Ruthenium(II)-Catalyzed Construction of Isocoumarins via Dual C-H/C-C Activation of Sulfoxonium Ylides

Article abstract of DOI:10.1021/acs.joc.9b02520

A ruthenium(II)-catalyzed annulation between two molecules of sulfoxonium ylides is achieved, generating a variety of substituted isocoumarins in reasonable yields. This strategy features dual C-H/C-C activation in one pot and has a wide substrate scope and good functional group tolerance.

Full text of DOI:10.1021/acs.joc.9b02520

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Note
Ruthenium(II)-Catalyzed Construction of Isocoumarins
via Dual C-H/C-C Activation of Sulfoxonium Ylides
Si Wen, Yanhui Chen, Zemin Zhao, Dan Ba, Weiwei Lv, and Guolin Cheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02520 • Publication Date (Web): 06 Dec 2019
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The Journal of Organic Chemistry
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Ruthenium(II)-Catalyzed Construction of Isocoumarins via
Dual C−H/C−C Activation of Sulfoxonium Ylides
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Si Wen, Yanhui Chen, Zemin Zhao, Dan Ba, Weiwei Lv, and Guolin Cheng*
College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
E-mail: glcheng@hqu.edu.cn
[RuCl2(p-cymene)]2 (5 mol %)
O
O
S
O
Na3PO4 (1.5 equiv)
MesCO2H (1.5 equiv)
R
R
O
R
HFIP, air, 110 oC, 24h
15 examples, up to 91% yield
ABSTRACT: A ruthenium(II)-catalyzed annulation between two molecules of sulfoxonium ylides is achieved, generating a variety
of substituted isocoumarins in reasonable yields. This strategy features dual C−H/C−C activation in one pot, and has a wide
substrate scope and good functional group tolerance.
Isocoumarin and its derivatives are important natural lactones,
which are generally found in natural products as a basic
structure.1 It was found that compounds with isocoumarin
structure have a certain physiological activity,2 which are
widely used in the treatment of cancer,3 allergy,4 sterilization,5
and other aspects.6 In addition, they could be used as key
synthetic intermediates in drug discovery.7 Thus, the synthesis
of compounds with such a skeleton has attracted great
interesting.8 Among the many synthetic methods to access of
these compounds, the transition metal-catalyzed C−H
activation/annulation cascade reactions of benzoic acid
derivatives with coupling partners represent one of the most
powerful and straightforward methods to isocoumarins.
However, the coupling partners are commonly limited to
internal alkynes (Scheme 1a).9 The use of coupling partners
other than internal alkynes will greatly enhance the scope of
metal-catalyzed synthesis of isocoumarins.
Sulfoxonium ylides are carbene precursors that are easier to
prepare, and more stable and safer than diazonium
compounds.10 Sulfoxonium ylides have been used as
alkylating reagents in a variety of reactions.11-15 Since the first
example of rhodium(III)-catalyzed C−H alkylation of arenes
with sulfoxonium ylides was independently discovered by
Aïssa11 and Li,12 sulfoxonium ylides have been widely used as
alkylating reagents in transition metal-catalyzed C−H
functionalization of a range of arenes.13 Recently, Li's work
illuminated the method of synthesizing isocoumarins from N-
methoxybenzamides, using sulfoxonium ylides as coupling
partners and rhodium(III) as a catalyst (Scheme 1b).14
Subsequently, a method for the formation of isocoumarins via
ruthenium(II)-catalyzed C−H activation/annulation of benzoic
acids and sulfoxonium ylides was reported by Ackermann
(Scheme 1c).15 Inspired by the works of Li and Ackermann,
we questioned whether sulfoxonium ylides could be able to
serve as both arenes16 and coupling partners in transition
metal-catalyzed C−H activation. As our ongoing interest in
C−H activation17 and C−C cleavage,18 herein, we disclose a
ruthenium(II)-catalyzed dual C−H/C−C activation of
sulfoxonium ylides for the synthesis of isocoumarins (Scheme
1d).19
Scheme 1. Synthesis of Isocoumarins via C–H Activation
a) Transition metal-catalyzed C-H activation/annulation of benzoic acids with internal alkynes
O
O
Rh, Ru, Ir, Pd, and Co
O
R1
R2
+
OH
R2
H
R1
b) Rh-catalyzed C-H activation/annulation of benzamides with sulfoxonium ylides
O
O
[RhCp*Cl2]2
O
O
S
O
NHOMe
+
R
R
H
c) Ru-catalyzed C-H activation/annulation of benzoic acids with sulfoxonium ylides
O
O
O
O
[RuCl2(p-cymene)]2
O
OH
+
S
R
R
H
This work:
d)
Ru-catalyzed dual C-H/C-C activation of sulfoxonium ylides
O
O
O
R1
R1
O
O
S
[RuCl2(p-cymene)]2
S
O
+
R2
R2
H
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mL) at 110 °C under an air atmosphere for 24 h. bThe yields were
We initiated our investigation on the model reaction of
sulfoxonium ylide (1a) to optimize various reaction
parameters. The results are summarized in Table 1. To our
delight, under reaction conditions using [RuCl2(p-cymene)]2 as
the catalyst, 2,4,6-trimethylbenzoic acid (MesCO2H) being an
additive, and Na3PO4 as the base in HFIP at 110 °C under an
air atmosphere for 24 h, the desired product (2a) was obtained
in 78% yield (entry 1). Investigations on various solvents
indicated that other solvents did not perform as well as HFIP
(entries 1−6). Probably, protic solvents with low pKa values,
such as HFIP (pKa = 9.3) and 2,2,2-trifluoroethanol (TFE,
pKa = 12.4),19 are favored in this transformation. Substituting
other inorganic bases for Na3PO4 decreased the productivity,
giving 2a in yields of 20–76% (entries 7−14). Removal of
Na3PO4 from the reaction significantly reduced the reaction
efficiency (entry 15). Only 20% yield of products was
obtained in the absence of an additive (entry 16). These
experiments indicated that both the base and additive were
essential for this reaction. Ac-Gly-OH was not as a suitable
additive as MesCO2H for this reaction, and the yield of 2a
reduced to 64% (entry 17). Val-Boc-OH almost inhibited the
reaction, and only trace of 2a was observed (entry 18). Further
screening the reaction temperature showed that the reaction
profile did not improve (entries 19 and 20). Finally, no
reaction occurred in the absence of [RuCl2(p-cymene)]2 (entry
21). Then, the optimized reaction conditions were identified as
follows: 1a (0.2 mmol), [RuCl2(p-cymene)]2 (5 mol %),
Na3PO4 (0.75 equiv) and MesCO2H (0.75 equiv) in HFIP (1
mL) at 110 °C under an air atmosphere for 24 h (entry 1).
1
2
3
4
5
6
7
8
determined by 1H NMR analysis of the crude product using
c
CH2Br2 as the internal standard. Isolated yield. dReaction was
carried out at 100 °C. eReaction was carried out at 120 °C.
fWithout [RuCl2(p-cymene)]2. HFIP = 1,1,1,3,3,3-hexafluoro-2-
propanol. DMF
dichloroethane.
= N,N-dimethylformamide. DCE = 1,2-
Scheme 2 Scope of Sulfoxonium Ylides
[RuCl2(p-cymene)]2 (5 mol %)
O
O
O
R
Na3PO4 (0.75 equiv)
R
S
O
MesCO2H (0.75 equiv)
R
9
HFIP, air, 110 oC, 24h
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2
1
O
O
O
O
O
O
Me
tBu
Me
tBu
2a
, 75%
O
2c
, 42%
O
2b
, 75%
O
O
O
O
F3C
PhO
MeO
MeO
CF3
OPh
OMe
OMe
2e
2f
, 53%
O
, 70%
2d
, 57%
O
O
Me
O
O
O
OMe
Me
OMe
2g
, 74%
2h'
2h
2h 2h'
:
62%,
=0.68:1
O
O
O
O
Cl
O
O
Cl
F
Cl
Table 1. Screen of the Reaction Conditionsa
Cl
F
2j'
2j
2i,
91%
2j 2j'
: =1:20
30%,
[RuCl2(p-cymene)]2 (5 mol %)
O
O
S
O
base (0.75 equiv)
additive (0.75 equiv)
O
O
OMe O
O
OPh
O
F3C
solvent, air, 110 oC, 24h
O
OMe
O
OPh
CF3
1a
2a
2l
2m, 43%
, 48%
O
2k
, 78%
Entry
1
2
3
4
5
6
7
8
Solvent
HFIP
iPrOH
DMF
CH3CN
DCE
Base
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na2CO3
K2CO3
Cs2CO3
NaHCO3
KHCO3
NaH2PO4
K3PO4
Additive
Yield(%)b
78 (75)c
15
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
MesCO2H
-
O
Cl
F
O
O
O
O
Cl
F
30
14
0
20
30
20
30
76
60
52
20
44
40
20
64
trace
72
R
R
2n
, 67%
2o
, 34%
2p
2q
R = NO2,
R = CO2Me, , trace
2r
, 0%
R = CN,
, 0%
toluene
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
O
O
O
O
O
S
O
O
O
S
9
2u
, 0%
2t
, 0%
2s
, 0%
10
11
12
13
14
15
16
17
18
19d
20e
21f
With the optimized reaction conditions in hand, we paid our
attention to the scope of a series of benzoyl sulfoxonium
ylides (Scheme 2). The sulfoxonium ylide derivatives bearing
electron-donating or electron-withdrawing groups on benzoyl
moieties, all could be smoothly carried out to give the
substituted isocoumarin products in moderate to good yields
(2a−o). The reactivity of this transformation was not sensitive
to the electronic properties of the benzoyl groups. For
sulfoxonium ylides with a para-substituent on phenyl rings,
such as methyl, tert-butyl, methoxyl, phenoxyl, and
trifluoromethyl, showed moderate to good reactivity, giving
products (2b−f) in 42-75% yields. For meta-methyl and
KH2PO4
-
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Ac-Gly-OH
Val-Boc-OH
MesCO2H
MesCO2H
MesCO2H
70
0
aReaction conditions: 1a (0.2 mmol), base (0.15 mmol), additive
(0.15 mmol), and [RuCl2(p-cymene)]2 (5 mol %) in solvent (1
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trifluoromethyl benzoyl sulfoxonium ylides, the C−H
coordination of sulfoxonium ylide with Ru catalyst is
1
2
3
4
5
6
7
8
activation occurred at the sterically less hindered position,
giving the desired products in 74% and 78% yields,
respectively (2g and 2k). However, meta-methoxyl and meta-
chloro substituted substrates led to mixtures of two
regioisomers (2h/2h′ and 2j/2j′). Interestingly, exclusively
ortho-to-fluorine and highly ortho-to-chlorine selectivities
were obtained when meta-halogen substituted substrates were
used (2i and 2g). The reaction efficiency was slightly retarded
by steric hindrance, and ortho-substituted substrates only gave
the desired products (2l−o) in 34-67% yields. This reaction
was not applicable to 4-nitro, 4-ester, and 4-cyano substituted
substrates, as well as furyl and thienyl substituted
substrates(2p−t). Finally, the sulfoxonium ylides with an
alkanoyl group failed to produce the desired product, probably
due to the difficulty to active the C(sp3)−H bond (2u).
irreversible (Scheme 4c and 4d). Moreover, no deuterated
incorporation was observed, when isocoumarin (2a) was
allowed to undergo H/D exchange (Scheme 4e). These
experiments indicated that the H/D exchange process is
slightly faster than the formation of the final isocoumarins.
Scheme 4 Control Experiments
O
O
O
S
standard
conditions
Me
Me
CO2H
O
OMe
a)
b)
c)
9
+
+
2l
OMe
20%
10
11
12
13
14
15
16
17
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19
20
21
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4a
, 40%
3a
1l
(0.2 mmol)
(0.1 mmol)
R
O
R
O
OMe O
S
standard conditions
OH
OMe
3b
1y
R = MeO,
R = MeO, , 0%
To demonstrate the applicability of the method, a gram-
scale experiment of 1a was also feasible, giving 2a in 65%
yield (eq. 1).
1z
R = F,
3c
R = F,
, 0%
D
O
8%
O
O
S
standard conditions
CH3OH-D4 (0.2 mL)
O
O
O
O
S
CO2H
standard conditions
33%
D
O
O
(1)
1a
2a
D-
not detected
1a
, 0.982 g (5 mmol)
2a
, 0.361 g, 65%
13% D
Me
O
O
standard conditions
CH3OH-D4 (0.2 mL)
O
In addition, we found that under the standard reaction
Me
S
Me
d)
conditions, the cross-over reaction of 1a and 1l could generate
isocoumarins (2v), (2w), (2a), and (2l) in 31%, 35%, 49%, and
33% yields, respectively (Scheme 3a). Significantly, the cross-
coupling reaction could be carried out using an aroyl substrate
(1h) and an alkanoyl substrate (1x) to give the corresponding
product 2x in 30% yield together with a mixture of 2h and 2h'
in 21% combined yield (Scheme 3b).
35%
D
1g
2g
D-
O
0% D
O
standard conditions
CH3OH-D4 (0.2 mL)
O
O
e)
0%
D
2a
2a
Scheme 3 Cross-Over Reactions
Scheme 5 Plausible Catalytic Cycle
O
OMe O
O
O
S
standard
conditions
O
O
S
O
O
+
O
a)
+
Ph
OMe
R1
R2
O
O
S
O
R1 = 2-MeOC6H4,
,
31% R2 = Ph,
,
35%
2u
2w
1a
1l
(0.1 mmol)
R1 = Ph,
,
49%
R2 = 2-MeOC6H4,
, 33%
(0.1 mmol)
2a
2l
R
1
2
RuII
O
O
standard
conditions
O
O
S
S
O
O
O
O
ligands on Ru were omitted
MeO
S
+
+
2h
2h'
S
+
Me
Me
Ru
b)
O
OMe
21%
1h
2x
O
Ru
,
30%
1x
(0.1 mmol)
(0.2 mmol)
E
A
R
O
In order to further understand the reaction mechanism,
1
several control experiments were performed. The reaction of
3-methylbenzoic acid (3a) and sulfoxonium ylide (1l) could
deliver isocoumarin (4a) in 40% yield (Scheme 4a).15
However, the reaction of 2,6-disubstituted benzoyl
sulfoxonium ylides (1y or 1z) under the standard reaction
conditions failure to give 2,6-disubstituted benzoic acids,
which indicated that benzoic acids may not be involved in this
reaction (Scheme 4b). Furthermore, the compounds (1a) and
(1g) were subjected to the standard reaction conditions
independently using CH3OH-D4 (0.2 mL) as a co-solvent,
leading to H/D exchange occurred at the C4 and C8 positions
of the corresponding products, which suggested that the ortho-
C−H cleavage process is reversible (Scheme 4c and 4d). Since
the incorporation of deuterium (D) on the aromatic ring at C3
position of the product was not occurred, we proposed that the
base
O
DMSO
O
S
S
O
Ru
Ru
O
S
O
O
O
B
R
O
R
D
Ru
H
C
R
O
On the basis of the above results and literature reports,15,16
a
plausible catalytic cycle is proposed as shown in Scheme 5.
Initially, the coordination of carbonyl oxygen of sulfoxonium
ylide (1) to a Ru(II) catalyst is followed by ortho-C−H
activation to give a five-membered Ru(II) complex (A). Then
3
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A is captured by 1 to form Ru(II) carbene complex (B), which
6H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 181.0, 166.6,
1
2
3
4
5
6
7
8
could deliver a six-membered Ru(II) complex (C) via carbene
migratory insertion. The protonolysis of C leads the alkylated
intermediate (D). Finally, the enolization of D under basic
condition forms intermediate (E), following by intramolecular
cyclization of E, affording the isocoumarins (2) along with the
cleavage of a C−C bond.
142.8, 131.8, 129.4, 126.5, 69.6, 52.1, 42.3.
O
O
S
NC
1r
4-(2-(dimethyl(oxo)-λ6-sulfanylidene)acetyl)benzonitrile
(1y) as a white solid, m.p. 216 - 218 °C. 1H NMR (500 MHz,
DMSO-d6) δ 7.95 – 7.92 (m, 2H), 7.90 – 7.87 (m, 2H), 5.78 (s,
1H), 3.59 (s, 6H); 13C{1H} NMR (126 MHz, DMSO-d6) δ
177.9, 143.4, 132.2, 127.1, 118.7, 112.5, 74.0, 40.5; HRMS
(ESI-TOF) m/z: calcd for C11H12NO2S+: 222.0583 (M + H)+,
found: 222.0584.
CONCLUSION
In summary, we have demonstrated a strategy for the
formation of isocoumarins via ruthenium(II)-catalyzed dual
C−H/C−C activation of sulfoxonium ylides. This novel
method has a broad substrates scope, and a range of
substituted isocoumarins have been synthesized with moderate
to good yields.
9
10
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12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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32
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34
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40
41
42
43
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49
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52
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O
O
O
S
EXPERIMENTAL SECTION
1s
2-(dimethyl(oxo)-λ6-sulfanylidene)-1-(furan-2-yl)ethan-1-
one (1s)22 as a brown solid. 1H NMR (500 MHz, Chloroform-d)
δ 7.45 – 7.36 (m, 1H), 6.95 – 6.87 (m, 1H), 6.47 – 6.39 (m,
1H), 5.03 (s, 1H), 3.50 (d, J = 14.9 Hz, 6H); 13C{1H} NMR
(126 MHz, Chloroform-d) δ 172.2, 153.3, 143.3, 111.4, 111.2,
68.4, 42.3.
General Information. All the solvents were used without
further purification. The other commercial chemicals were
used without further purification. All reactions were
performed under an inert atmosphere of nitrogen in flame-
dried glassware, unless otherwise stated. Analytical thin layer
chromatography was performed on 0.25 mm silica gel 60-
F254. Visualization was carried out with UV light and Vogel’s
permanganate. Preparative TLC was performed on 1.0 mm
silica gel. 1H NMR spectra were recorded on Bruker DRX-500
instrument (500 MHz). 13C NMR spectra were recorded on
Bruker DRX-500 instrument (126 MHz) were fully decoupled
by broad band proton decoupling. High-resolution mass
spectra (HRMS) were recorded on an Agilent 1290 Mass
spectrometer using ESI-TOF (electrospray ionization-time of
flight). NMR spectra were recorded in CDCl3. 1H NMR
spectra were referenced to residual CHCl3 at 7.26 ppm, and
13C NMR spectra were referenced to the central peak of CDCl3
at 77.0 ppm. Chemical shifts (δ) are reported in ppm, and
coupling constants (J) are in Hertz (Hz). Multiplicities are
reported using the following abbreviations: s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet.
O
O
S
S
1t
2-(dimethyl(oxo)-λ6-sulfanylidene)-1-(thiophen-2-yl)ethan-
1-one (1v)21 as
a
white solid. 1H NMR (500 MHz,
Chloroform-d) δ 7.49 – 7.37 (m, 2H), 7.05 (s, 1H), 4.89 (s,
1H), 3.51 (s, 6H); 13C{1H} NMR (126 MHz, Chloroform-d) δ
175.6, 145.6, 129.0, 127.5, 127.0, 67.1, 42.8.
OMe O
O
S
OMe
1y
Procedure for the Synthesis of 1
1 was synthesized following a literature procedure20
1-(2,6-dimethoxyphenyl)-2-(dimethyl(oxo)-λ6-
sulfanylidene)ethan-1-one (1y) as a white solid, m.p. 146 –
147 °C. 1H NMR (500 MHz, Chloroform-d) δ 7.22 – 7.15 (m,
1H), 6.56 – 6.50 (m, 2H), 4.53 (s, 1H), 3.82 – 3.75 (m, 6H),
3.55 – 3.46 (m, 6H); 13C{1H} NMR (126 MHz, Chloroform-d)
δ 182.2, 156.9 (d, J = 2.2 Hz), 129.2, 121.2, 103.9, 72.2, 55.9,
42.4; HRMS (ESI-TOF) m/z: calcd for C12H17O4S+: 257.0842
(M + H)+, found: 257.0845.
O
O
S
O2N
1p
2-(dimethyl(oxo)-λ6-sulfanylidene)-1-(4-nitrophenyl)ethan-
1-one (1p)21 as a brown solid. 1H NMR (500 MHz, DMSO-d6)
δ 8.32 – 8.27 (m, 2H), 8.06 – 8.03 (m, 2H), 5.85 (s, 1H), 3.65
(s, 6H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 177.6, 148.4,
145.2, 127.6, 123.5, 74.5, 40.5.
F
O
O
S
O
O
S
F
MeO
1z
1-(2,6-difluorophenyl)-2-(dimethyl(oxo)-λ6-
O
1q
Methyl-4-(2-(dimethyl(oxo)-λ6-
sulfanylidene)ethan-1-one (1z) as a white solid, m.p. 135 °C.
1H NMR (500 MHz, Chloroform-d) δ 7.29 – 7.20 (m, 1H),
6.87 (q, J = 8.3 Hz, 2H), 4.71 (d, J = 2.9 Hz, 1H), 3.54 (d, J =
7.5 Hz, 6H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 175.0,
160.8 (d, J = 7.7 Hz), 158.8 (d, J = 7.6 Hz), 130.0 (d, J = 20.4
sulfanylidene)acetyl)benzoate (1q)21 as a white solid. 1H
NMR (500 MHz, Chloroform-d) δ 8.08 – 8.02 (m, 2H), 7.88 –
7.80 (m, 2H), 5.04 (s, 1H), 3.95 – 3.90 (m, 3H), 3.55 – 3.52 (m,
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+
Hz), 130.0, 111.6 (d, J = 5.2 Hz), 111.5 (d, J = 5.1 Hz), 74.2,
34.8, 31.2, 31.0; HRMS (ESI-TOF) m/z: calcd for C23H27O2 :
42.2; HRMS (ESI-TOF) m/z: calcd for C10H11F2O2S+:
335.2006 (M + H)+, found: 335.2010.
1
2
3
233.0442 (M + H)+, found: 233.0445.
O
Procedure for the Synthesis of 2.
O
A dried 10 mL Schlenk tube was charged with sulfoxonium
ylide 1 (0.2 mmol), [RuCl2(p-cymene)]2 (5 mol %) (3.1 mg,
0.005 mmol, 5 mol %), Na3PO4 (24.6 mg, 0.15 mmol),
MesCO2H (24.6 mg, 0.15 mmol), and HFIP (1 mL). This
mixture was heated to 110 °C on a heating plate for 24 h.
Upon completion, the reaction mixture was cooled to room
temperature, diluted with ethyl acetate, and filtered through a
pad of celite. The filtrate was concentrated under vacuum, and
the resulting residue was purified by preparative thin layer
chromatography (PTLC) with ethyl acetate: hexane to give the
corresponding products.
4
5
6
7
8
9
MeO
OMe
2d
6-methoxy-3-(4-methoxyphenyl)-1H-isochromen-1-one (2d)
(15.7 mg, 57%) was prepared from typical procedure (ethyl
acetate: hexane = 1 : 10) as orange solid, m.p. 147 - 148 °C.
1H NMR (500 MHz, Chloroform-d) δ 8.20 (d, J = 8.8 Hz, 1H),
7.84 – 7.79 (m, 2H), 7.01 – 6.98 (m, 1H), 6.98 – 6.95 (m, 2H),
6.84 (d, J = 2.4 Hz, 1H), 6.77 (s, 1H), 3.92 (s, 3H), 3.87 (s,
3H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 164.7, 162.3,
161.0, 154.2, 140.2, 131.8, 126.8, 124.5, 116.1, 114.2, 113.3,
107.6, 100.3, 55.6, 55.4; HRMS (ESI-TOF) m/z: calcd for
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
Safety Precaution of High-Pressure Reactions
We have NOT encountered any explosion during the synthesis
of all isocoumarins. However, for safety concerns, we
C17H15O4 : 283.0965 (M + H)+, found: 283.0968.
+
O
O
recommend using a plastic shield.
O
PhO
O
OPh
2e
6-phenoxy-3-(4-phenoxyphenyl)-1H-isochromen-1-one (2e)
(21.5 mg, 53%) was prepared from typical procedure (ethyl
acetate: hexane = 1 : 30) as yellow solid, m.p. 125 - 126 °C.
1H NMR (500 MHz, Chloroform-d) δ 8.24 (d, J = 8.7 Hz, 1H),
7.82 – 7.78 (m, 2H), 7.47 – 7.42 (m, 2H), 7.40 – 7.36 (m, 2H),
7.28 – 7.24 (m, 1H), 7.19 – 7.15 (m, 1H), 7.14 – 7.11 (m, 2H),
7.09 – 7.02 (m, 5H), 6.87 (d, J = 2.4 Hz, 1H), 6.74 (s, 1H);
13C{1H} NMR (126 MHz, Chloroform-d) δ 163.5, 161.8,
159.2, 156.1, 154.8, 153.9, 139.9, 132.2, 130.2, 129.9, 127.0,
126.5, 125.1, 124.1, 120.6, 119.6, 118.3, 118.1, 114.7, 111.8,
2a
3-phenyl-1H-isochromen-1-one (2a)9k (16.7 mg, 75%) as a
white solid. 1H NMR (500 MHz, Chloroform-d) δ 8.32 (d, J =
8.2 Hz, 1H), 7.92 – 7.87 (m, 2H), 7.75 – 7.71 (m, 1H), 7.54 –
7.42 (m, 5H), 6.97 (s, 1H)
；
13C{1H} NMR (126 MHz,
Chloroform-d) δ 162.3, 153.6, 137.5, 134.9, 131.9, 130.0,
129.6, 128.8, 128.1, 126.0, 125.2, 120.5, 101.8.
O
O
Me
+
100.7; HRMS (ESI-TOF) m/z: calcd for C27H19O4 : 407.1278
(M + H)+, found: 407.1277.
Me
2b
O
6-methyl-3-(p-tolyl)-1H-isochromen-1-one (2b) (18.7 mg,
O
75%) was prepared from typical procedure (ethyl acetate:
1
F3C
hexane = 1 : 30) as yellow solid, m.p. 150 - 152 °C. H NMR
CF3
(500 MHz, Chloroform-d) δ 8.17 (d, J = 8.0 Hz, 1H), 7.76 (d,
J = 8.2 Hz, 2H), 7.30 – 7.24 (m, 4H), 6.84 (s, 1H), 2.47 (s, 3H),
2.40 (s, 3H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 162.5,
153.8, 145.9, 140.1, 137.8, 129.5, 129.5, 129.3, 129.2, 125.8,
125.1, 118.0, 101.0, 22.0, 21.4; HRMS (ESI-TOF) m/z: calcd
2f
6-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)-1H-
isochromen-1-one (2f) (24.9 mg, 70%) was prepared from
typical procedure (ethyl acetate: hexane = 1 : 30) as white
solid, m.p. 170 - 172 °C. 1H NMR (500 MHz, Chloroform-d) δ
8.46 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 8.2 Hz, 2H), 7.83 (s, 1H),
7.77 (t, J = 7.7 Hz, 3H), 7.11 (s, 1H); 13C{1H} NMR (126
MHz, Chloroform-d) δ 160.6, 153.4, 137.3, 136.6 (q, J = 33.0
Hz), 134.6, 132.2 (q, J = 32.9 Hz), 130.8, 126.7 (q, J = 68.0
Hz), 126.0 (q, J = 3.8 Hz), 125.7, 125.0 (q, J = 3.5 Hz), 123.7
(q, J = 272.4 Hz), 123.4 (q, J = 4.0 Hz), 123.1 (q, J = 273.4
+
for C17H15O2 : 251.1067 (M + H)+, found: 251.1070.
O
O
tBu
tBu
2c
6-(tert-butyl)-3-(4-(tert-butyl)phenyl)-1H-isochromen-1-one
(2c) (14.1 mg, 42%) was prepared from typical procedure
(ethyl acetate: hexane = 1 : 30) as light yellow solid, m.p. 143
°C. 1H NMR (500 MHz, Chloroform-d) δ 8.23 (d, J = 8.4 Hz,
1H), 7.85 – 7.81 (m, 2H), 7.56 – 7.53 (m, 1H), 7.50 – 7.46 (m,
3H), 6.94 (s, 1H), 1.39 (s, 9H), 1.36 (s, 9H); 13C{1H} NMR
(126 MHz, Chloroform-d) δ 162.5, 158.8, 153.7, 153.2, 137.7,
129.4, 129.3, 125.9, 125.8, 125.0, 122.2, 118.0, 101.6, 35.4,
+
Hz), 102.6; HRMS (ESI-TOF) m/z: calcd for C17H9F6O2 :
359.0501 (M + H)+, found: 359.0502.
O
Me
O
Me
2g
7-methyl-3-(m-tolyl)-1H-isochromen-1-one (2g) (18.6 mg,
74%) was prepared from typical procedure (ethyl acetate:
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O
1
hexane = 1 : 30) as yellow white solid, m.p. 120 - 122 °C. H
F3C
O
1
2
3
4
5
6
7
8
NMR (500 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.72 (s, 1H),
7.66 (d, J = 7.9 Hz, 1H), 7.56 – 7.52 (m, 1H), 7.40 (d, J = 8.0
Hz, 1H), 7.34 (t, J = 7.7 Hz, 1H), 7.23 (d, J = 7.4 Hz, 1H),
6.93 (s, 1H), 2.48 (s, 3H), 2.42 (s, 3H); 13C{1H} NMR (126
MHz, Chloroform-d) δ 162.6, 152.9, 138.5, 138.4, 136.2,
135.1, 132.0, 130.5, 129.3, 128.7, 125.9, 125.7, 122.2, 120.4,
CF3
2k
7-(trifluoromethyl)-3-(3-(trifluoromethyl)phenyl)-1H-
isochromen-1-one (2k) (28 mg, 78%) was prepared from
typical procedure (ethyl acetate: hexane = 1 : 30) as white
solid, m.p. 168 - 169 °C. 1H NMR (500 MHz, Chloroform-d) δ
8.62 (s, 1H), 8.15 (s, 1H), 8.10 (d, J = 7.9 Hz, 1H), 8.00 – 7.96
(m, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H),
7.65 (t, J = 7.8 Hz, 1H), 7.09 (s, 1H); 13C{1H} NMR (126
MHz, Chloroform-d) δ 160.7, 154.0, 139.7, 132.1, 131.6 (q, J
= 32.8 Hz), 131.3 (q, J = 3.3 Hz), 130.7 (q, J = 33.7 Hz),
129.6, 128.6, 127.3 (q, J = 4.1 Hz), 127.1 (q, J = 3.7 Hz),
127.0, 123.7 (q, J = 272.6 Hz), 123.3 (q, J = 272.4 Hz), 122.3
(q, J = 3.8 Hz), 120.7, 102.0; HRMS (ESI-TOF) m/z: calcd for
+
101.7, 21.5, 21.4; HRMS (ESI-TOF) m/z: calcd for C17H15O2 :
251.1067 (M + H)+, found: 251.1064.
O
O
MeO
9
O
O
OMe
OMe
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
OMe
2h
2h'
2h and 2h’ (17.4 mg, 62%) was prepared from typical
procedure (ethyl acetate: hexane = 1 : 10) as cream solid, m.p.
120 °C. 1H NMR (500 MHz, Chloroform-d) δ 7.87 (d, J = 7.9
Hz, 1H), 7.71 (d, J = 2.7 Hz, 1H), 7.49 (d, J = 7.9 Hz, 1H),
7.45 – 7.29 (m, 8H), 7.14 (d, J = 8.0 Hz, 1H), 6.97 – 6.93 (m,
2H), 6.91 (s, 1H), 3.96 (s, 3H), 3.92 (s, 2H), 3.88 (d, J = 2.3
Hz, 6H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 162.4,
162.2, 159.9, 159.9, 159.5, 154.3, 152.6, 151.4, 133.6, 133.4,
131.1, 129.8, 129.7, 128.4, 128.0, 127.6, 124.7, 121.6, 121.3,
120.9, 117.6, 117.3, 115.7, 115.5, 114.3, 110.2, 110.1, 109.9,
101.9, 96.5, 55.9, 55.7, 55.4, 55.4. HRMS (ESI-TOF) m/z:
+
C17H9F6O2 : 359.0501 (M + H)+, found: 359.0500.
OMe O
O
OMe
2l
8-methoxy-3-(2-methoxyphenyl)-1H-isochromen-1-one (2l)
(13.2 mg, 48%) was prepared from typical procedure (ethyl
acetate: hexane = 1 : 6) as brown solid, m.p. 172 - 173 °C. 1H
NMR (500 MHz, Chloroform-d) δ 8.00 (d, J = 7.7 Hz, 1H),
7.61 (t, J = 8.1 Hz, 1H), 7.40 – 7.36 (m, 1H), 7.30 (s, 1H),
7.09 – 7.03 (m, 2H), 7.00 (d, J = 8.3 Hz, 1H), 6.93 (d, J = 8.3
Hz, 1H), 4.02 (s, 3H), 3.96 (s, 3H); 13C{1H} NMR (126 MHz,
Chloroform-d) δ 161.5, 159.4, 157.2, 150.7, 141.0, 135.5,
130.7, 128.9, 120.8, 120.6, 118.4, 111.2, 109.6, 109.4, 107.0,
+
calcd for C17H15O4 : 283.0965 (M + H)+, found: 283.0964;
（2h:2h’=0.68:1）
O
O
F
F
2i
5-fluoro-3-(3-fluorophenyl)-1H-isochromen-1-one (2i) (23.4
mg, 91%) was prepared from typical procedure (ethyl acetate:
hexane = 1 : 30) as yellowish white solid, m.p. 157 - 160 °C.
1H NMR (500 MHz, Chloroform-d) δ 8.15 – 8.11 (m, 1H),
7.70 (d, J = 7.9 Hz, 1H), 7.64 – 7.60 (m, 1H), 7.52 – 7.43 (m,
3H), 7.19 (s, 1H), 7.18 – 7.13 (m, 1H); 13C{1H} NMR (126
MHz, Chloroform-d) δ 163.1 (d, J = 246.8 Hz), 160.7, 157.3
(d, J = 252.8 Hz), 152.8, 133.8 (d, J = 8.1 Hz), 130.5 (d, J =
8.3 Hz), 128.9 (d, J = 7.8 Hz), 126.3 (d, J = 16.8 Hz), 125.4 (d,
J = 3.7 Hz), 122.0 (d, J = 4.1 Hz), 121.0 (d, J = 2.9 Hz), 120.4
(d, J = 19.8 Hz), 117.2 (d, J = 21.3 Hz), 112.5 (d, J = 23.9 Hz),
95.2 (d, J = 4.9 Hz); HRMS (ESI-TOF) m/z: calcd for
+
56.3, 55.6; HRMS (ESI-TOF) m/z: calcd for C17H15O4 :
283.0965 (M + H)+, found: 283.0970.
OPh O
O
OPh
2m
8-phenoxy-3-(2-phenoxyphenyl)-1H-isochromen-1-one (2m)
(17.3 mg, 43%) was prepared from typical procedure (ethyl
acetate: hexane = 1 : 30) as brown solid, m.p. 127 - 128 °C. 1H
NMR (500 MHz, Chloroform-d) δ 8.09 – 8.06 (m, 1H), 7.50 (t,
J = 8.0 Hz, 1H), 7.40 – 7.31 (m, 6H), 7.25 – 7.21 (m, 1H),
7.18 – 7.13 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H), 7.09 – 7.05 (m,
4H), 6.95 – 6.92 (m, 1H), 6.85 – 6.81 (m, 1H); 13C{1H} NMR
(126 MHz, Chloroform-d) δ 159.2, 158.4, 156.3, 156.3, 154.8,
150.1, 140.6, 135.3, 130.8, 130.0, 129.8, 129.1, 124.1, 123.8,
123.7, 123.2, 121.0, 119.7, 119.3, 119.0, 117.5, 111.6, 107.0;
+
C15H9F2O2 : 259.0565 (M + H)+, found: 259.0570.
O
O
Cl
O
O
Cl
Cl
Cl
2j'
2j
2j and 2j’ (8.6 mg, 30%) was prepared from typical procedure
(ethyl acetate: hexane = 1 : 30) as white solid, m.p. 172 - 173
°C. 1H NMR (500 MHz, Chloroform-d) δ 8.25 (d, J = 7.9 Hz,
1H), 7.92 (q, J = 1.5 Hz, 1H), 7.83 – 7.78 (m, 2H), 7.47 (d, J =
7.9 Hz, 1H), 7.45 – 7.43 (m, 2H), 7.34 (s, 1H); 13C{1H} NMR
(126 MHz, Chloroform-d) δ 161.1, 153.0, 135.2, 135.2, 135.1,
133.4, 130.8, 130.4, 130.2, 128.7, 128.5, 125.6, 123.6, 122.1,
+
HRMS (ESI-TOF) m/z: calcd for C27H19O4 : 407.1278 (M +
H)+, found: 407.1280.
F
O
O
F
2n
+
8-fluoro-3-(2-fluorophenyl)-1H-isochromen-1-one
(17.1 mg, 67%) was prepared from typical procedure (ethyl
acetate: hexane = 1 : 30) as white solid, m.p. 169- 171 °C. H
(2n)
98.8; HRMS (ESI-TOF) m/z: calcd for C15H9Cl2O2 : 290.9974
(M + H)+, found: 290.9979. (2j:2j’=1:20).
1
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OMe O
NMR (500 MHz, Chloroform-d) δ 8.04 – 7.99 (m, 1H), 7.72 –
7.67 (m, 1H), 7.44 – 7.39 (m, 1H), 7.32 – 7.26 (m, 2H), 7.21 –
1
2
3
4
5
6
7
8
O
7.15 (m, 3H); 13C{1H} NMR (126 MHz, Chloroform-d) δ
162.8 (d, J = 266.8 Hz), 160.1 (d, J = 253.3 Hz), 157.5 (d, J =
5.4 Hz), 149.0 (d, J = 5.2 Hz), 139.9, 136.2 (d, J = 10.2 Hz),
131.5 (d, J = 9.0 Hz), 128.5 (d, J = 1.7 Hz), 124.6 (d, J = 3.6
Hz), 122.3 (d, J = 4.4 Hz), 119.6 (d, J = 9.8 Hz), 116.4 (d, J =
22.8 Hz), 115.6 (d, J = 21.3 Hz), 109.5 (d, J = 7.2 Hz), 106.50
(dd, J = 16.0, 3.0 Hz); HRMS (ESI-TOF) m/z: calcd for
2w
8-methoxy-3-phenyl-1H-isochromen-1-one
prepared from typical procedure (ethyl acetate: hexane=1:10)
as a yellowish solid, m.p. 144 - 145 °C. H NMR (500 MHz,
Chloroform-d) δ 7.92 – 7.86 (m, 2H), 7.63 (t, J = 8.1 Hz, 1H),
7.5 – 7.4 (m, 3H), 7.04 (d, J = 7.7 Hz, 1H), 6.95 (d, J = 8.4 Hz,
1H), 6.86 (s, 1H), 4.03 (s, 3H); 13C{1H} NMR (126 MHz,
Chloroform-d) δ 161.6, 159.1, 153.9, 140.4, 135.8, 131.8,
129.9, 128.7, 125.3, 118.1, 109.8, 109.2, 101.8, 56.3; HRMS
(ESI-TOF) m/z: calcd for C16H13O3 : 253.0859 (M + H)+,
found: 253.0861.
(2w)
was
1
C15H9F2O2 : 259.0565 (M + H)+, found: 259.0567.
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
Cl
O
O
Cl
+
2o
8-chloro-3-(2-chlorophenyl)-1H-isochromen-1-one (2o) (9.6
Procedure for Synthesis of 2x
dried 10 mL Schlenk tube was charged with 2-
(dimethyl(oxo)-λ6-sulfanylidene)-1-(3-
mg, 34%) was prepared from typical procedure (ethyl acetate:
A
1
hexane = 1 : 30) as cream solid, m.p. 153 - 154 °C. H NMR
(500 MHz, Chloroform-d) δ 7.75 – 7.72 (m, 1H), 7.61 (t, J =
7.7 Hz, 1H), 7.58 – 7.55 (m, 1H), 7.52 – 7.48 (m, 1H), 7.42 –
7.36 (m, 3H), 6.97 (s, 1H); 13C{1H} NMR (126 MHz,
Chloroform-d) δ 158.8, 152.0, 140.0, 137.2, 134.6, 132.3,
131.4, 131.0, 130.9, 130.7, 130.6, 127.1, 125.2, 117.7, 107.4;
methoxyphenyl)ethan-1-one (1h) (0.1 mmol, 22.6 mg), 1-
(dimethyl(oxo)-λ6-sulfanylidene)propan-2-one (1x) (0.2
mmol, 26.8mg), [RuCl2(p-cymene)]2 (5 mol %) (3.1 mg, 0.005
mmol, 5 mol %), Na3PO4 (24.6 mg, 0.15 mmol), MesCO2H
(24.6 mg, 0.15 mmol), and HFIP (1 mL). This mixture was
heated to 110 °C on a heating plate for 24 h. Upon completion,
the reaction mixture was cooled to room temperature, diluted
with ethyl acetate, and filtered through a pad of celite. The
filtrate was concentrated under vacuum, and the resulting
residue was purified by preparative thin layer chromatography
(PTLC) with ethyl acetate: hexane to give the corresponding
+
HRMS (ESI-TOF) m/z: calcd for C15H9Cl2O2 : 290.9974 (M +
H)+, found: 290.9977.
Procedure for Synthesis of 2v, 2w
A
dried 10 mL Schlenk tube was charged with 2-
(dimethyl(oxo)-λ6-sulfanylidene)-1-phenylethan-1-one (1a)
(0.1 mmol, 19.6 mg), 2-(dimethyl(oxo)-λ6-sulfanylidene)-1-
(2-methoxyphenyl)ethan-1-one (1l) (0.1 mmol, 22.6 mg),
[RuCl2(p-cymene)]2 (5 mol %) (3.1 mg, 0.005 mmol, 5 mol %),
Na3PO4 (24.6 mg, 0.15 mmol), MesCO2H (24.6 mg, 0.15
mmol), and HFIP (1 mL). This mixture was heated to 110 °C
on a heating plate for 24 h. Upon completion, the reaction
mixture was cooled to room temperature, diluted with ethyl
acetate, and filtered through a pad of celite. The filtrate was
concentrated under vacuum, and the resulting residue was
purified by preparative thin layer chromatography (PTLC)
with (ethyl acetate: hexane) to give the (2v, 7.8 mg, 31%), (2w,
products.
O
O
OMe
2x
5-methoxy-3-methyl-1H-isochromen-1-one (2x) (5.7 mg,
30%) was prepared from typical procedure (ethyl acetate:
hexane=1:50) as a white solid, m.p. 41 - 43 °C H NMR (500
MHz, Chloroform-d) δ 7.85 – 7.82 (m, 1H), 7.38 (t, J = 8.0 Hz,
1H), 7.14 – 7.10 (m, 1H), 6.63 (t, J = 1.0 Hz, 1H), 3.92 (s, 3H),
2.29 (d, J = 1.0 Hz, 3H); 13C{1H} NMR (126 MHz,
Chloroform-d) δ 162.9, 153.9, 153.5, 128.3, 127.7, 120.9,
120.7, 114.3, 97.8, 55.9, 19.8; HRMS (ESI-TOF) m/z: calcd
for C11H11O3 : 191.0703 (M + H)+, found: 191.0706.
Procedure for Synthesis of 4a
1
9.0 mg, 35%), (2a, 10.9 mg, 49%), and (2l, 9.1 mg, 33%).
O
O
OMe
+
2v
A
dried 10 mL Schlenk tube was charged with 3-
methylbenzoic acid (3a) (0.1 mmol, 13.6 mg), 2-
(dimethyl(oxo)-λ6-sulfanylidene)-1-(2-
3-(2-methoxyphenyl)-1H-isochromen-1-one
(2v)
was
prepared from typical procedure (ethyl acetate: hexane=1:20)
1
as a yellow solid, m.p. 120 - 121 °C. H NMR (500 MHz,
methoxyphenyl)ethan-1-one (1l) (0.2 mmol, 45.3mg),
[RuCl2(p-cymene)]2 (5 mol %) (3.1 mg, 0.005 mmol, 5 mol %),
Na3PO4 (24.6 mg, 0.15 mmol), MesCO2H (24.6 mg, 0.15
mmol), and HFIP (1 mL). This mixture was heated to 110 °C
on a heating plate for 24 h. Upon completion, the reaction
mixture was cooled to room temperature, diluted with ethyl
acetate, and filtered through a pad of celite. The filtrate was
concentrated under vacuum, and the resulting residue was
Chloroform-d) δ 8.31 (d, J = 7.9 Hz, 1H), 8.01 – 7.95 (m, 1H),
7.75 – 7.67 (m, 1H), 7.53 – 7.47 (m, 2H), 7.42 – 7.37 (m, 2H),
7.08 (t, J = 7.6 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 3.97 (s, 3H);
13C{1H} NMR (126 MHz, Chloroform-d) δ 162.7, 157.1,
150.4, 138.0, 134.6, 130.7, 129.4, 128.8, 128.0, 126.3, 120.8,
120.7, 120.6, 111.3, 107.0, 55.6; HRMS (ESI-TOF) m/z: calcd
+
for C16H13O3 : 253.0859 (M + H)+, found: 253.0856.
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purified by preparative thin layer chromatography (PTLC)
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(3) Riveiro, M. E.; Moglioni, A.; Vazquez, R.; Gomez, N.; Facorro, G.; Piehl,
1
2
3
with ethyl acetate: hexane to give the corresponding products.
L.; de Celis, E. R.; Shayo, C.; Davio, C., Structural Insights into
Hydroxycoumarin-Induced Apoptosis in U-937 Cells. Bioorg. Med. Chem.
2008, 16, 2665-2675.
O
Me
O
OMe
4
5
6
7
8
9
(4) (a) Yoshikawa, M.; Harada, E.; Naitoh, Y.; Inoue, K.; Matsuda, H.;
Shimoda, H.; Yamahara, J.; Murakami, N., Development of Bioactive
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1674. Org. Lett. 2003, 5, 1083-1085.
4a
3-(2-methoxyphenyl)-7-methyl-1H-isochromen-1-one (4a)23
(10.7 mg, 40%) was prepared from typical procedure (ethyl
acetate: hexane=1:20) as a white solid. H NMR (500 MHz,
Chloroform-d) δ 8.12 (s, 1H), 7.99 – 7.95 (m, 1H), 7.54 – 7.51
(m, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.39 – 7.35 (m, 2H), 7.10 –
7.03 (m, 1H), 7.01 (d, J = 8.3 Hz, 1H), 3.96 (s, 3H), 2.47 (s,
3H); 13C{1H} NMR (126 MHz, Chloroform-d) δ 162.8, 157.1,
149.6, 138.3, 136.0, 135.5, 130.5, 129.1, 128.7, 126.2, 120.8,
120.5, 111.3, 107.0, 55.6, 21.4.
1
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Gram-Scale reaction experiment
A dried 100 mL Schlenk tube was charged with 2-
(dimethyl(oxo)-λ6-sulfanylidene)-1-phenylethan-1-one 1a
(0.981 g, 5.0 mmol), [RuCl2(p-cymene)]2 (76.5 mg, 0.125
mmol, 5 mol %), MesCO2H (0.615 g, 3.75 mmol), Na3PO4
(0.615 g, 3.75 mmol) and HFIP (50 mL). This mixture was
heated to 110 °C on a heating plate for 24 h. Upon completion,
the reaction mixture was cooled to room temperature, diluted
with ethyl acetate, and filtered through a pad of celite. The
filtrate was concentrated under vacuum, and the resulting
residue was purified by flash chromatography on silica gel
with ethyl acetate/hexane (1 : 30) to give the corresponding
products 3-phenyl-1H-isochromen-1-one (2a) (360.9 mg,
65%) as a white solid.
(6) Shikishima, Y.; Takaishi, Y.; Honda, G.; Ito, M.; Takeda, Y.; Kodzhimatov,
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P. T.; Paine, H. A.; Lloyd, M. D.; Thompson, A. S.; Threadgill, M. D.,
One-pot Tandem Hurtley-Retro-Claisen-Cyclisation Reactions in the
Synthesis of 3-Substituted Analogues of 5-Aminoisoquinolin-1-one (5-
AIQ), a Water-Soluble Inhibitor of PARPs. Bioorg. Med. Chem. 2013, 21,
5218-5227. (c) Li, W.; Wiesenfeldt, M. P.; Glorius, F., Ruthenium-NHC-
Diamine Catalyzed Enantioselective Hydrogenation of Isocoumarins. J.
Am. Chem. Soc. 2017, 139, 2585-2588.
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the
ACS Publications website.
1H and 13C NMR spectra of new compounds.
(8) (a) Napolitano, E., The Synthesis Of Isocoumarins over the Last Decade.
A Review. Org. Prep. Proced. Int. 1997, 29, 631-664. (b) Pal, S.; Chatare,
V.; Pal, M., Isocoumarin and Its Derivatives: An Overview on their
Synthesis and Applications. Curr. Org. Chem. 2011, 15, 782-800. (c)
Saeed, A.; Haroon, M.; Muhammad, F.; Larik, F. A.; El-Seedi, H.;
Channar, P. A., Advances in Transition-Metal-Catalyzed Synthesis of 3-
Substituted Isocoumarins. J. Organomet. Chem., 2017, 834, 88-103. (d)
Saikia, P.; Gogoi, S., Isocoumarins: General Aspects and Recent
Advances in their Synthesis. Adv. Synth. Catal. 2018, 360, 2063-2075.
(9) (a) Ueura, K.; Satoh, T.; Miura, M., Rhodium- and Iridium-Catalyzed
Oxidative Coupling of Benzoic Acids with Alkynes via Regioselective C-H
Bond Cleavage. J. Org. Chem. 2007, 72, 5362-5367. (b) Kudo, E.;
Shibata, Y.; Yamazaki, M.; Masutomi, K.; Miyauchi, Y.; Fukui, M.;
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Annulation of Arenecarboxylic and Acrylic Acids with Alkynes under
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Complex. Chem.-Eur. J. 2016, 22, 14190-14194. (c) Yedage, S. L.;
Bhanage, B. M., Ru(II)/PEG-400 as a Highly Efficient and Recyclable
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
Notes
glcheng@hqu.edu.cn
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the NSF of China (21672075)
and the Instrumental Analysis Center of Huaqiao University.
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