Carboxylate-Directed Addition of Aromatic C-H Bond to Aromatic Aldehydes under Ruthenium Catalysis

Article abstract of DOI:10.1021/acscatal.8b00680

We report that ruthenium complexes effectively catalyzed the carboxylate-directed addition of aromatic C-H bonds to aldehydes. The reactions of aromatic acids with a variety of aromatic aldehydes including unactivated ones proceeded efficiently to give the corresponding isobenzofuranone derivatives in high yields. The combination of ruthenium(II) complexes with tricyclohexylphosphine led to highly nucleophilic aryl-metal species, which enabled versatile [3 + 2] cycloaddition in the absence of a Lewis acid. This paper also demonstrates the application of supported ruthenium catalysts to the title reaction.

Full text of DOI:10.1021/acscatal.8b00680

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Article
Carboxylate-directed Addition of Aromatic C-H Bond
to Aromatic Aldehydes under Ruthenium Catalysis
Hiroki Miura, Sachie Terajima, and Tetsuya Shishido
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b00680 • Publication Date (Web): 31 May 2018
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Carboxylateꢀdirected Addition of Aromatic CꢀH Bond to
Aromatic Aldehydes under Ruthenium Catalysis
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Hiroki Miuraa,b,c*, Sachie Terajimaa, Tetsuya Shishidoa,b,c*
a
Department of Applied Chemistry, Graduate School of Urban Environmental Sciences,
Tokyo Metropolitan University, 1ꢀ1 MinamiꢀOsawa, Hachioji, Tokyo 192ꢀ0397, Japan
b Research Center for Hydrogen Energyꢀbased Society, Tokyo Metropolitan University, 1ꢀ1
MinamiꢀOsawa, Hachioji, Tokyo 192ꢀ0397, Japan
c
Elements Strategy Initiative for Catalysts & Batteries, Kyoto University, Katsura,
Nishikyoꢀku, Kyoto 615ꢀ8520, Japan
* Corresponding author: Tel: +81ꢀ42ꢀ677ꢀ2851 Fax: +81ꢀ42ꢀ677ꢀ2850 (H. Miura)
* Corresponding author: Tel: +81ꢀ42ꢀ677ꢀ2850 Fax: +81ꢀ42ꢀ677ꢀ2850 (T. Shishido)
Eꢀmail address: miuraꢀhiroki@tmu.ac.jp (H. Miura)
Eꢀmail address: shishidoꢀtetsuya@tmu.ac.jp (T. Shishido)
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Abstract
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We report that ruthenium complexes effectively catalyzed the carboxylateꢀdirected addition
of aromatic CꢀH bonds to aldehydes. The reactions of aromatic acids with a variety of
aromatic aldehydes including unactivated ones proceeded efficiently to give the
corresponding isobenzofuranone derivatives in high yields. The combination of ruthenium(II)
complexes with tricyclohexylphosphine led to highly nucleophilic arylꢀmetal species, which
enabled versatile [3+2] cycloaddition in the absence of a Lewis acid. This paper also
demonstrates the application of supported ruthenium catalysts to the title reaction.
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Keywords
Ruthenium, CꢀH activation, hydroxyalkylation, aromatic acids, aldehydes, isobenzofuranones
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1. Introduction
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The addition of an organometallic reagent to a carbon electrophile is one of the most
important tools for forming new CꢀC bonds. Grignard and related alkaline metallic reagents
are most commonly used for the labꢀscale syntheses of organic compounds due to their ease
of preparation from organohalides. However, these stoichiometric reactions form undesired
metallic wastes, which reduces their environmental compatibility. In contrast, direct
metalation of an aromatic CꢀH bond with the aid of chelating functionalities has recently been
regarded as a general method for the generation of arylꢀmetal species, and subsequent
functionalization by treatment with electrophiles and regeneration of an active metallic
reagent enables catalytic CꢀC bond formation.1 These concepts revolutionized the field of
arene functionalization since they avoid not only the formation of unwanted metallic waste
but also preactivation of the starting materials. In this context, direct aromatic CꢀH addition to
a carbonyl moiety by transitionꢀmetal catalysts can access stepꢀ and atomꢀeconomical
hydroxyalkylation.2–6 However, there are still remain some problems to be solved in this area.
The potentially low nucleophilicity of arylꢀtransition metal species requires highly
electrophilic coupling partners to achieve satisfactory catalytic turnover. In fact, substrates
with an electronꢀwithdrawing substituent on the carbonyl moiety have mainly been used in
examples of catalytic CꢀH hydroxyalkylation,7–12 which reduces the generality of this strategy
(Scheme 1(a)). Alternatively, the addition of Lewis acids to enhance the electrophilicity of the
carbonyl moiety improves the reaction efficiency and substrate scope (Scheme 1(b)).13,14
Nevertheless, the use of excess (more than 0.5 equivalents to substrate) of toxic metals would
still be undesirable from the perspective of green chemistry.
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On the other hand, much attention has been focused on the use of a carboxylate as a
chelating group in CꢀH activation,15 since this ubiquitous functionality can be introduced into
benzoꢀfused heterocycles by subsequent intramolecular cyclization.16–18 It can also be readily
removed from the products under transitionꢀmetal catalysis.19 However, the
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electronꢀwithdrawing nature of the carboxylate group decreases the rate of electrophilic CꢀH
metalation and the nucleophilicity of the generated arylꢀmetal species. Li’s group reported a
pioneering work on the Rhꢀcatalyzed [3+2] cycloaddition of aromatic acid with aldehyde,8
which realized the atomꢀ and stepꢀeconomical synthesis of isobenzofuranones, which are a
ubiquitous framework in natural products showing a broad range of bioactivity.20
Unfortunately, this catalysis is still severely limited with respect to the scope of aldehyde. On
the other hand, ruthenium complexes have been used as one of the most effective catalysts for
aromatic CꢀH functionalization.21,22 Particularly, [RuCl2(pꢀcymene)]2 showed high utility in
this synthetic method with the aid of bases. Very recently, the groups of Kim11, Ding12 and
Zhou14 independently demonstrated Ruꢀcatalyzed addition of aromatic CꢀH bond to aldehydes.
In these cases, however, the applicable aldehydes were limited to activated or lessꢀhindered
ones. These facts suggest that a novel strategy should be developed to establish a method for
efficient CꢀH addition to CꢀO multiple bonds with high generality regarding the substrate and
high environmental compatibility.
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Herein, we report rutheniumꢀcatalyzed the addition of an aromatic CꢀH bond to aldehydes.
A series of aromatic aldehydes, including unactivated ones, could be used under Ru catalysis
in the absence of a Lewis acid to give the corresponding isobenzofuranones in high yield.
Kinetic studies revealed that the combination of Ru catalysts with tricyclohexylphosphine
generated arylꢀmetal species with high nucleophilicity, which promoted the insertion of a
carbonyl moiety into an arylꢀmetal bond (Scheme 1(c)).
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Scheme 1. Transition metalꢀcatalyzed CꢀH addition to C=O bond.
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2. Results and discussion
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Initially, the catalytic effect of a ruthenium complex toward the carboxylateꢀdirected CꢀH
addition to an activated carbonyl moiety was investigated (Table 1). The combination of
oꢀtoluic acid (1a) and an aromatic aldehyde bearing a bistrifluoromethyl group (2a) in the
presence of a catalytic amount of base underwent functionalization of an aromatic CꢀH bond
and subsequent intramolecular cyclization to give isobenzofuranone 3aa as a sole product in a
moderate yield (entry 1). No reaction took place in the absence of KOAc (entry 2). The
addition of AgSbF6 significantly retarded the progress of the reaction (entry 3). Zinc salts as a
Lewis acid did not affect positively the present Ru catalysis (entries 4 and 5). In contrast, a
phosphine ligand enhanced the activity of Ru catalysts, and the reaction in the presence of
PPh3 gave 3aa in an improved yield (entry 6). Screening of the ligand showed that PCy3 was
the ligand of choice for the present Ru catalysis to provide 3aa in excellent yield (entry 7).
Airꢀstable HBF4 salt of PCy3 was also effective for the present catalytic reaction (entry 8). In
contrast, the addition of P(C6F5)3 did not result in the formation of any 3aa (entry 13),
indicating that strong electron donation from phosphine to the Ru center was crucial for the
present reaction. With the Ru/PCy3 catalytic system, the reaction of unactivated aldehyde (2b)
was carried out. Although the desired isobenzofuranone 3ab was obtained in only a very low
yield in the reaction under a diluted condition (entry 14), the reaction conducted under a
higher concentration of a Ru catalyst and 2b gave 3ab in an excellent yield of 96% (entry 17).
Despite the fact that organometallic reagents with high nucleophilicity generally exhibit poor
waterꢀtolerance, Ru catalysts often exhibit the high utility even for the reaction in aqueous
media.23–25 The present Ru/PCy3 system also showed high activity for the catalytic CꢀH
hydroxyalkylation even in the presence of 0.1 mL of water (entry 18). The reaction also
proceeded at 150 oC to give 3ab in good yield (entry 19), and an improved yield was obtained
under further concentrated condition (entry 20).
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Table 1. Optimization of reaction conditionsa
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entry
1
2c
3d
4d
additive
ꢀ
aldehyde / eq. to 1a product
Yield (%)b
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2a / 1.5
2b / 1.5
2b / 2.0
2b / 3.0
2b / 3.0
2b / 3.0
2b / 3.0
2b / 3.0
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ab
3ab
3ab
3ab
3ab
3ab
3ab
30
0
ꢀ
AgSbF6
ZnCl2
ZnBr2
PPh3
4
26
6
5d
6
52
99
85
37
35
61
2
7
PCy3
8
PCy3•HBF4
PnBu3•HBF4
PtBu3•HBF4
XPhos
SPhos
P(C6F5)3
PCy3
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17e
18e,f
19e,g
20g,h
0
7
PCy3
31
47
96
86
76
90
PCy3
PCy3
PCy3
PCy3
PCy3
aReaction conditions: 1a (0.50 mmol),
2
(1.5–3.0 eq. to 1a),
[RuCl2(pꢀcymene)]2 (0.025 mmol), KOAc (0.15 mmol), additive (0.05 mmol),
o
b
mesitylene (1.0 mL), at 170 C, 24 h, under Ar. Yields were determined by
c
GLC by using oꢀterphenyl as internal standard. Reaction without KOAc.
dAdditive (0.15 mmol) was used. Mesitylene (0.5 mL) was used. Water (0.1
e
f
g
o
h
mL) was added to the reaction mixture. Reaction at 150 C. Mesitylene
(0.25 mL) was used.
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With the present Ru/PCy3 catalytic system in hand, the scope of aromatic acid in the reaction
of unactivated aldehyde 2b was investigated (Table 2). The reactions of a series of ortho
methylꢀsubstituted aromatic acids (1b–1e) with unactivated aldehyde (2b) proceeded
efficiently to give the corresponding isoindolinones (3bb–3eb) in good to excellent yields.
1ꢀNaphthoic acid participated as a good coupling partner to produce 3fb in a good yield. The
reactions of metaꢀsubstituted aromatic acids also took place to afford 3gb and 3hb in
excellent yields. In these cases, functionalization predominantly occurred on the lessꢀhindered
ortho CꢀH bond. Both paraꢀsubstituted aromatic acids and the simplest aromatic acid, benzoic
acid, were also converted efficiently to 3ib–3mb. The doubleꢀfunctionalization of aromatic
CꢀH bonds was not observed under the present Ru catalysis. Furthermore,
orthoꢀfluoroꢀsubstituted isobenzofuranone 3ob was obtained in a satisfactory yield. Next, the
generality of aldehyde in the Ru/PCy3ꢀcatalyzed aromatic CꢀH addition was surveyed (Table
3). As demonstrated in the preceding study, aromatic aldehydes bearing electronꢀwithdrawing
groups on benzene rings were efficiently converted to the corresponding isobenzofuranones
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(3ac–3ah) in the reaction with 1a. Very recently, Gooßen and coworkers reported an elegant
study on carboxylateꢀdirected CꢀH arylation with aryl halide using a similar Ru catalytic
system,26 while the reactive bromo and iodo group on the arene remained intact during the
present CꢀH hydroxyalkylation. Isobenzofuranone with alkenyl and naphthyl group (3ai and
3aj) were obtained in high yield. The most intriguing feature of the present Ru catalysis is
reflected in the reaction of aromatic aldehydes with electronꢀdonating groups. The reaction of
paraꢀtolualdehyde efficiently proceeded to give 3ak in high yield. Furthermore, the present
Ru catalysis was effective even for the reaction of anisaldehydes to provide the corresponding
products (3al–3an) in high yields. Interestingly, steric hindrance by an orthoꢀmethoxy group
of aldehyde did not affect the reaction efficiency at all. Unfortunately, the reaction of aliphatic
aldehydes such as 1ꢀdecanal could not be used in the present catalytic system.
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Table 2. Scope of aromatic acida
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Table 3. Scope of aldehydea
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To learn more about the reaction mechanism, several kinetic studies on the CꢀH addition to
aldehydes were examined (Scheme 2). When 1c was treated with D2O in the presence of Ru
cat., KOAc and PCy3, 90% of the deuterium was incorporated at the orthoꢀposition of 1c
(Scheme 2, eq. (1)). This clearly indicates that the reaction involves the formation of a
ruthenacycle intermediate via carboxylateꢀdirected electrophilic metalation of an aromatic
CꢀH bond. Based on this result as well as the previous literature,2–8 a plausible mechanism for
the reaction under Ru catalysis is depicted in Scheme 3. Initially, the treatment of
[RuCl2(pꢀcymene)]2 with 2 equiv. of PCy3 gives mononuclear RuCl2(pꢀcymene)(PCy3).27
Then, ruthenium benzoate A is formed by treatment with potassium acetate. Subsequently,
carboxylateꢀdirected orthoꢀruthenation takes place to give ruthenacycle B, which undergoes
nucleophilic CꢀC bond formation to provide ruthenium alkoxide species D. Protonation of
two RuꢀO bonds by acids completes the catalytic cycle while generating
orthoꢀhydroxyalkylated aromatic acid. Finally, intramolecular dehydrative cyclization
provides isobenzofuranone as a final product. The remarkable effect of the addition of PCy3
on the catalytic activity should be reflected in the rateꢀlimiting step. The intermolecular
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kinetic isotope effect as estimated by the reaction of [D5]ꢀbenzoic acid (1k-d5) was found to
be 1.3 (Scheme 2, eq. (2)). This suggests that the formation of ruthenacycle via CꢀH bond
cleavage was not involved in the rateꢀlimiting step under the present Ru catalysis,28ꢀ30 which
is also supported by the reaction order of zero with respect to the benzoic acid concentration
(Figure 1(a)). In sharp contrast, the reaction orders for aldehyde and Ru catalyst were
estimated to be 0.8 and 1.3, respectively (Figures 1(b) and 1(c)). This indicates that the
nucleophilic addition of arylꢀmetal species to a carbonyl moiety should be the
rateꢀdetermining step in the present Ruꢀcatalyzed reaction. In general, Lewis acids are used to
increase the electrophilicity of a carbonyl moiety, which promotes coupling with a weakly
nucleophilic arylꢀmetal reagent. In contrast, a highly basic phosphine ligand was helpful for
enhancing the reaction rate under the present Ru catalysis. These results therefore suggest that
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the coordination of PCy3 to a Ru center should increase the nucleophilicity of the arylꢀmetal
species generated during the catalytic cycle, which remarkably promote the rateꢀlimiting CꢀC
bond formation step instead of activating aldehyde. Therefore, the generality of aromatic
aldehydes and environmental compatibility were improved. Preferential conversion of the
aromatic acid with an electronꢀdonating substituent in the intermolecular competition reaction
(Scheme 4) implies that electronꢀrich arenes are advantageous not only for the rapid
generation of ruthenacycle via electrophilic CꢀH metalation, but also for enhancing the
reactivity of arylꢀmetal nucleophiles.
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O
O
H
[RuCl2(p-cymene)]2
KOAc, PCy3
(D)
OH
(D)
OH
(1)
Mesitylene, D2O
170 oC, 24 h
H
90% D
D-1c
97% recovered
1c (0.50 mmol)
[RuCl2(p-cymene)]2
(0.025 mmol)
KOAc (0.15 mmol)
PCy3 (0.050 mmol)
O
O
O
+
O
OH
(2)
Mesitylene (0.5 mL)
H
Ph
d4
Ph
3nb-d4
d5
170 °C, 24 h, under Ar
1n-d5
2b
(0.50 mmol)
(1.5 mmol)
KIE = kH/kD = 1.3
Scheme 2. Deuterium labeling experiments
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[RuIICl2(p-cym)]2
1/2
4
5
PCy3
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O
R
RuIICl2(p-cym)(PCy3)
O
O
OH
OH
O
OH
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+ 2KOAc
R
H2O
1
3
4
2KCl + HOAc
ORuIIXL
O
H
2HX
HX
A
O
O
O
O
(L = PCy3)
(X = AcO- or ArCO2 )
RuIIL
II L
-
Ru
O
B
R
D
O
O
O
RuII L
R
H
2
O
R
H
C
Scheme 3. A plausible reaction mechanism
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Figure 1. Effects of concentration of 1a, 2b and Ru cat. on reactionꢀrate
Scheme 4. Intermolecular competition experiment
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On the other hand, considerable attention has recently focused on the use of supported metal
catalysts for organic transformations from the viewpoint of green chemistry due to the ease of
separation from the reaction mixture and recycling of the catalyst.31–34 In the course of our
study on the development of supported Ru catalysts that are effective for organic synthesis,35–
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we demonstrated that phosphineꢀmodified Ru/CeO2 catalysts efficiently promoted various
kinds of CꢀC bondꢀforming reactions involving CꢀH bond activation.40–42 Fortunately, we
found that Ru/CeO2 catalysts modified with 3 equivalents of PCy3 to Ru (3PCy3ꢀRu/CeO2)
promoted the coupling reaction of 1a with 2a to give 3aa in a good yield (Scheme 5). Notably,
the supported Ru catalyst required no external base for the reaction to proceed thanks to the
basic surface of CeO2. Furthermore, the solid Ru catalyst could be reused for the reaction to
furnish 3aa. Even though the present supported Ru catalyst still presents some problems
concerning the activity and durability of the catalyst and substrate scope, further studies to
optimize the catalysts and reaction conditions are expected to lead to a practical synthesis of
isobenzofuranones under Ru catalysis.
O
O
O
3PCy3-Ru/CeO2
(0.050 mmol as Ru)
O
CF3
H
OH
+
Mesitylene (1.0 mL)
170 °C, 24 h, under Ar
CF3
CF3
1a
(0.50 mmol)
2a
F3C
3aa
(0.75 mmol)
fresh
: 64%
1st reuse : 64%
2nd reuse : 34%
Scheme 5. Supported Ruꢀcatalyzed reaction
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3. Conclusion
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In summary, we have demonstrated a carboxylateꢀdirected CꢀH addition to aldehydes
under Ru catalysis. The reactions of a series of aromatic aldehydes including unactivated ones
in the absence of a Lewis acid proceeded to give isobenzofuranones in an atomꢀeconomical
and green manner. Moreover, we successfully applied a reusable supported Ru catalyst to CꢀH
hydroxyalkylation. The addition of a highly basic phosphine ligand was crucial for generating
arylꢀmetal species with high nucleophilicity, which promoted the rateꢀlimiting step of the
catalytic reaction. Further investigations on the underlying mechanism and the development
of novel catalytic reactions using this strategy are underway in our laboratory.
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4. Experimental
4.1. Materials
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All manipulations were performed under an argon atmosphere using standard Schlenk
techniques. [RuCl2(pꢀcymene)]2 (Aldrich), all of the aromatic acids and aldehydes (TCI),
sodium salt, mesitylene (Wako), cerium(III) nitrate hexahydrate, potassium hydroxide, and
tetrahydrofuran (THF; Wako) were obtained commercially and used without further
purification. Cerium dioxide (CeO2) was prepared by treating a solution of cerium(III) nitrate
hexahydrate (12.6 g, 29 mmol) in 400 mL of deionized water with 40 mL of 3M KOH
aqueous solution with stirring for 1 h at room temperature. The resulting precipitates were
collected by centrifugation, washed thoroughly with deionized water and then airꢀdried
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o
o
overnight at 80 C. The product was heated in a box furnace at a rate of 10 C minꢀ1 and
o
maintained at 400 C for 30 min to afford ceria in an excellent ceramic yield. 1k-d5 was
prepared from bromobenzeneꢀd5 according to the reported literature.43
4.2. Preparation of 3PCy3-Ru/CeO2 catalyst
Supported Ru catalysts were prepared through the method reported in our previous
literature.33–37 1.0 g of a support was added to a solution of [RuCl2(pꢀcymene)]2 (0.20 mmol)
in 10 mL of methanol in air at 50 oC After impregnation, the resulting powder was calcined in
air for 30 min to afford the Ru(2.0 wt%)/CeO2 catalyst. The modification of Ru/CeO2 catalyst
by 3 eq. of PCy3 to Ru was performed as follows: 250 mg (0.050 mmol as Ru) of Ru/CeO2
and PCy3 (0.15 mmol) were heated at 100 °C for 20 min under hydrogen atmosphere (1 atm)
without any solvent. Thus prepared catalysts are designated as 3PCy3ꢀRu/ CeO2.
4.3. Physical and analytical measurements
The products of the catalytic runs were analyzed by GCꢀMS (Shimadzu GCMSꢀQP2010,
o
CBPꢀ1 capillary column, i.d. 0.25 mm, length 30 m, at 50
−
250 C) and gas chromatography
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(Shimadzu GCꢀ2014, CBPꢀ10 capillary column, i.d. 0.25 mm, length 30 m at 50−250 C).
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NMR spectra were recorded on a JMNꢀECS400 (FT, 400 MHz (1H), 100 MHz (13C))
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instrument. Chemical shifts (
δ
) of H and 13C{1H} NMR spectra are referenced to SiMe4.
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Highꢀresolution mass spectra (FAB) were recorded on a JEOL JMSꢀ700 spectrometer with
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mꢀnitrobenzyl alcohol (mꢀNBA) as a matrix.
4.4 General Procedure for the carboxylate-directed addition of aromatic C-H bonds to
aldehydes in the presence of Ru catalysts
A 20 mL Schlenk tube was charged with aromatic carboxylic acids 1 (0.50 mmol), aldehyde
2 (0.75 mmol), [RuCl2(pꢀcymene)]2 (0.025 mmol), potassium acetate (0.15 mmol),
tricyclohexylphosphine (0.050 mmol), and mesitylene (1.0 mL) under an argon atmosphere.
The reaction mixture was stirred at 170 oC for 24 h on a hot stirrer with a cooling block. After
the reaction, the reaction solution was concentrated under reduced pressure. The products
were isolated by silicaꢀgel column chromatography (hexane/EtOAc).
4.5 Recycling of the 3PCy3-Ru/CeO2 catalyst
After the reaction, the solid was separated from the reaction mixture by centrifugation and
washed with 10 mL of diethyl ether, methanol/H2O (1:1), and again by diethyl ether. The
resulting solid was dried overnight at 80 °C and calcined in air at 400 °C for 30 min to
recover the Ru/CeO2 catalyst for reuse. Modification by 3 eq. of PCy3 to Ru was then
performed through the aforementioned procedure to give the 3PCy3ꢀRu/CeO2 catalyst for
reuse.
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4.6 Characterization data of the products
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3ꢀ(3,5ꢀbis(trifluoromethyl)phenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3aa): white solid; yield
94 %, 161 mg (0.50 mmol scale); hexane/EtOAc = 10/1; IR (Zn/SeꢀATR, neat) 1745 cm−1; 1H
NMR (400 MHz, CDCl3, ppm) δ 7.90 (s, 1H), 7.78 (s, 2H), 7.56 (t, J = 7.8 Hz, 1H), 7.37 (d, J
= 8.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 6.44 (s, 1H), 2.77 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm) δ 167.1. 145.6, 137.3 (d, JCꢀF = 80 Hz), 131.8, 129.7 (d, JCꢀF = 43.4 Hz), 128.9,
124.1, 121.4, 120.3, 119.8, 118.7, 117.0, 77.0, 14.6; HRMS (FAB) m/z [M + H]+ calcd for
C17H11F6O2 361.0663, found 361.0670.
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7ꢀmethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3ab): white solid; yield 67 %, 147 mg (1.0
1
mmol scale); hexane/EtOAc = 10/1; IR (Zn/SeꢀATR, neat) 1756 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.49 (t, J = 7.4 Hz, 1H), 7.36ꢀ7.37 (m, 3H), 7.26ꢀ7.29 (m, 3H), 7.11 (d, J = 7.6
Hz, 1H), 6.32 (s, 1H), 2.75 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.7, 150.2, 139.6,
136.8, 134.0, 130.9, 129.1, 128.9, 126.9, 123.0, 120.2, 81.8, 17.4; HRMS (FAB) m/z [M +
H]+ calcd for C15H13O2 225.0916, found 225.0918.
6,7ꢀdimethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3bb) : white solid; yield 92 %, 108 mg (0.50
1
mmol scale); hexane/EtOAc = 10/1; IR (Zn/SeꢀATR, neat) 1742 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.35ꢀ7.39 (m, 4H), 7.26ꢀ7.28 (m, 2H), 7.01 (d, J = 7.6 Hz, 1H), 6.27 (s, 1H),
2.69 (s, 3H), 2.36 (s, 3H) ; 13C NMR (100 MHz, CDCl3, ppm) δ 171.0, 148.0, 138.5, 138.1,
137.1, 135.6, 129.0, 128.8, 126.9, 122.9, 119.6, 81.1, 19.2, 13.3; HRMS (FAB) m/z [M + H]+
calcd for C16H15O2 239.1072, found 239.1067.
5,7ꢀdimethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3cb) :yellow oil ; yield 66 %, 78.5 mg (0.50
1
mmol scale); hexane/EtOAc = 10/1; IR (Zn/SeꢀATR, neat) 1734 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.36ꢀ7.38 (m, 3H), 7.26ꢀ7.29 (m, 2H), 7.09 (s, 1H), 6.89 (s, 1H), 6.26 (s, 1H),
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2.69 (s, 3H), 2.37 (s, 3H) ; 13C NMR (100 MHz, CDCl3, ppm) δ 170.7, 150.8, 145.2, 139.2,
137.0, 132.0, 129.0, 128.8, 126.9, 120.5, 120.4, 81.6, 21.9, 17.3; HRMS (FAB) m/z [M ꢀ H]ꢀ
calcd for C16H13O2 237.0921, found 237.0931.
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6ꢀmethoxyꢀ7ꢀmethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3db) : white solid ; yield 59 %, 74.7
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1745 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.35ꢀ7.36 (m, 3H), 7.26ꢀ7.28 (m, 2H), 7.04ꢀ7.10 (m, 2H), 6.26 (s, 1H),
3.87 (s, 3H), 2.61 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.7, 158.3, 141.4, 137.3,
129.0, 128.8, 127.9, 126.9, 124.0, 120.3, 116.1, 81.2, 56.2. 9.9; HRMS (FAB) m/z [M + H]+
calcd for C16H15O3 255.1021, found 255.1022.
6ꢀfluoroꢀ7ꢀmethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3eb) : yellow solid ; yield 92 %, 111
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1749 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.36ꢀ7.38 (m, 3H), 7.25ꢀ7.29 (m, 3H), 7.08 (dd, JCꢀF = 4.2 Hz, 1H), 6.30
(s, 1H), 2.66 (d, JHꢀF = 2.0 Hz, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 169.7, 161.4 (d, JCꢀF
= 246 Hz), 145.4, 136.4, 129.3, 1289.0, 126.9, 126.0 (d, JCꢀF = 20 Hz), 124.9 (d, JCꢀF = 6.5
Hz), 121.4 (d, JCꢀF = 25 Hz), 121.1 (d, JCꢀF = 8.7 Hz), 81.4, 9.1 (d, JCꢀF = 3.7 Hz) ; HRMS
(FAB) m/z [M + H]+ calcd for C15H12FO2 243.0821, found 243.0810.
3ꢀphenylnaphtho[1,2ꢀc]furanꢀ1(3H)ꢀone (3fb) : white solid ; yield 66 %, 84.5 mg (0.50 mmol
1
scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1749 cm−1; H NMR (400 MHz, CDCl3,
ppm) δ 9.07 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.76 (t, J =
7.2 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.30ꢀ7.39 (m, 6H), 6.46 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ170.8, 151.3, 136.0, 135.7, 133.4, 129.3, 129.2, 129.0, 128.5, 127.5, 127.2,
127.0, 123.7, 119.7, 119.3, 82.1; HRMS (FAB) m/z [M + H]+ calcd for C18H13O2 261.0916,
found 261.0925.
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6ꢀmethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3gb) : white solid ; yield 88 %, 95.8 mg (0.50
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mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1755 cm−1; H NMR (400 MHz,
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CDCl3, ppm) δ 7.75 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.36ꢀ7.37 (m, 3H), 7.26ꢀ7.28 (m, 2H),
7.21 (d, J = 7.6 Hz, 1H), 6.37 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
170.7, 147.1, 139.6, 136.6, 135.5, 129.2, 128.9, 126.9, 125.7, 125.5, 122.8, 122.5, 82.6, 21.3;
HRMS (FAB) m/z [M + H]+ calcd for C15H13O2 225.0916, found 225.0907.
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6ꢀmethoxyꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3hb) : white solid ; yield 93 %, 108 mg (0.50
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mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1748 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.36ꢀ7.38 (m, 4H), 7.25ꢀ7.27 (m, 2H), 7.20 (d, J = 1.6 Hz, 2H), 6.35 (s, 1H),
3.88 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ170.6, 160.8, 142.1, 136.6, 134.3, 129.2,
128.9, 1267.0, 123.7, 123.3, 107.2, 82.6, 55.8 ; HRMS (FAB) m/z [M + H]+ calcd for
C15H13O3 241.0865, found 241.0867.
5ꢀmethylꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3ib) : white solid ; yield 84 %, 94.6 mg (0.50
1
mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1742 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.83 (d, J = 7.6 Hz, 1H), 7.34ꢀ7.39 (m, 4H), 7.26ꢀ7.29 (m, 2H), 7.11 (s, 1H),
6.34 (s, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.6, 150.2, 145.6, 136.6,
130.5, 129.2, 128.9, 126.9, 125.4, 123.1, 122.9, 82.4, 22.1; HRMS (FAB) m/z [M + H]+ calcd
for C15H13O2 225.0916, found 225.0911.
5ꢀmethoxyꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3jb) : white solid ; yield 89 %, 109 mg (0.50
1
mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1739 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.85 (d, J = 8.4 Hz, 1H), 7.37ꢀ7.39 (m, 3H), 7.26ꢀ7.29 (m, 2H), 7.04 (d, J =
8.4 Hz, 1H), 6.72 (s, 1H), 6.31 (s, 1H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
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170.2, 164.9, 152.5, 136.5, 129.2, 129.0, 127.1, 127.0, 117.8, 116.9, 106.6, 82.1, 55.8; HRMS
(FAB) m/z [M + H]+ calcd for C15H13O3 241.0865, found 241.0868.
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50.3 mg (0.50 mmol scale); hexane/EtOAc = 1/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; 1H NMR
(400 MHz, DMSO, ppm) δ 7.45 (t, J = 7.6 Hz, 1H), 7.29ꢀ7.33 (m, 1H), 7.22ꢀ7.26 (m, 2H),
7.06ꢀ7.08 (m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.89 (t, J = 7.4 Hz, 1H), 6.80 (s, 1H), 3.92 (s, 3H),
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2.73 (s, 3H); C NMR (100 MHz, DMSO, ppm) δ 169.6, 169.3, 151.8, 145.0, 137.1, 129.1,
129.0, 126.9, 126.0, 119.9, 118.6, 111.7, 81.5, 24.3; HRMS (FAB) m/z [M + H]+ calcd for
C16H14NO3 268.0974, found 268.0984.
5ꢀhydroxyꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3lb) : brown solid ; yield 38%, 44.4 mg (0.50
1
mmol scale); hexane/EtOAc = 2/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; H NMR (400 MHz,
DMSO, ppm) δ 10.77 (s (br), 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.41ꢀ7.45 (m, 3H), 7.33ꢀ7.35 (m,
2H), 7.01 (dd, J = 8.4 and 2.0 Hz,1H), 6.72 (s, 1H), 6.60 (s, 1H); 13C NMR (100 MHz, DMSO,
ppm) δ 1169.7, 163.5, 153.0, 137.4, 129.0, 127.0, 126.7, 117.7, 115.2, 108.7, 80.9; HRMS
(FAB) m/z [M + H]+ calcd for C14H11O3 227.0708, found 227.0705.
5ꢀchloroꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3mb) : brown solid ; yield 43 %, 53.4 mg (0.50
1
mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.80 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.30ꢀ7.32 (m, 3H),
7.22ꢀ7.23 (m, 1H), 7.17ꢀ7.20 (m, 2H), 6.29 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ
169.3, 151.2, 141.0, 135.6, 130.1, 129.5, 129.1, 126.8, 126.7, 124.0, 123.2, 82.1; HRMS
(FAB) m/z [M + H]+ calcd for C14H10ClO2 245.0369, found 245.0378.
3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3nb) : white solid ; yield 95 %, 102 mg (0.50 mmol
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scale); hexane/EtOAc = 10/1; IR (Zn/SeꢀATR, neat) 1742 cm−1; 1H NMR (400 MHz, CDCl3,
ppm) δ 7.96 (d, J = 7.6 Hz, 1H), 7.65 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.37ꢀ7.39
(m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 7.26ꢀ7.29 (m, 2H), 6.41 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ 170.5, 149.6, 136.4, 134.3, 129.3, 129.3, 129.0, 127.0, 125.6, 125.5, 122.8,
82.7; HRMS (FAB) m/z [M + H]+ calcd for C14H11O2 211.0759, found 211.0749.
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7ꢀfluoroꢀ3ꢀphenylisobenzofuranꢀ1(3H)ꢀone (3ob) : yellow solid ; yield 37 %, 43.3 mg (0.50
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mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1738 cm−1; H NMR (400 MHz,
CDCl3, ppm) δ 7.61ꢀ7.66 (m, 1H), 7.38ꢀ7.40 (m, 3H), 7.27ꢀ7.29 (m, 2H), 7.18 (t, J = 8.4 Hz,
1H), 7.11 (d, J = 7.6 Hz, 1H), 6.39 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 166.5, 159.4
(d, JCꢀF = 264 Hz), 152.2, 136.9 (d, JCꢀF = 7.8 Hz), 135.8, 129.5, 129.0, 126.9, 118.8 (d, JCꢀF
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4.2 Hz), 116.3(d, JCꢀF = 18.5 Hz), 113.4 (d, JCꢀF = 14.3 Hz), 82.3 ; HRMS (FAB) m/z [M +
H]+ calcd for C14H10FO2 229.0655, found 229.0661.
3ꢀ(4ꢀfluorophenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3ac) : yellow solid ; yield 87 %, 100
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1746 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.51 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 7.2 Hz, 1H), 7.24ꢀ7.27 (m, 2H),
7.03ꢀ7.11 (m, 3H), 6.31 (s, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.4,
163.1 (d, JCꢀF = 271 Hz), 149.9, 139.7, 134.1, 132.6 (d, JCꢀF = 3.1 Hz), 131.0, 129.0 (d, JCꢀF
=
8.5 Hz), 123.0, 120.1, 115.9 (d, JCꢀF = 21.8 Hz), 81.1, 17.4; HRMS (FAB) m/z [M + H]+ calcd
for C15H12FO2 243.0821, found 243.0810.
3ꢀ(4ꢀbromophenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3ad) : yellow solid ; yield 96 %, 142
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1750 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.49ꢀ7.52 (m, 3H), 7.30 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H),
7.09 (d, J = 7.6 Hz, 1H), 6.28 (s, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
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170.4, 149.6, 139.8, 135.9, 134.1, 132.1, 131.1, 128.6, 123.2, 122.8, 120.0, 80.9, 17.4; HRMS
(FAB) m/z [M + H]+ calcd for C15H12BrO2 303.0021, found 303.0022.
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3ꢀ(4ꢀiodophenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3ae) : brown solid ; yield 63 %, 118.5
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ7.70 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.2 Hz,
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1H), 7.09 (d, J = 8.0 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.26 (s, 1H), 2.74 (s, 3H); C NMR
(100 MHz, CDCl3, ppm) δ 170.4, 149.6, 139.8, 138.0, 136.5, 134.1, 131.1, 128.7, 122.8,
120.0, 95.0, 81.0, 17.4; HRMS (FAB) m/z [M + H]+ calcd for C15H12IO2 350.9882, found
350.9897.
methyl 4ꢀ(4ꢀmethylꢀ3ꢀoxoꢀ1,3ꢀdihydroisobenzofuranꢀ1ꢀyl)benzoate (3af) : white solid ; yield
73 %, 101 mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1753 cm−1; 1H
NMR (400 MHz, CDCl3, ppm) δ 8.05 (d, J = 8.4 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.38 (d, J
= 8.4 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 7.6 Hz, 1H), 6.37 (s, 1H), 3.92 (s, 3H),
2.75 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.4, 166.4, 149.6, 141.7, 139.9, 134.2,
131.2, 130.8, 130.2, 126.6, 122.7, 120.0, 80.9, 52.3, 17.4; HRMS (FAB) m/z [M ꢀ H]ꢀ calcd
for C17H13O4 281.0819, found 281.0813.
4ꢀ(4ꢀmethylꢀ3ꢀoxoꢀ1,3ꢀdihydroisobenzofuranꢀ1ꢀyl)benzonitrile (3ag) : yellow solid ; yield
34 %, 43.8 mg (0.50 mmol scale); hexane/EtOAc = 3/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; 1H
NMR (400 MHz, CDCl3, ppm) δ 7.69 (d, J = 8.4 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.45 (d, J
= 8.4 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.38 (s, 1H), 2.75 (s, 3H);
13C NMR (100 MHz, CDCl3, ppm) δ 170.1, 149.0, 142.0, 140.1, 134.3, 132.7, 131.4, 127.3,
122.5, 119.9, 118.2, 112.9, 80.3, 17.4; HRMS (FAB) m/z [M + H]+ calcd for C16H12NO2
250.0868, found 250.0860.
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7ꢀmethylꢀ3ꢀ(3ꢀ(trifluoromethyl)phenyl)isobenzofuranꢀ1(3H)ꢀone (3ah) : yellow solid ; yield
97 %, 141.6 mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1748 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 7.63 (d, J = 7.6 Hz, 1H), 7.57 (s, 1H), 7.50ꢀ7.54 (m, 3H),
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7.33 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.38 (s, 1H), 2.76 (s, 3H); C NMR (100
MHz, CDCl3, ppm) δ 170.3, 149.3, 140.0, 138.0, 134.3, 131.5, 131.3, 131.2, 130.2, 129.5,
126.0 (d, JCꢀF = 3.5 Hz), 123.7 (q, JCꢀF = 3.7 Hz), 122.8, 120.0, 80.8, 17.4 ; HRMS (FAB) m/z
[M + H]+ calcd for C16H15O3 293.0789, found 293.0778.
(E)ꢀ7ꢀmethylꢀ3ꢀ(4ꢀstyrylphenyl)isobenzofuranꢀ1(3H)ꢀone (3ai) : yellow; yield 47 %, 77.0 mg
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(0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1740 cm−1; H NMR (400
MHz, CDCl3, ppm) δ7.48ꢀ7.52 (m, 5H), 7.36 (t, J = 8.0 Hz, 2H), 7.23ꢀ7.30 (m, 4H), 7.08ꢀ7.14
(m, 3H), 6.32 (s, 1H), 2.75 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.7, 150.1, 139.7,
138.2, 136.9, 135.8, 134.0, 130.9, 129.6, 128.7, 127.9, 127.7, 127.4, 126.9, 126.6, 123.0,
120.5, 81.6, 17.4; HRMS (FAB) m/z [M]+ calcd for C23H18O2 326.1307, found 326.1311.
7ꢀmethylꢀ3ꢀ(naphthalenꢀ2ꢀyl)isobenzofuranꢀ1(3H)ꢀone (3aj) : yellow solid ; yield 77 %, 100
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1750 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.81ꢀ7.84 (m, 4H), 7.46ꢀ7.52 (m, 3H), 7.29 (d, J = 7.6 Hz, 1H),
7.24ꢀ7.25 (m, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.48 (s, 1H), 2.77 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm) δ 170.8, 150.2, 139.7, 134.1, 134.0, 133.5, 133.0, 131.0, 129.0, 128.0, 127.8,
126.7, 126.6, 123.8, 123.0, 120.2, 82.0, 17.5; HRMS (FAB) m/z [M + H]+ calcd for C19H15O2
275.1072, found 275.1063.
7ꢀmethylꢀ3ꢀ(pꢀtolyl)isobenzofuranꢀ1(3H)ꢀone (3ak) : yellow oil ; yield 74 %, 85.0 mg (0.50
mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1755 cm−1; H NMR (400 MHz,
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CDCl3, ppm) δ 7.48 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.14ꢀ7.19 (m, 4H), 7.10 (d, J
= 7.6 Hz, 1H), 6.30 (s, 1H), 2.74 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
170.7, 150.3, 139.5, 139.1, 133.9, 133.8, 130.8, 129.5, 127.0, 123.1, 120.2, 81.8, 21.2, 17.4;
HRMS (FAB) m/z [M ꢀ H]ꢀ calcd for C16H13O2 237.0921, found 237.0931.
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3ꢀ(4ꢀmethoxyphenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3al) : white solid ; yield 65 %, 80.0
mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1748 cm−1; 1H NMR (400
MHz, CDCl3, ppm) δ 7.49 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.16ꢀ7.18 (m, 2H),
7.09 (d, J = 7.6 Hz, 1H), 6.87ꢀ6.89 (m, 2H), 6.29 (s, 1H), 3.80 (s, 3H), 2.74 (s, 3H); 13C NMR
(100 MHz, CDCl3, ppm) δ 170.7, 160.2, 153.5, 150.2, 139.5, 133.9, 130.8, 128.7, 123.2,
120.2, 114.2, 81.7, 55.2, 17.4; HRMS (FAB) m/z [M + H]+ calcd for C16H15O3 255.1021,
found 255.1022.
3ꢀ(3ꢀmethoxyphenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3am) : white solid ; yield 75 %,
91.0 mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1748 cm−1; 1H NMR
(400 MHz, CDCl3, ppm) δ 7.49 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.8 Hz, 2H), 7.13 (d, J = 8.0
Hz, 1H), 6.87ꢀ6.89 (m, 2H), 6.79 (s, 1H), 6.29 (s, 1H), 3.78 (s, 3H), 2.74 (s, 3H); 13C NMR
(100 MHz, CDCl3, ppm) δ 170.7,159.9, 150.1, 139.6, 138.3, 134.0, 130.9, 130.0, 122.8, 120.1,
119.1, 114.5, 112.3, 81.6, 55.3, 17.4; HRMS (FAB) m/z [M] calcd for C16H14O3 254.0943,
found 254.0942.
3ꢀ(2ꢀmethoxyphenyl)ꢀ7ꢀmethylisobenzofuranꢀ1(3H)ꢀone (3an) : yellow solid ; yield 74 %,
87.4 mg (0.50 mmol scale); hexane/EtOAc = 5/1; IR (Zn/SeꢀATR, neat) 1760 cm−1; 1H NMR
(400 MHz, CDCl3, ppm) δ 7.45 (t, J = 7.6 Hz, 1H), 7.29ꢀ7.33 (m, 1H), 7.22ꢀ7.26 (m, 2H),
7.06ꢀ7.08 (m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.89 (t, J = 7.4 Hz, 1H), 6.80 (s, 1H), 3.92 (s, 3H),
2.73 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.1, 156.9, 150.9, 139.4, 133.8, 130.6,
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129.9, 126.8, 125.4, 123.0, 120.8, 120.2, 110.9, 77.3, 55.6, 17.4; HRMS (FAB) m/z [M + H]+
calcd for C16H15O3 255.1021, found 255.1026.
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Author information
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Corresponding Authors
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*Eꢀmail: miuraꢀhiroki@tmu.ac.jp.
*Eꢀmail: shishidoꢀtetsuya@tmu.ac.jp.
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ORCID
Hiroki Miura: 0000ꢀ0002ꢀ2488ꢀ4432
Tetsuya Shishido: 0000ꢀ0002ꢀ8475ꢀ4226
Notes
The authors declare no competing financial interest.
Supporting Information
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Detailed optimization of reaction conditions and H and C NMR spectra for the products 3
(PDF)
Acknowledgement
This study was supported in part by the Program for Element Strategy Initiative for Catalysts
& Batteries (ESICB). This work was also supported in part by GrantsꢀinꢀAid for Scientific
Research (B) (Grant 17H03459) and Scientific Research on Innovative Areas (Grant
17H06443) commissioned by MEXT of Japan. We thank Ms. Yuriko Kimura for her kind
assistance to carry out experiments.
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