
furanones have attracted significant interest due to their inter- hydes under Perkin-Erlenmeyer conditions. However, this
1
method is not suitable for aliphatic aldehydes and it occasion-
Fig. 1 Naturally occurring 3-(arylidene/alkylidene)-5-(aryl/alkyl)-2(3H)-
furanones.
Department of Chemistry, Memorial University, St. John’s, Newfoundland, Canada
A1B 3X7. E-mail: spansare@mun.ca
1
13
†
Electronic supplementary information (ESI) available: H and C NMR spectra
Fig. 2 Strategies for the synthesis of (E)-3-arylidene-5-(aryl/alkyl)-2
(3H)-furnaones.
for compounds 7h, 7i, 8 and 10. See DOI: 10.1039/c8ob02063a
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previous studies on related reactions have employed Au(I)-
1
9
based catalytic systems, the combination of reactants that we
wanted to examine (cinnamic acids and aryl- or alkyl-substi-
tuted iodoacetylenes), and the scope of this reaction, has not
been studied previously. Nonetheless, we first investigated a
Fig. 3 Two-step synthesis of 2(3H)-furanones from iodoacetylenes and combination of AuCl(PPh
6
) and AgPF in toluene, conditions
3
cinnamic acids.
that are reported to efficiently catalyze the addition of aliphatic
carboxylic acids to iodoalkynes.
19e
Although these conditions
worked when 6a and 7a were used, the yield of 8aa was dis-
appointing (38%, entry 1, Table 1). Significant amounts of
unreacted 7a and the iodomethyl ketone 9, derived from the
iodoacetylene 7a, were also obtained in this reaction. Since 9
could have been formed by the hydrolysis of 8aa due to adven-
titious moisture in the solvent (toluene), we examined anhy-
drous toluene as the solvent. Surprisingly, this decreased the
yield of 8aa (Table 1, entry 2, 24%) but the amount of 9 was
only marginally affected. Since a competing (with hydroacyloxy-
lation) deacylation of 8aa by unreacted 6a could provide 9 and
the anhydride of 6a, the effect of using an excess (1.5 eq.) of
iodoacetylene 7a was also examined. However, the yield of 8aa
1
ally leads to a mixture of stereoisomeric furanones. Current
1
3
strategies involve the use of α-arylidene alkynoic acids,
1
4
15
allenyl ketones or Baylis–Hillman adducts as the starting
materials with additional carbons being introduced as aryl
aldehydes. The reaction of terminal alkynes with an acyl chlor-
ide and carbon monoxide under high temperature and
1
6
pressure, or an aryl halide and carbon monoxide, either
1
7a
under high temperature and pressure
or ambient condi-
2(3H)-furanones.
Adaptations of these strategies have provided E-3-alkylidene-
1
7b
tions,
also
provides
substituted
1
3,14
17
18
5
-alkyl,
E-3-alkylidene-5-aryl, E-3-arylidene-5-alkyl, and
1
5–17
(
6
70%) and 9 (12%) was not affected. Notably, the anhydride of
E-3-arylidene-5-aryl
2(3H)-furanones. Nonetheless, oppor-
1
a was not observed in this reaction ( H NMR of crude
tunities exist for the development of mild and stereoselective
protocols for the synthesis of such furanones. Herein, we
describe preliminary results on a modular synthesis of 3-aryli-
dene-5-(alkyl/aryl)-2(3H)-furanones via a two-step protocol that
involves iodoacetylenes and cinnamic acids as the starting
materials (Fig. 2).
2
3
product) and also in the other optimization reactions.
Clearly, a survey of additives and solvents for the reaction of 6a
and 7a was necessary and, accordingly, a combination of AuCl
(
PPh ) and selected silver salts was examined in toluene as the
3
6
solvent. Unfortunately, the use of AgOTf or AgSbF as the co-
catalysts did not improve the yield of 8aa even after extended
reaction times (entries 3 and 4, Table 1). These observations
prompted a survey of solvents for the reaction with the AuCl
Our strategy for the synthesis of 3-arylidene-5-(alkyl/aryl)-2
3H)-furanones relies on the intramolecular E-selective
Mizoroki–Heck reaction of iodoenoyl acrylates which, in turn,
can be obtained by the Z-selective addition of cinnamic acids
to iodoacetylenes (Fig. 3).
(
(
3 6
PPh )/AgPF catalyst system. The reaction failed when DMF or
acetonitrile was used (entries 5 and 6, Table 1) as the solvent
and ethereal solvents significantly slowed the reaction to
provide 8aa in very low yield (6% and 8%, entries 7 and 8,
Table 1). Notably, significant decomposition of 7a was also
observed in these reactions (only 17% and 21% recovery of 7a).
Although a similar trend was also observed in dichloro-
methane (entries 9 and 10, Table 1), the use of chloroform as
the solvent was beneficial (8aa (70%) and 9 (10%) entry 11,
Table 1). As with toluene, the use anhydrous chloroform was
not beneficial (68% yield of 8aa). We also ascertained that the
A brief analysis of the individual stereoselective steps pro-
posed in our retrosynthetic analysis is instructive. It may be
noted that extensive studies on the regioselective addition of
1
9a–d
carboxylic acids to haloacetylenes are available,
but a
Z-selective version of this reaction employing either aliphatic
or substituted benzoic acids as the nucleophiles was reported
1
9e
only recently.
Very limited information is available on the
addition of α,β-unsaturated acids to acetylenes and only a sole
example, the addition of cinnamic acid to 1-iodoct-1-yne, is
1
9e
reaction required both AuCl(PPh
4, Table 1) and that it was not catalyzed by protic acids in the
absence of AuCl(PPh )/AgPF (entries 15 and 16, Table 1).
3 6
) and AgPF (entries 13 and
reported.
Also, even though intramolecular Mizoroki–Heck
2
0
1
reactions of aryl halides are well known, the corresponding
version involving vinyl halides is less common. In addition,
3
6
2
1
Thus, the optimum conditions for preparing 8aa involve
the use of AuCl(PPh )/AgPF in CHCl at ambient temperature
entry 11, Table 1). These conditions also provided 8ba (83%,
the stereochemical outcome (formation of E or Z products)
2
2
and the regiochemistry (5-exo-trig vs. 6-endo-trig) of the pro-
posed intramolecular Mizoroki–Heck reaction can vary as a
function of the substrate structure and the reaction
conditions.
3
6
3
(
entry 17, Table 1) from the reaction of 6b and 7a. The stereo-
chemistry of 8aa and 8ba was confirmed by NOESY (inter-
action of the iodomethylidene hydrogen and the ortho hydro-
gens of the adjacent phenyl ring).
Having established the optimum conditions for the
addition of 6 to 7, we examined the conversion of 8 to the
Results and discussion
Our studies began with an investigation of the Au(I)-catalyzed target 2(3H) furanones 10. The feasibility of the intramolecular
addition of 4-methoxy cinnamic acid (6a) to (iodoethynyl) Mizoroki–Heck reaction of 8 was examined with pure 8ba
benzene (7a) to provide the iodoenol cinnamate 8aa. Although (Table 2). Since our objective was to develop an operationally
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Table 1 Optimization of the hydroacyloxylation of 7a
a
a
a
Entry
Acid
Solvent
Additive
Time (h)
8
(%)
Unreacted 7a (%)
9
(%)
1
2
3
4
5
6
7
8
9
6a
Toluene
Dry toluene
Toluene
Toluene
DMF
AgPF
AgPF
AgOTf
AgSbF
6
76
76
62
62
75
75
120
144
1
38
24
29
25
—
—
6
18
29
24
25
—
—
44
60
37
50
—
—
94
92
90
93
—
20
17
28
21
—
—
4
7
11
9
10
8
—
—
—
—
7
6
6
AgPF
AgPF
AgPF
AgPF
AgPF
AgPF
AgPF
AgPF
AgPF
—
6
6
6
6
6
6
6
6
6
Dry CH
Dioxane
Dry THF
3
CN
8
Dry CH
Dry CH
2
Cl
Cl
2
2
16
12
70
68
—
—
—
—
83
b
10
11
12
13
14
15
16
17
2
4
CHCl
Dry CHCl
3
23
23
72
70
75
75
37
3
c
CHCl
CHCl
CHCl
CHCl
CHCl
3
3
3
3
3
d
d
CF
CH
AgPF
3
CO
2
H
3
H
3
SO
6b
6
a
b
c
d
Isolated yield. Reaction at 0 °C. Reaction without AuCl(PPh)
3
.
reaction without AuCl(PPh
3
) and Ag salt.
Table 2 5-exo-trig cyclization of 8ba to 10ba
none product that would arise from the alternative 6-endo-trig
cyclization of 8ba was observed. Encouraged by the successful
conversion of 8ba to 10ba, we further simplified the synthesis
of 10ba by developing a protocol which avoided the chromato-
graphic purification of 8ba. Thus, after the completion of the
Au-catalyzed addition of 6b to 7a (TLC analysis), the reaction
mixture was directly filtered through a plug of silica gel, the fil-
trate was concentrated and the residue (mixture of the hydro-
acyloxylation product and some iodomethyl ketone) was used
for the subsequent Heck reaction. Pleasingly, this modified
procedure provided 10ba in 72% yield, which is comparable to
the yield of 10ba obtained from chromatographed 8ba (75%
over two steps). In subsequent studies on the scope of the
hydroacyloxylation reaction, all of the products 8 were isolated
and characterized. However, the simplified protocol for the
synthesis of 10 using crude 8 also proved to be successful for a
a
Solvent
CHCl
Toluene
2
Toluene/H O (3/1)
Toluene/DMF (1/1)
DMF
Temp. (°C)
Time (h)
Yield 10ba (%)
1
2
3
4
5
3
61
5
5
2
3
1
10
—
—
—
91
100
100
100
80
a
2
10 mol% of Pd(OAc) .
simple, and preferably a one-pot, procedure we initially chose variety of β-aryl acrylic acids (6a–d) and aryl (7a–c) or alkyl sub-
to examine the reaction of 8ba in the presence of Pd(OAc) and stituted 1-iodo-1-alkynes (7d–g). Thus, the 2(3H) furanones 10
KOAc in CHCl or toluene, since these solvents were suitable were obtained (43–72% over 2 steps, Fig. 4) by successive
2
3
for the synthesis of 8ba. However, the reaction of 8ba in CHCl3 hydroacyloxylation, Mizoroki–Heck reactions without isolation
provided 10ba in very low yield (10%) and the reaction failed and purification of the intermediate iodoenol β-aryl acrylates
when toluene, toluene/H O or toluene/DMF were used as the 8. In all cases, only the 2(3H) furanone product 10 was
2
solvents. However, when the reaction was conducted in DMF obtained and the isomeric pyranone was not detected. The
as the solvent, 10ba was obtained in excellent yield (91%, Mizoroki–Heck reactions for the aryl acetylene-derived sub-
Table 2).
strates were conducted at 80 °C, but the reactions for the alkyl
Notably, only the E-isomer of 10ba was obtained and its acetylene-derived substrates were conducted at lower tempera-
spectroscopic data was in agreement with that reported in the ture (40 °C) to prevent decomposition of the iodoenol acrylate
1
7
literature. The E-stereochemistry of the exocyclic double intermediate. The methodology works for several combi-
bond in 10ba was also confirmed by NOESY (interaction of the nations of the carboxylic acids 6 and the acetylenes 7 (Fig. 2).
C4 (ring) methine and the ortho hydrogens of both the phenyl All of the furanones 10 were assigned the E stereochemistry by
groups in 10ba). The formation of 10ba can be explained by a analogy to 10ba and the stereochemistry of 10ad was also con-
5
-exo-trig cyclization of 8ba. Notably, none of the isomeric pyra- firmed by NOESY.
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Scheme 1 Formal synthesis of BE-23372M (1).
carcinoma and MKN-7 human stomach cancer cell lines.
Reaction of the acid 6f and the iodoacetylene 7h according to
our protocol provided the iodoenol cinnamate 8fh.
Intramolecular Heck reaction of 8fh at ambient temperature
provided the tetraacetoxy 2(3H) furanone derivative 10fh which
2
5
can be deacetylated to provide 1.
Conclusions
In conclusion, a short synthesis of E-3-(arylidene)-5-(alkyl/
aryl)-2(3H)-furanones was developed from readily available
β-aryl acrylic acids and iodoacetylenes as the starting
materials. The modular, two step methodology has the poten-
tial to be modified to a one-pot protocol, making it particularly
attractive for the rapid synthesis of structurally diverse fura-
nones for further applications.
Fig. 4 Synthesis of 2(3H)-furanones from β-aryl acrylic acids and
iodoalkynes.
For reasons that are not well understood, the use of electron
rich reaction partners has limitations. For example the hydro-
acyloxylation reaction of 3,4-dimethoxy cinnamic acid (6e) with
7
a did not provide any of the expected product, and the reac-
Experimental
General
tion of 3,4-dimethoxyphenyl iodoacetylene (7g) with 6b pro-
vided only a trace of the hydroacyloxylation product (<10%).
Similarly 6e and 7g did not react with each other under the All commercially available reagents were used without purifi-
optimized reaction conditions. β-Alkyl acrylic acids were not cation. All reactions requiring anhydrous conditions were per-
examined in this study. The potential for further simplification formed under an atmosphere of dry nitrogen using oven dried
2
4
of our methodology to a one-pot protocol, by avoiding the glassware. Commercial pre-coated silica gel plates were used
silica plug filtration of the iodoenol acrylate, was also investi- for TLC. Silica gel for flash column chromatography was
gated. Thus, for the reactions of 6b with 7a and 7d, concen- 230–400 mesh. All melting points are uncorrected. IR spectra
tration of the reaction mixture (after the Au-catalyzed reaction) were recorded on a Bruker TENSOR 27 FT-IR instrument.
1
13
and replacement of the solvent (CHCl ) with DMF for the sub-
H NMR and C NMR spectra were recorded on a Bruker
sequent Mizoroki–Heck reaction provided 10ba (61%) and AVANCE III 300 or an AVANCE 500 instrument. Coupling con-
0bd (64%). Notably, the yield of 10bd obtained by the one-pot stants (J) are reported in Hz. Mass spectra were obtained on an
modification is higher than obtained previously (57%, Fig. 4). Agilent 6200 LC/MSD (TOF) chromatographic system.
Marginally higher loading of Pd(OAc) (15% compared to 10%
The carboxylic acids 6a–e are commercially available and 6f
for the protocol in Fig. 4) is required for the one-pot version of was prepared by acetylation of commercially available caffeic
3
1
2
2
6
the synthesis of 10.
acid. Spectroscopic data for 6f is in agreement with reported
The furanone synthesis methodology was applied in a data. Iodoacetylenes 7a, 7c, 7d, 7e, 7f, 7g and 7b
formal synthesis of BE-23372M (1, Scheme 1), a potent tyro- were prepared from the corresponding terminal acetylenes by
sine kinase inhibitor, which inhibits A431 human epidermoid deprotonation and iodination following the reported pro-
2
6
27
27
27
27
27
28
2
5
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2
7,28
cedures.
Spectroscopic data for 7a–f is in agreement with The reaction flask was wrapped with aluminium foil and the
2
7,28
reported data.
mixture was stirred at room temperature for 20 h. The mixture
was concentrated under reduced pressure and the residue
4
-(Iodoethynyl)-1,2-dimethoxybenzene (7g)
was purified by flash column chromatography on silica gel
(886 mg, (hexanes/EtOAc, 7 : 3) to provide 223 mg (43%) of 7h as a
2
9
Reaction of 4-ethynyl-1,2-dimethoxybenzene
5
.46 mmol) in THF (10 mL) and n-BuLi (1.07 M solution in clear oil.
hexanes, 6.63 mL, 7.10 mmol) at −78 °C followed by reaction = 0.28 (hexanes/EtOAc, 7 : 3); IR (neat): 2923, 2852, 1766,
with iodine (1.45 g, 5.73 mmol) in THF (5 mL) for 2 h by 1498, 1369, 1261, 1199, 1176, 1108, 1011, 895, 835, 649 cm
R
f
−
1
;
2
7
1
adaptation of a reported procedure provided 1.33 g (85%)
3
H NMR (300 MHz, CDCl ): δ 7.31 (dd, 1H, J = 8.4, 1.8, ArH),
of 7g as a yellow solid. This was used in the next step without 7.26 (d, 1H, J = 1.8, ArH), 7.13 (d, 1H, J = 8.4, ArH), 2.28 (s, 6H,
1
3
purification.
= 0.21 (hexanes/EtOAc, 8 : 2); mp: 120–122 °C; IR (neat): 142.9 (ArCipso), 141.9 (ArCipso), 130.8 (ArC), 127.5 (ArC), 123.6
994, 2957, 2929, 2856, 2831, 1597, 1578, 1507, 1236, 1133, (ArC), 122.1 (ArCipso), 92.5 (CuCI), 20.76 (CH ), 20.70 (CH ),
021, 843, 801, 764 cm ; H NMR (300 MHz, CDCl ): δ 7.03 8.0 (CuC–I); HRMS (ESI, pos.): 343.9553 (343.9546 calc. for
2 × OCOCH3); C NMR (75 MHz, CDCl ): δ 168.0 (2 × CvO),
3
R
f
2
1
3
3
−
1 1
3
+
(
(
dd, 1H, J = 8.3, 1.9, ArH), 6.92 (d, 1H, J = 1.9, ArH), 6.77
C
12
H
9
IO
4
4
, (M )) and 344.9627 (344.9624 calc. for C12H10IO ,
+
d, 1H, J = 8.3, ArH), 3.87 (s, 3H, OCH ), 3.85 (s, 3H, OCH ); (M + H) ).
3
3
1
3
C NMR (75 MHz, CDCl ): δ 150.0 (ArCipso), 148.5 (ArCipso),
3
General procedure for the synthesis of (Z)-β-iodoenol
1
25.8 (ArC), 115.6 (ArCipso), 114.9 (ArC), 110.8 (ArC), 94.2
cinnamates (8)
3
(Ar–CuC), 55.9 (2 × OCH ), 4.1 (CuC–I); HRMS (APPI, pos.):
+
m/z 287.9644 (287.9647 calc. for C H IO , (M )) and 288.9715 To a solution of the cinnamic acid (1 equiv.) and the iodo-
1
0
9
2
+
(288.9725 calc. for C10
H10IO
2
, (M + H) ).
alkyne (1 equiv.) in CHCl
and AgPF (5 or 10 mol%) at room temperature. The reaction
flask was wrapped with aluminium foil and the reaction
3 3
were added AuCl(PPh ) (5 or 10 mol%)
6
4
-(Iodoethynyl)-1,2-phenylene diacetate (7h)
3
0
4
4
-Bromo-1,2-phenylene diacetate was first converted into mixture was stirred at room temperature until consumption of
-((trimethylsilyl)ethynyl)-1,2-phenylene diacetate by an adap- the iodoalkyne (TLC). The mixture was then concentrated
tation of the literature procedure. To a solution of 4-bromo- under reduced pressure and the residue was purified by flash
,2-phenylene diacetate (700 mg, 2.56 mmol) in Et N (8 mL) column chromatography on silica gel. In some cases, traces
3
1
1
3
were added ethynyltrimethylsilane (0.54 mL, 3.85 mmol), of the iodomethyl ketone byproduct co-eluted with 8. This
Pd(PPh ) (59 mg, 0.050 mmol), CuI (20 mg, 0.10 mmol) and impurity was easily removed by dissolving the mixture in a
3
4
the mixture was heated to reflux for 2 h. The mixture was then minimum volume of pentane, cooling the solution to −78 °C
cooled to room temperature and concentrated under reduced and decanting the supernatant to provide pure 8 as a residual
pressure. The residue was dissolved in EtOAc (10 mL) and the semisolid or oil.
solution was filtered through a pad of Celite®. Water (5 mL)
was added to the filtrate and the mixture was extracted with
EtOAc (3 × 7 mL). The combined extracts were washed with
(
E)-((Z)-2-Iodo-1-phenylvinyl) 3-(4-methoxyphenyl)acrylate
(
8aa)
2 4
brine (1 × 10 mL), dried over Na SO and concentrated under The reaction of (E)-3-(4-methoxyphenyl)acrylic acid (6a)
reduced pressure. The residue was purified by flash column (53 mg, 0.30 mmol), iodoalkyne 7a (68 mg, 0.30 mmol),
chromatography on silica gel (hexanes/EtOAc, 8 : 2) to provide AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
3
6
7
03 mg (95%) of 4-((trimethylsilyl)ethynyl)-1,2-phenylene 0.015 mmol) in CHCl
3
(1.5 mL) for 23 h according to the General
diacetate as a white solid.
Procedure provided, after purification by flash chromatography
Rf = 0.22 (hexanes/EtOAc, 8 : 2); mp: 61–63 °C; IR (neat): on silica gel (hexanes/EtOAc, 9 : 1), 85 mg (70%) of 8aa as a pale
959, 2900, 2160, 1762, 1496, 1372, 1252, 1205, 1173, 1139, yellow solid and 7 mg (10%) of 9 as a colourless gum.
2
1
−
1 1
107, 1013, 962, 894, 838 cm ; H NMR (300 MHz, CDCl
3
):
f
R = 0.20 (hexanes/EtOAc, 9 : 1); mp: 101–103 °C; IR (neat):
δ 7.33 (dd, 1H, J = 8.3, 1.9, ArH), 7.29 (d, 1H, J = 1.9, ArH), 7.12 3080, 2918, 2849, 2837, 1721, 1625, 1598, 1571, 1508, 1492,
1
(
d, 1H, J = 8.3, ArH), 2.28 (s, 6H, 2 × OCOCH
3
), 0.23 (s, 9H, 1249, 1169, 1102, 1016, 982, 825, 744, 521 cm−1
; H NMR
1
3
Si(CH
3
)
3
); C NMR (75 MHz, CDCl
3
): δ 168.09 (CvO), 168.08 (500 MHz, CDCl ): δ 7.87 (d, 1H, J = 15.9, Ar–CHvCH), 7.56
3
(
CvO), 142.5 (ArCipso), 141.9 (ArCipso), 130.4 (ArC), 127.1 (ArC), (d, 2H, J = 8.7, ArH), 7.50–7.45 (m, 2H, ArH), 7.38–7.31 (m, 3H,
1
2
23.5 (ArC), 122.0 (ArCipso), 103.4 (Ar–CuC), 95.4 (CuC–Si), ArH), 6.94 (d, 2H, J = 8.7, ArH), 6.68 (s, 1H, CHIvC), 6.53
1
3
3 3 3 3 3
0.8 (OCOCH ), 20.7 (OCOCH ), 0.0 (Si(CH ) ); HRMS (APPI, (d, 1H, J = 15.9, Ar–CHvCH), 3.86 (s, 3H, OCH ); C NMR
+
pos.): m/z 290.0979 (290.0974 calc. for C H O Si, (M )) and (75 MHz, CDCl ): δ 163.6 (C–O), 161.9 (ArCipso), 155.1 (CvO),
2
1
5
18
4
3
+
91.1052 (291.1053 (calc. for C15
H
19
O
4
Si, (M + H) ).
147.2 (Ar–CvC), 133.8 (ArCipso), 130.2 (2 × ArC), 129.3 (ArC),
Conversion of the above TMS derivative into 7h was achieved 128.7 (2 × ArC), 126.8 (ArCipso), 125.2 (2 × ArC), 114.5 (2 × ArC),
3
2
by adaptation of a literature procedure. To a solution of 113.8 (Ar–CvC), 68.1 (OCH ), 55.4 (C–I); HRMS (APPI, pos.):
3
+
4
1
-((trimethylsilyl)ethynyl)-1,2-phenylene diacetate (440 mg, m/z 406.0066 (406.0066 calc. for C18
.51 mmol) in acetone (10 mL) were added N-iodosuccinimide (407.0144 (calc. for C18 16IO , (M + H) ). Spectroscopic data
850 mg, 3.78 mmol) and silver nitrate (103 mg, 0.604 mmol). for 9 is in agreement with the reported data.
H
15IO
+
3
, (M) ), 407.0133
H
3
3
3
(
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Organic & Biomolecular Chemistry
(E)-(Z)-2-Iodo-1-(naphthalen-2-yl)vinyl-3-(4-methoxyphenyl)
R
f
= 0.22 (hexanes/EtOAc, 93 : 7); mp: 102–104 °C; IR (neat):
acrylate (8ac)
3106, 3085, 3051, 3000, 1731, 1633, 1309, 1261, 1186, 1126,
1
015, 984, 861, 763, 733, 680, 488 cm− ; H NMR (300 MHz,
CDCl ): δ 7.92 (d, 1H, J = 16.0, ArCHvCH), 7.64–7.56 (m, 2H,
ArH), 7.50–7.39 (m, 5H, ArH), 7.37–7.31 (m, 3H, ArH), 6.69
1 1
The reaction of (E)-3-(4-methoxyphenyl)acrylic acid (6a)
3
(
(
0
54 mg, 0.30 mmol), iodoalkyne 7c (83 mg, 0.30 mmol), AuCl
PPh (7.40 mg, 0.015 mmol) and AgPF (3.80 mg,
.015 mmol) in CHCl (1.5 mL) for 15 h according to the
3
)
6
1
3
(
(
(
(
(
s, 1H, ArCvCHI), 6.66 (d, 1H, J = 16.0, Ar–CHvCH); C NMR
3
75 MHz, CDCl ): δ 163.4 (CvC–I), 155.1 (CvO), 147.6
Ar–CvC), 134.0 (ArCipso), 133.8 (ArCipso), 131.0 (ArC), 129.4
ArC), 129.1 (2 × ArC), 128.8 (2 × ArC), 128.5 (2 × ArC), 125.3
2 × ArC), 116.5 (Ar–CvC), 68.3 (CvC–I); HRMS (APPI, pos.):
m/z 375.9970 (375.9960 calc. for C H IO , (M) ) and 394.0309
3
General Procedure provided, after purification by flash chrom-
atography on silica gel (hexanes/EtOAc, 9 : 1), 85 mg (62%) of
8
ac as a semisolid.
Rf = 0.23 (hexanes/EtOAc, 95 : 5); IR (neat): 2920, 2840, 1733,
709, 1629, 1597, 1570, 1244, 1217, 1167, 1106, 1028, 823, 756,
+
1
7
13
2
1
5
+
47, 475 cm−
1
1
(394.0304 calc. for C17
H17INO
2
, (M + NH
4
) ).
;
H NMR (300 MHz, CDCl ): δ 7.92 (d, 1H,
3
J = 15.9, Ar–CHvCH), 7.90 (d, 1H, J = 1.4, ArH), 7.85–7.77
(
Z)-1-(4-Bromophenyl)-2-iodovinyl cinnamate (8bb)
The reaction of 6b (44 mg, 0.30 mmol), 7b (92 mg,
.30 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF
6
(
(
m, 3H, ArH), 7.58 (apparent d, 3H, J = 8.8, ArH), 7.52–7.42
m, 2H, ArH), 6.95 (d, 2H, J = 8.8, ArH), 6.83 (s, 1H, CvCHI),
0
3
6
.59 (d, 1H, J = 15.9, Ar–CHvCH), 3.86 (s, 3H, OCH3);
C NMR (75 MHz, CDCl ): δ 163.8 (C–O), 162.1 (ArCipso), 155.2
3
1
3
(3.8 mg, 0.015 mmol) in CHCl (1.5 mL) for 64 h according to
the General Procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 98 : 2), 86 mg
3
(CvO), 147.5 (Ar–CvC), 133.6 (ArCipso), 133.2 (ArCipso), 131.2
(ArCipso), 130.4 (2 × ArC), 128.7 (2 × ArC), 127.8 (ArC), 127.0
(ArCipso), 126.9 (ArC), 126.8 (ArC), 124.7 (ArC), 122.8 (ArC),
(
63%) of 8bb as a semisolid.
= 0.26 (hexanes/EtOAc, 98 : 2); IR (neat): 3082, 2923, 2853,
R
f
1
14.6 (2 × ArC), 114.0 (Ar–CvC), 68.9 (CvCI), 55.6 (OCH3);
−
1
1
733, 1677, 1634, 1584, 1485, 1123, 1005, 764, 485 cm ;
HRMS (APPI, pos.): m/z 456.0210 (456.0222 calc. for C H IO ,
2
2
17
3
1
+
+
H NMR (300 MHz, CDCl ): δ 7.92 (d, 1H, J = 16.0,
3
(
M ) and 457.0282 (457.0301 calc. for C22
3
H18IO , (M + H) ).
Ar–CHvCH), 7.65–7.57 (m, 2H, ArH), 7.51–7.40 (m, 5H, ArH),
7
1
1
1
1
.33 (d, 2H, J = 8.7, ArH), 6.72 (s, 1H, CvCHI), 6.65 (d, 1H, J =
(
E)-(Z)-1-Hexyl-2-iodovinyl 3-(4-methoxyphenyl)acrylate (8ad)
1
3
6.0, Ar–CHvCH); C NMR (75 MHz, CDCl ): δ 163.4 (C–O),
3
The reaction of (E)-3-(4-methoxyphenyl)acrylic acid (6a)
89 mg, 0.50 mmol), iodoalkyne (7d) (118 mg, 0.50 mmol),
AuCl(PPh ) (12.4 mg, 0.025 mmol) and AgPF (6.30 mg,
.025 mmol) in CHCl3 (2 mL) for 18 h according to the
54.2 (CvO), 148.0 (Ar–CvC), 134.0 (ArCipso). 132.9 (ArCipso),
32.1 (2 × ArC), 131.2 (ArC), 129.2 (2 × ArC), 128.6 (2 × ArC),
26.9 (2 × ArC), 123.7 (ArC), 116.4 (Ar–CvC), 69.2 (CvCHI);
(
3
6
0
2
HRMS (APPI, pos.): m/z 453.9040 (453.9065 calc. for C17H12BrIO ,
General Procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 93 : 7), 147 mg
+
+
(
M ) and 454.9109 (454.9144 calc. for C17
2
H13BrIO , (M + H) ).
(71%) of 8ad as a clear oil.
(Z)-2-Iodo-1-(naphthalen-2-yl)vinyl cinnamate (8bc)
Rf = 0.22 (hexanes/EtOAc, 93 : 7); IR (neat): 2953, 2927, 2856,
The reaction of 6b (44 mg, 0.30 mmol), 7c (83 mg, 0.30 mmol),
1
5
722, 1629, 1510, 1251, 1170, 1123, 1110, 1029, 980, 825,
AuCl(PPh ) (7.40 mg, 0.015 mmol) and AgPF (3.80 mg,
3
6
19 cm− ; H NMR (300 MHz, CDCl ): δ 7.78 (d, 1H, J = 16.0,
1
1
3
0
.015 mmol) in CHCl
3
(1.5 mL) for 67 h according to
ArCHvCH), 7.53 (d, 2H, J = 8.7, ArH), 6.93 (d, 2H, J = 8.7, ArH),
.40 (d, 1H, J = 16.0, ArCHvCH), 5.86 (t, 1H, J = 1.1, CvCHI),
the General Procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 95 : 5), 83 mg
6
3
1
.86 (s, 3H, OCH ), 2.43 (td, 2H, J = 7.6, 1.1, IHCvCCH CH ),
3
2
2
(
65%) of 8bc as a semisolid.
= 0.23 (hexanes/EtOAc, 98 : 2); IR (neat): 3082, 3058, 2923,
.54–1.44 (m, 2H, IHCvCCH
2
CH
CH
CDCl ): δ 163.7 (CvC–I), 161.8 (ArCipso), 158.1 (CvO), 146.6
2
), 1.38–1.23 (m, 6H,
R
f
1
3
(
CH
2
)
3
CH
3
), 0.91–0.83 (m, 3H, (CH
2
)
3
3
); C NMR (75 MHz,
−1
1
2
853, 1732, 1633, 1188, 1122, 980, 760, 475 cm
): δ 7.97 (d, 1H, J = 16, Ar–CHvCH), 7.90
d, 1H, J = 1.8, ArH), 7.86–7.77 (m, 3H, ArH), 7.68–7.61 (m, 2H,
; H NMR
3
(
(
300 MHz, CDCl
3
(
1
3
Ar–CvC), 130.1 (2 × ArC), 126.9 (ArCipso), 114.4 (2 × ArC),
14.2 (Ar–CvC), 64.9 (OCH
3 2
), 55.4 (CvC–I), 34.6 (CvC–CH ),
ArH), 7.59 (dd, 1H, J = 8.7, 1.9, ArH), 7.54–7.40 (m, 5H, ArH),
1.5 (CH ), 28.6 (CH ), 26.4 (CH ), 22.5 (CH ), 14.0 (CH );
13
2
2
2
2
3
6
.85 (s, 1H, H CvCHI), 6.73 (d, 1H, Ar–CHvCH); C NMR
HRMS (APPI, pos.): m/z 414.0699 (414.0692 calc. for
(
75 MHz, CDCl ): δ 163.4 (C–O), 155.0 (CvO), 147.6 (Ar–CvC),
3
+
(
(
C
18
H
23IO
+
3 3
, (M) ) and 415.0775 (415.0770 calc. for C18H24IO ,
1
1
34.1 (2 × ArCipso), 133.5 (ArCipso), 133.1 (ArCipso), 131.0 (ArC),
29.1 (2 × ArC), 128.7 (ArC), 128.6 (ArC), 128.5 (2 × ArC), 127.7
M + H) ).
(
(
ArC), 126.9 (ArC), 126.7 (ArC), 124.6 (ArC), 122.7 (ArC), 116.5
(
Z)-2-Iodo-1-phenylvinyl cinnamate (8ba)
Ar–CvC), 68.8 (CvCHI); HRMS (APPI, pos.): m/z 426.0112
+
The reaction of (E)-cinnamic acid (6b) (44 mg, 0.30 mmol), (426.0117 calc. for C21
iodoalkyne 7a (68 mg, 0.30 mmol), AuCl(PPh ) (14.8 mg, calc. for C21
.030 mmol) and AgPF6 (7.6 mg, 0.030 mmol) in CHCl3
1.5 mL) for 45 h according to the General Procedure provided,
after purification by flash chromatography on silica gel The reaction of (E)-cinnamic acid (6b) (74 mg, 0.50 mmol),
H
15IO
2
, (M ) and 427.0184 (427.0195
+
3
2
H16IO , (M + H) ).
0
(
(
Z)-1-Iodooct-1-en-2-yl cinnamate (8bd)
(hexanes/EtOAc, 95 : 5), 94 mg (83%) of 8ba as a white solid.
iodoalkyne 7d (118 mg, 0.500 mmol), AuCl(PPh ) (12.4 mg,
3
7976 | Org. Biomol. Chem., 2018, 16, 7971–7983
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0
.025 mmol) and AgPF
6
(6.30 mg, 0.025 mmol) in CHCl
3
2
HRMS (APPI, pos.): m/z 339.9970 (339.9960 calc. for C14H13IO ,
+
+
(2.5 mL) for 18 h according to the General Procedure provided, (M ) and 341.0042 (341.0038 calc. for C H IO , (M + H) ).
1
4
14
2
after purification by flash chromatography on silica gel
(
E)-(Z)-2-Iodo-1-phenylvinyl 3-(p-tolyl)acrylate (8ca)
(
hexanes/EtOAc, 95 : 5), 178 mg (93%) of 8bd as a clear oil.
Rf = 0.27 (hexanes/EtOAc, 95 : 5); IR (neat): 3082, 3028, 2953, The reaction of 6c (49 mg, 0.30 mmol), 7a (68 mg, 0.30 mmol),
927, 2856, 1729, 1632, 1328, 1308, 1194, 1129, 979, 763, AuCl(PPh ) (14.8 mg, 0.30 mmol) and AgPF (7.6 mg,
): δ 7.83 (d, 1H, J = 16.0, 0.030 mmol) in CHCl (1.5 mL) for 47 h according to
2
5
3
6
01 cm− ; H NMR (300 MHz, CDCl
1
1
3
3
Ar–CHvCH), 7.63–7.51 (m, 2H, ArH), 7.46–7.35 (m, 3H, ArH), the General Procedure provided, after purification by flash
.54 (d, 1H, J = 16.0, Ar–CHvCH), 5.87 (br t, 1H, J = 1.2, chromatography on silica gel (hexanes/EtOAc, 98 : 2), 77 mg
CvCHI), 2.44 (td, 2H, J = 7.6, 1.2, CH –CvCHI), 1.60–1.44 (66%) of 8ca as a semisolid.
Rf = 0.26 (hexanes/EtOAc, 98 : 2); IR (neat): 2955, 2923, 2854,
): δ 163.5 1734, 1633, 1607, 1267, 1224, 1199, 1177, 1124, 812, 752, 725,
6
2
(
0
m, 2H, IHCvCCH CH ), 1.40–1.20 (m, 6H, (CH ) CH ,
2
2
1
2 3
3
3
3 3
.95–0.80 (m, 3H, CH ); C NMR (75 MHz, CDCl
C–O), 158.2 (CvO), 147.0 (Ar–CvC), 134.2 (ArCipso), 130.9 495 cm− ; H NMR (300 MHz, CDCl
1
1
( ): δ 7.89 (d, 1H, J = 16.0,
(ArC), 129.1 (2 × ArC), 128.5 (2 × ArC), 117.0 (Ar–CvC), 65.2 Ar–CHvCH), 7.54–7.43 (m, 4H, ArH), 7.40–7.30 (m, 3H, ArH),
(CvCI), 34.7 (CH ), 31.6 (CH ), 28.7 (CH ), 26.5 (CH ), 22.6 7.23 (d, 2H, J = 7.9, ArH), 6.69 (s, 1H, CvCHI), 6.62 (d, 1H,
3
(CH ), 14.2 (CH ); HRMS (APPI, pos.): m/z 384.0596 (384.0586 J = 16.0, Ar–CHvCH), 2.40 (s, 3H, CH ); C NMR (75 MHz,
3
2
2
2
2
1
3
2
3
+
calc. for C H IO , (M) ) and 385.0668 (385.0664 calc. for CDCl ): δ 163.6 (C–O), 155.2 (CvO), 147.7 (Ar–CHvCH), 141.6
C
1
7
21
2
+
3
17
H
22IO
2
, (M + H) ).
(ArCipso), 133.9 (ArCipso), 131.5 (ArCipso), 129.9 (2 × ArC), 129.5
(
(
ArC), 128.9 (2 × ArC), 128.6 (2 × ArC), 125.4 (2 × ArC), 115.5
(
Z)-1-Cyclohexyl-2-iodovinyl cinnamate (8be)
Ar–CHvCH), 68.3 (CvCHI), 21.7 (CH ); HRMS (APPI, pos.):
3
+
The reaction of 6b (45 mg, 0.30 mmol), 7e (70 mg, 0.30 mmol), m/z 390.0121 (390.0117 calc. for C18
H
15IO
2
, (M ) and 391.0193
+
AuCl(PPh
.015 mmol) in CHCl3 (1.5 mL) for 47 h according to
the General Procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 98 : 2), 69 mg The reaction of 6c (49 mg, 0.30 mmol), 7d (71 mg, 0.30 mmol),
3 6 2
) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg, (391.0195 calc. for C18H16IO , (M + H) ).
0
(
E)-(Z)-1-Iodooct-1-en-2-yl 3-(p-tolyl)acrylate (8cd)
(60%) of 8be as a clear oil.
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
3
6
R
f
= 0.24 (hexanes/EtOAc, 98 : 2); IR (neat): 2925, 2852, 1728, 0.015 mmol) in CHCl
3
(1.5 mL) for 27 h according to
1
4
632, 1448, 1306, 1190, 1120, 1006, 978, 761, 702, 680, the General Procedure provided, after purification by flash
84 cm− ; H NMR (300 MHz, CDCl ): δ 7.83 (d, 1H, J = 16.0, chromatography on silica gel (hexanes/EtOAc, 95 : 5), 74 mg
1
1
3
Ar–CHvCH), 7.62–7.53 (m, 2H, ArH), 7.45–7.38 (m, 3H, ArH), (62%) of 8cd as a clear oil.
.55 (d, 1H, J = 16.0, Ar–CHvCH), 5.92 (d, 1H, J = 1.1, = 0.22 (hexanes/EtOAc, 97 : 3); IR (neat): 2954, 2927, 2857,
6
R
f
−
1
CvCHI), 2.43–2.27 (m, 1H, CHCH ), 2.00–1.85 (m, 2H, CH ), 1729, 1632, 1608, 1195, 1179, 1131, 982, 812, 498 cm
1
;
2
2
13
1
.84–1.73 (m, 2H, CH
2
), 1.37–1.13 (m, 6H, CH
2
); C NMR
3
H NMR (500 MHz, CDCl ): δ 7.80 (d, 1H, J = 16.0,
(
75 MHz, CDCl
3
): δ 163.4 (C–O), 162.0 (CvO), 146.9 (Ar–CvC), Ar–CHvCH), 7.47 (d, 2H, J = 7.9, ArH), 7.22 (d, 2H, J = 7.9,
34.2 (ArCipso), 130.8 (ArC), 129.1 (2 × ArC), 128.4 (2 × ArC), ArH), 6.49 (d, 1H, J = 16.0, Ar–CHvCH), 5.86 (s, 1H, CvCHI),
17.1 (Ar–CvC), 65.2 (CvCHI), 43.8 (CH), 30.7 (2 × CH ), 2.43 (t, 2H, J = 7.5, CH C–O), 2.39 (s, 3H, Ar–CH ), 1.51 (quint,
6.05 (CH ), 26.01 (2 × CH ); HRMS (APPI, pos.): m/z 382.0413 2H, J = 7.5, CH CH CH C–O), 1.37–1.23 (m, 6H, (CH CH ),
1
1
2
2
2
3
2
2
2
2
2
2
)
3
3
+
13
(
382.0430 calc. for C H IO , (M ) and 383.0486 (383.0508 0.88 (t, 3H, J = 6.7, CH CH ); C NMR (75 MHz, CDCl3):
17 19 2 2 3
+
calc. for C17
H
20IO
2
, (M + H) ).
δ 163.6 (C–O), 158.1 (CvO), 146.9 (Ar–CvC), 141.3 (ArCipso),
31.4 (ArCipso), 129.7 (2 × ArC), 128.4 (2 × ArC), 115.7
1
(
Z)-1-Cyclopropyl-2-iodovinyl cinnamate (8bf)
The reaction of 6b (45 mg, 0.30 mmol), 7f (58 mg, 0.30 mmol), 26.4 (CH
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg, (APPI, pos.): m/z 398.0741 (398.0743 calc. for C18
.015 mmol) in CHCl3 (1.5 mL) for 24 h according to the and 399.0813 (399.0821 calc. for C H IO , (M + H) ).
(
Ar–CvC), 65.0 (CvCHI), 34.6 (CH ), 31.5 (CH ), 28.6 (CH ),
2
2
2
2
), 22.5 (CH
2
), 21.5 (Ar–CH
3
), 14.1 (CH
2
CH
3
); HRMS
+
3
6
H
23IO
2
, (M )
+
0
18
24
2
General Procedure provided, after purification by flash chrom-
atography on silica gel (hexanes/EtOAc, 98 : 2), 64 mg (63%) of
(
E)-(Z)-1-Cyclopropyl-2-iodovinyl 3-(p-tolyl)acrylate (8cf)
The reaction of 6c (49 mg, 0.30 mmol), 7f (58 mg, 0.30 mmol),
= 0.22 (hexanes/EtOAc, 98 : 2); IR (neat): 3083, 3008, 2921, AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
729, 1632, 1190, 1124, 1048, 762 cm ; H NMR (300 MHz, 0.015 mmol) in CHCl (1.5 mL) for 24 h according to the
8
bf as a clear oil.
R
f
3
6
−
1 1
1
3
CDCl ): δ 7.83 (d, 1H, J = 16.0, Ar–CHvCH), 7.62–7.52 (m, 2H, General Procedure provided, after purification by flash
3
ArH), 7.46–7.36 (m, 3H, ArH), 6.53 (d, 1H,
J = 16.0, chromatography on silica gel (hexanes/EtOAc, 95 : 5), 72 mg
Ar–CHvCH), 5.94 (d, 1H, J = 0.7, CvCHI), 1.85–1.73 (m, 1H, (68%) of 8cf as a clear oil.
1
3
CH(CH ) ), 0.83–0.68 (m, 4H, CH(CH ) ); C NMR (75 MHz,
Rf = 0.20 (hexanes/EtOAc, 98 : 2); IR (neat): 3083, 3011, 2919,
2
2
2 2
CDCl
3
): δ 163.4 (C–O), 158.2 (CvO), 147.2 (Ar–CvC), 134.2 2854, 1725, 1692, 1629, 1607, 1191, 1177, 1111, 1045, 809, 750,
ArCipso), 130.9 (ArC), 129.1 (2 × ArC), 128.5 (2 × ArC), 116.8 495 cm− ; H NMR (300 MHz, CDCl
1 1
(
(
3
): δ 7.80 (d, 1H, J = 16.0,
Ar–CvC), 63.9 (CvCHI), 15.1 (CH(CH ) ), 5.8 (CH(CH ) ); Ar–CHvCH), 7.47 (d, 2H, J = 8.1, ArH), 7.21 (d, 2H, J = 8.1,
2
2
2 2
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ArH), 6.48 (d, 1H, J = 16.0, Ar–CHvCH), 5.93 (d, 1H, J = 0.7,
R
f
= 0.26 (hexanes/EtOAc, 98 : 2); IR (neat): 2953, 2926, 2856,
CvCHI), 2.39 (s, 3H, CH ), 1.85–1.73 (m, 1H, CH(CH ) ), 1724, 1620, 1199, 1182, 1122, 1044, 968, 856, 828, 704,
3
2 2
1
3
−1 1
0
2 2 3 3
.82–0.68 (m, 4H, (CH ) ); C NMR (75 MHz, CDCl ): δ 163.6 489 cm ; H NMR (300 MHz, CDCl ): δ 7.92 (dt, 1H, J = 15.7,
(
(
(
(
C–O), 158.3 (CvO), 147.2 (Ar–CvC), 141.5 (ArCipso), 131.5 0.8, Ar–CHvCH), 7.43 (dt, 1H, 5.1, 0.8, ArH), 7.31 (br m, 1H,
ArCipso), 129.9 (2 × ArC), 128.5 (2 × ArC), 115.7 (Ar–CvC), 63.8 ArH), 7.08 (dd, 1H, J = 5.1, 3.6, ArH), 6.32 (d, 1H, J = 15.7,
CvCHI), 21.7 (CH
APPI, pos.): m/z 354.0120 (354.0117 calc. for C15
3 2 2 2
), 15.2 (CH(CH ) ), 5.7 (2 × CH ); HRMS Ar–CHvCH), 5.86 (t, 1H, J = 1.1, CvCHI), 2.46–2.38 (m, 2H,
+
H
15IO
2
, (M ) CH
2 2 2
–CvCHI), 1.56–1.43 (m, 2H, CH CH CvCHI), 1.39–1.21
+
13
and 355.0193 (355.0195 calc. for C H IO , (M + H) ).
(m, 6H, (CH ) CH ), 0.92–0.83 (m, 3H, CH );
C NMR
): δ 163.3 (C–O), 158.1 (CvO), 139.4 (ArCipso),
39.3 (Ar–CvC), 131.8 (ArC), 129.4 (ArC), 128.4 (ArC), 115.6
The reaction of 6d (77 mg. 0.50 mmol), 7a (114 mg, (Ar–CvC), 65.2 (CvCI), 34.7 (CH ), 31.6 (CH ), 28.7 (CH ),
1
5
16
2
2 3
3
3
(
1
75 MHz, CDCl
3
(
E)-(Z)-2-Iodo-1-phenylvinyl 3-(thiophen-2-yl)acrylate (8da)
2
2
2
0
(
.500 mmol), AuCl(PPh
6.3 mg, 0.025 mmol) in CHCl
the General Procedure provided, after purification by flash (391.0229 calc. for C H IO S, (M + H) ).
3
) (12.4 mg, 0.025 mmol) and AgPF
6
2 2 3
26.5 (CH ), 22.6 (CH ), 14.2 (CH ); HRMS (APPI, pos.): m/z
+
3
(2.5 mL) for 50 h according to 390.0141 (390.0150 calc. for C15
2
H19IO S, (M ) and 391.0214
+
1
5
20
2
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 138 mg
4
3
-((E)-3-(((Z)-1-(3,4-Diacetoxyphenyl)-2-iodovinyl)oxy)-
-oxoprop-1-en-1-yl)-1,2-phenylene diacetate (8fh)
(72%) of 8da as a semisolid.
Rf = 0.28 (hexanes/EtOAc, 95 : 5); IR (neat): 3082, 2922, 2853,
1
9
1
7
725, 1673, 1619, 1266, 1218, 1199, 1174, 1115, 1040, 1019, The reaction of cinnamic acid 6f (198 mg, 0.750 mmol),
69, 748, 485 cm−1; 1H NMR (300 MHz, CDCl
): δ 8.00 (br dt, iodoalkyne 7h (258 mg, 0.750 mmol), AuCl(PPh ) (56 mg,
H, J = 15.6, 0.7, Ar–CHvCH), 7.51–7.41 (m, 3H, ArH), 0.15 mmol) and AgPF (28 mg, 0.15 mmol) in CHCl (5 mL)
3
3
6
3
.39–7.30 (m, 4H, ArH), 7.09 (dd, 1H, J = 5.1, 3.7, ArH), 6.68 for 69 h according to the General Procedure provided, after
13
2 2
(s, 1H, CvCHI), 6.45 (d, 1H, J = 15.6, Ar–CHvCH); C NMR purification by flash chromatography on silica gel (CH Cl /
(
75 MHz, CDCl ): δ 163.3 (C–O), 155.1 (CvO), 139.9 (Ar–CvC), MeOH, 99.8 : 0.2), 246 mg (54%) of 8fh as a clear oil.
3
1
39.3 (ArCipso), 133.8 (ArCipso), 132.1 (ArC), 129.6 (ArC), 129.5
f
R = 0.26 (hexanes/EtOAc, 6 : 4); IR (neat): 3084, 2925, 2853,
(
(
(
ArC), 128.9 (2 × ArC), 128.4 (ArC), 125.3 (2 × ArC), 115.2 1769, 1735, 1637, 1503, 1370, 1201, 1186, 1111, 1041, 902,
Ar–CvC), 68.4 (CvCHI); HRMS (APPI, pos.): m/z 381.9506 516 cm− ; H NMR (300 MHz, CDCl ): δ 7.84 (d, 1H, J = 16.0,
1 1
3
+
381.9524 calc. for C15
H
11IO
2
S, (M ) and 382.9578 (382.9603 Ar–CHvCH), 7.52–7.42 (m, 2H, ArH), 7.34 (dd, 1H, J = 8.5, 2.2,
+
calc. for C15
H
12IO S, (M + H) ).
2
ArH), 7.30–7.26 (m, 2H, ArH), 7.19 (d, 1H, J = 8.5, ArH), 6.72
s, 1H, CHI), 6.58 (d, 1H, J = 16.0, Ar–CHvCH) 2.32 (s, 3H,
C(O)CH ), 2.31 (s, 3H, C(O)CH ), 2.28 (s, 6H, 2 × C(O)CH );
C NMR (75 MHz, CDCl ): δ 168.0 (C(O)CH ), 167.91
(
(
(
E)-(Z)-1-(4-Bromophenyl)-2-iodovinyl-3-(thiophen-2-yl)acrylate
8db)
3
3
3
13
3
3
The reaction of 6d (46 mg, 0.30 mmol), 7b (92 mg, (C(O)CH3), 167.87 (C(O)CH3), 167.85 (C(O)CH3), 162.6
.30 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (CvC–O), 153.4 (CH–CvO), 145.7 (Ar–CHvCH), 144.1
3.8 mg, 0.015 mmol) in CHCl (1.5 mL) for 66 h according to (ArCipso), 142.9 (ArCipso), 142.6 (ArCipso), 142.2 (ArCipso), 132.7
0
3
6
(
3
the General Procedure provided, after purification by flash (ArCipso), 132.4 (ArCipso), 126.9 (ArC), 124.1 (ArC), 123.8 (ArC),
chromatography on silica gel (hexanes/EtOAc, 97 : 3), 106 mg 123.4 (ArC), 123.1 (ArC), 120.5 (ArC), 117.5 (Ar–CHvCH), 69.6
(
77%) of 8db as a semisolid.
3 3
(C–I), 20.7 (2 × C(O)CH ), 20.6 (2 × C(O)CH ); HRMS (APPI,
−
R = 0.20 (hexanes/EtOAc, 98 : 2); IR (neat): 3082, 1728, 1620, neg.): m/z 608.0199 (608.0179 calc. for C H IO , (M) ) and
f
25 21 10
−
1
1
−
1
218, 1200, 1174, 1119, 1006, 831, 709, 468 cm
;
H NMR 607.0128 (607.0101 calc. for C25
H
20IO10, (M − H) ).
(
7
300 MHz, CDCl
.51–7.44 (m, 3H, ArH), 7.38–7.29 (m, 3H, ArH), 7.10 (dd, 1H,
3
): δ 8.00 (d, 1H, J = 15.7, Ar–CHvCH),
General procedure for the synthesis of furanones from
cinnamic acids and iodoalkynes
J = 5.1, 3.7, ArH), 6.71 (s, 1H, CvCHI), 6.43 (d, 1H, J = 15.7,
Ar–CHvCH); C NMR (75 MHz, CDCl
1
3
3
): δ 163.2 (C–O), 154.2 To a solution of the cinnamic acid (1 equiv.) and the iodoalk-
(
(
CvO), 140.2 (Ar–CvC), 139.2 (ArCipso), 132.9 (ArC), 132.3 yne (1 equiv.) in CHCl were added AuCl(PPh ) (5 or 10 mol%)
3 3
6
ArC), 132.1 (2 × ArC), 129.8 (ArC), 128.5 (ArC), 126.8 (2 × ArC), and AgPF (5 or 10 mol%) at room temperature. The reaction
1
23.7 (ArCipso), 114.9 (Ar–CvC), 69.2 (CvCHI); HRMS (APPI, flask was wrapped with aluminium foil and the reaction
+
pos.): m/z 459.8622 (459.8630 calc. for C H BrIO S, (M ) and mixture was stirred at room temperature until consumption of
4
1
5
10
2
+
60.8685 (460.8708 calc. for C15
H
11BrIO
2
S, (M + H) ).
the iodoalkyne (TLC). The mixture was directly applied to a
short column of flash silica (5 cm height in a standard Pasteur
pipette, approximately 600 mg of flash silica) packed in
(
E)-(Z)-1-Iodooct-1-en-2-yl-3-(thiophen-2-yl)acrylate (8dd)
The reaction of 6d (46 mg, 0.30 mmol), 7d (71 mg, CH
.300 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF and the combined eluates were concentrated under reduced
3.80 mg, 0.015 mmol) in CHCl (1.5 mL) for 50 h according to pressure to provide the crude (Z)-β-iodoenol cinnamate.
2
2 2 2
Cl . The column was then washed with CH Cl (5 × 1 mL)
0
(
3
6
3
the General Procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 95 : 5), 83 mg Pd(OAc)
To a solution of the (Z)-β-iodoenol cinnamate (1 equiv.) and
(10 mol%) in DMF (purged with N for 15 min) was
2
2
(71%) of 8dd as a clear oil.
added KOAc (2.5 equiv.) at room temperature. The mixture was
7978 | Org. Biomol. Chem., 2018, 16, 7971–7983
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Paper
stirred at 40 °C or at 80 °C until consumption of the iodoenol 55.5 (OCH
3
); HRMS (APPI, pos.): 328.1098 (328.1099 calc. for
+
cinnamate (TLC). The reaction mixture was then cooled to C H O , (M) ) and 329.1169 (329.1178 calc. for C H O
2
2
16
3
+
22 17
3
2
ambient temperature, H O (1 mL) was added and the mixture (M + H) ).
was extracted with EtOAc (3 × 2 mL). The combined extracts
were dried over Na SO and concentrated under reduced
(E)-5-Hexyl-3-(4-methoxybenzylidene)furan-2(3H)-one (10ad)
2
4
pressure. The residue was purified by flash column chromato- The reaction of 6a (89 mg, 0.50 mmol), 7d (118 mg,
graphy on silica gel. 0.50 mmol), AuCl(PPh ) (12.4 mg, 0.025 mmol) and AgPF
6.3 mg, 0.025 mmol) in CHCl (2 mL) for 18 h according to
3
6
(
3
(E)-3-(4-Methoxybenzylidene)-5-phenylfuran-2(3H)-one (10aa)
the General Procedure provided 208 mg of the crude iodoenol
The reaction of 6a (54 mg, 0.30 mmol), 7a (68 mg, 0.30 mmol), cinnamate. Reaction of the crude iodoenol cinnamate
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg, (208 mg, 0.50 mmol), KOAc (123 mg, 1.25 mmol) and Pd(OAc)2
3
6
0
.015 mmol) in CHCl
3
(1.5 mL) for 15 h according to the (11.2 mg. 0.05 mmol) in DMF at 40 °C for 54 h according to
general procedure provided 138 mg of the crude iodoenol cin- the General Procedure provided, after purification by flash
namate. Reaction of the crude iodoenol cinnamate (122 mg, chromatography on silica gel (hexanes/EtOAc, 9 : 1), 79 mg
0
.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
2
(6.70 mg. (55%) of 10ad as a clear oil.
= 0.21 (hexanes/EtOAc, 9 : 1); IR (neat): 2954, 2928, 2856,
0
.03 mmol) in DMF at 80 °C for 5 h according to the General
R
f
−
1
Procedure provided, after purification by flash chromatography 1763, 1628, 1593, 1511, 1304, 1252, 1165, 1028, 924, 827 cm
on silica gel (hexanes/EtOAc, 8 : 2), 49 mg (59%) of 10aa as a
;
1
3
H NMR (300 MHz, CDCl ): δ 7.52 (d, 2H, J = 8.7, ArH), 7.25
yellow solid.
(s, 1H, ArCHvC), 6.94 (d, 2H, J = 8.7, ArH), 6.24 (br q, 1H, J =
Rf = 0.29 (hexanes/EtOAc, 8 : 2); mp: 170–172 °C; IR (neat): 0.9, CHvC–CH ), 3.86 (s, 3H, OCH ), 2.47 (t, 2H, J = 7.1,
2
3
2
7
927, 2836, 1753, 1600, 1582, 1509, 1247, 1163, 1027, 999, 829, CH
2
CvCH), 1.65 (quint, 2H,
J
=
2 2
7.1, CH CH CvCH),
41 cm−
1
1
3 3 2 3
; H NMR (300 MHz, CDCl ): δ 7.79–7.72 (m, 2H, 1.45–1.23 (m, 6H, CH (CH ) ), 0.90 (br t, J = 6.7, 3H,
1
3
ArH), 7.61 (d, 2H, J = 8.7, ArH), 7.48–7.37 (m, 4H, ArH and CH (CH ) ; C NMR (75 MHz, CDCl ): δ 170.4 (CvO), 161.2
3
2 3
3
Ar–CHvC), 6.99 (d, 2H, J = 8.7, ArH), 6.92 (br d, 1H, J = 1.2, (CvC–O or ArCipso) 161.1 (ArCipso or CvC–O), 133.9 (Ar–
1
3
3 3
CHvC–O), 3.88 (s, 3H, OCH ); C NMR (75 MHz, CDCl ): CHvC), 131.8 (2 × ArC), 127.9 (C–CvO), 122.9 (ArCipso), 114.5
δ 169.9 (CvO), 161.5 (ArCipso), 156.0 (CHvC–O), 135.5 (2 × ArC), 100.9 (CHvC–O), 55.4 (OCH ), 31.5 (CHvC–CH ),
3
2
(
(
1
Ar–CHvC), 132.1 (2 × ArC), 130.2 (ArC), 128.9 (2 × ArC), 128.3 28.9 (CH
2
), 28.8 (CH
2
), 26.0 (CH
2
), 22.5 (CH
2
), 14.1 (CH
3
);
22 3
ArCipso or C–CvO), 128.0 (C–CvO or ArCipso), 125.2 (2 × ArC), HRMS (APPI, pos.): m/z 286.1569 (286.1569 calc. for C18H O ,
+
+
23.0 (ArCipso), 114.7 (2 × ArC), 99.9 (Ph–CvCH), 55.5 (OCH3); (M )) and 287.1642 (287.1647 calc. for C H O , (M + H) ).
18 23 3
HRMS (APPI, pos.): m/z 278.0947 (278.0943 calc. for C18
H
14
O
3
,
1
7a
+
+
(E)-3-Benzylidene-5-phenylfuran-2(3H)-one (10ba)
The reaction of 6b (30 mg, 0.20 mmol), 7a (46 mg, 0.20 mmol),
AuCl(PPh (10 mg, 0.020 mmol) and AgPF (5.0 mg,
.020 mmol) in CHCl (1 mL) for 43 h according to the General
(M) ) and 279.1018 (279.1021 calc. for C18
H
15
O
3
, (M + H) ).
(
E)-3-(4-Methoxybenzylidene)-5-(naphthalen-2-yl)furan-2(3H)-
3
)
6
1
0
one (10ac)
0
3
The reaction of 6a (54 mg. 0.30 mmol), 7c (83 mg, 0.30 mmol), Procedure provided 75 mg of the crude iodoenol cinnamate.
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg, Reaction of the crude iodoenol cinnamate (75 mg, 0.20 mmol),
.015 mmol) in CHCl (1.5 mL) for 15 h according to the KOAc (49 mg, 0.50 mmol) and Pd(OAc) (4.5 mg, 0.02 mmol) in
3
6
0
3
2
General Procedure provided 138 mg of the crude iodoenol cin- DMF at 80 °C for 1 h according to general procedure provided,
namate. Reaction of the crude iodoenol cinnamate (138 mg, after purification by flash chromatography on silica gel
0
.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
2
(6.7 mg. (hexanes/EtOAc, 9 : 1), 36 mg (72%) of 10ba as a yellow solid.
Rf = 0.21 (hexanes/EtOAc, 95 : 5); mp: 153–155 °C; IR (neat):
0
.030 mmol) in DMF at 80 °C for 1 h according to the General
Procedure provided, after purification by flash chromatography 3120, 3025, 2999, 1754, 1625, 1450, 1278, 1003, 756, 733,
on silica gel (hexanes/EtOAc, 9 : 1), 51 mg (52%) of 10ac as a 682 cm−1
1
3
; H NMR (300 MHz, CDCl ): δ 7.79–7.71 (m, 2H,
yellow solid.
= 0.29 (hexanes/EtOAc, 9 : 1); mp: 121–122 °C (Lit.
ArH), 7.65–7.59 (m, 2H, ArH), 7.50–7.37 (m, 7H, 6 × ArH and
Ph-CHvC), 6.92 (d, 1H, J = 1.1, Ph-CHvC); C NMR (75 MHz,
1
0
13
R
f
1
1
23–124 °C); IR (neat): 2954, 2912, 2833, 1755, 1592, 1567, CDCl
3
): δ 169.4 (CvO), 157.0 (C–O), 135.5 (Ph–CHvC), 135.2
H NMR (300 MHz, (ArCipso), 130.6 (ArC), 130.3 (ArC), 130.1 (2 × ArC), 129.2
): δ 8.26 (br s, 1H, ArH), 7.94–7.81 (m, 3H, ArH), 7.77 (2 × ArC), 128.9 (2 × ArC), 128.1 (C–CvO), 125.5 (ArCipso),
dd, 1H, J = 8.7, 1.7, ArH), 7.64 (d, 2H, J = 8.7, ArH), 7.58–7.48 125.4 (2 × ArC), 99.9 (CHvC–O); HRMS (APPI, pos.): m/z
−
1 1
510, 1246, 1169, 1012, 814, 746 cm
;
CDCl
(
3
+
(m, 2H, ArH), 7.43 (s, 1H, CHvC–O), 7.03 (s, 1H, Ph–CHvC), 248.0849 (248.0837 calc. for C H O , (M) ) and 249.0921
17 12 2
1
3
+
7
.00 (d, 2H, J = 8.7, ArH), 3.89 (s, 3H, OCH
): δ 169.9 (CvO), 161.5 (ArCipso), 156.0
CHvC–O), 135.5 (Ar–CHvC), 134.0 (ArCipso), 133.2 (ArCipso),
32.2 (2 × ArC), 128.8 (ArC), 128.7 (ArC), 128.1 (ArC), 127.8 The reaction of 6b (44 mg. 0.30 mmol), 7b (92 mg,
ArC), 127.4 (ArC), 127.0 (ArCipso), 125.4 (C–CvO), 125.3 (ArC), 0.30 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF
23.0 (ArCipso), 121.9 (ArC), 114.8 (2 × ArC), 100.5 (CHvC–O), (3.8 mg, 0.015 mmol) in CHCl (1.5 mL) for 64 h according to
3 13 2
); C NMR (249.0916 calc. for C17H O , (M + H) ).
(75 MHz, CDCl
3
1
7b
(E)-3-Benzylidene-5-(4-bromophenyl)furan-2(3H)-one (10bb)
(
1
(
1
3
6
3
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Paper
Organic & Biomolecular Chemistry
the General Procedure provided 137 mg of the crude iodoenol by flash chromatography on silica gel (hexanes/EtOAc, 95 : 5),
cinnamate. Reaction of the crude iodoenol cinnamate 73 mg (57%) of 10bd as a yellow oil.
(
(
137 mg, 0.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
6.7 mg. 0.030 mmol) in DMF at 80 °C for 45 min according to 1770, 1629, 1451, 1173, 1156, 1028, 961, 762, 689 cm
2
f
R = 0.27 (hexanes/EtOAc, 95 : 5); IR (neat): 2954, 2928, 2857,
−
1
;
1
the general procedure provided, after purification by flash
H NMR (300 MHz, CDCl ): δ 7.58–7.52 (m, 2H, ArH),
3
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 51 mg 7.47–7.34 (m, 3H, ArH), 7.30 (br s, 1H, ArCH), 6.26 (br q, 1H,
(
52%) of 10bb as a yellow solid.
Rf = 0.27 (hexanes/EtOAc, 9 : 1); mp: 208–210 °C; IR (neat): (quint, 2H,
128, 3026, 2921, 1752, 1619, 1585, 1449, 1278, 1170, 1067, CH (CH CH
C NMR (75 MHz, CDCl
J = 1.1, CH
2
CvCH), 2.48 (br t 2H, J = 7.5, CH
2
CvCH), 1.65
J
=
7.5, CH CH C–O), 1.45–1.23 (m, 6H,
2
2
3
9
3
2
)
3
2
), 0.94–0.84 (br t, 3H, J = 6.8, CH
3 2 3 2
(CH ) CH );
91, 823, 801, 755, 730, 675, 540 cm−1
;
1
H NMR (300 MHz,
13
): δ 169.9 (CvO), 162.3 (C–O),
3
CDCl ): δ 7.66–7.55 (m, 6H, ArH and Ar–CHvC), 7.52–7.40 (m, 135.2 (ArCipso), 133.9 (Ar–CHvC), 129.9 (3 × ArC), 129.0
3
1
3
4
H, ArH), 6.94 (d, 1H, J = 1.0, CHvC–O); C NMR (75 MHz, (2
CDCl ): δ 169.0 (CvO), 156.0 (C–O), 136.2 (Ar–CHvC), 135.1 (CHvC–CH
ArCipso), 132.2 (2 × ArC), 130.5 (C–CvO), 130.2 (2 × ArC), 14.0 (CH ); HRMS (APPI, pos.): m/z 256.1461 (256.1463
×
ArC), 125.4 (C–CvO), 101.1 (CHvC–CH
2
), 31.5
3
2
), 28.9 (CH ), 28.8 (CH ), 25.9 (CH ), 22.5 (CH
2
2
2
2
),
(
3
+
1
1
3
20 2
29.2 (2 × ArC), 127.0 (ArCipso), 126.7 (2 × ArC), 125.2 (ArCipso), calc. for C17H O , (M) ) and 274.1812 (274.1807 calc. for
+
24.9 (ArCipso), 100.4 (CHvC–O); HRMS (APPI, pos.): m/z
17 2 4
C H24NO , (M + NH ) ).
7
9
+
25.9932 (325.9942 calc. for C H
BrO , (M) ) and 327.0014
1
7
11
2
7
9
+
(E)-3-Benzylidene-5-cyclohexylfuran-2(3H)-one (10be)
(
(
327.0021 calc. for
328.9999 calc. for C17
C
17
8
H
12 BrO
11 BrO
2
,
(M
+
H) ), 328.9996
1
+
H
2
, (M + H) ).
The reaction of 6b (45 mg. 0.30 mmol), 7e (70 mg, 0.30 mmol),
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
3
6
0
.015 mmol) in CHCl
3
(1.5 mL) for 47 h according to the
(
E)-3-Benzylidene-5-(naphthalen-2-yl)furan-2(3H)-one
1
0,17a
General Procedure provided 115 mg of the crude iodoenol cin-
namate. Reaction of the crude iodoenol cinnamate (115 mg,
(10bc)
The reaction of 6b (44 mg. 0.30 mmol), 7c (83 mg, 0.30 mmol),
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
.015 mmol) in CHCl3 (1.5 mL) for 67 h according to the
0.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
2
(6.7 mg.
3
6
0.030 mmol) in DMF at 40 °C for 118 h according to
0
the general procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 39 mg
General Procedure provided 128 mg of the crude iodoenol
cinnamate. Reaction of the crude iodoenol cinnamate (128 mg,
0
0
procedure provided, after purification by flash chromatography
on silica gel (hexanes/EtOAc, 9 : 1), 45 mg (51%) of 10bc as a
yellow solid.
(
51%) of 10be as a clear oil.
.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc) (6.7 mg.
2
R = 0.26 (hexanes/EtOAc, 9 : 1); IR (neat): 3051, 2923, 2851,
f
.030 mmol) in DMF at 80 °C for 1 h according to the general
762, 1621, 1447, 1157, 1126, 990, 929, 760 cm−
1
;
1
H NMR
): δ 7.58–7.52 (m, 2H, ArH), 7.46–7.34 (m, 3H,
ArH), 7.31 (br s, 1H, Ph-CHvC), 6.21 (t, 1H, J = 1.1,
CHvC–O), 2.51–2.37 (m, 1H, (CH CHC–O), 2.06–1.96 (m, 2H,
CH ), 1.87–1.68 (m, 3H, CH ), 1.46–1.18 (m, 5H, CH );
C NMR (75 MHz, CDCl ): δ 170.0 (CvO), 166.2 (C–O), 135.2
1
(
300 MHz, CDCl
3
(
2
1
0
f
R = 0.29 (hexanes/EtOAc, 9 : 1); mp: 173–174 °C (Lit. mp:
2
2
2
1
1
1
72–173 °C); IR (neat): 3057, 3025, 1758, 1623, 1302, 1261,
1
3
015, 803, 759 cm− ; H NMR (300 MHz, CDCl ): δ 8.27 (br s,
1
1
3
3
(
1
(
ArCipso), 134.0 (Ar–CHvC), 129.9 (3 × ArC), 129.0 (2 × ArC),
25.4 (C–CvO), 96.8 (CHvC–O), 37.6 (CH –CH), 29.7
2 × CH ), 25.9 (CH ), 25.6 (2 × CH ); HRMS (APPI, pos.): m/z
H, ArH), 7.95–7.81 (m, 3H, ArH and Ph–CHvC), 7.77 (dd, 1H,
2
J = 8.6, 1.6, ArH), 7.70–7.62 (m, 2H, ArH), 7.58–7.39 (m, 6H,
ArH), 7.04 (s, 1H, CHvC–O); C NMR (75 MHz, CDCl3):
δ 169.4 (CvO), 157.0 (C–O), 135.5 (Ph–CHvC), HHH135.3
1
3
2
2
2
+
2
54.1311 (254.1307 calc. for C17
18 2
H O , (M) ) and 255.1383
, (M + H) ).
+
(
255.1385 calc. for C17
H
19
O
2
(naphthylCipso), 134.2 (ArCipso or C–CvO), 133.1 (C–CvO or
ArCipso), 130.3 (ArC), 130.2 (2 × ArC), 129.2 (2 × ArC), 128.9
(E)-3-Benzylidene-5-cyclopropylfuran-2(3H)-one (10bf)
(
(
ArC), 128.8 (ArC), 127.9 (ArC), 127.6 (ArC), 127.0 (ArC), 125.7
ArC), 125.5 (ArC), 125.2 (ArC), 122.0 (ArC), 100.5 (CvC–O);
The reaction of 6b (45 mg, 0.30 mmol), 7f (58 mg, 0.30 mmol),
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
3
6
HRMS (APPI, pos.): m/z 298.0998 (298.0994 calc. for C H O ,
(
2
1
14 2
0
.015 mmol) in CHCl
3
(1.5 mL) for 24 h according to general
+
+
M) ) and 299.1066 (299.1072 calc. for C21
15 2
H O , (M + H) ).
procedure 3 provided 102 mg of the crude iodoenol cinnamate.
Reaction of the crude iodoenol cinnamate (102 mg,
(
E)-3-Benzylidene-5-hexylfuran-2(3H)-one (10bd)
2
0.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc) (6.7 mg,
The reaction of 6b (74 mg, 0.50 mmol), 7d (118 mg, 0.030 mmol) in DMF at 40 °C for 72 h according to the
.500 mmol), AuCl(PPh ) (12.4 mg, 0.0250 mmol) and AgPF General Procedure provided, after purification by flash chrom-
(2.5 mL) for 24 h according atography on silica gel (hexanes/EtOAc, 9 : 1), 34 mg (54%) of
to the General Procedure provided 178 mg of the crude 10bf as a clear oil.
iodoenol cinnamate. Reaction of the crude iodoenol cinna- R = 0.25 (hexanes/EtOAc, 9 : 1); IR (neat): 3090, 3015, 1769,
mate (178 mg, 0.460 mmol), KOAc (113 mg, 1.15 mmol) and 1631, 1300, 1048, 1022, 966, 759, 697 cm−
Pd(OAc) (10 mg, 0.046 mmol) in DMF at 40 °C for 24 h (300 MHz, CDCl ): δ 7.57–7.51 (m, 2H, ArH), 7.46–7.33 (m, 3H,
according to the general procedure provided, after purification ArH), 7.21 (s, 1H, Ar–CHvC), 6.32 (s, 1H, CHvC–O), 1.83–1.71
0
3
6
(6.30 mg, 0.0250 mmol) in CHCl
3
f
1
1
;
H NMR
2
3
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13
(
m, 1H, CH
2 2 2 2
CHCH ), 1.09–0.93 (m, 4H, CH CHCH ); C NMR (E)-5-Cyclopropyl-3-(4-methylbenzylidene)furan-2(3H)-one
(
75 MHz, CDCl ): δ 169.7 (CvO), 162.9 (C–O), 135.3 (ArCipso), (10cf)
3
1
1
32.5 (Ar–CHvC), 129.8 (2 × ArC), 129.7 (ArC), 129.0 (2 × ArC),
25.4 (C–CvO), 99.6 (CHvC–O), 10.2 (CH), 7.1 (2 × CH );
The reaction of 6c (49 mg, 0.30 mmol), 10f (58 mg,
.30 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF
2
0
3
6
HRMS (APPI, pos.): m/z 212.0836 (212.0837 calc. for C H O ,
1
4
12 2
(
3
3.8 mg, 0.015 mmol) in CHCl (1.5 mL) for 24 h according to
+
+
(M) ) and 213.0909 (213.0916 calc. for C14
13 2
H O , (M + H) ).
the General Procedure provided 106 mg of the crude iodoenol
cinnamate. Reaction of the crude iodoenol cinnamate
1
7a
(E)-3-(4-Methylbenzylidene)-5-phenylfuran-2(3H)-one (10ca)
(
(
106 mg, 0.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
6.7 mg. 0.030 mmol) in DMF at 40 °C for 70 h according to
2
The reaction of 6c (49 mg. 0.30 mmol), 7a (68 mg, 0.30 mmol),
the general procedure provided, after purification by flash
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 35 mg
AuCl(PPh ) (14.8 mg, 0.0300 mmol) and AgPF (7.6 mg,
3
6
0
.030 mmol) in CHCl3 (1.5 mL) for 47 h according to the
(
55%) of 10cf as a clear oil.
R = 0.25 (hexanes/EtOAc, 9 : 1); IR (neat): 3093, 3015, 2923,
General Procedure provided 117 mg of the crude iodoenol
cinnamate. Reaction of the crude iodoenol cinnamate (117 mg,
f
773, 1631, 1246, 1045, 1021, 967, 812 cm−
1
;
1
H NMR
1
(
0
0
.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc) (6.7 mg.
.030 mmol) in DMF at 80 °C for 1 h according to the general
2
300 MHz, CDCl ): δ 7.44 (d, 2H, J = 8.2, ArH), 7.22 (d, 2H, J =
3
8
(
.2, ArH), 7.19 (s, 1H, Ar–CHvC), 6.30 (s, 1H, CHvC–O), 2.39
s, 3H, CH ), 1.82–1.71 (m, 1H, CH CHCH ), 1.07–0.91 (m, 4H,
CH CHCH ); C NMR (75 MHz, CDCl ): δ 169.9 (CvO), 162.2
procedure provided, after purification by flash chromatography
on silica gel (hexanes/EtOAc, 95 : 5), 43 mg (53%) of 10ca as a
yellow solid.
3
2
2
1
3
2
2
3
(
(
(
C–O), 140.3 (ArCipso), 132.8 (Ar–CHvC), 132.6 (ArCipso) 129.9
2 × ArC), 129.7 (2 × ArC), 124.4 (C–CvO), 99.7 (CvC–O), 21.5
CH ), 10.1 (CH), 7.0 (2 × CH ); HRMS (APPI, pos.): 226.1000
Rf = 0.27 (hexanes/EtOAc, 95 : 5); mp: 150–152 °C; IR (neat):
3
7
043, 2913, 2852, 1753, 1448, 1278, 1169, 1001, 883, 802,
34 cm−
1
;
1
H NMR (300 MHz, CDCl
): δ 7.79–7.73 (m, 2H,
3
2
3
+
(
226.0994 calc. for C H O , (M) ) and 227.1073 (227.1072
ArH), 7.54 (d, 2H, J = 8.3, ArH), 7.48–7.38 (m, 4H, ArH and Ar–
CHvC), 7.27 (d, 2H, J = 8.3, ArH), 6.93 (d, 1H, J = 0.9, CHvC–
15 14
2
+
calc. for C15
H
15
O
2
, (M + H) ).
1
3
O), 2.42 (s, 3H, OCH
3
); C NMR (75 MHz, CDCl
3
): δ 169.6
(
(
E)-5-Phenyl-3-(thiophen-2-ylmethylene)furan-2(3H)-one
(
(
CvO), 156.5 (C–O), 141.0 (ArCipso), 135.7 (Ar–CHvC), 132.5
ArCipso), 130.4 (ArC), 130.2 (2 × ArC), 129.9 (2 × ArC), 128.9
3
4
10da)
(2 × ArC), 128.2 (ArCipso), 125.3 (2 × ArC), 124.5 (ArC), 100.0
The reaction of 6d (77 mg. 0.50 mmol), 7a (114 mg,
(
(
CHvC–O), 21.6 (OCH ); HRMS (APPI, pos.): m/z 262.1001
3
0.500 mmol), AuCl(PPh ) (12.4 mg, 0.0250 mmol) and AgPF
3
6
+
262.0994 calc. for C H O , (M) ) and 263.1074 (263.1072
1
8
14
+
2
(6.3 mg, 0.025 mmol) in CHCl (2.5 mL) for 50 h according to
3
15 2
calc. for C18H O , (M + H) ).
the General Procedure 3 provided 191 mg of the crude iodo-
enol cinnamate. Reaction of the crude iodoenol cinnamate
(191 mg, 0.500 mmol), KOAc (122 mg, 1.25 mmol) and
(
E)-5-Hexyl-3-(4-methylbenzylidene)furan-2(3H)-one (10cd)
Pd(OAc) (11 mg. 0.050 mmol) in DMF at 80 °C for 1 h accord-
ing to the General Procedure provided, after purification by
flash chromatography on silica gel (hexanes/EtOAc, 9 : 1),
2
The reaction of 6c (49 mg, 0.30 mmol), 7d (71 mg, 0.30 mmol),
AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF (3.8 mg,
3
6
0
.015 mmol) in CHCl
3
(1.5 mL) for 27 h according to the
6
9 mg (54%) of 10da as a brown solid.
= 0.28 (hexanes/EtOAc, 9 : 1); mp: 130–132 °C; IR (neat):
118, 3103, 3054, 1752, 1618, 1583, 1418, 1277, 1257, 1197,
General Procedure provided 120 mg of the crude iodoenol cin-
namate. Reaction of the crude iodoenol cinnamate (120 mg,
R
f
3
9
0
.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
2
(6.70 mg.
96, 881, 734, 680 cm−
1
;
1
3
H NMR (300 MHz, CDCl ):
0
.03 mmol) in DMF at 40 °C for 72 h according to the general
δ 7.79–7.72 (m, 2H, ArH), 7.58 (dt, 1H, J = 5.1, 1.0, ArH), 7.56
d, 1H, J = 1.0, Ar–CHvC), 7.48–7.37 (m, 2H), 7.43 (d, 1H, J =
procedure provided, after purification by flash chromatography
on silica gel (hexanes/EtOAc, 95 : 5), 43 mg (53%) of 10cd as a
yellow semisolid.
(
1
6
.4), 7.4 (dt, 1H, J = 3.8, 0.8), 7.14 (dd, 1H, J = 5.1, 3.7, ArH),
.91 (d, 1H, J = 1.0, CHvC–O); C NMR (75 MHz, CDCl ):
3
1
3
R = 0.27 (hexanes/EtOAc, 95 : 5); IR (neat): 2954, 2925, 2856,
f
−
1
1
δ 169.5 (CvO), 156.1 (C–O), 139.5 (ArCipso), 134.1 (Ar–CHvC),
31.2 (ArC), 130.6 (ArC), 129.0 (2 × ArC), 128.5 (ArC), 128.2
1
(
763, 1630, 1601, 1169, 1031, 928, 812 cm
500 MHz, CDCl ): δ 7.45 (d, 2H, J = 8.0, ArH), 7.27 (s, 1H, Ar–
CHvC), 7.23 (d, 2H, J = 8.0, ArH), 6.25 (br m, 1H, CHvC–O),
.47 (t, 2H, J = 7.5, CH C–O), 2.39 (s, 3H, CH ), 1.64 (quint, 2H,
J = 7.5, CH CH C–O), 1.42–1.26 (m, 6H, CH (CH CH ), 0.89
br t, 3H, J = 6.7, CH (CH ) CH ); C NMR (75 MHz, CDCl3):
;
H NMR
1
3
(
(
C–CvO), 127.4 (ArC), 125.5 (2 × ArC), 122.9 (ArCipso), 100.5
CHvC–O); HRMS (APPI, pos.): m/z 254.0412 (254.0402 calc.
2
2
3
+
for
C
C
15
H
10
O
2
S, (M) ) and 255.0487 (255.0480 calc. for
2
2
3
2
)
3
2
+
1
3
15
H
11
O
2
S, (M + H) ).
(
3
2 3
2
δ 170.2 (CvO), 161.7 (C–O), 140.5 (ArCipso), 134.1 (Ar–CHvC),
32.4 (ArCipso), 130.0 (2 × ArC), 129.8 (2 × ArC), 124.4
(
E)-5-(4-Bromophenyl)-3-(thiophen-2-ylmethylene)furan-2(3H)-
one (10db)
); HRMS (APPI, The reaction of 6d (46 mg. 0.30 mmol), 7b (92 mg,
1
(
C–CvO), 101.1 (CHvC–O), 31.5 (CH ), 28.9 (CH ), 28.8 (CH ),
2
2
2
2
5.9 (CH
2
), 22.5 (CH
2
), 21.6 (CH
3
), 14.0 (CH
3
+
22 2 3 6
pos.): m/z 270.1627 (270.1620 calc. for C18H O , (M) ) and 0.30 mmol), AuCl(PPh ) (7.4 mg, 0.015 mmol) and AgPF
2
+
71.1701 (271.1698 calc. for C H O , (M + H) ).
(3.8 mg, 0.015 mmol) in CHCl (1.5 mL) for 66 h according to
1
8
23
2
3
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the General Procedure provided 138 mg of the crude iodoenol Ar–CHvC), 7.30 (d, 2H, J = 8.5, ArH), 6.83 (s, 1H, CHvC–O),
cinnamate. Reaction of the crude iodoenol cinnamate 2.34 (s, 3H, OCOCH ), 2.32 (br s, 6H, 2 × OCOCH ), 2.31 (s, 3H,
3
3
13
(
(
138 mg, 0.300 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
6.7 mg. 0.030 mmol) in DMF at 80 °C for 20 min according to (CvO), 168.02 (CvO), 167.91 (CvO), 167.89 (CvO), 156.0
2
OCOCH
3
); C NMR (75 MHz, CDCl
3
): δ 168.5 (CvO), 168.05
the general procedure provided, after purification by flash (C–O), 143.9 (ArCipso), 143.5 (ArCipso), 142.60 (ArCipso), 142.57
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 61 mg (ArCipso), 134.0 (Ar–CHvC), 133.7 (ArCipso), 128.4 (ArC), 126.7
(61%) of 10db as a yellow semisolid.
(ArCipso or C–CvO), 126.1 (C–CvO or ArCipso), 124.6 (ArC),
R = 0.27 (hexanes/EtOAc, 9 : 1); IR (neat): 2920, 2851, 1750, 124.22 (ArC), 124.20 (ArC), 123.7 (ArC), 120.7 (ArC), 100.2
f
−1 1
1
615, 1400, 992, 822, 805, 739, 690 cm ; H NMR (300 MHz, (CHvC–O), 20.73 (CH
3 3 3 3
), 20.69 (CH ), 20.68 (CH ), 20.62 (CH );
CDCl
H, ArH), 7.16 (dd, 1H, J = 5.1, 3.8, ArH), 6.94 (d, 1H, J = 0.8, (M) ) and 539.1136 (539.1190 calc. for C H O , (M + OAc) ).
3
): δ 7.65–7.54 (m, 6H, ArH and Ar–CHvC), 7.45–7.41 (m, HRMS (APPI, neg.): m/z 480.1065 (480.1057 calc. for C25H O ,
20 10
−
−
1
2
7
23 12
1
3
CHvC–O); C NMR (75 MHz, CDCl
3
): δ 169.0 (CvO), 154.9
C–O), 139.3 (ArCipso), 134.3 (Ar–CHvC), 132.2 (2 × ArC), 131.4
ArC), 128.5 (ArC), 127.9 (ArC), 127.0 (C–CvO), 126.7 (2 × ArC),
General procedure for the one-pot synthesis of furanones from
cinnamic acids and iodoalkynes
(
(
1
24.7 (ArCipso), 122.5 (ArCipso), 100.9 (CHvC–O); HRMS (APPI, To a solution of the cinnamic acid (1 equiv.) and the iodo-
7
9
+
pos.): m/z 331.9511 (331.9507 calc. for C15
3
H
9
BrO
2
S, (M )), alkyne (1 equiv.) in CHCl3 (1.5 mL) were added AuCl(PPh3)
8
1
33.9470 (333.9486 calc. for C H BrO S).
(5 or 10 mol%) and AgPF (5 or 10 mol%) at room temperature.
1
5
9
2
6
The reaction flask was wrapped with aluminium foil and the
(
E)-5-Hexyl-3-(thiophen-2-ylmethylene)furan-2(3H)-one (10dd)
reaction mixture was stirred at room temperature until con-
The reaction of 6d (46 mg, 0.30 mmol), 7d (71 mg, sumption of the iodoalkyne (TLC). The reaction mixture was
.30 mmol), AuCl(PPh ) (7.4 mg, 0.025 mmol) and AgPF
concentrated under reduced pressure. To a solution of the
3.8 mg, 0.025 mmol) in CHCl (1.5 mL) for 50 h according to residue (crude (Z)-β-iodoenol cinnamate) and Pd(OAc)2
0
(
3
6
3
the General Procedure provided 117 mg of the crude iodoenol (15 mol%) in DMF (1.5 mL, purged with N for 15 min) was
2
cinnamate. Reaction of the crude iodoenol cinnamate added KOAc (2.5 equiv.) at room temperature. The mixture was
(117 mg, 0.30 mmol), KOAc (74 mg, 0.75 mmol) and Pd(OAc)
2
heated at the specified temperature until consumption of the
(6.70 mg. 0.03 mmol) in DMF at 40 °C for 96 h according to iodoenol cinnamate (TLC). The reaction mixture was then
the General Procedure provided, after purification by flash cooled to ambient temperature, H O (1 mL) was added and the
2
chromatography on silica gel (hexanes/EtOAc, 9 : 1), 24 mg mixture was extracted with EtOAc (3 × 2 mL). The combined
(43%) of 10dd as a white semisolid.
2 4
extracts were dried over Na SO and concentrated under
R
f
= 0.29 (hexanes/EtOAc, 9 : 1); IR (neat): 2952, 2927, 2854, reduced pressure. The residue was purified by flash column
−
1
1
1
759, 1625, 1604, 1147, 1020, 925, 847, 731, 707 cm
NMR (300 MHz, CDCl ): δ 7.53 (dt, 1H, J = 5.1, 1.0, ArH), 7.43
q, 1H, J = 1.0, Ar–CHvCH), 7.35 (dt, 1H, J = 3.7, 1.0, ArH),
;
H
chromatography on silica gel.
E)-3-Benzylidene-5-phenylfuran-2(3H)-one (10ba)
3
1
7
(
(
7
.11 (dd, 1H, J = 5.1, 3.7, ArH), 6.26 (q, 1H, J = 1.0, CHvC–O),
The reaction of (E)-cinnamic acid 6b (44 mg. 0.30 mmol),
2
.49 (t, 2H, J = 7.6, 2H, CH –C–O), 1.66 (quint, 2H, J = 7.6,
2
iodoalkyne 7a (68 mg, 0.30 mmol), AuCl(PPh ) (15 mg,
3
1
3
CH
2
), 1.45–1.23 (m, 6H, (CH
): δ 169.9 (CvO), 161.5 (C–O), 139.4
ArCipso), 133.4 (Ar–CHvC), 130.5 (ArC), 128.2 (ArC), 126.0
ArC), 122.8 (C–CvO), 101.6 (CHvC–O), 31.5 (CH –C–O), 29.0
CH ), 28.8 (CH ), 26.0 (CH ), 22.5 (CH ), 14.1 (CH ); HRMS
APPI, pos.): m/z 262.1031 (262.1028 calc. for C H O S, (M) )
2
)
3
, 0.90 (br t, 3H, J = 7.0, CH
3
);
C
0
4
.030 mmol), AgPF (7.6 mg, 0.030 mmol) in CHCl (stirred for
6
3
NMR (75 MHz, CDCl
(
(
(
3
5 h), followed by reaction of Pd(OAc)
2
(10.0 mg, 0.044 mmol),
KOAc (74 mg, 0.750 mmol) and DMF at 80 °C for 50 min
according to general procedure provided, after purification by
flash column chromatography on silica gel (hexanes/EtOAc,
9 : 1), 45 mg (61%) of 10ba as a yellow solid.
2
2
2
2
2
3
+
(
1
5
18 2
+
19 2
and 263.1102 (263.1106 calc. for C15H O S, (M + H) ).
(
E)-3-Benzylidene-5-hexylfuran-2(3H)-one (10bd)
The reaction of (E)-cinnamic acid 6b (44 mg. 0.30 mmol),
iodoalkyne 7d (71 mg, 0.30 mmol), AuCl(PPh ) (7.4 mg,
.015 mmol) and AgPF (3.8 mg, 0.015 mmol) in CHCl
(stirred for 24 h), followed by reaction of Pd(OAc) (10.0 mg,
(
E)-4-(4-(3,4-Diacetoxybenzylidene)-5-oxo-4,5-dihydrofuran-2-
2
5
yl)-1,2-phenylene diacetate (10fh)
3
The reaction of iodoenol cinnamate 8fh (237 mg, 0.390 mmol),
0
6
3
KOAc (96 mg, 0.97 mmol) and Pd(OAc) (8.8 mg, 0.039 mmol)
2
2
in DMF at room temperature for 64 h according to the General
Procedure provided, after purification by flash chromatography
on silica gel (CH Cl /EtOAc, 98 : 2), 103 mg (55%) of 10fh as a
0.044 mmol) and KOAc (74 mg, 0.75 mmol) in DMF at 40 °C
for 27 h according to general procedure provided, after purifi-
cation by flash column chromatography on silica gel (hexanes/
EtOAc, 95 : 5), 49 mg (64%) of 10bd as a yellow oil.
2
2
yellow solid.
= 0.27 (CH
2
4
R
f
2
2
Cl /EtOAc, 96 : 4); mp: 157–158 °C (Lit.
1
1
57–159 °C); IR (neat): 2927, 1764, 1499, 1428, 1370, 1194,
170, 1114, 1010, 947, 900 cm ; H NMR (500 MHz, CDCl ):
3
−
1 1
Conflicts of interest
δ 7.64 (dd, 1H, J = 8.5, 1.8, ArH), 7.58 (d, 1H, J = 1.8, ArH), 7.48
(dd, 1H, J = 8.5, 1.8, ArH), 7.44 (d, 1H, J = 1.8, ArH), 7.38 (s, 1H, There are no conflicts to declare.
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Paper
and V. A. Sedavkina, Chem. Heterocycl. Compd., 1997, 33,
Acknowledgements
910.
These investigations were supported by the Natural Sciences 19 (a) Z. Chen, J. Li, H. Jiang, S. Zhu, Y. Li and C. Qi, Org.
and Engineering Research Council of Canada and the Canada
Foundation for Innovation.
Lett., 2010, 12, 3262; (b) N. Okamoto, Y. Miwa, H. Minami,
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