Stereoselective synthesis of 3-methyleneisoindolin-1-ones via base-catalyzed intermolecular reactions of electron-deficient alkynes with N -hydroxyphthalimides

Article abstract of DOI:10.1021/acs.joc.5b00002

Highly stereoselective intermolecular reactions of electron-deficient alkynes with N-hydroxyphthalimides for efficient construction of N-unprotected 3-methyleneisoindolin-1-ones have been developed through base catalytic strategies. The reaction of alkynoates with N-hydroxyphthalimides catalyzed by Bu₃P in DMF at 150 °C gave the corresponding 3-methyleneisoindolin-1-ones with a (Z)-configuration, while the reaction of alkynoates with N-hydroxyphthalimides catalyzed by K₂CO₃ in DMF at 60°C gave the corresponding 3-methyleneisoindolin-1-ones with an (E)-configuration, and (Z)-3-methyleneisoindolin-1-ones were obtained when alkyne ketones reacted with N-hydroxyphthalimide.

Full text of DOI:10.1021/acs.joc.5b00002

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Note
Stereoselective Synthesis of 3-Methyleneisoindolin-1-
ones via Base-Catalyzed Intermolecular Reactions of
Electron-Deficient Alkynes with N-Hydroxyphthalimides
Xin Chen, Fei-Fei Ge, Tao Lu, and Qing-Fa Zhou
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 24 Feb 2015
Downloaded from http://pubs.acs.org on February 25, 2015
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Stereoselective Synthesis of 3-Methyleneisoindolin-1-ones via Base-Catalyzed Intermolecular
Reactions of Electron-Deficient Alkynes with N-Hydroxyphthalimides
7
8
9
Xin Chen, a FeiꢀFei Ge,a Tao Lu a* and QingꢀFa Zhou a,b*
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a School of Basic Sciences, China Pharmaceutical University, Nanjing, 210009, P. R. China
b State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, P. R.
China
Fax: +86-025-86285179 ; Tele.: +86-025-86185160
E-mail: zhouqingfa@cpu.edu.cn (Q. Zhou), lut163@163.com (T. Lu)
EWG
R
NH
O
R
R
R
EWG
NH
O
R
R
EWG = Ester Group
Bu3P (20 mol%)
DMF, 150 oC
NOH
K2CO3 (20 mol%)
DMF, 60 oC
11 examples
29%~73% yields
O
+
O
EWG
EWG
11 examples
EWG = Ester Group
NH
71%~99% yields
O
EWG = Ketone Group
3 examples
50%~60% yields
ABSTRACT: Highly stereoselective intermolecular reactions of electronꢀdeficient alkynes with
Nꢀhydroxyphthalimides for efficient construction of Nꢀunprotectedꢀ3ꢀmethyleneisoindolinꢀ1ꢀones have
been developed through bases catalytic strategies. The reaction of alkynoates with
Nꢀhydroxyphthalimides catalyzed by Bu3P in DMF at 150 oC gave the corresponding
3ꢀmethyleneisoindolinꢀ1ꢀones with (Z)ꢀconfiguration, while the reaction of alkynoates with
Nꢀhydroxyphthalimides catalyzed by K2CO3 in DMF at 60 oC gave the corresponding
3ꢀmethyleneisoindolinꢀ1ꢀones with (E)ꢀconfiguration and (Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones were
obtained when alkyne ketones reacted with Nꢀhydroxyphthalimide.
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Isoindolinones are important scaffolds in organic chemistry and medicinal chemistry due to their
prevalence in numerous synthetic and naturally occurring bioactive molecules. In particular,
3ꢀmethyleneisoindolinꢀ1ꢀones have been recognized as core structures in natural compounds such as
enterocarpam II, the secophthalide–isoquinoline eneꢀlactam fumaridine,1 magallanesine, an
isoindolobenzazocine isolated from the SouthꢀAmerican plant Berberis darwinii.2 And
3ꢀmethyleneisoindolinꢀ1ꢀones have shown a diverse range of bioactivities, such as vasorelaxant
property,3 local anesthetic activity.4 In addition, 3ꢀmethyleneisoindolinꢀ1ꢀones are also important
intermediates for the synthesis of other useful alkaloids.5 Owing to their great importance, many
methods have been developed for the preparation of 3ꢀmethyleneisoindolinꢀ1ꢀones. These methods
mainly involved the traditional condensation reaction of phthalimides with stabilized phosphoranes,6 or
addition of organometallic reagents followed by dehydration of the resulting 3ꢀhydroxyphthalimidines,7
the Horner condensation of 3ꢀ(diphenylphosphinoyl)isoindolinꢀ1ꢀones with aldehydes,8
ortholithiation–anionic cyclization of Nꢀacylꢀ2ꢀbromobenzamides,9 electrophilic cyclizations of
2ꢀalkynylbenzamides10 and recently developed metalꢀcatalyzed cascade reactions.11 However, most of
the present procedures suffer from one or more drawbacks such as the use of expensive metal reagents
or poor stereoselectivity of the products, therefore more efficient and simple protocols to
stereoselectively prepare 3ꢀmethyleneisoindolinꢀ1ꢀone would be highly desirable.
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Over the past twenty years, baseꢀcatalyzed annulation has grown significantly and represents one of
the most powerful synthetic methodologies for preparing various heterocyclic compounds. Nonetheless,
base catalytic, direct syntheses of 3ꢀmethyleneisoindolinꢀ1ꢀone derivatives have seen considerably less
progress. We have recently developed a convenient phosphineꢀcatalyzed [3+2] annulation of
electronꢀdeficient alkynes with Nꢀhydroxyphthalimide (NHPI) for the synthesis of
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3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀones (Scheme 1).12 In the context of ongoing projects for
the diversely functionalized construction of isoindolinꢀ1ꢀones, we wish to report the novel process for
stereoselective synthesis of 3ꢀmethyleneisoindolinꢀ1ꢀones (Scheme 1).
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Scheme 1. Phosphineꢀcatalyzed reactions of 2ꢀhydroxyisoindolineꢀ1,3ꢀdione and ethyl propiolate.
We
started
our
investigation
by examining the
Bu3Pꢀcatalyzed reaction
of
2ꢀhydroxyisoindolineꢀ1,3ꢀdione 1a and ethyl propiolate 2a (Table 1). First, the reaction of 1a with 2a
in the presence of Bu3P (10 mol%) in DMF at room temperature for 48 h afforded the
(E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone
4a
in
the
yield
of
42%
accompanied
with
3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀone derivative 3 in the yield of 48% (entry 1, Table 1). It
was interesting to note that 3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀone derivative 3 was not found
and the (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a was formed in good yield beside a little amount of
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 5a when the loading of the catalyst Bu3P was increased to 20 mol%
or 50 mol% (entries 2 and 3, Table 1). To improve the reaction selectivity, the temperature was then
evaluated. To our delight, an excelent yield of 5a was obtained when the reaction was carried out at 150
oC (entry 8, Table 1). And the (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a was formed in good yield
accompanied with a small quantity of its (Z)ꢀisomer 5a when the reaction was disposed at 60 oC for 6h
or
100
oC
for
2h
(entries
6
and
7,
Table
1).
However,
only
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3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀone derivative 3 was given when the reaction was
performed at ꢀ20 oC (entry 4, Table 1). When shifting the solvent to THF, CH2Cl2, CH3CN, or toluene,
the reaction did not give the better results (entries 9ꢀ15, Table 1). Other nucleophilic phosphine was
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also tested and both Ph3P and Ph2PEt were proved to be as useable catalyst for 5a at 150 C
(entries17ꢀ20, Table 1). The base containing nitrogen, such as Et3N, was also examined in the reaction,
only the Michael addition product was observed (entry 21, Table 1). It is highlighted here that only
(E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a was given in 73% yield when the reaction was performed in DMF
at 60 oC for 4h using inorganic base K2CO3 as catalyst and the sole product 5a was formed in 74% yield
when the reaction was performed in DMF at 100 oC for 6h (entries 22 and 23, Table 1). Herein we
established the optimal reaction conditions for the stereoselective synthesis of Nꢀunprotected
3ꢀmethyleneisoindolinꢀ1ꢀone derivatives via the reaction conditions’ control.
Table 1. Evaluation of conditions for the reaction of 1a with ethyl propiolate (2a) a.
Entry
Catalyst
Solvent Temperature Time(h)
(oC)
Yield of 3 Yield of 4a Yield of 5a
(mol%)
(%) b
48
0
(%) b
42
69
76
36
0
(%) b
0
1
2
3
4
5
6
7
8
Bu3P (10)
Bu3P (20)
Bu3P (50)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
r.t c
r.t
48
24
2
11
6
r.t
0
0
48
6
40
97
0
14
0
ꢀ20
60
6
74
80
0
17
11
95
100
150
2
0
2
0
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Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Bu3P (20)
Ph3P(20)
Ph3P(20)
THF
reflux
48
48
48
48
12
48
12
18
16
18
14
4
0
0
0
10
11
12
13
14
15
17
18
19
20
21 d
22
23
CH2Cl2 r.t
18
38
31
0
28
35
49
65
19
51
40
0
5
CH2Cl2 reflux
CH3CN r.t
11
10
13
trace
21
31
62
42
92
0
10
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60
CH3CN reflux
toluene r.t
30
0
toluene reflux
DMF
DMF
100
150
100
150
60
0
0
Ph2PEt(20) DMF
Ph2PEt(20) DMF
0
51
0
0
Et3N (20)
DMF
0
0
K2CO3(20) DMF
K2CO3(20) DMF
60
4
0
73
0
trace
74
100
6
0
a Unless noted otherwise, reaction of Nꢀhydroxyphthalimide 1a (0.3 mmol), ethyl propiolate 2a (0.36
b
c
mmol) was performed in 1 mL of solvent under N2. Isolated yield based on 1a. r.t. = Room
temperature. d The Michael addition product was formed in 77% yield.
To understand these novel processes, 3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀone derivative 3
and (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a were treated under different conditions (Scheme 2). We found
that compound 3a could be effectively transformed to (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a in the
o
present of catalytic amount of both K2CO3 and Bu3P at 60 C, while it was fully transformed to
o
o
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 5a at 150 C in the presence of Bu3P or at 100 C in the presence of
K2CO3. And we also found that (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a could be effectively transformed
to (Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 5a in the present of catalytic amount of both K2CO3 and Bu3P at a
higher temperature, which shows a novel example that (E)ꢀconfiguration of carbonꢀcarbon double bond
could be transformed to (Z)ꢀconfiguration of carbonꢀcarbon double bond. It is worth mentioning here
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that, compound 3a could also be transformed to (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 4a and
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 5a in the absence of catalyst, and compound 4a could also be
transformed to its isomer 5a. There is an obvious intramolecular hydrogen bonding of the N−H group
of 5a in its crystal structure and this could be the cause of the Zꢀstereoselectivity under higher
temperature.13
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Scheme 2. Transformation of isoindolinone derivatives at different conditions.
With these results in hand, we first investigated the scope of alkynoates for the synthesis of
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones (Table 2). As shown in Table 2, all terminal alkynoates were proved
to be applicable to this reaction and selectively gave product (Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones in good
to excellent yields under the optimized reaction conditions. The alkynoates bearing both little alkyl
units, namely ethyl and methyl, and branched bulky alkyl group, such as tꢀbutyl, could give the
products in 95, 99 and 99% yields respectively (entries1ꢀ3, Table 2). The nature of the substituent on
the benzene ring of the benzyl propiolate did impact on the yields. For example, for substrates with a
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halogen Cl or methoxy group attached on the benzene ring, the yields of the corresponding products
were obtained in the yields of 98% and 86%, respectively (entries 5 and 8, Table 2). Gratifyingly,
furanꢀ2ꢀylmethyl propiolate also reacted smoothly with 2a to give the desired
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone 5i in an excellent yield (entry 9, Table 2). It is worthy to note that
phenyl propiolate could also proceed with 2a to provide the corresponding
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(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀone
5j
in
the
yield
of
71%.
However,
only
the
3aꢀhydroxyisoxazolo[3,2ꢀa]isoindolꢀ8(3aH)ꢀone products were formed, when βꢀsubstituted alkynoates
were applied in the reaction.
Table 2. Bu3P catalyzed synthesis of Zꢀ3ꢀmethyleneisoindolinꢀ1ꢀones.a
Entry
R
Time (h)
Product
5a
Yield（%）
1
2
Et
2
2
2
2
2
2
4
6
2
6
95
99
99
99
98
94
90
86
99
71
Me
5b
5c
3
tꢀBu
4
PhCH2
5d
5e
5
4ꢀClꢀC6H4CH2
4ꢀBrꢀC6H4CH2
4ꢀMeꢀC6H4CH2
4ꢀMeOꢀC6H4CH2
2ꢀfurylꢀCH2
Ph
6
5f
7
5g
8
5h
5i
9
10
5j
a All the reactions were carried out with 1a (0.3 mmol) and 2 (0.36 mmol) at 150 oC in 1.0 mL of DMF
under N2 and isolated yields were reported.
We then investigated the scope of alkynoates for the synthesis of (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones
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in the presence of K2CO3 (Table 3). As exemplified in Table 3, a wide array of alkynoates was suitable
for present strategy despite that some examples need to be careful about the reaction temperature. For
example, the (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones were effectively given at room temperature when
methyl propiolate or 4ꢀbromophenyl propiolate was used in this reaction, however the
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60
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(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones were formed as major products at 60 C for 2h (entries 2 and 6,
Table 3). Notably, phenyl propiolate was also compatible with the standard reaction conditions but in a
decreased yield (entry 10, Table 3).
Table 3. K2CO3 catalyzed synthesis of Eꢀ3ꢀmethyleneisoindolinꢀ1ꢀones.a
Entry
1
R
Time (h)
Product
4a
Yield （%）
Et
4
73
66
62
60
62
60
60
57
63
29
2b
3
Me
12
4
4b
4c
tꢀBu
4
Ph CH2
4
4d
4e
5
4ꢀClꢀC6H4CH2
4ꢀBrꢀC6H4CH2
4ꢀMeꢀC6H4CH2
4ꢀMeOꢀC6H4CH2
2ꢀfuryl ꢀCH2
Ph
4
6 b
7
12
6
4f
4g
8
6
4h
4i
9
4
10
6
4j
a Unless noted otherwise, the reactions were carried out with 1a (0.3 mmol) and 2 (0.36 mmol) at 60 oC
in 1.0 mL of DMF under N2 and isolated yields were reported. b Room temperature.
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To
examine
the
scope
of
2ꢀhydroxyisoindolineꢀ1,3ꢀdione,
5
6
7
8
5,6ꢀdichloroꢀ2ꢀhydroxyisoindolineꢀ1,3ꢀdione (1b) was investigated. As expected, the (Z)ꢀethyl
2ꢀ(5,6ꢀdichloroꢀ3ꢀoxoisoindolinꢀ1ꢀylidene)acetate (6) was formed in 90% yield when the reaction was
performed in DMF at 150 oC for 2h in the presence of Bu3P, while the (E)ꢀethyl
2ꢀ(5,6ꢀdichloroꢀ3ꢀoxoisoindolinꢀ1ꢀylidene)acetate (7) was formed in 65% yield when K2CO3 was used
as catalyst in DMF at 60 oC for 2h (Scheme 3).
9
10
11
12
13
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15
16
17
18
19
20
21
22
23
24
25
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36
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49
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60
CO2Et
O
NOH
Cl
Cl
Bu3P (20 mol%)
NH
CO2Et
Cl
DMF,150 oC, 2h
90%
Cl
O
2a
2a
O
6
1b
1b
EtO2C
O
Cl
Cl
Cl
K2CO3 (20 mol%)
NH
NOH
CO2Et
Cl
DMF,60 oC, 2h
65%
O
O
7
Scheme 3. Reaction of 5,6ꢀdichloroꢀ2ꢀhydroxyisoindolineꢀ1,3ꢀdione (1b) with ethyl propiolate (2a).
Subsequently, promoted by the successful base catalyzed direct selective synthesis of
3ꢀmethyleneisoindolinꢀ1ꢀones with alkynoates, a range of alkyne ketones were also examined with
respect to 2ꢀhydroxyisoindolineꢀ1,3ꢀdione 1a to synthesize 3ꢀmethyleneisoindolinꢀ1ꢀone compounds.
To our surprise, the (Z) 3ꢀmethyleneisoindolinꢀ1ꢀones were given when alkyne ketones 8 and 1a were
o
disposed in DMF at 60 C in the presence of K2CO3, while the reactions were very complicated when
the reactions were carried out in the presence of Bu3P under deferent temperatures. Both aromatic and
aliphatic alkyne ketones could proceed smoothly to give (Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones in good
yields (Scheme 4).
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Scheme 4. Reactions of 2ꢀhydroxyisoindolineꢀ1,3ꢀdione (1a) with alkyne ketones (8).
Next, the free N−H group of 4a was attempted to protect with 1ꢀ(bromomethyl)ꢀ4ꢀnitrobenzene (10)
o
(2.0 equiv) in the presence NaH (2.0 equiv) in THF at 40 C for 1 h. In the reaction, Nꢀbenzyl
ꢀprotected compound 11 was obtained in 88% yield (eq 1).
Conclusion
In conclusion, we have developed an efficient and metalꢀfree protocol to synthesize
(E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones and (Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones via baseꢀcatalyzed selective
reactions of electronꢀdeficient alkynes with Nꢀhydroxyphthalimides. The present catalytic process
provides
a
mild and general access to the (E)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones and
(Z)ꢀ3ꢀmethyleneisoindolinꢀ1ꢀones, respectively. Especially, the structures of these products are
attractive for potential drug discovery.
Experimental Section
General Methods. All reactions were performed in anhydrous solvents under an N2 atmosphere.
THF, Et2O, and toluene were distilled from K and Na metal, respectively. DMF, CH2Cl2 and acetone
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were distilled from CaH2. CH3CN was distilled from P2O5. PE refers to petroleum ether (boiling range
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60–90 °C). Melting points were obtained on a melting point apparatus and are uncorrected. H and 13
C
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NMR spectra were recorded in DMSOꢀd6 using a 300 MHz spectrometer: chemical shifts (δ) are given
in parts per million, coupling constants (J) in Hz. Highꢀresolution mass spectra were recorded in ESI
mode on a QTOF MS spectrometer.
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General procedure for reaction of electron-deficient alkynes with N-hydroxyphthalimide. To
the solution of electronꢀdeficient alkyne (0.36 mmol) and Nꢀhydroxyphthalimide (0.3 mmol) in dry
DMF (1 mL) was added Ph3P (15.7 mg, 0.06 mmol). The resulting mixture was stirred at room
temperature under nitrogen atmosphere for the required period of time. After completion of the reaction
as monitored by TLC, the reaction mixture was quenched with CH2Cl2 (15 mL), which was washed
with water and brine successively, dried over MgSO4, filtered, and concentrated in vacuo. Purification
by flash chromatography (SiO2; ethylacetate/PE, 1:10~1:3) yielded the desired products.
(E)-Ethyl 2-(3-oxoisoindolin-1-ylidene)acetate (4a)
47.54 mg, 73% isolated yield; white solid. mp: 95ꢀ97 oC. IR (KBr) 3744, 3722, 3651, 2360, 2345, 1770,
1
1750, 1734, 1717, 1700, 1683, 1657, 1562, 1504, 1458, 794 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
10.34 (s, 1H), 8.11 (d, J = 7.3 Hz, 1H), 7.82 (d, J = 7.3 Hz, 1H), 7.72 (dt, J = 18.5, 7.2 Hz, 2H), 6.11 (s,
1H), 4.23 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.9, 166.2,
146.6, 136.5, 133.1, 131.7, 128.7, 123.1, 122.0, 92.0, 59.9, 14.1. ESIHRMS: Calcd for C12H12NO3:
(M+H)+ 218.0812. Found: m/z 218.0815.
(E)-Methyl 2-(3-oxoisoindolin-1-ylidene)acetate (4b)
o
40.20 mg, 66% isolated yield; white solid. mp: 197ꢀ199 C; IR (KBr) 3167, 3113, 3086, 1744, 1715,
1643, 1694, 1632, 1607, 1454, 1373, 1302, 1273, 1157, 1115, 845, 773, 696 cmꢀ1. 1H NMR (300 MHz,
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DMSOꢀd6): δ 10.92 (s, 1H), 8.95 (d, J = 7.6 Hz, 1H), 7.83–7.66 (m, 3H), 5.80 (s, 1H), 3.72 (s, 3H). 13
C
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NMR (75 MHz, DMSOꢀd6): δ 169.3, 167.8, 150.0, 135.5, 134.9, 133.7, 133.1, 129.5, 124.7, 99.7, 53.2.
ESIHRMS: Calcd for C11H9NNaO3: (M+Na)+ 226.0475. Found: m/z 226.0479.
(E)-Tert-butyl 2-(3-oxoisoindolin-1-ylidene)acetate (4c)
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o
45.59 mg, 62% isolated yield; white solid. mp: 162ꢀ164 C. IR (KBr) 3318, 2963, 2928, 1713, 1694,
1634, 1614, 1271, 1146, 1136, 1098, 1076, 856, 812, 696 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
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10.88 (s, 1H), 8.95 (d, J = 8.6 Hz, 1H), 7.79 (t, J = 6.8 Hz, 2H), 7.74–7.65 (m, 1H), 5.73 (s, 1H), 1.51
(s, 9H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.4, 165.0, 147.2, 133.6, 132.9, 131.6, 131.2, 127.7,
122.7, 100.2, 79.9, 27.8. ESIHRMS: Calcd for C14H16NO3: (M+H)+ 246.1125. Found: m/z 246.1129.
(E)-Benzyl 2-(3-oxoisoindolin-1-ylidene)acetate (4d)
o
50.24 mg, 60% isolated yield; white solid. mp:185ꢀ187 C. IR (KBr) 3181, 3080, 3071, 3030, 2994,
2843, 1721, 1701, 1643, 1634, 1468, 1454, 1155, 1140, 1117, 851, 741, 696 cmꢀ1. 1H NMR (300 MHz,
CDCl3): δ 9.41 (s, 1H), 9.09 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.66 (dt, J = 25.0, 7.4 Hz,
2H), 7.39 (dd, J = 14.6, 7.0 Hz, 5H), 5.97 (s, 1H), 5.28 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 171.9,
168.3, 150.1, 138.5, 136.7, 136.0, 134.1, 133.7, 131.2, 131.1, 130.8, 130.8, 125.8, 102.5, 69.0.
ESIHRMS: Calcd for C17H14NO3: (M+H)+ 280.0968. Found: m/z 280.0972.
(E)-4-Chlorobenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (4e)
o
58.23 mg, 62% isolated yield; white solid. mp: 194ꢀ196 C. IR (KBr) 3204, 3192, 3115, 1753, 1715,
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1651, 1454, 1265, 1223, 1153, 1107, 837, 808, 768 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ 10.98 (s,
1H), 8.94 (d, J = 7.5 Hz, 1H), 7.75 (ddd, J = 13.0, 11.4, 7.1 Hz, 3H), 7.53–7.35 (m, 4H), 5.83 (s, 1H),
5.21 (s, 2H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.4, 165.2, 148.6, 135.2, 133.5, 133.0, 132.6, 131.8,
131.1, 129.8, 128.3, 127.6, 122.8, 97.4, 64.6. ESIHRMS: Calcd for C17H12ClNNaO3: (M+Na)+
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336.0398. Found: m/z 336.0402.
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(E)-4-Bromobenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (4f)
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9
o
64.26 mg, 60% isolated yield; white solid. mp: 215ꢀ217 C. IR (KBr) 3306, 3275, 1722, 1682, 1667,
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1651, 1470, 1416, 1294, 1280, 1200, 1125, 1063, 824, 770, 696 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6):
δ 10.98 (s, 1H), 8.94 (d, J = 7.6 Hz, 1H), 7.81 (s, 1H), 7.72 (ddd, J = 18.0, 10.5, 4.2 Hz, 2H), 7.57 (d, J
= 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 5.83 (s, 1H), 5.19 (s, 2H). 13C NMR (75 MHz, DMSOꢀd6): δ
167.4, 165.2, 148.7, 135.6, 134.2, 133.5, 133.0, 131.9, 131.3, 131.1, 130.1, 127.6, 122.8, 97.4, 64.6.
ESIHRMS: Calcd for C17H13BrNO3: (M+H)+ 358.0073. Found: m/z 358.0078.
(E)-4-Methylbenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (4g)
52.76 mg, 60% isolated yield; white solid. mp:166ꢀ168 oC. IR (KBr) 3418, 3410, 3404, 1748, 1712,
1703, 1694, 1651, 1643, 1634, 1267, 1152, 1146, 1107, 847, 808 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6):
δ 10.96 (s, 1H), 8.95 (d, J = 7.6 Hz, 1H), 7.92–7.55 (m, 3H), 7.30 (d, J = 7.7 Hz, 2H), 7.18 (d, J = 7.6
Hz, 2H), 5.81 (s, 1H), 5.16 (s, 2H), 2.29 (s, 3H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.4, 165.3, 148.4,
137.3, 133.5, 133.1, 133.0, 131.8, 131.1, 128.9, 128.1, 127.6, 122.8, 97.7, 65.3, 20.6. ESIHRMS: Calcd
for C18H16NO3: (M+H)+ 294.1125. Found: m/z 294.1131.
(E)-4-Methoxybenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (4h)
52.86 mg, 57% isolated yield; white solid. mp:203ꢀ205 oC. IR (KBr) 3418, 3400, 2359, 2342, 1732,
1713, 1645, 1634, 1614, 1520, 1277, 1256, 1117, 843 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6): δ 10.95 (s,
1H), 8.95 (d, J = 7.5 Hz, 1H), 7.8 –7.64 (m, 3H), 7.36 (d, J = 8.6 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H),
5.79 (s, 1H), 5.14 (s, 2H), 3.74 (s, 3H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.4, 165.3, 159.1, 148.3,
133.5, 133.0, 131.8, 131.1, 130.0, 128.0, 127.6, 122.8, 113.7, 97.8, 65.2, 55.0. ESIHRMS: Calcd for
C18H16NO4: (M+H)+ 310.1074. Found: m/z 310.1081.
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(E)-Furan-2-ylmethyl 2-(3-oxoisoindolin-1-ylidene)acetate (4i)
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50.86 mg, 63% isolated yield; white solid. mp: 154ꢀ155 C. IR (KBr) 3192, 3183, 3136, 3112, 1728,
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1705, 1636, 1613, 1267, 1157, 1142, 1105, 1076, 1001, 841, 752, 696 cmꢀ1. H NMR (300 MHz,
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CDCl3): δ 9.32 (s, 1H), 9.05 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 7.2 Hz, 1H), 7.65 (dt, J = 24.5, 7.4 Hz,
2H), 7.45 (s, 1H), 6.47 (d, J = 2.9 Hz, 1H), 6.39 (d, J = 1.7 Hz, 1H), 5.90 (s, 1H), 5.20 (s, 2H). 13C
NMR (75 MHz, DMSOꢀd6): δ 168.0, 165.5, 149.9, 149.2, 144.2, 134.0, 133.6, 132.4, 131.7, 128.1,
123.4, 113.3, 113.2, 97.8, 57.9. ESIHRMS: Calcd for C15H12NO4: (M+H)+ 270.0761. Found: m/z
270.0764.
(E)-Phenyl 2-(3-oxoisoindolin-1-ylidene)acetate (4j)
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23.06 mg, 29% isolated yield; white solid. mp: 196ꢀ198 C. IR (KBr) 3161, 3088, 3071, 1713, 1643,
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1634, 1611, 1591, 1493, 1271, 1204, 1136, 1096, 1072, 839, 775, 689 cmꢀ1. H NMR (300 MHz,
CDCl3): δ 9.10 (d, J = 6.7 Hz, 1H), 8.68 (s, 1H), 7.92 (dd, J = 5.5, 1.8 Hz, 1H), 7.73–7.62 (m, 2H),
7.46 (t, J = 7.8 Hz, 2H), 7.31 (d, J = 7.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 6.09 (s, 1H). 13C NMR (75
MHz, CDCl3): δ 167.2, 153.2, 151.6, 136.5, 136.2, 135.6, 134.5, 133.5, 132.1, 131.5, 128.5, 126.0,
124.3, 101.2. ESIHRMS: Calcd for C16H12NO3: (M+H)+ 266.0812. Found: m/z 266.0813.
(Z)-Ethyl 2-(3-oxoisoindolin-1-ylidene)acetate (5a)
o
61.87 mg, 95% isolated yield; white solid. mp167ꢀ169 C. IR (KBr) 3187, 1728, 1682, 1634, 1607,
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1470, 1296, 1271, 1153, 1138, 1100, 1076, 854, 779, 698 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
10.95 (s, 1H), 8.98 (d, J = 7.6 Hz, 1H), 7.91–7.60 (m, 3H), 5.80 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 1.28
(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.4, 165.5, 148.0, 133.6, 133.0, 131.7, 131.2,
127.6, 122.7, 98.2, 59.8, 14.1. ESIHRMS: Calcd for C12H12NO3: (M+H)+ 218.0812. Found: m/z
218.0815.
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(Z)-Methyl 2-(3-oxoisoindolin-1-ylidene)acetate (5b)
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60.31 mg, 99% isolated yield; white solid. mp: 122ꢀ124 oC. IR (KBr) 3404, 1732, 1667, 1651, 1645,
1634, 1614, 1441, 1283, 1209, 1128, 1097, 764, 692 cmꢀ1. 1H NMR (300 MHz, CDCl3): δ 9.63 (s, 1H),
7.88 (d, J = 4.2 Hz, 1H), 7.70 (d, J = 4.2 Hz, 1H), 7.64 (dd, J = 11, 4.2 Hz, 2H), 5.78 (s, 1H), 3.82 (s,
3H). 13C NMR (75MHz, CDCl3): δ 168.0, 167.9, 147.5, 136.4, 132.8, 131.6, 129.6, 124.0, 121.01, 91.2,
51.7. ESIHRMS: Calcd for C11H10NO3: (M+H)+ 204.0655. Found: m/z 204.0657.
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(Z)-Tert-butyl 2-(3-oxoisoindolin-1-ylidene)acetate (5c)
72.80 mg, Yield: 99% isolated yield; white solid. mp: 140ꢀ142 oC. IR (KBr) 3188, 3175, 3078, 1720,
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1699, 1707, 1682, 1643, 1368, 1279, 1258, 1153, 1138, 1115, 775, 694 cmꢀ1. H NMR (300 MHz,
CDCl3): δ 9.65 (s, 1H), 7.88 (d, J = 4.4 Hz, 1H), 7.67 (d, J = 4.4 Hz, 1H), 7.61 (dt, J = 8.8, 4.2 Hz, 2H),
5.72 (s, 1H), 1.55 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 168.0, 167.0, 146.6, 136.7, 132.6, 131.3,
129.6, 123.9, 120.8, 93.6, 81.3, 28.2. ESIHRMS: Calcd for C14H16NO3: (M+H)+ 246.1125. Found: m/z
246.1128.
(Z)-Benzyl 2-(3-oxoisoindolin-1-ylidene)acetate (5d)
82.89 mg, 99% isolated yield; white solid. mp: 146ꢀ148 oC. IR（KBr）3322, 1742, 1692, 1668, 1645,
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1424, 1298, 1277, 1211, 1198, 1177, 1161, 1128, 1065, 770, 692 cmꢀ1. H NMR (300 MHz, CDCl3): δ
9.66 (s, 1H), 7.89 (d, J = 4.2 Hz, 1H), 7.75–7.57 (m, 3H), 7.40 (dt, J = 8.6, 4 Hz, 5H), 5.85 (s, 1H),
5.28 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 168.0, 167.3, 147.9, 136.4, 135.7, 132.8, 131.6, 129.6,
128.6, 128.4, 128.3, 124.1, 121.0, 91.2, 66.4. ESIHRMS: Calcd for C17H14NO3: (M+H)+ 280.0968.
Found: m/z 280.0975.
(Z)-4-Chlorobenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (5e)
o
92.04 mg, 98% isolated yield; white solid. mp 180ꢀ182 C. IR (KBr) 3325, 1740, 1688, 1667, 1422,
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1296, 1275, 1196, 1171, 1126, 1094, 1063, 812, 768, 692 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
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10.43 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.80 (d, J = 6.7 Hz, 1H), 7.72 (dd, J = 18.0, 7.3 Hz, 2H), 7.45 (s,
4H), 6.15 (s, 1H), 5.23 (s, 2H). 13C NMR (75MHz, DMSOꢀd6): δ 168.0, 165.8, 147.1, 136.4, 135.3,
133.1, 132.5, 131.7, 129.8, 128.7, 128.3, 123.1, 122.0, 91.5, 64.5. ESIHRMS: Calcd for C17H13ClNO3:
(M+H)+ 314.0578. Found: m/z 314.0585.
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(Z)-4-Bromobenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (5f)
o
100.68 mg, 94% isolated yield; white solid. mp: 191ꢀ193 C. IR (KBr) 3327, 1738, 1688, 1682, 1667,
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1422, 1294, 1275, 1196, 1171, 1126, 1063, 808, 768, 692 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
10.44 (s, 1H), 8.10 (d, J = 7.3 Hz, 1H), 7.80 (d, J = 7.2 Hz, 1H), 7.70 (dt, J = 18.5, 7.2 Hz, 2H), 7.58 (d,
J = 8.2 Hz, 2H), 7.39 (d, J = 8.3 Hz, 2H), 6.15 (s, 1H), 5.22 (s, 2H). 13C NMR (75 MHz, DMSOꢀd6): δ
168.0, 165.8, 147.1, 136.4, 135.7, 133.1, 131.7, 131.2, 130.1, 128.7, 123.1, 122.0, 121.1, 91.5, 64.5.
ESIHRMS: Calcd for C17H12BrNO3: (M+H)+ 358.0073. Found: m/z 358.0077.
(Z)-4-Methylbenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (5g)
o
79.14 mg, 90% isolated yield; white solid. mp: 154ꢀ156 C. IR (KBr) 3327, 1744, 1682, 1667, 1422,
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1273, 1294, 1273, 1196, 1179, 1125, 1063, 814, 768, 691 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
10.39 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.80 (d, J = 7.2 Hz, 1H), 7.70 (dd, J = 10.7, 7.3 Hz, 2H), 7.31
(d, J = 7.8 Hz, 2H), 7.18 (d, J = 7.7 Hz, 2H), 6.13 (s, 1H), 5.19 (s, 2H), 2.29 (s, 3H). 13C NMR (75
MHz, DMSOꢀd6): δ 167.9, 166.0, 146.9, 137.2, 136.4, 133.1, 133.1, 131.7, 128.8, 128.7, 128.1, 123.1,
122.0, 91.7, 65.2, 20.6. ESIHRMS: Calcd for C18H16NO3: (M+H)+ 294.1125. Found: m/z 294.1131.
(Z)-4-Methoxybenzyl 2-(3-oxoisoindolin-1-ylidene)acetate (5h)
o
79.75 mg, 86% isolated yield; white solid. Mp: 173ꢀ175 C. IR (KBr) 3339, 1742, 1682, 1667, 1660,
1651, 1645, 1634, 1514, 1470, 1120, 1173, 1060, 822, 168, 694 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6):
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δ 10.39 (s, 1H), 8.09 (d, J = 7.5 Hz, 1H), 7.81 (d, J = 7.0 Hz, 1H), 7.70 (dd, J = 10.6, 7.4 Hz, 2H), 7.37
(d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.5 Hz, 2H), 6.13 (s, 1H), 5.17 (s, 2H), 3.75 (s, 3H). 13C NMR (75
MHz, DMSOꢀd6): δ 168.5, 166.6, 159.7, 147.4, 137.0, 133.6, 132.3, 130.6, 129.2, 128.6, 123.7, 122.5,
114.3, 92.3, 65.8, 55.6. ESIHRMS: Calcd for C18H15NNaO4: (M+Na)+ 332.0893. Found: m/z 332.0896.
(Z)-Furan-2-ylmethyl 2-(3-oxoisoindolin-1-ylidene)acetate (5i)
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o
79.92 mg, 99% isolated yield; white solid. mp: 119ꢀ121 C. IR (KBr) 3426, 3333, 1746, 1732, 1688,
1665, 1645, 1422, 1198, 1177, 1126, 1062, 780, 687 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6): δ 10.98 (s,
1H), 8.95 (d, J = 7.6 Hz, 1H), 7.84 – 7.66 (m, 4H), 6.58 (d, J = 3.0 Hz, 1H), 6.48 (s, 1H), 5.77 (s, 1H),
5.19(s, 2H). 13C NMR (75 MHz, DMSOꢀd6): δ 168.5, 166.3, 149.9, 147.8, 144.1, 136.9, 133.6, 132.3,
129.2, 123.7, 122.6, 111.3, 111.2, 91.8, 57.8. ESIHRMS: Calcd for C15H12NO4: (M+H)+ 270.0761.
Found: m/z 270.0764.
(Z)-Phenyl 2-(3-oxoisoindolin-1-ylidene)acetate (5j)
o
56.46 mg, 71% isolated yield; white solid. mp: 134ꢀ136 C. IR (KBr) 3242, 1713, 1694, 1643, 1634,
1275, 1202, 1153, 1117, 1096, 1057, 692 cmꢀ1. 1H NMR (300 MHz, CDCl3): δ 9.58 (s, 1H), 4.8 (d, J =
7.3 Hz, 1H), 7.78 (d, J = 4.4 Hz, 1H), 7.68 (dt, J = 12.1, 4.4 Hz, 2H), 7.44 (t, J = 4.6 Hz, 2H), 7.28 (dd,
J = 5.4, 3.1 Hz, 1H), 7.19 (d, J = 4.9 Hz, 2H), 6.02 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 167.9, 166.1,
150.4, 149.2, 136.3, 133.0, 131.9, 129.4, 126.0, 124.2, 121.5, 121.2, 114.9, 90.4. ESIHRMS: Calcd for
C16H12NO3: (M+H)+ 266.0812. Found: m/z 266.0816.
(Z)-Ethyl 2-(5,6-dichloro-3-oxoisoindolin-1-ylidene)acetate (6)
76.95 mg, 90% isolated yield; yellow solid. mp: 194ꢀ196 oC. IR (KBr) 3390, 3381, 3242, 1737, 1732,
1694, 1682, 1651, 1645, 1634, 1614, 1557, 1537, 1505, 1271, 1067, 906, 854 cmꢀ1. 1H NMR (300 MHz,
DMSOꢀd6): δ 10.53 (s, 1H), 8.49 (s, 1H), 8.01 (s, 1H), 6.20 (s, 1H), 4.21 (q, J = 6.9 Hz, 2H), 1.26 (t, J
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= 7.0 Hz, 3H). 13C NMR (75 MHz, DMSOꢀd6): δ 167.9, 167.7, 146.4, 138.3, 137.9, 136.3, 130.8,
127.0, 126.3, 95.9, 62.0, 16.0. ESIHRMS: Calcd for C12H9Cl2N1NaO3: (M+Na)+ 307.9852. Found: m/z
307.9857.
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(E)-Ethyl 2-(5,6-dichloro-3-oxoisoindolin-1-ylidene)acetate (7)
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55.58 mg, 65% isolated yield; white solid. mp: 215ꢀ217 C. IR (KBr) 3200, 3109, 1743, 1732, 1713,
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1694, 1643, 1634, 1607, 1393, 1280, 1145, 1105, 1036, 910, 850. H NMR (300 MHz, DMSOꢀd6): δ
11.18 (s, 1H), 9.10 (s, 1H), 7.95 (s, 1H), 5.77 (s, 1H), 4.18 (q, J = 7.0 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, DMSOꢀd6): δ 167.3, 167.2, 147.9, 137.5, 136.6, 135.0, 133.3, 131.2, 126.5, 101.5,
62.1, 15.9. ESIHRMS: Calcd for C12H10Cl2N1O3: (M+H)+ 286.0032. Found: m/z 286.0037.
(Z)-3-(2-Oxopropylidene) isoindolin-1-one (9a)
o
33.67 mg, 60% isolated yield; white solid. mp: 116ꢀ118 C. IR (KBr) 3443, 3426, 3347, 3333, 1728,
1694, 1682, 1674, 1614, 1607, 1360, 1227, 1098, 760, 694 cmꢀ1. H NMR (300 MHz, DMSOꢀd6): δ
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10.55 (s, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.80 (m, 2H), 7.75–7.68 (m, 1H), 6.52 (s, 1H), 2.28 (s, 3H). 13
C
NMR (75 MHz, DMSOꢀd6): δ 200.2, 170.4, 146.4, 138.8, 136.1, 135.0, 133.8, 125.3, 124.7, 123.7,
101.4, 32.8. ESIHRMS: Calcd for C11H10NO2: (M+H)+ 188.0707. Found: m/z 188.0706.
(Z)-3-(2-Oxo-2-phenylethylidene) isoindolin-1-one (9b)
37.36 mg, 50% isolated yield; yellow solid. mp: 165ꢀ167 oC. IR (KBr) 3333, 1720, 1651, 1599, 1300,
1227, 1018, 760, 710 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6): δ 10.89 (s, 1H), 8.34 (d, J = 7.5 Hz, 1H),
8.19 (d, J = 7.4 Hz, 2H), 7.81 (dd, J = 14.9, 7.4 Hz, 2H), 7.75–7.62 (m, 2H), 7.58 (t, J = 7.3 Hz, 2H),
7.39 (s, 1H). 13C NMR (75 MHz, DMSOꢀd6): δ 191.7, 170.6, 149.4, 139.7, 139.0, 135.1, 134.9, 133.9,
130.6, 130.3, 130.0, 125.2, 124.4, 97.5. ESIHRMS: Calcd for C16H12NO2: (M+H)+ 250.0867. Found:
m/z 250.0863.
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(Z)-3-(2-(Naphthalen-2-yl)-2-oxoethylidene) isoindolin-1-one (9c)
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45.76 mg, 51% isolated yield; white solid. mp: 211ꢀ213 C. IR (KBr) 3426, 3412, 3381, 3352, 1715,
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1694, 1645, 1593, 810, 768 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6): δ 10.95 (s, 1H), 8. 96 (s, 1H), 8.41
(d, J = 7.5 Hz, 1H), 8.18 (t, J = 8.6 Hz, 2H), 8.06 (dd, J = 15.2, 8.0 Hz, 2H), 7.86 (t, J = 8.4 Hz, 2H),
7.81 – 7.63 (m, 3H), 7.58 (s, 1H). 13C NMR (75 MHz, DMSOꢀd6): δ 191.5, 170.7, 149.3, 139.1, 137.1,
136.9, 135.1, 134.1, 133.9, 131.8, 131.4, 130.5, 130.4, 130.3, 129.6, 128.8, 125.7, 125.3, 124.4, 97.7.
ESIHRMS: Calcd for C20H14NO2: (M+H)+ 300.1019. Found: m/z 300.1026.
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(E)-Ethyl 2-(2-(4-nitrobenzyl)-3-oxoisoindolin-1-ylidene)acetate (11)
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98.76 mg, 88% isolated yield; white solid. mp: 138ꢀ140 C. IR (KBr) 3389, 3381, 1720, 1709, 1694,
1634, 1610, 1520, 1342, 1323, 1188, 1155, 1101, 829, 772, 708 cmꢀ1. 1H NMR (300 MHz, DMSOꢀd6):
δ 8.94 (d, J = 7.4 Hz, 1H), 8.20 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 7.2 Hz, 1H), 7.86 – 7.66 (m, 2H), 7.51
(d, J = 8.4 Hz, 2H), 5.78 (s, 1H), 5.22 (s, 2H), 4.17 (dd, J = 13.8, 6.9 Hz, 2H), 1.22 (t, J = 6.9 Hz, 3H).
13C NMR (75 MHz, DMSOꢀd6): δ 168.3, 167.0, 148.6, 145.9, 136.4, 135.5, 134.9, 133.7, 129.6, 129.3,
125.7, 125.1, 124.7, 101.3, 62.1, 43.6, 15.9. ESIHRMS: Calcd for C19H16N2NaO5: (M+H)+ 375.0951.
Found: m/z 375.0955.
ASSOCIATED CONTENT
Supporting information. The ORTEP diagrams of 4a and 5a, 1H and 13C NMR spectra of the products
as well as the Xꢀray crystallographic data (CIF files) of 4a and 5a. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: zhouqingfa@cpu.edu.cn, lut163@163.com
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENT.
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This work was financially supported by the National Natural Science Foundation of China (Grant
No.21102179).
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