Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with Internal Alkynes via C-H Functionalization in Poly(ethylene glycol)

Article abstract of DOI:10.1021/acs.joc.9b00580

A novel Co(III)-catalyzed oxidative annulation of aromatic aldehydes with internal alkynes for accessing isocoumarins is described, which is achieved by oxidation, weak chelation-assisted C-H bond functionalization, and annulation cascades with excellent functional group compatibility, high atom economy, and step efficiency. By using environmentally benign and inexpensive poly(ethylene glycol)-400 (PEG-400), the Co/Cu/PEG-400 system could be recycled and reused.

Full text of DOI:10.1021/acs.joc.9b00580

Article
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with
Internal Alkynes via C−H Functionalization in Poly(ethylene glycol)
Li-Ming Tao,* Chuan-Hua Li, Jun Chen, and Hui Liu
Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds Research and Application, Xiangnan University,
Chenzhou 423000, China
S
* Supporting Information
ABSTRACT: A novel Co(III)-catalyzed oxidative annulation
of aromatic aldehydes with internal alkynes for accessing
isocoumarins is described, which is achieved by oxidation,
weak chelation-assisted C−H bond functionalization, and
annulation cascades with excellent functional group compat-
ibility, high atom economy, and step efficiency. By using
environmentally benign and inexpensive poly(ethylene glycol)-400 (PEG-400), the Co/Cu/PEG-400 system could be recycled
and reused.
examples using abundant, nontoxic, air-stable cobalt catalysts
are rare.4 To our knowledge, only a paper that employs
aldehydes as the weak chelation carboxyl group precursors
using the N-heterocyclic carbene/rhodium(III) catalysis has
been reported (Scheme 1b).5e In view of significant economic
and environmental reasons from both academic and industrial
perspectives, development of efficient routes, especially
including recyclable catalytic process, to access isocoumarins
is therefore appealing.
Herein, we report a cobalt(III)-catalyzed oxidative [4 + 2]
annulation of aromatic aldehydes with internal alkynes. The
reaction allows the formation of isocoumarins through a
sequence of oxidation of aldehydes6 and weak chelation-
assisted C−H bond functionalization and annulation (Scheme
1c). Importantly, this reaction employs an abundant, nontoxic,
air-stable cobalt catalyst and environmentally benign, inex-
pensive PEG-400 medium7 to allow the Co/Cu/PEG-400
system recycle and reuse.
1. INTRODUCTION
Isocoumarins are a very important class of O-heterocyclic
compounds that are found in a wide range of natural products
and pharmaceuticals.1,2 For these reasons, tremendous
attention has been attracted on the development of efficient
strategies for assembling isocoumarins. Among them, the
annulation reaction with unsaturated hydrocarbons (e.g.,
alkynes and alkenes) via weak chelation-assisted C−H bond
functionalization is particularly attractive due to its high atom
and step economy.2,3 Generally, these transformations focus on
transition metal-catalyzed annulation of aromatic acids and
their derivatives with internal alkynes,2−5 where the carboxyl
group serves as the weak chelation group4,5 to selectively
enable functionalization of its ortho-C(sp2)−H bond, leading
to isocoumarins (Scheme 1a). However, most of such
transformations are restricted by the requirement of noble
metal catalysts (e.g., Rh, Ru, and Pd) and toxic solvents,5 and
Scheme 1. Synthesis of Isocoumarins via Annulations
2. RESULTS AND DISCUSSION
At the outset of our investigation, the reaction between
benzaldehyde 1a and diphenylethyne 2a was chosen to explore
the optimal reaction conditions (Table 1). The reaction of 1a
with 2a in the presence of Cp*Co(CO)I2 (10 mol %), CuO (2
equiv), and O2 (1 atm) was performed in PEG-400 (2 g) at
100 °C, affording the target 3,4-diphenyl-1H-isochromen-1-
one 3aa in 83% yield (entry 1). Notably, both Cp*Co(CO)I2
and CuO played a key role in the reaction as the absence of
one resulted in no reaction (entries 2 and 8). A lower amount
of Cp*Co(CO)I2 (5 mol %) had a negative effect even after
prolonging the reaction time (entry 3), whereas a higher
amount of Cp*Co(CO)I2 (15 mol %) gave identical results to
that proceeded at 10 mol % loading (entry 4). Other Co
Received: February 27, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b00580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
a
Table 1. Screening of the Reaction Conditions
Table 2. Variations of the Aromatic Aldehydes (1) and
a
Alkynes (2)
entry
variation from the standard conditions
yield (%)
1
2
3
4
5
6
7
8
none
83
0
51/55
85
38
without Cp*Co(CO)I2
Cp*Co(CO)I2 (5 mol %)
Cp*Co(CO)I2 (15 mol %)
[Cp*CoI2]2 instead of Cp*Co(CO)I2
Co(acac)3 instead of Cp*Co(CO)I2
CoI2 instead of Cp*Co(CO)I2
without CuO
b
15
trace
trace
76
9
CuO (1.5 equiv)
10
11
12
13
14
15
16
17
18
19
Cu(OAc)2 instead of CuO
CuCl2 instead of CuO
Cu2O instead of CuO
without molecular sieves
at 80 °C
at 110 °C
air instead of O2
argon instead of O2
13
6
trace
71
55
81
58
7
31
toluene (3 mL) instead of PEG-400
DMF (3 mL) instead of PEG-400
none
65
79
c
20
a
Reaction conditions: 1a (0.6 mmol), 2a (0.3 mmol), Cp*Co(CO)I2
(10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (100 mg),
a
Reaction conditions: 1 (0.6 mmol), 2 (0.3 mmol), Cp*Co(CO)I2
PEG-400 (2 g), 100 °C, and 24 h. Some by-products, including
b
(10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (100 mg),
PEG-400 (2 g), 100 °C, and 24 h. The regioselectivity ratio is >99:1.
benzoic acid, were observed as determined by GC−MS analysis. For
b
c
48 h. 1a (2 mmol), 2a (1 mmol), PEG-400 (8 g), and 48 h.
catalysts, such as [Cp*CoI2]2, Co(acac)3, and CoI2, were
tested (entries 5−7), and they all were less efficient than
Cp*Co(CO)I2. A lower loading (1.5 equiv) CuO decreased
the yield to 76% (entry 9). Three other Cu salts, including
Cu(OAc)2, CuCl2, and Cu2O, proved to be inferior to CuO
(entries 10−12). We found that the reaction could be
promoted by molecular sieves (entry 1 vs entry 13). Extensive
optimization revealed that 100 °C was the best option as a
lower temperature (90 °C) diminished the yield and a higher
temperature (110 °C) had no further improvement of the yield
(entries 14 and 15). The reaction stunted the formation of 3aa
with moderate yield when using air-replaced O2 (entry 16),
and replacement of O2 by argon led to a lower yield (entry 17).
Two conventional solvents, toluene and DMF, were tested,
and they both were less reactive than PEG-400 (entries 18 and
19). Gratifyingly, the reaction was applicable to a 1 mmol scale
of diphenylethyne 2a, giving 3aa in a good yield (entry 20).
Having established the optimized reaction conditions, we
turned our attention to investigate the substrate scope of this
annulation reaction (Table 2). The optimal conditions were
compatible with a wide range of internal alkynes 2a−2e and
2g−2l, including diaryl, dialkyl, and alkylarylacetylenes
(products 3ab−3ae and 3ga−3al), but unsuitable for bulky
ortho-substituted diaryl acetylene 2f and terminal alkyne 2m
(products 3fa and 3ma). For symmetric diarylacetylenes, a
number of substituents, namely, Me, MeO, and Cl, on the aryl
ring were well tolerated, and the electron properties affected
their reactivity (products 3ab−3ae). While alkynes, possessing
an electron-donating group (e.g., Me and MeO) at para or
meta position, afforded 3ab, 3ac, and 3ae in 81−87% yields,
alkynes with a weak electron-donating Cl group provided 3ad
in diminishing yield. A heteroarylacetylene, 1,2-di(thiophen-2-
yl)ethyne, was found to be suitable for assembling 3ag in a
moderate yield. For dialkylacetylenes, the reaction was
efficiently executed to afford 3ah and 3ai in high yields.
Gratifyingly, unsymmetrical alkylacetylenes were suitable
substrates and regioselectively furnished 3aj−3al in good
yields. It should be noted that this reaction can be applicable to
construction of estrone-containing 1H-isochromen-1-one 3al,
in which the estrone unit has unique bioactive properties.8
Unfortunately, the reaction failed to annulation with terminal
alkyne (3am).
Subsequently, a variety of aromatic aldehydes 1b−1k with
diphenylethyne 2a were investigated under the optimal
conditions (products 3ba−3ka). We found that several
substituents, including Me, MeO, Br, Cl, CN, and MeCO,
on the aryl ring were perfectly tolerated. Aldehydes possessing
a Me group at para, meta, or ortho position were all converted
efficiently into the corresponding products 3ba, 3ha, and 3ia.
To our delight, halogens, such as bromide and chloride, were
tolerated well, giving 3da and 3ea, respectively, in satisfactory
yields. Aldehydes 1f−1g bearing an electron-withdrawing CN
or acetyl group were viable for the synthesis of 3fa−3ga, albeit
with diminishing yield. Using diMeO-substituted aldehyde
enable the formation of 3ja in 74% yield. The optimal
conditions were also compatible with thiophene-2-carbalde-
hyde, giving 3ka in a moderate yield.
The recycle experiments of benzaldehyde 1a with
diphenylethyne 2a were performed on the Cp*Co(CO)I2/
B
DOI: 10.1021/acs.joc.9b00580
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CuO/molecular sieves/PEG 400 system (Scheme 2, eq 1).7 A
constant rate of conversion was observed under the optimal
4. EXPERIMENTAL SECTION
4.1. General Considerations. The 1H and 13C NMR spectra
were recorded in CDCl3 solvent on an NMR spectrometer using TMS
as the internal standard. High-resolution mass spectrometry (HRMS)
was measured on an electrospray ionization (ESI) apparatus using
time-of-flight (TOF) mass spectrometry. Melting points are
uncorrected.
Scheme 2. Recycle Experiments and Control Experiments
4.2. Typical Experimental Procedure for Cobalt(III)-Cata-
lyzed Oxidative Annulation of Benzaldehydes with Internal
Alkynes. A mixture of benzaldehydes 1 (0.6 mmol), alkynes 2 (0.3
mmol), Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), O2 (1 atm),
molecular sieves (100 mg), and PEG-400 (2 g) was prepared in a 25
mL Schlenk tube and heated to 100 °C (oil bath temperature). The
reaction mixture was stirred at 100 °C for 24 h until complete
consumption of the starting material, as monitored by thin-layer
chromatography (TLC) and/or gas chromatography−mass spectrom-
etry (GC−MS) analysis. After the reaction was finished, the reaction
was allowed to cool to room temperature and extracted with hexane/
diethyl ether (10:1; 5 × 10 mL). The combined organic layer was
washed with brine (3 × 5 mL), dried over anhydrous Na2SO4, and
concentrated in vacuo. The resulting residue was purified by silica gel
column chromatography (hexane/ethyl acetate = 25:1) to afford the
desired 1H-isochromen-1-ones 3.
conditions without the addition Cp*Co(CO)I2, CuO, and
PEG-400 in the every cycles. To our delight, the reaction is still
efficient after recycling for three times by replenishing it with
oxygen every time. The yield slightly decreased because there
are some losses of the Co catalyst in every recycle process.
Notably, using benzoic acid 1k to react with alkyne 2a afforded
3aa in 86% yield under the optimal conditions (Scheme 2, eq
2).
After extracting with diethyl ether/hexane (1:1), the mixture of
Cp*Co(CO)I2, CuO, PEG-400, and molecular sieves was solidified
(cooled and then evaporated under vacuo) and subjected to a second
run of the annulation reaction by charging with the same substrates
(aldehyde 1, alkyne 2, and O2).
The possible mechanisms for this annulation protocol are
proposed (Scheme 3).2−5 Aldehyde 1a is oxidized and
Scheme 3. Possible Mechanisms
4.3. Synthesis Experimental Procedure for a Scale up to 1
mmol of Diphenylethyne 2a. A mixture of benzaldehyde 1a (2
mmol), diphenylethyne 2a (1 mmol), Cp*Co(CO)I2 (10 mol %),
CuO (2 equiv), O2 (1 atm), molecular sieves (200 mg), and PEG-400
(8 g) was prepared in a 25 mL Schlenk tube and heated to 100 °C (oil
bath temperature). The reaction mixture was stirred at 100 °C for 48
h until complete consumption of the starting material, as monitored
by TLC and/or GC−MS analysis. After the reaction was finished, the
reaction was allowed to cool to room temperature and extracted with
hexane/diethyl ether (10:1; 5 × 15 mL). The combined organic layer
was washed with brine (3 × 5 mL), dried over anhydrous Na2SO4,
and concentrated in vacuo. The resulting residue was purified by silica
gel column chromatography (hexane/ethyl acetate = 25:1) to afford
the desired 1H-isochromen-1-one 3aa (235.4 mg, 79% yield).
4.3.1. 3,4-Diphenyl-1H-isochromen-1-one (3aa).5m,9a 74.2 mg,
83% yield; white solid; mp 171.8−173.5 °C (lit.5m,9a 172−174 °C);
1H NMR (500 MHz, CDCl3): δ (ppm) 8.41−8.40 (m, 1H), 7.65−
transformed into the acid intermediate A by the Co(III)/
CuO/O2 system. Subsequently, insertion of the active Co(III)
species into C−H bond of the acid intermediate A forms the
intermediate B.2,4 Coordination of the intermediate B with
alkyne 2a results in the formation of the intermediate C, which
sequentially undergoes cis-addition to afford the intermediate
D.4 Annulation and reductive elimination of the intermediate
D provides the desired product 3aa and the Co(I) species.
Oxidation of the Co(I) species by the Cu(II) species
regenerates the active Co(III) species. We also cannot rule
out the reaction via the peroxide intermediate E.
7.62 (m, 1H), 7.53−7.50 (m, 1H), 7.43−7.40 (m, 3H), 7.33 (t, J =
7.0 Hz, 2H), 7.27−7.25 (m, 3H), 7.22−7.17 (m, 3H); 13C NMR (125
MHz, CDCl3): δ (ppm) 162.3, 151.0, 138.9, 134.7, 134.3, 133.0,
131.2, 129.6, 129.2, 129.1, 129.0, 128.2, 128.1, 127.9, 125.4, 120.4,
116.9; LRMS (EI, 70 eV) m/z (%): 298 (M+, 100), 270 (25), 221
(33), 165 (26), 105 (88).
4.3.2. 3,4-Di-p-tolyl-1H-isochromen-1-one (3ab).5m 83.1 mg, 85%
yield; light yellow solid; mp 152.5−154.3 °C (lit.5m 153−155 °C); 1H
NMR (500 MHz, CDCl3): δ (ppm) 8.39 (d, J = 7.5 Hz, 1H), 7.61 (t,
J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.26−7.19 (m, 5H), 7.14 (d,
J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.29 (s, 3H);
13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 151.0, 139.3, 139.0,
137.8, 134.6, 131.4, 131.0, 130.2, 129.8, 129.5, 129.1, 128.6, 127.8,
125.3, 120.3, 116.3, 21.4, 21.3; LRMS (EI, 70 eV) m/z (%): 326 (M+,
100), 298 (45), 235 (25), 178 (18), 119 (51).
3. CONCLUSIONS
In summary, we have reported the first recyclable Co(III)/
CuO/PEG-400 system for oxidative annulation of aromatic
aldehydes with internal alkynes involving C−H functionaliza-
tion. By using both abundant, nontoxic, air-stable Cp*Co(III)
catalyst and environmentally benign and inexpensive PEG-400,
diverse functional groups were tolerated, and the resulting
isocoumarins were obtained in good yields and excellent
selectivity. Most importantly, the Co(III)/CuO/PEG-400
system were recycled and reused three times and showed
high efficiency every time.
4.3.3. 3,4-Bis(4-methoxyphenyl)-1H-isochromen-1-one (3ac).9b
107.0 mg, 87% yield; light yellow solid; mp 156.8−158.3 °C (lit.9b
158.4−159.7 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.38−8.36
(m, 1H), 7.63−7.59 (m, 1H), 7.49−7.46 (m, 1H), 7.30−7.28 (m,
2H), 7.21−7.16 (m, 3H), 6.96 (d, J = 8.5 Hz, 2H), 6.72 (d, J = 9.0
Hz, 2H), 3.86 (s, 3H), 3.76 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
(ppm) 162.5, 159.9, 159.3, 150.9, 139.5, 134.6, 132.3, 130.7, 129.5,
127.7, 126.6, 125.4, 125.2, 120.2, 115.4, 114.6, 113.3, 55.3, 55.2;
C
DOI: 10.1021/acs.joc.9b00580
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The Journal of Organic Chemistry
Article
LRMS (EI, 70 eV) m/z (%): 410 (M+, 96), 354 (100), 297 (17), 221
(25), 161 (33).
2.97 (m, 2H), 2.56−2.52 (m, 1H), 2.51−2.46 (m, 1H), 2.38 (t, J =
10.5 Hz, 1H), 2.21−1.91 (m, 6H), 1.70−1.65 (m, 3H), 1.59−1.49
(m, 4H), 0.99−0.87 (m, 5H), 0.26−0.21 (m, 2H); 13C NMR (125
MHz, CDCl3): δ (ppm) 220.9, 162.6, 153.6, 141.2, 139.9, 136.1,
134.5, 130.6, 129.8, 129.5, 127.7, 127.1, 124.7, 124.5, 120.5, 114.2,
50.6, 48.0, 44.6, 38.0, 35.9, 31.6, 29.4, 26.5, 25.6, 21.6, 13.9, 10.2,
10.1, 9.2; IR (KBr): νCO 1741, 1735 cm−1; HRMS m/z (ESI) calcd
for C30H31O3 [M + H]+, 439.2273; found, 439.2281.
4.3.4. 3,4-Bis(4-chlorophenyl)-1H-isochromen-1-one (3ad).9a
85.6 mg, 78% yield; light yellow solid; mp 171.0−172.5 °C (lit.9a
172.6−173.6 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.40 (d, J =
7.5 Hz, 1H), 7.68−7.65 (m, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.43 (d, J =
8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 7.20 (t, J = 8.5 Hz, 4H), 7.16
(d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.8,
150.0, 138.2, 135.3, 135.0, 134.5, 132.5, 131.1, 130.5, 129.8, 129.6,
128.6, 128.4, 125.1, 120.4, 116.1; LRMS (EI, 70 eV) m/z (%): 366
(M+, 100), 338 (54), 303 (38), 239 (42), 139 (76).
4.3.12. 6-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ba).5m,9a
79.6 mg, 85% yield; white solid; mp 184.3−187.0 °C (lit.9a 186−188
°C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.30 (d, J = 8.0 Hz, 1H),
7.42 (t, J = 5.5 Hz, 3H), 7.35−7.31 (m, 3H), 7.26−7.24 (m, 2H),
7.22−7.17 (m, 3H), 6.97 (s, 1H), 2.37 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 162.4, 151.0, 145.8, 138.9, 134.4, 133.1, 131.3,
129.6, 129.5, 129.3, 129.1, 128.9, 128.1, 127.8, 125.3, 118.1, 116.9,
22.3; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284 (30), 235
(23), 178 (20), 105 (45).
4.3.5. 3,4-Di-m-tolyl-1H-isochromen-1-one (3ae).9a 79.2 mg, 81%
yield; white solid; mp 120.1−122.8 °C; 1H NMR (500 MHz, CDCl3):
δ (ppm) 8.40 (d, J = 7.5 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.51 (t, J =
7.5 Hz, 1H), 7.30 (d, J = 7.5 Hz, 2H), 7.21 (t, J = 5.5 Hz, 2H), 7.06
(t, J = 13.5 Hz, 5H), 2.35 (s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 162.5, 150.9, 139.1, 138.7, 137.5, 134.6, 134.3,
132.8, 131.7, 129.7, 129.7, 129.5, 128.9, 128.8, 128.3, 128.0, 127.6,
126.4, 125.5, 120.4, 116.9, 21.5, 21.4; LRMS (EI, 70 eV) m/z (%):
326 (M+, 95), 298 (45), 235 (38), 178 (30), 119 (100).
4.3.13. 6-Methoxy-3,4-diphenyl-1H-isochromen-1-one (3ca).9a
81.7 mg, 83% yield; white solid; mp 175.5−177.0 °C (lit.9a 178−
180 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.34 (d, J = 8.5 Hz,
1H), 7.40 (t, J = 7.0 Hz, 3H), 7.32 (d, J = 7.5 Hz, 2H), 7.26−7.25 (m,
2H), 7.23−7.17 (m, 3H), 7.07−7.05 (m, 1H), 6.58 (d, J = 2.0 Hz,
1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 164.7,
162.1, 151.5, 141.2, 134.4, 133.0, 131.9, 131.2, 129.3, 129.1, 129.0,
128.2, 127.8, 116.8, 115.7, 113.7, 108.5, 55.5; LRMS (EI, 70 eV) m/z
(%): 328 (M+, 100), 300 (25), 251 (30), 152 (22), 105 (60).
4.3.14. 6-Bromo-3,4-diphenyl-1H-isochromen-1-one (3da).5m
73.3 mg, 65% yield; white solid; mp 199.0−202.6 °C (lit.5m 198−
200 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.25−8.23 (m, 1H),
7.63 (d, J = 8.5 Hz, 1H), 7.43 (d, J = 5.0 Hz, 3H), 7.33−7.30 (m,
3H), 7.24 (t, J = 5.5 Hz, 3H), 7.21−7.18 (m, 2H); 13C NMR (125
MHz, CDCl3): δ (ppm) 161.7, 152.2, 140.4, 133.6, 132.6, 131.5,
131.2, 131.1, 130.5, 129.3, 129.3, 129.3, 128.5, 128.1, 128.0, 119.1,
116.0; LRMS (EI, 70 eV) m/z (%): 376 (M+, 38), 348 (9), 299 (18),
163 (41), 105 (100).
4.3.6. 3,4-Di(thiophen-2-yl)-1H-isochromen-1-one (3ag). 56.7
1
mg, 61% yield; yellow solid; mp 183.9−185.0 °C; H NMR (500
MHz, CDCl3): δ (ppm) 8.34−8.32 (m, 1H), 7.66−7.63 (m, 2H),
7.50−7.46 (m, 1H), 7.41−7.40 (m, 1H), 7.33−7.32 (m, 1H), 7.29−
7.26 (m, 1H), 7.16−7.12 (m, 2H), 6.99−6.97 (m, 1H); 13C NMR
(125 MHz, CDCl3): δ (ppm) 161.2, 148.2, 139.7, 135.0, 134.6, 133.7,
130.8, 130.0, 129.5, 129. 5, 129.0, 128.4, 128.0, 127.0, 125.2, 119.7,
107.2; IR (KBr): νCO 1732 cm−1; LRMS (EI, 70 eV) m/z (%): 310
(M+, 81), 282 (100), 253 (66), 221 (32), 111 (30); HRMS m/z
(ESI) calcd for C17H11O2S2 [M + H]+, 311.0200; found, 311.0221.
4.3.7. 3,4-Diethyl-1H-isochromen-1-one (3ah).9a 50.3 mg, 83%
yield; white solid; mp 57.0−59.5 °C (lit.9a 59−64 °C); 1H NMR (500
MHz, CDCl3): δ (ppm) 8.32 (d, J = 8.0 Hz, 1H), 7.76−7.72 (m, 1H),
7.55 (d, J = 8.5 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 2.68−2.60 (m, 4H),
1.29 (t, J = 7.5 MHz,3H), 1.21 (t, J = 7.5 MHz,3H); 13C NMR (125
MHz, CDCl3): δ (ppm) 163.0, 155.0, 137.8, 134.6, 130.9, 127.1,
122.5, 120.9, 113.1, 24.1, 19.3, 14.4, 12.6; LRMS (EI, 70 eV) m/z
(%): 202 (M+, 100), 187 (92), 259 (30), 131 (83), 115 (46).
4.3.8. 3,4-Dibutyl-1H-isochromen-1-one (3ai).5g 61.9 mg, 80%
yield; colorless oil; 1H NMR (500 MHz, CDCl3): δ (ppm) 8.32−8.30
(m, 1H), 7.75−7.71 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.47−7.44 (m,
1H), 2.62−2.57 (m, 4H), 1.73−1.67 (m, 2H), 1.56−1.51 (m, 2H),
1.48−1.39 (m, 4H), 1.00−0.94 (m, 6H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 163.0, 154.2, 138.0, 134.6, 129.8, 127.0, 122.68,
120.8, 112.3, 31.9, 30.6, 30.0, 25.9, 22.9, 22.5, 14.0, 13.9; LRMS (EI,
70 eV) m/z (%): 258 (M+, 42), 215 (45), 173 (100), 145 (20), 131
(20).
4.3.15. 6-Chloro-3,4-diphenyl-1H-isochromen-1-one (3ea).9a
72.7 mg, 73% yield; white solid; mp 167.2−171.7 °C (lit.9a 168−
170 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.33 (d, J = 8.5 Hz,
1H), 7.48−7.42 (m, 4H), 7.32−7.31 (m, 2H), 7.26−7.24 (m, 3H),
7.21−7.18 (m, 2H), 7.16 (d, J = 2.0 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 161.5, 152.2, 141.7, 140.4, 133.6, 132.6, 131.3,
131.1, 129.3 (3C), 128.6, 128.5, 128.0, 125.0, 118.7, 116.1;LRMS (EI,
70 eV) m/z (%): 332 (M+, 89), 304 (20), 255 (28), 163 (32), 105
(100).
4.3.16. 1-Oxo-3,4-diphenyl-1H-isochromene-6-carbonitrile
(3fa).9a 63.0 mg, 65% yield; light yellow solid; mp 174.6−177.2 °C
(lit.9a 176−178 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.48 (d,
J = 8.0 Hz, 1H), 7.74−7.72 (m, 1H), 7.50−7.46 (m, 4H), 7.34−7.32
(m, 2H), 7.28−7.20 (m, 5H); 13C NMR (125 MHz, CDCl3): δ
(ppm) 160.7, 152.8, 139.5, 132.9, 132.1, 131.0, 130.5, 130.2, 129.7,
129.7, 129.6, 129.3, 128.9, 128.1, 123.0, 118.2, 117.7, 115.7; LRMS
(EI, 70 eV) m/z (%): 323 (M+, 100), 295 (21), 246 (20), 105 (65).
4.3.17. 6-Acetyl-3,4-diphenyl-1H-isochromen-1-one (3ga).9a 71.4
mg, 70% yield; light yellow solid; mp 173.1−174.9 °C; 1H NMR (500
MHz, CDCl3): δ 8.48 (d, J = 8.0 Hz, 1H), 8.04−8.02 (m, 1H), 7.76
(s, 1H), 7.49−7.41 (m, 3H), 7.36−7.31 (m, 2H), 7.30−7.24 (m, 3H),
7.23−7.17 (m, 2H), 2.53 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
197.4, 161.5, 151.8, 141.6, 139.2, 133.6, 132.5, 131.1, 130.2, 129.3
(3C), 128.6, 128.0, 126.9, 125.4, 123.2, 116.8, 27.0; LRMS (EI, 70
eV) m/z (%): 340 (M+, 100), 312 (20), 239 (27), 105 (81), 111
(31).
4.3.9. 4-Methyl-3-phenyl-1H-isochromen-1-one (3aj).5g 49.6 mg,
70% yield; white solid; mp 91.2−93.8 °C (lit.5g 92−94 °C); 1H NMR
(500 MHz, CDCl3): δ (ppm) 8.39−8.37 (m, 1H), 7.82−7.79 (m,
1H), 7.64 (d, J = 8.0 Hz, 1H), 7.60−7.58 (m, 2H), 7.57−7.53 (m,
1H), 7.48−7.44 (m, 3H), 2.32 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 162.6, 151.2, 138.8, 134.8, 133.3, 129.8, 129.5,
129.4, 128.3, 128.0, 123.4, 120.8, 109.2, 13.6; LRMS (EI, 70 eV) m/z
(%): 236 (M+, 93), 208 (100), 178 (25), 105 (31), 77 (52).
4.3.10. 4-Cyclopropyl-3-phenyl-1H-isochromen-1-one (3ak).9b
56.6 mg, 72% yield; light yellow solid; mp 114.5−116.0 °C (lit.9b
1
115−117 °C); H NMR (500 MHz, CDCl3): δ (ppm) 8.33 (d, J =
8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.82−7.79 (m, 1H), 7.75−7.73
(m, 2H), 7.53 (t, J = 7.5 Hz, 1H), 7.47−7.43 (m, 3H), 1.94−1.89 (m,
1H), 1.00−0.93 (m, 2H), 0.21−0.17 (m, 2H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 162.5, 153.5, 139.7, 134.5, 133.2, 129.5 (2C),
129.4, 127.9, 124.6, 120.6, 114.6, 10.0, 9.1; LRMS (EI, 70 eV) m/z
(%): 262 (M+, 72), 233 (21), 217 (52), 185 (63), 105 (100).
4.3.11. 4-Cyclopropyl-3-((8R,9S,13S,14S)-13-methyl-17-oxo-
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]-
phenanthren-3-yl)-1H-isochromen-1-one (3al). 90.7 mg, 69% yield;
light yellow solid; mp 225.3−227.9 °C; 1H NMR (500 MHz, CDCl3):
δ (ppm) 8.33 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.80 (t, J
= 7.5 Hz, 1H), 7.55−7.51 (m, 3H), 7.35 (d, J = 8.0 Hz, 1H), 2.99−
4.3.18. 7-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ha).5m,9a
78.6 mg, 84% yield; white solid; mp 169.6−172.1 °C (lit.5m,9a 171−
173 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.20 (d, J = 0.5 Hz,
1H), 7.45−7.38 (m, 4H), 7.33−7.31 (m, 2H), 7.25−7.23 (m, 2H),
7.21−7.17 (m, 3H), 7.09 (d, J = 8.5 Hz, 1H), 2.46 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ (ppm) 162.5, 150.1, 138.5, 136.4, 136.0, 134.5,
133.0, 131.2, 129.3, 129.2, 129.1, 128.8, 128.1, 127.9, 125.4, 120.3,
116.9, 21.3; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284 (28),
235 (40), 178 (25), 105 (80).
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Article
4.3.19. 8-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ia).5m
72.1 mg, 77% yield; white solid; mp 142.0−144.6 °C (lit.5m 143−
144 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 7.45 (t, J = 7.8 Hz,
1H), 7.42−7.38 (m, 3H), 7.31 (t, J = 7.5 Hz, 3H), 7.25−7.23 (m,
2H), 7.22−7.16 (m, 3H), 7.00 (d, J = 8.0 Hz, 1H), 2.91 (s, 3H); 13C
NMR (125 MHz, CDCl3): δ (ppm) 161.6, 150.6, 143.5, 140.5, 135.0,
133.8, 133.0, 131.4, 131.1, 129.1, 129.1, 128.8, 128.0, 127.8, 123.7,
118.9, 117.0, 23.6; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284
(34), 235 (20), 178 (23), 105 (86).
(2) For reviews on the synthesis of isocoumarins via C-H
functionalization, see: (a) Datsenko, V. P.; Nelyubina, Y. V.;
Smol’yakov, A. F.; Loginov, D. A. Cyclooctadiene iridium complexes
[Cp*Ir(COD)X]+ (X = Cl, Br, I): Synthesis and application for
oxidative coupling of benzoic acid with alkynes. J. Organomet. Chem.
2018, 874, 7−12. (b) Saikiaa, P.; Gogoi, S. Isocoumarins: General
Aspects and Recent Advances in their Synthesis. Adv. Synth. Catal.
2018, 360, 2063−2075.
(3) For selective reviews on the annulation reaction involving C-H
functionalization using Co catalysis, see: (a) Chirila, P. G.; Whiteoak,
C. J. Recent advances using[Cp*Co(CO)I2] catalysts as a powerful
tool for C−H functionalisation. Dalton Trans. 2017, 46, 9721−9739.
(b) Ujwaldev, S. M.; Harry, N. A.; Divakar, M. A.; Anilkumar, G.
Cobalt-catalyzed C−H activation: recent progress in heterocyclic
chemistry. Catal. Sci. Technol. 2018, 8, 5983−6018. (c) Prakash, S.;
Kuppusamy, R.; Cheng, C.-H. Cobalt-Catalyzed Annulation Reactions
via C-H Bond Activation. ChemCatChem 2018, 10, 683−705. Using
diverse transition-metal catalysis, see: (d) Song, G.; Wang, F.; Li, X.
C−C, C−O and C−N bond formation via rhodium(III)-catalyzed
oxidative C−H activation. Chem. Soc. Rev. 2012, 41, 3651−3678.
(e) Ackermann, L. Carboxylate-Assisted Ruthenium-Catalyzed Alkyne
Annulations by C−H/Het−H Bond Functionalizations. Acc. Chem.
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Ackermann, L. Weakly Coordinating Directing Groups for
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4.3.20. 5,7-Dimethoxy-3,4-diphenyl-1H-isochromen-1-one
(3ja).5m 79.5 mg, 74% yield; white solid; mp 157.8−160.3 °C
(lit.5m 159−161 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 7.49 (d,
J = 2.5 Hz, 1H), 7.24−7.21 (m, 5H), 7.18−7.11 (m, 5H), 6.68 (d, J =
2.6 Hz, 1H), 3.93 (s, 3H), 3.32 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ (ppm) 162.5, 160.3, 157.6, 149.0, 137.6, 133.6, 130.7,
129.5, 128.3, 127.6, 127.4, 126.7, 122.9, 122.1, 115.5, 106.9, 102.1,
55.9, 55.8; LRMS (EI, 70 eV) m/z (%): 358 (M+, 100), 315 (20), 253
(60), 105 (45).
4.3.21. 4,5-Diphenyl-7H-thieno[2,3-c]pyran-7-one (3ka).9a 42.0
mg, 46% yield; light yellow solid; mp 146.2−149.0 °C (lit.9a 146−148
1
°C); H NMR (500 MHz, CDCl3): δ (ppm) 7.78−7.77 (m, 1H),
7.40−7.38(m, 4H), 7.35 (d, J = 8.0 Hz, 2H), 7.28−7.27 (m, 2H),
7.22−7.19 (m, 2H), 6.96 (m, 1H); 13C NMR (125 MHz, CDCl3): δ
(ppm) 158.2, 153.4, 149.5, 136.3, 134.9, 132.4, 130.3, 129.3, 129.2,
129.1, 128.2, 128.0, 125.2, 122.8, 115.9; LRMS (EI, 70 eV) m/z (%):
304 (M+, 100), 276 (21), 227 (41), 171 (25), 105 (50).
356, 1461−1479. (g) Gulías, M.; Mascarenas, J. L. Metal-Catalyzed
̃
Annulations through Activation and Cleavage of C−H Bonds. Angew.
Chem. Int. Ed. 2016, 55, 11000−11019. (h) Wang, Z.; Xie, P.; Xia, Y.
Recent progress in Ru(II)-catalyzed C−H activations with oxidizing
directing groups. Chin. Chem. Lett. 2018, 29, 47−53. (i) da Silva
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b00580.
■
S
́
Junior, E. N.; Jardim, G. A.; Gomes, R. S.; Liang, Y.-F.; Ackermann, L.
Weakly-coordinating N-oxide and carbonyl groups for metal-catalyzed
C−H activation: the case of A-ring functionalization. Chem. Commun.
2018, 54, 7398−7411.
Spectra of products (PDF)
(4) For papers on the Co catalysis, see: (a) Mandal, R.; Sundararaju,
B. Cp*Co(III)-Catalyzed Annulation of Carboxylic Acids with
Alkynes. Org. Lett. 2017, 19, 2544−2547. (b) Nguyen, T. T.;
Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed Coupling of Benzoic
Acid C−H Bonds with Alkynes, Styrenes, and 1,3-Dienes. Angew.
Chem. Int. Ed. 2018, 57, 1688−1691.
AUTHOR INFORMATION
Corresponding Author
*E-mail: lmt_ao@126.com.
ORCID
■
Li-Ming Tao: 0000-0001-9258-0441
(5) For papers on other transition-metal catalysis, see: (a) Ueura, K.;
Satoh, T.; Miura, M. An Efficient Waste-Free Oxidative Coupling via
Regioselective C−H Bond Cleavage: Rh/Cu-Catalyzed Reaction of
Benzoic Acids with Alkynes and Acrylates under Air. Org. Lett. 2007,
9, 1407−1409. (b) 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. (c) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. Waste-
Free Synthesis of Condensed Heterocyclic Compounds by Rhodium-
Catalyzed Oxidative Coupling of Substituted Arene or Heteroarene
Carboxylic Acids with Alkynes. J. Org. Chem. 2009, 74, 3478−3483.
(d) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Synthesis of
Functionalized α-Pyrone and Butenolide Derivatives by Rhodium-
Catalyzed Oxidative Coupling of Substituted Acrylic Acids with
Alkynes and Alkenes. J. Org. Chem. 2009, 74, 6295−6298. (e) Youn,
S. W.; Yoo, H. J. One-Pot Sequential N-Heterocyclic Carbene/
Rhodium(III) Catalysis: Synthesis of Fused Polycyclic Isocoumarins.
Adv. Synth. Catal. 2017, 359, 2176−2183. (f) Ackermann, L.;
Pospech, J.; Graczyk, K.; Rauch, K. Versatile Synthesis of
Isocoumarins and α-Pyrones by Ruthenium-Catalyzed Oxidative C−
H/O−H Bond Cleavages. Org. Lett. 2012, 14, 930−933. (g) Yu, Y.;
Huang, L.; Wu, W.; Jiang, H. Palladium-Catalyzed Oxidative
Annulation of Acrylic Acid and Amide with Alkynes: A Practical
Route to Synthesize α-Pyrones and Pyridones. Org. Lett. 2014, 16,
2146−2149. (h) Warratz, S.; Kornhass, C.; Cajaraville, A.; Niepoetter,
B.; Stalke, D.; Ackermann, L. Ruthenium(II)-Catalyzed C-H
Activation/Alkyne Annulation by Weak Coordination with O2 as
the Sole Oxidant. Angew. Chem., Int. Ed. 2015, 54, 5513−5517. (i) Yu,
J.-L.; Zhang, S.-Q.; Hong, X. Mechanisms and Origins of Chemo- and
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Key Scientific Research Project of Hunan
Provincial Education Department of China (nos. 15A175 and
15A176) and the Science and Technology Plan Project of
Chenzhou City (nos. CZ2014038 and CKJ2016020) for the
financial support.
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