Regioselective Synthesis of 5-Metalated 2-Pyrones by Intramolecular Oxymetalation of Carbonyl-ene-yne Compounds Using Indium Trihalide

Article abstract of DOI:10.1021/acs.joc.9b02186

The oxyindation of carbonyl-ene-yne compounds with indium trihalides proceeded efficiently to give di-, tri-, and tetrasubstituted 2-pyrones bearing a carbon-indium bond. The metalated 2-pyrone and a zwitterion intermediate were identified by X-ray crystallographic analysis. The application of organoindium compounds to oxidation or cross-coupling provided easy access to various multifunctionalized 2-pyrones. Some 2-pyrone derivatives show intense fluorescence only in the solid state (aggregation-induced emission).

Full text of DOI:10.1021/acs.joc.9b02186

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Note
Regioselective Synthesis of 5-Metalated 2-Pyrones by Intramolecular
Oxymetalation of Carbonyl-Ene-Yne Compounds Using Indium Trihalide
Tetsuji Yata, Yuji Kita, Yoshihiro Nishimoto, and Makoto Yasuda
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02186 • Publication Date (Web): 09 Oct 2019
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The Journal of Organic Chemistry
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Regioselective Synthesis of 5-Metalated 2-Pyrones by Intramolecular
Oxymetalation of Carbonyl-Ene-Yne Compounds Using Indium Tri-
halide
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Tetsuji Yata,‡ Yuji Kita,‡ Yoshihiro Nishimoto,*† and Makoto Yasuda*‡
†Frontier Research Base for Global Young Researchers, Center for Open Innovation Research and Education (COiRE),
Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
‡Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-
0871, Japan
Supporting Information Placeholder
ABSTRACT: The oxyindation of carbonyl-ene-yne compounds with indium trihalides proceeded efficiently to give di-, tri-, and
tetrasubstituted 2-pyrones bearing a carbon-indium bond. The metalated 2-pyrone and a zwitterion intermediate were identified by
X-ray crystallographic analysis. The application of organoindium compounds to oxidation or cross-coupling provided easy access to
various multi-functionalized 2-pyrones. Some 2-pyrone derivatives show intensefluorescence only in the solid state (aggregation-
induced emission).
2-Pyrones are an important class of oxygen-containing
heterocycles with a broad range of biological activities and are
versatile building blocks in organic synthesis.1 Therefore, the
development of general and selective synthetic methods for
highly substituted 2-pyrones, particularly tetra-substituted
versions, holds great significance. Intramolecular or
intermolecular ring-forming reactions catalyzed by transition
metals have been recognized as typical methods for the
construction of 2-pyrone frameworks. Established general pro-
cedures are sufficient for the synthesis of di- and trisubstiututed
2-pyrones.2 In contrast, only a few studies have focused on the
synthesis of tetrasubstituted 2-pyrones.3 Larock reported a
palladium-catalyzed intermolecular [2+4] cyclization between
to this three-compornet reaction (Scheme 1C).3c The Larock
group established transition-metal-catalyst-free
a
iodolactonization of carbonyl-ene-ynes with I2. In this case,
tetrasubstituted 2-pyrones were synthesized, but the
regioselectivity in the cyclization was low (Scheme 1D).3d In
this context, we envisioned a strategy employing 2-pyrones
with a carbon-metal bond (metalated 2-pyrones) after receiving
a hint from our developed oxyindation to afford metalated
isocoumarins.6,7 Transformations of the metal-carbon bond
selectively gives multi-substituted pyrones.4 Herein, we
describe a novel selective synthetic method for highly
substituted 2-pyrones, including tetrasubstituted versions, by
using metalated 2-pyrones synthesized via the intramolecular
oxyindation carbonyl-ene-yne compounds 1 with InI3 (Scheme
1E). With this method, it is possible to obtain tetrasubstituted 2-
pyrones containing bromine, iodine, and ketone moieties, which
have not been prepared by previous methods.
3a
internal alkynes and α,β-unsaturated esters. This reaction
system is an efficient methodology to achieve regioselective
synthesis of di-, tri-, and tetrasubstituted 2-pyrones containing
aryl, alkyl, silyl, and ester groups (Scheme 1A). Miura and
Satoh reported a rhodium-catalyzed oxidative coupling of
substituted acrylic acids with alkynes, in which only symmetric
alkynes were used for tetrasubstituted 2-pyrones (Scheme
1B).3b Ryu and Fukuyama accomplished a Ru-catalyzed
[3+2+1] cycloaddition of α,β-unsaturated ketones with silylated
alkynes and CO toward the synthesis of tetrasubstituted 2-
pyrones. Alkynes other than silylacetylenes were not applicable
Scheme 1. (A) Reported Work: The Synthesis of Tetrasub-
stituted 2-Pyrones; (B) This Work: Oxyindation of Car-
bonyl-ene-yne Compound 1 with InI3 to Access Di-, Tri- and
Tetrasubstituted Metalated 2-Pyrones
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First, various metal salts were surveyed in an intramolecular
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oxymetalation of carbonyl-ene-yne 1a (Table 1). Recently, we
reported an indium salt-mediated oxymetalation of 2-
alkynylbenzoates to synthesize metalated isocoumarins.6
Therefore, oxyindations of 1a were conducted using indium
halides. A solution of 1a and InX3 (X = Cl, Br, and I) in toluene
was heated at 80 °C, and then the reaction mixture was
Table 1. Effect of Lewis Acids on the Oxymetalation of 1a,
1b, and 1ca.
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entry 1 (R1, R2)
MtXn
InCl3
InBr3
InI3
yield of 2 /%
1
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1a (H, H)
1b (H, Ph)
1b (H, Ph)
1c (Et, Ph)
2a:0
2
3c
2a:88
2a:100 (2a-d:82% D)
4
BBr3
ZnBr2
AlBr3
GaBr3
PdCl2
AuCl
AgOTf
InI3
2a:0
2a:14
2a:0
2a:45
2a:0
2a:6
2a:0
2b:92
2b:0
2c:95
b
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12d
13
ClBcat
InI3
A metalated 2-pyrone is the key compound in our stratey.
Almost all reported syntheses of metalated 2-pyrones depend
on a halogen-metal exchange of halogenated 2-pyrones.
Therefore, the lack of a facile synthetic procedure for di- or
trisubstituted halogenated 2-pyrones5 has led to an
underdevelopment in the synthesis of highly substituted
metalated 2-pyrones (Scheme 2A).4 In addition, a synthesis of
tetrasubstituted 2-pyrones has not been achieved (Scheme 2B).
With the present synthetic method, the establishment of an
oxymetalation of fully substituted carbonyl-ene-ynes 1, which
are easily synthesized from iodoacrylate derivatives and
acetylene derivatives, achieves the preparation of 5-metalated
2-pyrones A, which includes di-, tri-, and tetrasubstituted
versions. This is the first report of the synthesis of
tetrasubstituted metalated 2-pyrones.
a1 (0.5 mmol), MXn (0.5 mmol), toluene (1 mL) The yield of 2
was determined by 1H NMR. cThe reaction mixture was quenched
by 1 M DCl in D2O (1 mL) and a subsequent addition of H2O (10
mL).d1b (0.5 mmol), ClBcat (1.4 eq.), toluene (1 mL) 24 h, 100 °C,
and then quenched by pinacol (3 eq.) and NEt3 (1 mL).
quenched using 1 M HCl aq. The use of InCl3 resulted in no
reaction (Table 1, entry 1). On the other hand, InBr3 and InI3
gave the desired product 2a in 88 and 100% yields, respectively
(Table 1, entries 2 and 3). When the reaction using InI3 was
quenched by DCl in D2O, product 2a-d deuterated at the 5-
position was obtained. Typical Lewis acids such as BBr3, ZnBr2,
AlBr3 and GaBr3 were unsuitable (Table 1, entries 4-7).
Subjecting the other alkynophilic Lewis acids such as PdCl2,
AuCl, and AgOTf to the present oxymetalation resulted in
decomposition or recovery of the starting material 1a (Table 1,
entries 8-10). To our delight, a more substituted carbonyl-ene-
yne 1b or 1c afforded the highly substituted 2-pyrones 2b or 2c,
respectively (Table 1, entries 11 and 13). Blum and co-workers
reported an oxyboration of carbonyl-ene-yne 1a using B-
chlorocatecholborane (ClBcat) to afford borylated 2-pyrone,8
but the oxyboration system was not applicable to multi-
substituted substrates such as 1b (Table 1, entry 12).
Scheme 2. Retrosynthesis of Metalated 2-Pyrones: (A) Di-
and Trisubstituted Metalated 2-Pyrones, (B) Tetrasubsti-
tuted Metalated 2-Pyrones
When the reaction of 1b with InI3 was performed under the
optimal conditions (Table 1, entry 11) without acid-quenching,
metalated 2-pyrone 3b bearing an InI2 group at the 5-position
was obtained as a white solid (Scheme 3(i), (A)) and protonated
product 2b was hardly observed. This result suggested the
oxyindation proceeded. The structure of a 3b·pyridine complex
was identified by X-ray crystallographic analysis (Scheme 3(ii),
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(A)). (See Supporting Information (SI) for details of the
of the 3b·pyridine complex. Thus, the positive charge was
delocalized in the ester moiety.9 Subjecting zwitterion 4b to
heating conditions gave metalated 2-pyrone 3b via the
elimination of MeI.
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experiments). Oxyindation at room temperature also afforded a
white solid (Scheme 3(i), (B)), and, interestingly, it was not 3b.
1H NMR spectroscopic and X-ray crystallographic analysis
clarified the formation as that of zwitterion 4b (Scheme 3(ii),
(B)). An indium atom (In1) of 4b in the solid state was bound
to three iodine atoms (I1, I2, and I3) and a carbon atom (C2),
and displayed a
To gain insight into the reaction mechanism, the coordination
mode of carbonyl-ene-yne 1a to a Lewis acid was investigated
by DFT calculation (Scheme 3(iii)). In the coordination of
either the alkyne moiety (B) or the carbonyl oxygen (A) in 1a
to InBr3, the Gibbs energy changes were -17.2 kcal mol-1 and -
30.5 kcal mol-1, respectively. Therefore, both complexations
were thermodynamically stable, but carbonyl coordination was
more favorable. The energy gap between carbonyl complex A
and alkyne complex B of AlBr3 was very large (GA to B = 24.5
kcal mol-1), but InBr3 showed a relatively small value (GA to B
= 13.3 kcal mol-1). Consequently, InBr3 was more susceptible
to the subsequent alkyne coordination compared with AlBr3
after dissociation of the carbonyl coordination (See SI).
Scheme 3. Mechanistic Studies and Proposed Mechanism
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A possible reaction mechanism is depicted in Scheme 3(iv).
First, InI3 acts as an efficient π-electrophilic Lewis acid for the
activation of the alkyne moiety of carbonyl-ene-yne 17, and then
the intramolecular nucleophilic attack of a carbonyl oxygen
atom occurs to generate zwitterion 4. Then, the elimination of
MeI gives metalated 2-pyrone 3. The elimination is a rate-
determinig step.
Scheme 4. Sequential Oxymetalation/halogenation of Vari-
ous Types of Carbonyl-ene-ynea
aFirst step: 1 (0.5 mmol), InI3 (0.5 mmol), toluene (1 mL), 80 °C,
24 h. Second step: PhI(OAc)2 (1.0 mmol), THF (2 mL), rt, 12 h.
The isolated yields are shown. bInBr3 was used instead of InI3.
aThe thermal ellipsoids shown at 50% probability. bB3LYP/6-
31+G(d,p) for H, C, DGDZVP for Al, Ga, In and Br.
distorted tetrahedral geometry. One of the iodine atoms on In1
coordinated to InI3 in a crystal structure. The bond lengths of
the two carbon-oxygen bonds (C1-O1 = 1.300(10) Å, C1-O2 =
1.327(11) Å) in 4b showed values that fell between that of a
typical C-O double bond (1.233 Å) and a single bond (1.401 Å)
Various types of carbonyl-ene-ynes 1 were applied to the
synthesis of 2-pyrone derivatives via the present oxyindation
(Scheme 4). Oxyindation of 1a using InI3 followed by oxidation
of 3a with PhI(OAc)2 was carried out in a one-pot procedure to
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afford 5-iodo-2-pyrone 5a in a 96% yield.6 Substrates 1 with
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1
substituents such as Me, tert-Bu, MeO, Cl, and F groups on the
aromatic ring bindng to an alkyne moiety gave the target
products 5d, 5e, 5f, 5g, and 5h, respectively. The substrates
bearing aliphatic alkyne moieties 1i and 1j also worked well.
Dicarbonyl-ene-yne compound 1k provided the desired
trisubstituted 2-pyrone 5k in a moderate yield. Subjecting 1b to
halogenation yielded 5-iodo-4,6-diphenyl-2-pyrone 5b. α,β-
Disubstituted substrate 1c was surveyed in the sequential
oxyindation/halogenation process to afford tetrasubstituted 2-
pyrone 5c. Gratifyingly, 2-pyrone 5l bearing four different
substituents on the ring was produced by the reaction using 1l.
The oxyindation of 1m proceeded in 6-endo cyclization to ex-
clusively give 2-pyrone 5m in contrast to Larockʼs iodocycliza-
tion of 1m with ICl giving a 5-membered oxacycle as a major
product.3d Therefore, this result shows our developed method is
more effective for the synthesis of multisubstituted 2-pyrones.
To our delight, subjecting InBr3 instead of InI3 to the
oxyindation reaction provided fully substituted brominated 2-
pyrones 5n in a moderate yield. Therefore, our approach
accomplished the synthesis of tetrasubstituted brominated 2-
pyrones as well as iodinated ones. Iodinated 2-pyrone 5m was
used for further transformations with Migita-Kosugi-Stille
coupling to give tetra-carbon-substitued 2-pyrones (Scheme
5).10
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Scheme 5. Synthesis of Tetrasubstituted 2-Pyrones Using
Stille Coupling
aOxyindation conditions: 1 (0.5 mmol), InI3 (0.5 mmol), toluene (1
mL), 80 °C, 24 h. Second step conditions: Pd2dba3 (0.025 mmol),
NaOMe (1.0 mmol), ArI (Ar = 0.35 mmol), DMF (2.5 mL), 110 °C,
b
24 h. Oxyindation conditions: 1 (0.5 mmol), InI3 (0.5 mmol),
toluene (1 mL), 80 °C, 24 h. Second step conditions: Pd2dba3 (0.025
Palladium-catalyzed, cross-coupling syntheses of metalated
2-pyrones 3 with aryl iodides or acid chlorides were performed
(Scheme 6).11 After the oxyindation of 1a with InI3,
iodobenzene, Pd2(dba)3 catalyst, NaOMe, and DMF were added
to the reaction mixture involving InI2-substituted 2-pyrone 3a.
The Pd-catalyzed coupling reaction between 3a and
iodobenzene smoothly proceeded to produce 5,6-diphenyl-2-
pyrone 6a in a 96% yield. The trisubstituted metalated 2-pyrone
derived from 1b also underwent coupling to afford 4,5,6-
triphenyl-2H-pyran-2-one 6b. Various types of tetrasubstituted
metalated 2-pyrones derived from 1c, and 1l-1o were employed
to produce tetra-carbon-substitued 2-pyrones 6c and 6l-6o,
respectively.
mmol), R4COCl (1.0 mmol), 1,3-dimethyl-2-imidazolidinone (2.5
c
mL), 80 °C, 24 h. The isolated yields are shown. The cross
coupling was run at 80 °C and KCl was used instead of NaOMe.
Both electron-rich and -poor aryl iodides worked as feasible
coupling partners to afford 2-pyrones 6n and 6o bearing four
different carbon substitutents. Furthermore, the Pd-catalyzed
cross coupling of InI2-substituted 2-pyrones 3 with an acid
chloride also proceeded under condition B to give multi-
functionalized 2-pyrones 7a-7c, 7l, and 7m. The structure of 2-
pyrone 7l was confirmed by X-ray crystallographic analysis.
The present oxyindation/cross-coupling sequential process
established a modular synthesis of multi-functionalized 2-
pyrones.
Scheme 6. One-pot Formation of Highly Substituted 2-Py-
rones by Palladium-catalyzed Cross Coupling
Tetrasubstituted 2-pyrones 6m and 7m had no fluorescence
properties in the solution, but an aggregation-induced emission
(AIE) was observed in the solid state. Triphenylated 2-pyrone
2c is known to possess AIE properties and exhibit a higher
quantum yield than Alq3, which is generally used in
electroluminescence devices.12 However, tetrasubstituted 2-
pyrones have not been investigated in detail because relatively
little is known about a facile synthetic method. We expected to
improve the light emission properties by installing a substituent
at the 5-position, and thus 6m and 7m exhibited greater
quantum yields than 2c (Figure 1A). This result can be ascribed
to the fact that the installation of either a phenyl- or an aloyl
group changed the intermolecular interactions in the solid state.
Figure 1B shows the molecular packing diagrams of compound
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6m, 7m and 2c12. In the crystal structure of these compounds,
herein could contribute to a modular synthesis of multi-
functionalized 2-pyrones.
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there are C-H···π interactions and/or hydrogen bonds among
molecules. These interactions limited the molecular motions,
giving rise to the emission enhancement in the solid state. A
quenching effect is caused by the stacking interactions between
2-pyrone structures in 6m and 2c, but not in 7m. Inhibition of
the stacking by the steric hindrance of benzoyl group at the 5-
position achieved the strongest light emission of 7m. The dis-
tance between the 2-pyrone skeleton of 6m is longer than that
of 2c due to the Ph group at the 5-position, so 6m shows
stronger light emission than 2c.
EXPERIMENTAL SECTION
General Information.
NMR spectra were recorded on a JEOL JNM-400 (400 MHz for 1H
NMR and 100 MHz for 13C NMR) spectrometer. Chemical shifts
were reported in ppm on the δ scale relative to tetramethylsilane (δ
= 0 for 1H NMR) and residual CHCl3 (δ = 77.0 for 13C NMR) as an
internal reference. New compounds were characterized by 1H, 13C,
13C off-resonance techniques, COSY, HMQC, and HMBC. Infra-
red (IR) spectra were recorded on a JASCO FT/IR-6200 Fourier
transform infrared spectrophotometer. Column chromatographies
were performed with silica gel. Purification by recycle HPLC was
performed using the SHIMADZU recycle HPLC system (SPD-20A,
RID-10A, DGU-20A, LC-6AD, and FCV-20H2) from the Japan
Analytical Industry Co. (NEXT recycling preparative HPLC).
High-resolution mass spectra were obtained using a magnetic sec-
tor type mass spectrometer. Reactions were carried out in dry sol-
vents under a nitrogen atmosphere, unless otherwise stated. Rea-
gents were purchased from Aldrich or Tokyo Chemical Industry
Co., Ltd. (TCI), FUJIFILM Wako Pure Chemical Corporation and
used either after purification by distillation or without purification
for solid substrates. X-ray diffraction analysis was carried out via
Rigaku XtaLAB Synergy with a Hypix-6000HE. Steady-state
emission spectra were recorded on a HAMAMATSU C11347-01
spectrometer with an integrating sphere.
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Materials
Dehydrated solvents, such as toluene, THF, 1,4-dioxane, DMF, and
DMI were purchased from FUJIFILM Wako Pure Chemical Corpora-
tion and used as obtained. PhI(OAc)2 was purchased from Tokyo
Chemical Industry Co., Ltd., and used without further purification. Car-
bonyl-ene-yne compounds, 1a, 1b, 1d-1k, and 1m were synthesized by
reported procedures, and the spectral data for these compounds are pro-
vided in the Supporting Information. Carbonyl-ene-ynes 1c and 1l are
new compounds, and the synthetic methods and spectral data for these
compounds are shown below. InI3 (Indium Triiodide 99.99%) was pur-
chased from Kojundo Chemical Laboratory. All other reagents were
commercially available.
General Procedure for the synthesis of carbonyl-ene-yne
1a3d, 1b13, 1d14, 1e14, 1f14, 1g14, 1h14, 1i15, 1j8, 1k16, and 1m.3d
To a solution of methyl (Z)-3-iodoacrylate (5 mmol, 1 equiv) in Et3N
(20 mL) were added PdCl2(PPh3)2 (0.1 mmol, 0.02 equiv), CuI (0.1
mmol, 0.02 equiv) and acetylene (6.5 mmol, 1.3 equiv). The resulting
mixture was heated under nitrogen atmosphere at 55 °C by oil bath.
The reaction was monitored by TLC to establish completion. When the
reaction was complete, the mixture was quenched by NH4Cl aq (30 mL).
The solution was extracted by Et2O (3 x 30 mL) and dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography. Product-containing fractions were
combined and concentrated in vacuo to afford 1.
Figure 1. (A) Fluorescence spectra of 6m and 7m and 2c in the
solid state upon excitation at 365 nm. The fluorescence
intensities of their compounds were calculated based on
quantum yield. (B) Packing mode and multiple interactions of
compound 6m and 7m and 2c.
In conclusion, we developed a process fo the oxyindation of
carbonyl-ene-yne compounds to give 2-pyrones bearing a
carbon-indium bond at the 5-position. Metalated 2-pyrones 3
and zwitterion intermediate 4 were fully characterized by X-ray
crystallographic analysis and NMR spectroscopy. These results
supported a reaction mechanism that is composed of two steps:
an indium trihalide-mediated cyclic oxymetalation and the
sequential elimination of MeI from 4. The bromination or
iodination of 3 provided 5-halo-2-pyrones 5 which are quite
useful as synthetic precursors to multi-substituted 2-pyrones.
We developed a general synthesis method for highly substituted
2-pyrones via a cross-coupling reaction using 3. The
synthesized tetrasubstituted 2-pyrones showed aggregation-
induced emission (AIE). The oxyindation chemistry described
methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate (1c)
The 3-Phenyl-2-propyn-1-ol (20.2 mmol, 2.67 g), dry Et2O (30 mL),
and CuI (2.35 mmol, 0.448 g) were added to a three-necked flask. To
the cooled, stirred mixture at 0 °C was added a 3.0M EtMgBr in diethyl
ether (17 mL). Upon complete addition of the Grignard reagent, the
mixture was allowed to warm up to room temperature and stirred for
20 h. The dark green mixture was then cooled to 0 °C and I2 (22.2 mmol,
5.63 g) was added. After warming up to room temperature and stirring
at room temperature for 1 h, the reaction mixture was cooled to 0 °C
and quenched with sat. NH4Cl aq (20 mL). The organic layer was sep-
arated and the aqueous layer was extracted with ether (3 x 50 mL). The
combined ether layers were dried over MgSO4, filtered, and concen-
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trated in vacuo and then the crude (Z)-2-{iodo(phenyl)methylene}bu-
102.5 (s), 75.8 (s), 51.7 (q), 23.7 (t), 13.5 (q), 9.1 (t), 0.7 (d), HRMS:
tan-1-ol (12.3 mmol, 3.56 g) was obtained. The crude (Z)-2-{iodo(phe-
nyl)methylene}butan-1-ol was used without further purification.
To a solution of (Z)-2-{iodo(phenyl)methylene}butan-1-ol (12.3
mmol, 3.56 g), CH2Cl2 (123 mL), and MnO2 (247 mmol, 21.8 g) were
added to a three-necked flask. The reaction mixture was stirred at room
temperature for 2 h. The black precipitate was filtered off and the fil-
trate was concentrated in vacuo and then the crude (Z)-2-{iodo(phe-
nyl)methylene}butanal (11.7 mmol, 3.34 g) was obtained. The crude
(Z)-2-{iodo(phenyl)methylene}butanal was used without further puri-
fication.
The (Z)-2-{iodo(phenyl)methylene}butanal (11.7 mmol, 3.34 g),
MeOH (150 mL), NaCN (47.7 mmol, 2.34 g), AcOH (17.5 mmol, 1.05
g), and MnO2 (238 mmol, 20.7 g) were added to a three-necked flask.
The mixture was stirred at room temperature for 12 h under N2 atm.
The black precipitate was filtered off and the filtrate was concentrated
under vacuo. The resulting residue was partitioned between 80 mL of
H2O and 80 mL of Et2O. The organic layer was separated and the aque-
ous layer was extracted with ether (3 x 50 mL). The combined ether
layers were dried over MgSO4, filtered, and concentrated in vacuo. The
resulting oily residue was purified by column chromatography (hex-
ane/ethyl acetate = 5:95, column length 11 cm, diameter 26 mm, spher-
ical silica gel). Product-containing fractions were combined and con-
centrated in vacuo to give the methyl (Z)-2-{iodo(phenyl)meth-
ylene}butanoate (9) as a yellow oil (3.45 g, 54%).
(CI, 70 eV) Calculated (C17H19O2): 255.1385 [M+H]+Found 255.1387
1
2
3
4
5
6
7
8
General Procedure for oxymetalation of methyl (Z)-5-phe-
nylpent-2-en-4-ynoate followed by protonolysis (Table 1)
In a glove box filled for nitrogen, to a sealed vial, InI3 (0.5 mmol, 1
equiv), toluene (1 mL) and methyl (Z)-5-phenylpent-2-en-4-ynoate 1a
(0.5 mmol, 1 equiv) were added. The solution was stirred at 80 °C for
24 h in a heated aluminum block and the reaction mixture was
quenched by 1 M HCl aq (1 mL). After addition of water (10 mL), the
solution was extracted with CH2Cl2 (5 mL x 3). The collected organic
layer was dried over MgSO4. The solvent was evaporated and the yield
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
of 6-phenyl-2H-pyran-2-one 2 was determined by H NMR using in-
ternal standards (1,1,2,2-tetrachloroethane)
Oxymetalation of a carbonyl-ene-yne using InI3 (1.0 mmol
Scale)
To a 10 mL vial filled with InI3 (0.999 mmol, 0.495 g) in toluene (2
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate 1a (1.01mmol,
0.187 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h in a heated aluminum block and
the reaction mixture was quenched by water (10 mL) and 1 M HCl aq
(2 mL). The solution was extracted by dichloromethane (3 x 10 mL)
and the combined organic solution was dried over MgSO4, filtered, and
concentrated in vacuo. The resulting oily residue was purified by col-
umn chromatography (hexane/ethyl acetate = 95:5, column length 11
cm, diameter 26 mm, spherical silica gel). Fractions containing the de-
sired product were combines and concentrated in vacuo to give the
product 2a as a pale yellow solid (0.115 g, 67%). (The experimental
procedure at 0.5 mmol scale and characterization of 2a were shown
below)
IR: (neat) 1733 (C=O) cm-1, 1H NMR: (400 MHz, CDCl3) 7.38-7.32
(m, 2H), 7.30-7.24 (m, 3H), 3.88 (s, 3H), 2.25 (q, J = 7.4 Hz, 2H), 0.98
(t, J = 7.4 Hz, 3H), 13C{1H} NMR: (100 MHz, CDCl3) 169.6 (s), 144.7
(s), 142.5 (s), 128.3 (d), 127.7 (d), 96.8 (s), 52.3 (q), 26.2 (t), 13.1 (q),
HRMS: (EI, 70 eV) Calculated (C12H13O2I) 315.9960 (M+) Found
315.9962
To a solution of methyl (Z)-2-{iodo(phenyl)methylene}butanoate
(5.43 mmol, 1.72 g) in Et3N (20 mL) were added PdCl2(PPh3)2 (0.114
mmol, 0.0800 g), CuI (0.105 mmol, 0.0200 g) and phenylacetylene
(6.51 mmol, 0.665 g). The resulting mixture was heated under nitrogen
atmosphere at 55 °C. The reaction was monitored by TLC to establish
completion. When the reaction was complete, the mixture was
quenched by NH4Cl aq (30 mL). The solution was extracted by Et2O (3
x 30 mL) and dried over MgSO4, filtered, and concentrated in vacuo.
The resulting oily residue was purified by column chromatography
(hexane/ethyl acetate = 95:5, column length 11 cm, diameter 26 nm,
spherical silica gel). Product-containing fractions were combined and
concentrated in vacuo to give the product as a yellow oil (1.24 g, 78%).
IR: (neat) 2196 (C≡C), 1721 (C=O) cm-1, 1H NMR: (400 MHz, CDCl3)
7.43-7.26 (m, 10H), 3.90 (s, 3H), 2.40 (q, J = 7.4 Hz, 2H), 1.04 (t, J =
7.4 Hz, 3H), 13C NMR: (100 MHz, CDCl3) 168.8 (s), 141.4 (s), 138.2
(s), 131.6 (d), 128.5 (d), 128.4 (d), 128.3 (d), 128.2 (d), 128.0 (s), 128.0
(s), 123.1 (s), 96.8 (s), 89.1 (s), 51.9 (q), 24.0 (t), 13.4 (q), HRMS: (EI,
70 eV) Calculated (C20H18O2) 290.1307 (M+) Found 290.1306
1
Observation of Zwitterion Intermediate 4b by H NMR spec-
troscopy and X-ray Crystallographic Analysis (Scheme 3)
Oxyindation of methyl (Z)-3,5-diphenylpent-2-en-4-ynoate 1b (0.501
mmol, 0.131 g) with InI3 (0.505 mmol, 0.250 g) was carried out in tol-
uene (1 mL) at room temperature for 2 h to give a white solid, and then
the toluene was evaporated and the residual solid was dissolved in
CDCl3. 1H NMR spectroscopy measurements showed that the solid was
mixture of two compounds, which were neither the metalated pyrone
3b nor the starting material 1b. Recrystallization of the mixture from
CHCl3 and heptane provided a crystal and X-ray crystallographic anal-
ysis revealed that the one of the two components was the zwitterion
intermediate 4b (CCDC 1910563).
Isolation of Organoindium Compounds 3b and 3b·pyridine
(Scheme 3-i-A and Scheme 3-ii-A)
All operations were carried out in a nitrogen-filled glove box. To a
10 mL vial filled with InI3 (0.502 mmol, 0.249 g) in toluene (1 mL)
was added methyl (Z)-3,5-diphenylpent-2-en-4-ynoate (0.493 mmol,
0.129 g). The vial was sealed, and the mixture was stirred at 80 °C for
24 h. Then, the solvent was removed by decantation to obtain a white
solid and the solid was washed by CHCl3 (3 mL x 6). The residue was
dried under vacuum to give the product 3b as a white solid (0.297 g,
81%). 3b was added to pyridine (0.399 mmol, 0.0316 g) and recrystal-
lized from CHCl3 and heptane to give a single crystal of 3b·pyridine.
The structure was determined by X-ray crystallographic analysis
(CCDC 1910738). Characterization by NMR study was also carried out.
1H NMR: (400 MHz, CDCl3) 8.27 (d, J = 4.8 Hz, 2H, 15-H x 2), 7.77-
7.72 (m, 3H), 7.54-7.48 (m, 2H, 8-H x 2), 7.36-7.34 (m, 6H), 7.28-7.26
(m, 2H, 16-H x 2), 6.35 (s, 1H, 3-H), 13C NMR: (100 MHz, CDCl3)
167.2 (s, C-6), 162.7 (s), 162.6 (s), 148.0 (d, C-15), 141.1 (s, C-7),
139.1 (d, C-17), 136.0 (s, C-11), 131.2 (d), 130.1 (d), 129.6 (d), 129.09
(d), 129.06 (d), 127.7 (d, C-8), 124.9 (d, C-16), 118.9 (s, C-5), 111.8
(d, C-3).
methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-en-4-ynoate
(1l)
To a solution of methyl (Z)-2-{iodo(phenyl)methylene}butanoate
(9) (2.91 mmol, 0.921 g) (The experimental procedure and characteri-
zation of this compound (9) were described in experimental procedure
of methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate (1c)) in Et3N (12
mL) were added PdCl2(PPh3)2 (0.0329 mmol, 0.0231 g), CuI (0.0735
mmol, 0.0140 g) and phenylacetylene (3.49 mmol, 0.230 g). The re-
sulting mixture was heated under an N2 atmosphere at 55 °C. The reac-
tion was monitored by TLC to establish completion. When the reaction
was complete, the mixture was quenched by NH4Cl aq (10 mL). The
solution was extracted by Et2O (3 x 10 mL) and dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 nm, spherical silica gel). Product-containing
fractions were combined and concentrated in vacuo to give the product
as a yellow oil (0.443 g, 60%). IR: (KBr) 2212 (C≡C), 1722 (C=O) cm-
General Procedure for oxymetalation of carbonyl-ene-yne
compounds followed by halogenation (Scheme 4)
1
1; H NMR: (400 MHz, CDCl3) 7.38-7.27 (m, 5H), 3.84 (s, 3H), 2.30
(q, J = 7.5 Hz, 2H), 1.43-1.36 (m, 1H), 0.97 (t, J = 7.5 Hz, 3H), 0.86-
0.82 (m, 2H), 0.76-0.72 (m, 2H), 13C{1H} NMR: (100 MHz, CDCl3)
169.0 (s), 139.9 (s), 138.8 (s), 128.7 (s), 128.2 (d), 128.1 (d), 127.8 (d),
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The Journal of Organic Chemistry
In a glove box filled with nitrogen, to a sealed vial, InI3 (0.5 mmol,
3-ethyl-4,6-diphenyl-2H-pyran-2-one (2c)
1 equiv), toluene (1 mL) and carbonyl-ene-yne compound 1 (0.5 mmol,
1 equiv) were added. After stirring at 80 °C for 24 h in a heated alumi-
num block, the suspension was diluted by THF (2.5 mL) and PhI(OAc)2
(1.0 mmol, 1 equiv) was added to the solution in the glove box. The
reaction mixture was stirred at rt for 24 h and then quenched by water
(5 mL) and 1 M HCl aq (1 mL). The solution was extracted with CH2Cl2
(30 mL x 2) and the collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by column chro-
matography.
1
2
3
4
5
6
7
8
To a 10 mL vial filled with InI3 (0.504 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate
(0.502 mmol, 0.146 g) in a nitrogen-filled glove box. The vial was
sealed and the mixture was stirred at 80 °C for 24 h and the mixture
was quenched by water (3 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (2 x 30 mL) and combined organic
solution was dried over MgSO4, filtered, and concentrated in vacuo.
The resulting oily residue was purified by column chromatography
(hexane/ethyl acetate = 95:5, column length 11 cm, diameter 26 mm,
spherical silica gel). Product-containing fractions were combined and
concentrated in vacuo to give the product as a white solid (0.126 g,
90%). IR: (KBr) 1716 (C=O) cm-1, mp: 59-61 °C, 1H NMR: (400 MHz,
CDCl3) 7.82 (d, J = 5.1 Hz, 2H), 7.51-7.41 (m, 6H), 7.35 (d, J = 7.4 Hz,
2H), 6.62 (s, 1H), 2.50 (q, J = 7.4 Hz, 2H), 1.16 (t, J = 7.4 Hz, 3H),
13C{1H} NMR: (100 MHz, CDCl3) 163.2 (s), 156.3 (s), 152.2 (s), 137.9
(s), 131.4 (s), 130.2 (d), 128.7 (d), 128.6 (d), 127.4 (d), 125.5 (s), 125.2
(d), 104.6 (d), 21.2 (t), 13.3 (q), HRMS:(EI, 70 eV) Calculated
(C19H16O2) 276.1150 (M+) Found 276.1151.
General Procedure for oxymetalation of carbonyl-ene-yne
compounds followed by palladium catalyzed cross coupling
with iodoarenes (Scheme 6, Conditions A)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In a glove box filled with nitrogen, to a sealed vial, InI3 (0.5 mmol,
1.4 equiv), toluene (1 mL) and carbonyl-ene-yne compound 1 (0.5
mmol, 1.4 equiv) were added, and the solution was stirred at 80 °C for
24 h in a heated aluminum block. Pd2(dba)3 (0.025 mmol, 0.071 equiv),
a base such as KCl and NaOMe (2.9 equiv or none), ArI (0.35 mmol,
1 equiv) and DMF (2.5 mL) was added to the reaction mixture in the
glove box and the mixture was stirred at 110 °C for 24 h. The reaction
mixture was quenched by water (5 mL) and 1 M HCl aq (1 mL). The
solution was extracted with dichloromethane (3 x 30 mL) and the col-
lected organic layer was dried over MgSO4. The solvent was evapo-
rated and the residue was purified by column chromatography.
5-iodo-6-phenyl-2H-pyran-2-one (5a)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate (0.500 mmol,
0.931 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h. Then, iodobenzene diacetate
(0.331 g, 1.03 mmol) in THF (2.5 mL) was added to the reaction mix-
ture at room temperature. After stirring for 24 h, the mixture was
quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was ex-
tracted by dichloromethane (2 x 30 mL) and the combined organic so-
lution was washed by sat. Na2S2O3 aq. (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.143 g, 96%). The NMR date was agreement with
the literature3d.
General Procedure for oxymetalation of carbonyl-ene-yne
compounds followed by palladium catalyzed cross coupling
with acid chlorides (Scheme 6, Conditions B)
In a glove box filled with nitrogen, to a sealed vial, InI3 (0.5 mmol,
1 equiv), toluene (1 mL) and carbonyl-ene-yne compound 1 (0.5 mmol,
1 equiv) were added, and the solution was stirred at 80 °C for 24 h in a
heated aluminum block. Pd2(dba)3 (0.025 mmol, 0.05 equiv), 4-
methylbenzoyl chloride (1.0 mmol, 2 equiv) and 1,3-dimethyl-2-imid-
azolidinone (2.5 mL) was added to the reaction mixture in the glove
box and the mixture was stirred at 80 °C for 24 h in a heated aluminum
block. The reaction mixture was quenched by water (5 mL) and 1 M
HCl aq (1 mL). The solution was extracted with dichloromethane (3 x
30 mL) and the collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by column chro-
matography.
5-iodo-4,6-diphenyl-2H-pyran-2-one (5b)
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate (0.500 mmol,
0.931 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h. Then, iodobenzene diacetate
(0.331 g, 1.03 mmol) in THF (2.5 mL) was added to the reaction mix-
ture at room temperature. After stirring for 24 h, the mixture was
quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was ex-
tracted by dichloromethane (2 x 30 mL) and the combined organic so-
lution was washed by sat. Na2S2O3 aq. (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.123 g, 66%). The NMR date was agreement with
the literature16.
6-phenyl-2H-pyran-2-one (2a)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate (0.500mmol,
0.0931 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h and the reaction mixture was
quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was ex-
tracted by dichloromethane (2 x 30 mL) and the combined organic so-
lution was dried over MgSO4, filtered, and concentrated in vacuo. The
resulting oily residue was purified by column chromatography (hex-
ane/ethyl acetate = 95:5, column length 11 cm, diameter 26 mm, spher-
ical silica gel) Product-containing fractions were combines and concen-
trated in vacuo to give the product as a yellow solid (0.0797 g, 93%).
The NMR date was agreement with the literature17.
3-ethyl-5-iodo-4,6-diphenyl-2H-pyran-2-one (5c)
To a 10 mL vial filled with InI3 (0.518 mmol, 0.257 g) in toluene (1
mL) was added methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate
(0.502 mmol, 0.146 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.195 g, 0.604 mmol) in THF (2.5 mL) was added to the re-
action mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (3 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (2 x 30 mL) and combined organic
solution was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel). Product-containing
fractions were combined and concentrated in vacuo to give the product
as a yellow solid (0.139 g, 69%). IR: (KBr) 1714 (C=O) cm-1, mp: 143-
144 °C, 1H NMR: (400 MHz, CDCl3) 7.71-7.69 (m, 2H), 7.50-7.46 (m,
4,6-diphenyl-2H-pyran-2-one (2b)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-3,5-diphenylpent-2-en-4-ynoate
(0.500mmol, 0.131 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h and the reaction
mixture was quenched by water (5 mL), 1 M HCl aq (1 mL). The solu-
tion was extracted by dichloromethane (2 x 30 mL) and the combined
organic solution was dried over MgSO4, filtered, and concentrated in
vacuo. The resulting oily residue was purified by column chromatog-
raphy (hexane/ethyl acetate = 95:5, column length 11 cm, diameter 26
mm, spherical silica gel) Product-containing fractions were combines
and concentrated in vacuo to give the product as a white solid (0.100 g,
81%). The NMR date was agreement with the literature2a.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 13
6H), 7.16 (d, J = 6.8 Hz, 2H), 2.35 (q, J = 7.4 Hz, 2H), 1.04 (t, J = 7.4
6-(4-chlorophenyl)-5-iodo-2H-pyran-2-one (5g)
Hz, 3H), 13C{1H} NMR: (100 MHz, CDCl3) 162.1 (s), 157.9 (s), 155.7
(s), 140.8 (s), 134.9 (s), 130.3 (d), 129.6 (d), 128.6 (d), 128.5 (d), 128.0
(d), 127.5 (d), 127.3 (s), 77.5 (s), 23.4 (t), 13.1 (q), HRMS: (EI, 70 eV)
Calculated (C19H15O2I) 402.0122 (M+) Found 402.0117.
1
2
3
4
5
6
7
8
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-5-(4-chlorophenyl)pent-2-en-4-ynoate
(0.499 mmol, 0.110 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.324 g, 1.01 mmol) in THF (2.5 mL) was added to the reac-
tion mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (5 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (2 x 30 mL) and the combined or-
ganic solution was washed by sat. Na2S2O3 aq (25 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The resulting oily residue
was purified by column chromatography (hexane/ethyl acetate = 95:5,
column length 11 cm, diameter 26 mm, spherical silica gel) Product-
containing fractions were combined and concentrated in vacuo to give
the product as a yellow solid (0.115 g, 71%). IR: (KBr) 1715 (C=O)
cm-1, mp: 129-130 °C, 1H NMR: (400 MHz, CDCl3) 7.70 (d, J = 8.2 Hz,
2H), 7.63 (d, J = 9.7 Hz, 1H), 7.43 (d, J = 8.2 Hz, 2H), 6.12 (d, J = 9.7
Hz, 1H), 13C{1H} NMR: (100 MHz, CDCl3) 160.3 (s), 159.4 (s), 152.8
(d), 136.8 (s), 131.6 (s), 130.5 (d), 128.4 (d), 115.6 (d), 66.8 (s), HRMS:
(EI, 70 eV) Calculated (C11H6ClO2I) 331.9101 (M+) Found 331.9098.
5-iodo-6-(p-tolyl)-2H-pyran-2-one (5d)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-5-(p-tolyl)pent-2-en-4-ynoate (0.510 mmol,
0.102 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h. Then, iodobenzene diacetate
(0.324 g, 1.01 mmol) in THF (2.5 mL) was added to the reaction mix-
ture at room temperature. After stirring for 24 h, the mixture was
quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was ex-
tracted by dichloromethane (2 x 30 mL) and the combined organic so-
lution was washed by sat. Na2S2O3 aq. (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.131 g, 84%). IR: (KBr) 1715 (C=O) cm-1, mp: 83-
84 °C, 1H NMR: (400 MHz, CDCl3) 7.68-7.61 (m, 3H), 7.27 (d, J = 7.7
Hz, 2H), 6.09 (d, J = 9.7 Hz, 1H), 2.42 (s, 3H), 13C{1H} NMR: (100
MHz, CDCl3) 161.05 (s), 160.98 (s), 153.2 (d), 141.4 (s), 130.5 (s),
129.2 (d), 128.9 (d), 115.2 (d), 66.2 (s), 21.6 (q), HRMS : (EI, 70 eV)
Calculated (C12H9O2I) 311.9647 (M+) Found 311.9649.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6-(3-fluorophenyl)-5-iodo-2H-pyran-2-one (5h)
To a 10 mL vial filled with InI3 (0.507 mmol, 0.251 g) in toluene (1
mL) was added methyl (Z)-5-(3-fluorophenyl)pent-2-en-4-ynoate
(0.509 mmol, 0.104 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.195 g, 0.604 mmol) in THF (2.5 mL) was added to the re-
action mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (3 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (2 x 30 mL) and combined organic
solution was washed by sat. Na2S2O3 aq (25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel). Product-containing
fractions were combined and concentrated in vacuo to give the product
as a yellow solid (0.126 g, 80%). IR: (KBr) 1724 (C=O) cm-1, mp: 82-
83 °C, 1H NMR: (400 MHz, CDCl3) 7.64 (d, J = 9.7 Hz, 1H), 7.55 (d,
J = 7.7 Hz, 1H), 7.46-7.43 (m, 2H), 7.20 (m, 1H), 6.14 (d, J = 9.7 Hz,
6-{4-(tert-butyl)phenyl}-5-iodo-2H-pyran-2-one (5e)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-5-{4-(tert-butyl)phenyl}pent-2-en-4-ynoate
(0.499 mmol, 0.121 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.331 g, 1.03 mmol) in THF (2.5 mL) was added to the reac-
tion mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was
extracted by dichloromethane (2 x 30 mL) and the combined organic
solution was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethel acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.150 g, 84%). IR: (KBr) 1731 (C=O) cm-1,mp: 107-
109 °C, 1H NMR: (400 MHz, CDCl3) 7.71 (d, J = 8.7 Hz, 2H), 7.63 (d,
J = 9.2 Hz, 1H), 7.47 (d, J = 8.7 Hz, 2H), 6.08 (d, J = 9.2 Hz, 1H), 1.35
(s, 9H), 13C{1H} NMR: (100 MHz, CDCl3) 160.92 (s), 160.88 (s), 154.3
(s), 153.2 (d), 130.4 (s), 129.0 (d), 125.1 (d), 115.1 (d), 66.0 (s), 35.0
(s), 31.1 (q), HRMS : (EI, 70 eV) Calculated (C15H15O2I) 354.0117
(M+) Found 354.0111.
1
1H), 13C{1H} NMR: (100 MHz, CDCl3) 162.1 (d, JCF = 247.4 Hz),
160.3 (s), 159.2 (s), 152.9 (d), 135.1 (d, 3JCF = 8.2 Hz), 130.0 (dd, 3JCF
= 8.2 Hz), 125.1 (dd, 4JCF = 3.3 Hz), 117.9 (dd, 2JCF = 21.3 Hz), 116.5
(dd, 2JCF = 23.8 Hz), 116.0 (d), 67.0 (s), HRMS : (EI, 70 eV) Calculated
(C11H6FO2I) 315.9397 (M+) Found 315.9397.
6-hexyl-5-iodo-2H-pyran-2-one (5i)
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-undec-2-en-4-ynoate (0.500 mmol, 0.0971
g) in a nitrogen-filled glove box. The vial was sealed, and the mixture
was stirred at 80 °C for 24 h. Then, iodobenzene diacetate (0.331 g,
1.03 mmol) in THF (2.5 mL) was added to the reaction mixture at room
temperature. After stirring for 24 h, the mixture was quenched by water
(5 mL), 1 M HCl aq (1 mL). The solution was extracted by dichloro-
methane (2 x 30 mL) and the combined organic solution was washed
by sat. Na2S2O3 aq. (1 x 25 mL), dried over MgSO4, filtered, and con-
centrated in vacuo. The resulting oily residue was purified by column
chromatography (hexane/ethyl acetate = 95:5, column length 11 cm,
diameter 26 mm, spherical silica gel). Product-containing fractions
were combines and concentrated in vacuo to give the product as a yel-
low oil (0.115 g, 75%). The NMR date was agreement with the litera-
ture15.
5-iodo-6-(4-methoxyphenyl)-2H-pyran-2-one (5f)
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-5-(4-methoxyphenyl)pent-2-en-4-ynoate
(0.513 mmol, 0.111 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.330 g, 1.02 mmol) in THF (2.5 mL) was added to the reac-
tion mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (5 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (2 x 30 mL) and the combined or-
ganic solution was washed by sat. Na2S2O3 aq (25 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The resulting oily residue
was purified by column chromatography (hexane/ethyl acetate = 95:5,
column length 11 cm, diameter 26 mm, spherical silica gel). Product-
containing fractions were combined and concentrated in vacuo to give
the product as a yellow solid (0.139 g, 85%). IR: (KBr) 1748 (C=O)
cm-1, mp: 117-118 °C, 1H NMR: (400 MHz, CDCl3) 7.74 (d, J = 8.7 Hz,
2H), 7.62 (d, J = 9.7 Hz, 1H), 6.95 (d, J = 8.7 Hz, 2H), 6.05 (d, J = 9.7
Hz, 1H), 3.85 (s, 3H), 13C{1H} NMR: (100 MHz, CDCl3) 161.3 (s),
160.9 (s), 160.5 (s), 153.3 (d), 130.9 (d), 125.4 (s), 114.5 (d), 113.4 (d),
65.5 (s), 55.3 (q), HRMS : (EI, 70 eV) Calculated (C12H9O3I) 327.9596
(M+) Found 327.9601.
6-cyclopropyl-5-iodo-2H-pyran-2-one (5j)
To a 10 mL vial filled with InI3 (0.501 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-5-cyclopropylpent-2-en-4-ynoate (0.507
mmol, 0.0762 g) in a nitrogen-filled glove box. The vial was sealed,
and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene diac-
etate (0.334 g, 1.04 mmol) in THF (2.5 mL) was added to the reaction
mixture at room temperature. After stirring for 24 h, the mixture was
quenched by water (3 mL) and 1 M HCl aq (1 mL). The solution was
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The Journal of Organic Chemistry
extracted by dichloromethane (2 x 30 mL) and combined organic solu-
tion was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
as a yellow solid (0.1424 g, 63%). The NMR date was agreement with
the literature3d.
1
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel). Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.105 g, 64%). IR: (KBr) 1714 (C=O) cm-1, mp: 87-
88 °C, 1H NMR: (400 MHz, CDCl3) 7.44 (d, J = 9.2 Hz, 1H), 5.92 (d,
J = 9.2 Hz, 1H), 2.24-2.17 (m, 1H), 1.21-1.20 (m, 2H), 1.07-1.05 (m,
2H), 13C{1H} NMR: (100 MHz, CDCl3) 165.3 (s), 160.7 (s), 151.9 (d),
113.1 (d), 66.2 (s), 17.5 (d), 9.8 (t), HRMS: (EI, 70 eV) Calculated
(C8H7O2I) 261.9491 (M+) Found 261.9490.
2
3
4
5
6
7
8
9
5-bromo-3-ethyl-4,6-diphenyl-2H-pyran-2-one (5n)
To a 10 mL vial filled with InBr3 (0.499 mmol, 0.177 g) in toluene
(1 mL) was added methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate
(0.496 mmol, 0.144 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.324 g, 1.01 mmol) in THF (2.5 mL) was added to the reac-
tion mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (3 mL) and 1 M HCl aq (1 mL). The solution
was extracted by dichloromethane (3 x 20 mL) and combined organic
solution was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel). Product-containing
fractions were combined and concentrated in vacuo to give the product
as a yellow solid (0.0812 g, 46%). IR: (KBr) 1714 (C=O) cm-1, mp:
114-116 °C, 1H NMR: (400 MHz, CDCl3) 7.79-7.78 (m, 2H), 7.50-7.46
(m, 6H), 7.20 (d, J = 6.8 Hz, 2H), 2.33 (q, J = 7.2 Hz, 2H), 1.05 (t, J =
7.2 Hz, 3H), 13C{1H} NMR: (100 MHz, CDCl3) 161.7 (s), 155.0 (s),
153.6 (s), 137.3 (s), 132.6 (s), 130.3 (d), 129.3 (d), 128.5 (d), 128.4 (d),
128.2 (s), 128.1 (d), 127.6 (d), 102.7 (s), 22.9 (t), 13.0 (q), HRMS: (EI,
70 eV) Calculated (C19H15O2Br) 354.0255 (M+) Found 354.0253
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
methyl 5-iodo-2-oxo-6-phenyl-2H-pyran-3-carboxylate (5k)
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added dimethyl 2-(3-phenylprop-2-yn-1-ylidene)malonate
(0.501 mmol, 0.122 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene
diacetate (0.318 g, 0.987 mmol) in THF (2.5 mL) was added to the re-
action mixture at room temperature. After stirring for 24 h, the mixture
was quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was
extracted by dichloromethane (2 x 30 mL) and combined organic solu-
tion was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
as a yellow solid (0.0920 g, 52%). IR: (KBr) 1757 (C=O) cm-1, mp:
144-146 °C, 1H NMR: (400 MHz, CDCl3) 8.53 (s, 1H), 7.82 (d, J = 7.2
Hz, 2H), 7.58-7.47 (m, 3H), 3.94 (s, 3H), 13C{1H} NMR: (100 MHz,
CDCl3) 165.5 (s), 162.7 (s), 158.9 (d), 156.6 (s), 132.5 (s), 131.8 (d),
129.4 (d), 128.3 (d), 115.7 (s), 64.8 (s), 53.0 (q), HRMS: (EI, 70 eV)
Calculated (C13H9O4I) 355.9546 (M+) Found 355.9550.
5,6-diphenyl-2H-pyran-2-one (6a)
To a 10 mL vial filled with InI3 (0.507 mmol, 0.251 g) in toluene (1
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate (0.499 mmol,
0.0930 g) in a nitrogen-filled glove box. The vial was sealed and the
mixture was stirred at 80 °C for 24 h. Then, Pd2dba3 (0.0317 mmol,
0.0290 g), NaOMe (1.02 mmol, 0.0551 g), iodobenzene (0. 350 mmol,
0.0715 g), DMF (2.5 mL) were added to the reaction mixture at room
temperature. After stirring at 110 °C for 24 h, the mixture was quenched
by water (5 mL), and 1 M HCl aq (1 mL). The solution was extracted
by dichloromethane (3 x 30 mL) and dried over MgSO4, filtered, and
concentrated in vacuo. The resulting oily residue was purified by col-
umn chromatography (hexane/ethyl acetate = 80:20, column length 11
cm, diameter 26 mm, spherical silica gel). Product-containing fractions
were combined and concentrated in vacuo to give the product as a pale
yellow solid (0.0834 g, 96%). The NMR date was agreement with the
literature3b.
6-cyclopropyl-3-ethyl-5-iodo-4-phenyl-2H-pyran-2-one (5l)
To a 10 mL vial filled with InI3 (0.301 mmol, 0.149 g) in toluene (1
mL) was added methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-en-
4-ynoate (0.30 mmol, 0.0765 g) in a nitrogen-filled glove box. The vial
was sealed, and the mixture was stirred at 80 °C for 24 h. Then, iodo-
benzene diacetate (0.195 g, 0.604 mmol) in THF (2.5 mL) was added
to the reaction mixture at room temperature. After stirring for 24 h, the
mixture was quenched by water (3 mL), 1 M HCl aq (1 mL). The solu-
tion was extracted by dichloromethane (2 x 30 mL) and combined or-
ganic solution was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The resulting oily residue
was purified by column chromatography (hexane/ethyl acetate = 95:5,
column length 11 cm, diameter 26 mm, spherical silica gel). Product-
containing fractions were combines and concentrated in vacuo to give
the product as a yellow solid (0.0701 g, 64%). IR: (KBr) 1714 (C=O)
4,5,6-triphenyl-2H-pyran-2-one (6b)
To a 10 mL vial filled with InI3 (0.505 mmol, 0.250 g) in toluene (1
mL) was added methyl (Z)-3,5-diphenylpent-2-en-4-ynoate (0.499
mmol, 0.131 g) in a nitrogen-filled glove box. The vial was sealed and
the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3 (0.0317 mmol,
0.0290 g), NaOMe (1.02 mmol, 0.0551 g), iodobenzene (0. 350 mmol,
0.0715 g), DMF (2.5 mL) were added to the reaction mixture at room
temperature. After stirring at 110 °C for 24 h, the mixture was quenched
by water (5 mL), and 1 M HCl aq (1 mL). The solution was extracted
by dichloromethane (3 x 30 mL) and dried over MgSO4, filtered, and
concentrated in vacuo. The resulting oily residue was purified by col-
umn chromatography (hexane/ethyl acetate = 80:20, column length 11
cm, diameter 26 mm, spherical silica gel). Product-containing fractions
were combined and concentrated in vacuo to give the product as a pale
yellow solid (0.0727 g, 64%). The NMR date was agreement with the
literature18.
1
cm-1, mp: 83-84 °C, H NMR: (400 MHz, CDCl3) 7.49-7.40 (m, 3H),
7.08-7.05 (m, 2H), 2.40-2.38 (m, 1H), 2.24 (q, J = 7.5 Hz, 2H), 1.28-
1.16 (m, 2H), 1.05-1.00 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H), 13C{1H}
NMR: (100 MHz, CDCl3) 161.9 (s), 161.1 (s), 155.6 (s), 140.7 (s),
128.40 (d), 128.36 (d), 127.3 (s), 125.0 (s), 76.5 (s), 23.1 (t), 18.3 (d,
C-13), 13.1 (q, C-8), 9.4 (t, C-14), HRMS: (EI, 70 eV) Calculated
(C16H15O2I) 366.0117 (M+) Found 366.0113.
5-iodo-3,4,6-triphenyl-2H-pyran-2-one (5m)
To a 10 mL vial filled with InI3 (0.503 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-2,3,5-triphenylpent-2-en-4-ynoate (0.499
mmol, 0.1691 g) in a nitrogen-filled glove box. The vial was sealed,
and the mixture was stirred at 80 °C for 24 h. Then, iodobenzene diac-
etate (0.331 g, 1.03 mmol) in THF (2.5 mL) was added to the reaction
mixture at room temperature. After stirring for 24 h, the mixture was
quenched by water (5 mL), 1 M HCl aq (1 mL). The solution was ex-
tracted by dichloromethane (2 x 30 mL) and the combined organic so-
lution was washed by sat. Na2S2O3 aq (1 x 25 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The resulting oily residue was pu-
rified by column chromatography (hexane/ethyl acetate = 95:5, column
length 11 cm, diameter 26 mm, spherical silica gel) Product-containing
fractions were combines and concentrated in vacuo to give the product
3-ethyl-4,5,6-triphenyl-2H-pyran-2-one (6c)
To a 10 mL vial filled with InI3 (0.507 mmol, 0.251 g) in toluene (1
mL) was added methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate
(0.503 mmol, 0.146 g) in a nitrogen-filled glove box. The vial was
sealed and the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3
(0.0317 mmol, 0.0290 g), NaOMe (1.02 mmol, 0.0551 g), iodobenzene
(0. 350 mmol, 0.0715 g), DMF (2.5 mL) were added to the reaction
mixture at room temperature. After stirring at 110 °C for 24 h, the mix-
ture was quenched by water (5 mL), and 1 M HCl aq (1 mL). The so-
lution was extracted by dichloromethane (3 x 30 mL) and dried over
MgSO4, filtered, and concentrated in vacuo. The resulting oily residue
was purified by column chromatography (hexane/ethyl acetate = 80 :
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The Journal of Organic Chemistry
Page 10 of 13
20, column length 11 cm, diameter 26 mm, spherical silica gel). Prod-
(C=O) cm-1, mp: 109-111 °C, 1H NMR: (400 MHz, CDCl3) 7.16-7.06
uct-containing fractions were combined and concentrated in vacuo to
give the product as a pale yellow solid (0.0987 g, 80%). IR: (KBr) 1706
(C=O) cm-1, mp: 159-161 °C, 1H NMR: (400 MHz, CDCl3) 7.28 (d, J
= 8.7 Hz, 2H), 7.22-7.14 (m, 6H), 7.04-6.99 (m, 3H), 6.95-6.92 (m, 2H),
6.86-6.82 (m, 2H), 2.37 (q, J = 7.4 Hz, 2H), 1.09 (t, J = 7.4 Hz, 3H),
13C{1H} NMR: (100 MHz, CDCl3) 162.8 (s), 154.7 (s), 154.5 (s), 136.3
(s), 135.1 (s), 132.7 (s), 131.1 (d), 129.1 (d), 128.1 (d), 127.9 (d),
127.81 (d), 127.78 (d), 127.4 (d), 127.0 (d), 126.7 (s), 119.4 (s), 22.0
(t), 13.3 (q), HRMS: (EI, 70 eV) Calculated (C25H20O2) 352.1463 (M+)
Found 352.1465.
(m, 6H), 6.80-6.78 (m, 2H), 6.60 (d, J = 8.2 Hz, 1H), 3.58 (s, 3H), 2.32-
2.22 (m, 2H), 1.56-1.51 (m, 1H), 1.20-1.18 (m, 2H), 1.02 (t, J = 7.5 Hz,
3H), 0.81-0.76 (m, 2H), 13C{1H} NMR: (100 MHz, CDCl3) 163.3 (s),
159.1 (s), 157.0 (s), 154.8 (s), 136.7 (s), 132.5 (d), 129.2 (d), 127.8 (d),
127.6 (d), 127.2, 127.15, 127.10, 124.0 (s), 123.5 (d), 120.0 (d), 114.7
(s), 110.2 (d), 54.9 (q), 21.7 (t), 13.4 (q), 12.2 (d), 8.13 (t), 8.06 (t),
HRMS: (EI, 70 eV) Calculated (C23H22O3) 346.1569 (M+) Found
346.1570.
1
2
3
4
5
6
7
8
6-cyclopropyl-3-ethyl-5-(4-nitrophenyl)-4-phenyl-2H-pyran-
2-one (6o)
9
6-cyclopropyl-3-ethyl-4,5-diphenyl-2H-pyran-2-one (6l)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To a 10 mL vial filled with InI3 (0.520 mmol, 0.258 g) in toluene (1
mL) was added methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-en-
4-ynoate (0.500 mmol, 0.127 g) in a nitrogen-filled glove box. The vial
was sealed and the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3
(0.0263 mmol, 0.0241 g), NaOMe (0.990 mmol, 0.0540 g), 1-iodo-4-
nitrobenzene (0.354 mmol, 0.0881 g), and DMF (2.5 mL) were added
to the reaction mixture at room temperature. After stirring at 110 °C for
24 h, the mixture was quenched by water (5 mL) and 1 M HCl aq (1
mL). The solution was extracted by dichloromethane (3 x 30 mL) and
dried over MgSO4, filtered, and concentrated in vacuo. The resulting
oily residue was purified by column chromatography (hexane/ethyl ac-
etate = 80:20, column length 11 cm, diameter 26 mm, spherical silica
gel). Product-containing fractions were combined and concentrated in
vacuo to give the product as a yellow solid (0.102 g, 80%). IR: (KBr)
1714 (C=O) cm-1, mp: 167-169 °C, 1H NMR: (400 MHz, CDCl3) 8.01
(d, J = 8.2 Hz, 2H), 7.24-7.15 (m, 5H), 6.93-6.86 (m, 2H), 2.29 (q, J =
7.4 Hz, 2H), 1.52-1.46 (m, 1H), 1.30-1.24 (m, 2H), 1.03 (t, J = 7.4 Hz,
3H), 0.90-0.83 (m, 2H), 13C{1H} NMR: (100 MHz, CDCl3) 162.2 (s),
159.6 (s), 152.8 (s), 146.7 (s), 142.6 (s), 135.8 (d), 132.1 (d), 128.2 (s),
128.0 (s), 127.8 (s), 124.5 (s), 123.1 (d), 116.6 (s), 21.7 (t), 13.3 (q),
12.6 (d), 8.9 (t), HRMS: (EI, 70 eV) Calculated (C22H19NO4) 361.1314
(M+) Found 361.1312.
To a 10 mL vial filled with InI3 (0.300 mmol, 0.148 g) in toluene
(0.6 mL) was added methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-
en-4-ynoate (0.300 mmol, 0.0763 g) in a nitrogen-filled glove box. The
vial was sealed and the mixture was stirred at 80 °C for 24 h. Then,
Pd2dba3 (0.0165mmol, 0.0151 g), NaOMe (0.583 mmol, 0.0315 g), io-
dobenzene (0.225 mmol, 0.046 g), DMF (1.5 mL) were added to the
reaction mixture at room temperature. After stirring at 110 °C for 24 h,
the mixture was quenched by water (5 mL), and 1 M HCl aq (1 mL).
The solution was extracted by dichloromethane (3 x 30 mL) and dried
over MgSO4, filtered, and concentrated in vacuo. The resulting oily res-
idue was purified by column chromatography (hexane/ethyl acetate =
80:20, column length 11 cm, diameter 26 mm, spherical silica gel).
Product-containing fractions were combined and concentrated in vacuo
to give the product as a pale yellow solid (0.0605 g, 85%). IR: (KBr)
1699 (C=O) cm-1, mp: 138-140 °C, 1H NMR: (400 MHz, CDCl3) 7.18-
7.10 (m, 6H), 7.00 (d, J = 7.7 Hz, 2H), 6.90 (d, J = 7.2 Hz, 2H), 2.28
(q, J = 7.4 Hz, 2H), 1.62-1.57 (m, 1H), 1.23-1.19 (m, 2H), 1.02 (t, J =
7.4 Hz, 3H), 0.83-0.78 (m, 2H), 13C{1H} NMR: (100 MHz, CDCl3)
162.9 (s), 159.2 (s), 154.1 (s), 136.6 (s), 135.1 (s), 131.0 (d), 128.0 (d),
127.9 (d), 127.7 (d), 127.3 (d), 126.9 (d), 123.7 (s), 118.3 (s), 21.7 (t),
13.4 (q), 12.4 (d), 8.5 (t), HRMS: (EI, 70 eV) Calculated (C22H20O2)
316.1463 (M+) Found 316.1460.
5-(4-methylbenzoyl)-6-phenyl-2H-pyran-2-one (7a)
3,4,5,6-tetraphenyl-2H-pyran-2-one (6m)
To a 10 mL vial filled with InI3 (0.502 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-5-phenylpent-2-en-4-ynoate (0.499 mmol,
0.0930 g) in a nitrogen-filled glove box. The vial was sealed, and the
mixture was stirred at 80 °C for 24 h. Then, Pd2dba3 (0.0262 mmol,
0.0240 g), p-toluoyl chloride (0.990 mmol, 0.153 g), DMI (2.5 mL)
were added to the reaction mixture at room temperature. After stirring
at 110 °C for 24 h, the mixture was quenched by water (5 mL), and 1
M HCl aq (1 mL). The solution was extracted by dichloromethane (3 x
30 mL) and dried over MgSO4, filtered, and concentrated in vacuo. The
resulting oily residue was purified by column chromatography (hex-
ane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm,
spherical silica gel). Product-containing fractions were combined and
concentrated in vacuo to give the product as a yellow oil (0.0595 g,
41%). IR: (neat) 1743 (C=O), 1651 (C=O) cm-1, 1H NMR: (400 MHz,
CDCl3) 7.60 (d, J = 8.2 Hz, 2H), 7.57 (d, J = 9.4 Hz, 1H), 7.47 (d, J =
8.2 Hz, 2H), 7.32-7.27 (m, 1H), 7.23 (t, J = 8.2 Hz, 2H), 7.08 (d, J =
8.2 Hz, 2H), 6.39 (d, J = 9.4 Hz, 1H), 2.31 (s, 3H), 13C{1H} NMR: (100
MHz, CDCl3) 193.3 (s), 163.0 (s), 160.7 (s), 144.7 (s), 144.5 (d), 133.5
(s), 131.22 (d), 131.16 (s), 129.8 (d), 129.2 (d), 128.9 (d), 128.4 (d),
116.6 (s), 113.6 (d), 21.6 (q), HRMS: (EI, 70 eV) Calculated
(C19H14O3) 290.0943 (M+) Found 290.0941.
To a 10 mL vial filled with InI3 (0.300 mmol, 0.148 g) in toluene
(0.6 mL) was added methyl (Z)-2,3,5-triphenylpent-2-en-4-ynoate
(0.300 mmol, 0.0763 g) in a nitrogen-filled glove box. The vial was
sealed and the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3
(0.0165mmol, 0.0151 g), NaOMe (0.583 mmol, 0.0315 g), iodoben-
zene (0.225 mmol, 0.046 g), DMF (1.5 mL) were added to the reaction
mixture at room temperature. After stirring at 110 °C for 24 h, the mix-
ture was quenched by water (5 mL), and 1 M HCl aq (1 mL). The so-
lution was extracted by dichloromethane (3 x 30 mL) and dried over
MgSO4, filtered, and concentrated in vacuo. The resulting oily residue
was purified by column chromatography (hexane/ethyl acetate = 80:20,
column length 11 cm, diameter 26 mm, spherical silica gel). Product-
containing fractions were combined and concentrated in vacuo to give
the product as a white solid (0.0712 g, 79%). The NMR date was agree-
ment with the literature3b. This compound was identified by X-ray crys-
tallographic analysis (CCDC 1910558).
6-cyclopropyl-3-ethyl-5-(4-methoxyphenyl)-4-phenyl-2H-py-
ran-2-one (6n)
To a 10 mL vial filled with InI3 (0.520 mmol, 0.258 g) in toluene (1
mL) was added methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-en-
4-ynoate (0.500 mmol, 0.127 g) in a nitrogen-filled glove box. The vial
was sealed and the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3
(0.0285 mmol, 0.0261 g), NaOMe (0.102 mmol, 0.0551 g), 4-iodoan-
isole (0.0351 mmol, 0.0821 g), and DMF (2.5 mL) were added to the
reaction mixture at room temperature. After stirring at 110 °C for 24 h,
the mixture was quenched by water (5 mL), and 1 M HCl aq (1 mL).
The solution was extracted by dichloromethane (3 x 30 mL) and dried
over MgSO4, filtered, and concentrated in vacuo. The resulting oily res-
idue was purified by column chromatography (hexane/ethyl acetate =
80:20, column length 11 cm, diameter 26 mm, spherical silica gel).
Product-containing fractions were combined and concentrated in vacuo
to give the product as a yellow solid (0.101 g, 80%). IR: (KBr) 1698
5-(4-methylbenzoyl)-4,6-diphenyl-2H-pyran-2-one (7b)
To a 10 mL vial filled with InI3 (0.507 mmol, 0.251 g) in toluene (1
mL) was added methyl (Z)-3,5-diphenylpent-2-en-4-ynoate (0.511
mmol, 0.134 g) in a nitrogen-filled glove box. The vial was sealed, and
the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3 (0.0247 mmol,
0.0226 g), p-toluoyl chloride (0.100 mmol, 0.155 g), DMI (2.5 mL)
were added to the reaction mixture at room temperature. After stirring
at 110 °C for 24 h, the mixture was quenched by water (5 mL), and 1
M HCl aq (1 mL). The solution was extracted by dichloromethane (3 x
30 mL) and dried over MgSO4, filtered, and concentrated in vacuo. The
resulting oily residue was purified by column chromatography (hex-
ane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm,
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The Journal of Organic Chemistry
spherical silica gel). Product-containing fractions were combined and
concentrated in vacuo. The resulting oily residue was purified by col-
umn chromatography (hexane/ethyl acetate = 80 : 20, column length 11
cm, diameter 26 mm, spherical silica gel). Product-containing fractions
were combined and concentrated in vacuo to give the product as a white
solid (0.0419 g, 39%). IR: (KBr) 1715 (C=O), 1659 (C=O) cm-1, mp:
concentrated in vacuo to give the product as a white solid (0.101 g,
55%). IR: (KBr) 1724 (C=O), 1662 (C=O) cm-1, mp: 199-201 °C, d1H
NMR: (400 MHz, CDCl3) 7.58-7.53 (m, 4H), 7.32-7.19 (m, 8H), 7.05
(d, J = 8.2 Hz, 2H), 6.36 (s, 1H), 2.29 (s, 3H), 13C{1H} NMR: (100
MHz, CDCl3) 193.4 (s), 161.0 (s), 159.9 (s), 157.2 (s), 144.8 (s), 135.9
(s), 134.7 (s), 131.5 (s), 130.9 (d), 129.4 (d), 129.3 (d), 128.6 (d),
128.52 (d), 128.45 (d), 127.5 (d), 118.0 (s), 113.2 (d), 21.7 (q), HRMS :
(EI, 70 eV) Calculated (C25H18O3) 366.1256 (M+) Found 366.1259.
1
2
3
4
5
6
7
8
1
120-121 °C, H NMR: (400 MHz, CDCl3) 7.60 (d, J = 8.2 Hz, 2H),
7.17-7.15 (m, 5H), 6.99-6.98 (m, 2H), 2.37 (s, 3H), 2.29 (q, J = 7.4 Hz,
2H), 1.62-1.58 (m, 1H), 1.26-1.25 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H),
0.88-0.86 (m, 2H), 13C{1H} NMR: (100 MHz, CDCl3) 194.0 (s), 162.1
(s), 160.5 (s), 151.3 (s), 144.6 (s), 135.2 (s), 135.1 (s), 129.5 (d), 129.2
(d), 128.1 (d), 128.0 (d), 127.7 (d), 124.5 (s), 118.2 (s), 21.7 (q), 21.1
(t), 13.2 (q), 12.9 (d), 8.9 (t), HRMS: (EI, 70 eV) Calculated (C24H22O3)
358.1569 (M+) Found 358.1567. This compound was identified by X-
ray crystallographic analysis (CCDC 1910561).
3-ethyl-5-(4-methylbenzoyl)-4,6-diphenyl-2H-pyran-2-one
(7c)
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13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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31
32
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34
35
36
37
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39
40
41
42
43
44
45
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47
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60
To a 10 mL vial filled with InI3 (0.502 mmol, 0.249 g) in toluene (1
mL) was added methyl (Z)-2-ethyl-3,5-diphenylpent-2-en-4-ynoate
(0.506 mmol, 0.147 g) in a nitrogen-filled glove box. The vial was
sealed, and the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3
(0.0263 mmol, 0.0229 g), p-toluoyl chloride (0.996 mmol, 0.154 g),
DMI (2.5 mL) were added to the reaction mixture at room temperature.
After stirring at 110 °C for 24 h, the mixture was quenched by water (5
mL), and 1 M HCl aq (1 mL). The solution was extracted by dichloro-
methane (3 x 30 mL) and dried over MgSO4, filtered, and concentrated
in vacuo. The resulting oily residue was purified by column chroma-
tography (hexane/ethyl acetate = 80:20, column length 11 cm, diameter
26 mm, spherical silica gel). Product-containing fractions were com-
bined and concentrated in vacuo to give the product as a white solid
(0.0749 g, 38%). IR: (KBr) 1715 (C=O), 1661 (C=O) cm-1, mp: 192-
194 °C, 1H NMR: (400 MHz, CDCl3) 7.55 (d, J = 7.2 Hz, 2H), 7.49 (d,
J = 8.2 Hz, 2H), 7.28-7.20 (m, 6H), 7.03 (d, J = 8.2 Hz, 4H), 2.36 (q, J
= 7.2 Hz, 2H), 2.29 (s, 3H), 1.08 (t, J = 7.2 Hz, 3H), 13C{1H} NMR:
(100 MHz, CDCl3) 193.7 (s), 162.2 (s), 155.5 (s), 151.6 (s), 144.6 (s),
134.8 (s), 131.5 (s), 130.4 (d), 129.4 (d), 129.1 (d), 128.4 (d), 128.25
(d), 128.22 (d), 128.1 (d), 127.8 (d), 127.3 (s), 119.0 (s), 21.6 (s), 21.5
(s), 13.2 (s), HRMS: (EI, 70 eV) Calculated (C27H22O3) 394.1569 (M+)
Found 394.1574.
3,4,6-triphenyl-5-(phenylethynyl)-2H-pyran-2-one (8)
To a solution of 5-iodo-3,4,6-triphenyl-2H-pyran-2-one (0.206
mmol, 0.0928 g) and PdCl2(PPh3)2 (0.0245 mmol, 0.0172 g) in 1,4-di-
oxane (1 mL) was added tributyl(phenylethynyl)stannane (0.249 mmol,
0.0977 g). The mixture was stirred at 90 °C for 14 h. The mixture was
quenched by H2O (1 mL) and was extracted with dichloromethane (3 x
10 mL). The collected organic layer was dried over MgSO4. The sol-
vent was evaporated and the residue was purified by column chroma-
tography (hexane/ethyl acetate = 99:1, column length 10 cm, diameter
26 mm silica gel) to give the product (0.0555 g, 63%) IR: (KBr) 1722
(C=O) cm-1, mp : 208-210 °C, 1H NMR: (400 MHz, CDCl3) 8.30-8.26
(m, 2H), 7.52-7.50 (m, 3H), 7.28-7.16 (m, 13H), 6.95 (dd, J = 8.0, 1.7
Hz, 2H), 13C{1H} NMR: (100 MHz, CDCl3) 161.0 (s), 154.9 (s), 136.1
(s), 133.3 (s), 131.8 (s), 131.0 (s), 130.7 (d), 130.5 (d), 129.3 (d), 128.7
(d), 128.3 (d), 128.2 (d), 128.1 (d), 127.7 (d), 127.61 (d), 127.57 (d),
125.5 (d), 124.4 (s), 122.5 (s), 104.9 (d), 102.7 (s), 97.6 (s), 84.4 (s),
HRMS: (EI, 70 eV) Calculated (C31H20O2) 424.1463 (M+) Found
424.1466 This compound was identified by X-ray crystallographic
analysis (CCDC 1915263).
5-(4-methylbenzoyl)-3,4,6-triphenyl-2H-pyran-2-one (7m)
ASSOCIATED CONTENT
To a 10 mL vial filled with InI3 (0.500 mmol, 0.248 g) in toluene (1
mL) was added methyl (Z)-2,3,5-triphenylpent-2-en-4-ynoate (0.501
mmol, 0.169 g) in a nitrogen-filled glove box. The vial was sealed, and
the mixture was stirred at 80 °C for 24 h. Then, Pd2dba3 (0.0263 mmol,
0.0229 g), p-toluoyl chloride (1.01 mmol, 0.157 g), DMI (2.5 mL) were
added to the reaction mixture at room temperature. After stirring at
110 °C for 24 h, the mixture was quenched by water (5 mL), and 1 M
HCl aq (1 mL). The solution was extracted by dichloromethane (3 x 30
mL) and dried over MgSO4, filtered, and concentrated in vacuo. The
resulting oily residue was purified by column chromatography (hex-
ane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm,
spherical silica gel). Product-containing fractions were combined and
concentrated in vacuo to give the product as a white solid (0.0750 g,
Supporting Information
The Supporting Information is available free of charge on theACS
Publications websiteat DOI:.
Electronic Supplementary Information of NMR Spectra (PDF)
Electronic Supplementary Information of Computational Section
(PDF)
Electronic Supplementary Information of Observation of Zwitter-
ion 4b and Metalated 2-Pyrone 3b (PDF)
Electronic Supplementary Information of X-Ray Diffraction Data
of 6m, 7m, 7l, 8, 3b·pyridine, 4b (PDF)
34%). IR: (KBr) 1722 (C=O), 1663 (C=O) cm-1, mp: 158-159 °C, H
1
NMR: (400 MHz, CDCl3) 7.62 (d, J = 8.2 Hz, 2H), 7.56 (d, J = 8.2 Hz,
2H), 7.35-7.26 (m, 3H), 7.21-6.89 (m, 12H), 2.29 (s, 3H), 13C{1H}
NMR: (100 MHz, CDCl3) 193.5 (s), 161.5 (s), 157.5 (s), 152.7 (s),
144.7 (s), 134.9 (s), 134.8 (s), 133.0 (s), 131.5 (s), 130.8 (d), 130.6 (d),
129.4 (d), 129.2 (d), 128.9 (d), 128.51 (d), 128.50 (d), 128.1 (d), 127.8
(d), 127.7 (d), 125.2 (s), 119.3 (s), 21.7 (q), HRMS : (EI, 70 eV) Cal-
culated (C31H22O3) 442.1569 (M+) Found 442.1571. This compound
was identified by X-ray crystallographic analysis (CCDC 1910562).
AUTHOR INFORMATION
Corresponding Author
*nishimoto@chem.eng.osaka-u.ac.jp
*yasuda@chem.eng.osaka-u.ac.jp
ORCID
Tetsuji Yata: 0000-0002-2470-4905
Yuji Kita: 0000-0002-3729-4087
Yoshihiro Nishimoto: 0000-0002-7182-0503
Makoto Yasuda: 0000-0002-6618-2893
6-cyclopropyl-3-ethyl-5-(4-methylbenzoyl)-4-phenyl-2H-py-
ran-2-one (7l)
To a 10 mL vial filled with InI3 (0.301 mmol, 0.149 g) in toluene
(0.6 mL) was added methyl (Z)-5-cyclopropyl-2-ethyl-3-phenylpent-2-
en-4-ynoate (0.300 mmol, 0.0763 g) in a nitrogen-filled glove box. The
vial was sealed, and the mixture was stirred at 80 °C for 24 h. Then,
Pd2dba3 (0.0154 mmol, 0.0141 g), p-toluoyl chloride (0.598 mmol,
0.0924 g), DMI (1.6 mL) were added to the reaction mixture at room
temperature. After stirring at 110 °C for 24 h, the mixture was quenched
by water (5 mL), and 1 M HCl aq (1 mL). The solution was extracted
by dichloromethane (3 x 30 mL) and dried over MgSO4, filtered, and
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by JSPS KAKENHI grant number
JP15H05848 in the Middle Molecular Strategy, and also grants
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 13
and selective Stille cross-coupling of benzylic and allylic bromides us-
number JP16K05719, JP18K19079, JP18H01977, and
JP19K05455. Y. N. acknowledges support from the Frontier Re-
search Base for Global Young Researchers, Osaka University, of
the MEXT program, and from the Mitsui Chemicals Award in Syn-
thetic Organic Chemistry, in addition to the Shorai Foundation for
Science and Technology. We would like to thank Prof. Dr S. Mina-
kata and Prof. Dr Y. Takeda (Department of Applied Chemistry,
Osaka University, Japan) for suggestions concerning the analysis
of AIE.
ing bromobis(triphenylphosphine)(N-succinimide)palladium(II), Tet-
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Wagner, E. Troschke, J. T. W. Bray, S. B. Duckett, L. A. Hammarback,
J. S. Ward, J. Milani, N. E. Pridmore, A. C. Whitwood, J. M. Lynam,
I. J. S. Fairlamb, Manganese(I)‐Catalyzed C−H Activation: The Key
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Role of a 7‐Membered Manganacycle in H‐Transfer and Reductive
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