Ruthenium(II)-catalyzed N-substituted phthalimide synthesis via C-H activation/[3+2] annulation

Article abstract of DOI:10.1016/j.jorganchem.2014.12.016

Ruthenium-catalyzed intermolecular [3 + 2] annulation pathway for aromatic acids with isocyanates to afford N-substituted phthalimide in one step is demonstrated, which provides an efficient process to direct preparation of phthalimide from commercially a

Full text of DOI:10.1016/j.jorganchem.2014.12.016

Journal of Organometallic Chemistry 779 (2015) 55e61
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Ruthenium(II)-catalyzed N-substituted phthalimide synthesis via CeH
activation/[3þ2] annulation
Xue-Fen Dong, Juan Fan, Xian-Ying Shi*, Ke-Yan Liu, Peng-Min Wang, Jun-Fa Wei*
Key Laboratory of Applied Surface and Colloid Chemistry (Ministry of Education), Key Laboratory for Macromolecular Science of Shaanxi Province,
School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Ruthenium-catalyzed intermolecular [3 þ 2] annulation pathway for aromatic acids with isocyanates to
afford N-substituted phthalimide in one step is demonstrated, which provides an efficient process to
direct preparation of phthalimide from commercially available starting materials and environmentally
benign catalysts. This cascade cyclization involves the direct functionalization of an ortho CeH bond and
the subsequent intramolecular nucleophilic substitution. There is no theoretical waste except for water
generated in the reaction.
Received 4 September 2014
Received in revised form
24 November 2014
Accepted 16 December 2014
Available online 25 December 2014
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Ruthenium
N-Substituted phthalimide
[3þ2] Annulation
Amidation
CeH functionalization
Introduction
advantages, these methods have a drawback in common: they
require starting materials that are not readily available.
N-Substituted phthalimides are well known as a core structure
of numerous natural products and important biologically com-
pounds [1]. They also make a vital contribution in the treatment of
acquired immunodeficiency syndrome (AIDS) [2], leprosy [3], and
other diseases [4]. Moreover, phthalimide derivatives have been
found important applications as synthetic intermediates in pesti-
cides [5], liquid crystals [6], and functional materials [7], polymer
industries [8]. As a result, the synthesis of this privileged structure
has attracted considerable attention. Typically, phthalimide de-
rivatives are synthesized via the condensation of phthalic acids or
anhydrides and amines [9]. However, the limited availability of
differently substituted phthalic acids, mostly due to the harsh re-
action conditions in their preparation, calls for alternative pro-
tocols. Alternative approaches include carbonylative cyclization of
ortho-dihaloarenes or ortho-halobenzoates and primary amines
[10]; cycloaminocarbonylation of ortho-dihaloarenes, ortho-hal-
obenzoic acids, and ortho-haloesters with formamides [11]; reac-
tion between 1,2-phenylenedimethanol and amines [12]; coupling
of isocyanates with ortho-iodobenzoates [13]. Despite their
In recent years, the selective functionalization of CeH bonds in
directing group-containing arenes has attracted a substantial in-
terest attributable to the potential shortening of synthetic steps
[14]. Meanwhile, the chelation-assisted transition metal-catalyzed
CeH activationeannulation reaction has become one of the most
important and powerful approaches for the construction of het-
erocyclic compounds in organic synthesis [15]. Employing this
strategy, Chatani and Rovis developed sequentially ruthenium and
rhodium catalyzed oxidative carbonylation phthalimide synthesis
via CeH/NeH activation [16]. However, commercially unavailable
starting reagents and the using of poisonous gas of carbon mon-
oxide are the most disadvantages in these two reports. Very
recently, direct synthesis of N-substituted phthalimides by amida-
tion of benzoic acids was described [17]. But this method required
an expensive rhodium catalyst and long reaction time.
Up to now, the use of Ru(II) complexes as inexpensive, readily
available and environmentally benign catalysts for CeH activation
reactions has received considerable attention [18]. Yet, there is only
one report that utilized Ru catalyst in CeH activation directed by
carboxyl group [19]. Our continuous interest in the metal-catalyzed
functionalization of CeH promoted us to explore the ruthenium-
catalyzed reactions of aromatic acids with isocyanates. Herein,
the ruthenium-catalyzed CeH activation/annulation reaction for
* Corresponding authors.
E-mail addresses: shixy@snnu.edu.cn (X.-Y. Shi), weijf@snnu.edu.cn (J.-F. Wei).
http://dx.doi.org/10.1016/j.jorganchem.2014.12.016
0022-328X/© 2014 Elsevier B.V. All rights reserved.

56
X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
the facile preparation of N-substituted phthalimides via [3 þ 2]
annulation reaction from commercially available starting materials
is presented.
is obtained in 55% yield. Subsequently, various conditions con-
cerning the reaction time, the amount of isocyanate and additives
was examined to optimize the formation of this cyclization product
with 1,4-dioxane as the solvent. The yield of 3a could be enhanced
to 65% by increasing the amount of phenyl isocyanate from
2 equiv to 2.5 equiv (Table 1, entry 20). Then, the introduction of
25% CuI and CuBr as an additive increased the yield greatly to 81%
and 78%, respectively (Table 1, entries 21 and 22).
Results and discussion
The cyclization reaction was carried out by using o-toluic acid
and phenyl isocyanate as the starting materials. Gratifyingly, when
o-toluic acid (1a) was treated with 2 equiv of phenyl isocyanate (2a)
in the presence of 5 mol% [RuCl2(p-cymene)]2, 25 mol% AgOTf and
2 equiv NaOAc at 130 ꢀC for 24 h, the desired product was obtained
in 39% yield (Table 1, entry 2). Control experiment revealed that the
reaction did not proceed in the absence of ruthenium. However,
there was no target product formed without NaOAc, suggesting that
the salt is very crucial for the success of the present catalytic re-
action. Therefore, a series of salts were examined for the reaction.
Unfortunately, the uses of other alkali metal salts such as Na2CO3,
K2HPO4 and Na2HPO4 exclusively decreased the yield of target
product (Table 1, entries 3e5). Alternatively, acetates of metals
other than sodium such as AgOAc, Cu(OAc)2, Cu(OAc)2$H2O, KOAc
and CsOAc displayed a low or no catalytic activity (Table 1, entries
6e10). Ag2CO3 and Cs2CO3 also failed to give the target product
(Table 1, entries 11 and 12).
Having these satisfactory results, the substrate scope was
examined with respect to the benzoic acid derivatives and phenyl
isocyanate (Table 2, compounds 3be3m′). A significant electronic
effect of the substituent on the reactivity was observed. Benzoic
acid afforded the N-substituted phthalimide in 55% (3b). The strong
electron withdrawing group such as NO2, obviously restrained the
reaction and could not afford the desired product under the stan-
dard reactions. It was found that the moderate yields of cyclization
products were obtained when methyl was introduced to the aro-
matic acid ring (3ce3g). Contrary to our previous report [17], 2-
methoxylbenzoic acid was found to be compatible in this catal-
ysis system and provided the desired products in 33% (3h).
Compared with other benzoic acids, meta-alkoxy and meta-boc-
amino substituted benzoic acids were easily converted into the
corresponding products in a higher yield, and non-symmetrical
meta-substituted benzoic acids afforded two isomers (3ie3l0). In
this case, there are two possible CeH activation sites: C2 and C6. For
example, 76% yield of desired product was isolated using 3,4,5-
trimethoxylbenzoic acid (3i). Piperonylic acid produced a 9:5 (3k,
3k′) mixture of products and 3-methoxylbenzoic acid gave two
regioisomers in a ratio of 39:35 (3j, 3j′). As for meta-Boc-amino
benzoic acid, the activation occurred at the sterically less hindered
C6 rather than C2 (3l, 3l′). In addition, 2-naphthoic acid also un-
derwent the reaction to generate the two corresponding products
3m and 3m′.
A screening of solvents revealed that common solvent such as
1,4-dioxane, THF, PhCl, toluene and xylene also can be used in the
titled reaction in addition to acetonitrile (Table 1, entries 13e17).
1,4-Dioxane is the best solvent for this transformation, in which 3a
Table 1
Selected results for the optimal reaction conditions.a
To further explore the scope of the reaction, we investigated the
reactions of various isocyanates with 3,4,5-trimethoxylbenzoic acid
under the optimized conditions (3ne3x). 3-Methyl, 4-methyl, 4-
methoxyl phenylisocyanates afforded the corresponding products
in good yields of 70%, 64%, and 52%, respectively (3n, 3o, 3p). This
reaction was also compatible with halogen-substituted phenyl-
isocyanates furnishing the respective products in good yields
(3qe3t). Particularly noteworthy was that halo groups (Cl, Br) on
the aromatic ring of isocyanate remained intact in the product,
which provided the possibility for the further useful trans-
formations through common cross-coupling strategies. This
transformation tolerated dual-substitution, for example, 3,5-
dimethylphenyl isocyanate and 3,4-dichlorophenyl isocyanate
proceeded smoothly to afford products in 55% and 68% yields,
respectively (3u, 3v). However, 4-nitrophenyl isocyanate only gave
a low yield (20% 1H NMR yield) of desired product. The N-sub-
stituents are not limited to aryl groups. N-Butyl, N-2-chloroethyl
substracts also can react with 3,4,5-trimethoxylbenzoic acid in
somewhat lower yield (3w, 3x).
Based on the known metal-catalyzed, directing-group assisted
CeH bond activation reactions, a possible mechanism to account
for this reaction is proposed in Scheme 1. First dissociation of the
dimer precatalyst [RuCl2(p-cymene)]2 gives the coordinatively
unsaturated monomer, which undergoes a ligand exchange with
AgOTf to give the species A. With the help of NaOAc, five-
membered intermediate C is formed by an O-metalation CeH
activation with concomitant formation of trifluoroacetic acid. After
coordination with isocyanate and insertion of C]N bond to the
intermediate C, the ruthenium alkoxide E is generated together
with the formation of a new CeC bond. The intramolecular nucle-
ophilic substitution of ruthenium alkoxide E provides the final
product F and regenerates the active Ru species.
Entry
Additive (equiv)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
None
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
1,4-Dioxane
THF
Toluene
C6H5Cl
0
NaOAc (2.0)
K2HPO4 (2.0)
Na2CO3 (2.0)
Na2HPO4 (2.0)
AgOAc (2.0)
Cu(OAc)2 (2.0)
Cu(OAc)2$H2O
CsOAc (2.0)
KOAc (2.0)
39
10
7
8
4
NDc
ND
ND
ND
ND
ND
55
43
24
34
35
26
54
65
78
81(76)g
9
10
11
12
13
14
15
16
17
18d
19e
20f
21f
22f
Ag2CO3
Cs2CO3
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0), CuBr (0.25)
NaOAc (2.0), CuI (0.25)
Xylene
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
a
Reaction conditions: 1a (0.1 mmol), 2b (0.2 mmol), [RuCl2(p-cymene)]2
(5 mol%), AgOTf (25 mol%), additive, solvent (0.5 mL), 130 ꢀC for 24 h, under argon in
pressure tubes.
b
Determined by 1H NMR analysis of the crude reaction mixture using mesitylene
as internal standard.
c
ND ¼ not detected.
d
Run at 115 ꢀC.
e
Run at 150 ꢀC.
Phenyl isocyanate (0.25 mmol) was used.
Isolated yield.
f
g

X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
57
Table 2
Substrate scope for the synthesis of phthalimides via CeH functionalization.a
Entry
1
Product
Yield (%)
55
Entry
12
Product
Yield (%)
3b
3c
3m
52 (22:30)
2
50
3m′
3
4
5
6
7
8
9
3d
3e
3f
43
13
14
15
16
17
18
19
3n
3o
3p
3q
3r
3s
3t
70
64
52
62
80
73
63
52
56
3g
3h
3i
45
33
76
3j
74 (39:35)
(continued on next page)

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X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
Table 2 (continued )
Entry
Product
Yield (%)
Entry
20
Product
Yield (%)
55
3j′
3k
3k′
3l
3u
3v
3w
3x
10
70 (45:25)
21
22
23
68
33
27
11
77 (67:10)
3l′
a
Reaction conditions: substituted benzoic acid (0.2 mmol), isocyanate (0.5 mmol), [RuCl2(p-cymene)]2 (5 mol%), AgOTf (25 mol%), NaOAc (2 equiv), CuI (0.25 equiv), solvent
(1.0 mL), 130 ꢀC for 24 h, under argon in pressure tubes. Yield of purified product is reported.
Conclusion
In summary, we have developed a Ru(II)-catalyzed [3 þ 2]
cascade cyclization reaction of aromatic acids with isocyanates.
This protocol, which provides a convenient access to the synthesis
of useful N-substituted phthalimides derivatives, allows us to use
cheap Ru(II) as catalyst, readily available acids and isocyanates as
starting materials. This methodology is expected to be an important
route for the synthesis of natural products and biological active
substance.
Experimental section
General
All commercials were used as received without further purifi-
cation. 1H NMR spectra were measured on a 300 MHz, 400 MHz or
500 MHz spectrometer, 13C NMR spectra were measured on a
500 MHz spectrometer or 600 MHz spectrometer (13C NMR
125 MHz or 150 MHz), with tetramethylsilane (TMS) as the internal
standard at room temperature. Chemical shifts are given in
d rela-
tive to TMS, the coupling constants J are given in hertz (Hz). High-
resolution mass spectra (HRMS) were obtained from a Bruker
Avance Mass Spectrometer (maXis, ESI).
Scheme 1. Plausible mechanism for the ruthenium-catalyzed cascade cyclization.

X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
59
General experimental procedure for the synthesis of N-substituted
phthalimide
137.2, 132.5, 131.8, 129.0, 127.8, 126.6, 125.8, 122.0, 21.8, 17.6. HRMS
(ESI) m/z: calculated for C16H13NO2, [MþH] 252.1052; found:
252.1013.
A mixture of [RuCl2(p-cymene)]2 (6.1 mg, 0.01 mmol, 5 mol%)
and AgOTf (12.8 mg, 0.05 mmol, 25 mol%) in 0.1 mL dioxane in an
oven-dried tube was stirred at room temperature for about 30 min.
Then, substituted benzoic acid (0.2 mmol), isocyanates (0.5 mmol),
NaOAc (32.8 mg, 0.4 mmol, 200 mol%), and CuI (9.5 mg, 0.05 mmol,
25 mol%) were added. After the tube was evacuated and purged
with argon three times, the remaining dioxane was added to the
system by syringe. The mixture was stirred at 130 ꢀC for 24 h. When
the reaction completed, the resulting mixture was cooled to room
temperature, filtered through a short silica gel pad, transferred to
silica gel column directly and eluted with hexane and dichloro-
ethane or dichloroethane to give the products.
4,6-Dimethyl-2-phenylisoindoline-1,3-dione (3g) [17]
White solid (45% yield, 22.6 mg): mp 122ꢁ123 ꢀC, Rf ¼ 0.8
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.58 (s, 1H),
7.51e7.47 (m, 2H), 7.43e7.38 (m, 3H), 7.33 (s, 1H), 2.69 (s, 3H), 2.49
(s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 168.0, 167.5, 145.1, 138.2,
137.2, 132.5, 131.8, 129.0, 127.8, 126.6, 125.8, 122.0, 21.8, 17.6. HRMS
(ESI) m/z: calculated for C16H13NO2, [MþH] 252.1052; found:
252.1013.
4-Methoxy-2-phenylisoindoline-1,3-dione (3h) [17]
White solid (33% yield, 16.7 mg): mp 177ꢁ179 ꢀC, Rf ¼ 0.3 (n-
hexane/dichloroethane ¼ 1:2); 1H NMR (CDCl3, 300 MHz)
d (ppm)
Charaterization data of the desired products
7.85 (d, J ¼ 8.31 Hz, 1H), 7.53e7.50 (m, 2H), 7.48e7.37 (m, 4H), 7.23
(dd, J ¼ 8.31 Hz, 2.31 Hz, 1H), 3.95 (s, 3H); 13C NMR (CDCl3,
4-Methyl-2-phenylisoindoline-1,3-dione (3a) [20]
125 MHz) d (ppm) 167.1, 167.0, 164.9, 134.3, 131.8, 129.0,127.9, 126.5,
White solid (76% yield, 18.0 mg): mp 150ꢁ151 ꢀC, Rf ¼ 0.7
125.4, 123.5, 120.4, 108.1, 56.1. HRMS (ESI) m/z: calculated for
15H11NO3, [MþNa] 276.0637; found: 276.0629.
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.78 (d,
C
J ¼ 7.32 Hz, 1H), 7.64 (t, J ¼ 7.54 Hz, 1H), 7.54e7.48 (m, 3H),
7.44e7.38 (m, 3H), 2.75 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm)
4,5,6-Trimethoxy-2-phenylisoindoline-1,3-dione (3i) [17]
168.1, 167.3, 138.5, 136.7, 133.9, 132.2, 131.7, 129.1, 128.4, 128.0, 126.7,
121.4, 17.8. HRMS (ESI) m/z: calculated for C15H11NO2, [MþNa]
260.0687; found: 260.0675.
White solid (76% yield, 47.6 mg): mp 149ꢁ150 ꢀC, Rf ¼ 0.4
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.52e7.47 (m,
2H), 7.42e7.36 (m, 3H), 7.27 (s, 1H), 4.19 (s, 3H), 4.01 (s, 3H), 3.95 (s,
3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 166.7, 165.3, 158.9, 151.8,
2-Phenylisoindoline-1,3-dione (3b) [21]
146.5, 131.7, 129.0, 128.4, 127.8, 126.5, 114.6, 102.7, 62.6, 61.5, 56.7.
HRMS (ESI) m/z: calculated for C17H15NO5, [MþNa] 336.0848;
found: 336.0846.
White solid (55% yield, 24.5 mg): mp 197ꢁ199 ꢀC, Rf ¼ 0.6
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d (ppm) 7.98e7.94 (m,
2H), 7.82e7.77 (m, 2H), 7.53e7.50 (m, 2H), 7.45e7.39 (m, 3H); 13C
NMR (CDCl3, 125 MHz) (ppm) 167.3, 134.4,131.7, 131.6, 129.1, 128.1,
d
4-Methoxy-2-phenylisoindoline-1,3-dione (3j) [22]
126.6, 123.7. HRMS (ESI) m/z: calculated for C14H9NO2, [MþNa]
White solid (39% yield, 19.7 mg): mp 177ꢁ179 ꢀC, Rf ¼ 0.3 (n-
246.0531; found: 246.0521.
hexane/dichloroethane ¼ 1:2); 1H NMR (CDCl3, 300 MHz)
d (ppm)
7.85 (d, J ¼ 8.31 Hz, 1H), 7.53e7.50 (m, 2H), 7.48e7.37 (m, 4H), 7.23
5-Methyl-2-phenylisoindoline-1,3-dione (3c) [21]
(dd, J ¼ 8.31 Hz, 2.31 Hz, 1H), 3.95 (s, 3H); 13C NMR (CDCl3,
White solid (50% yield, 23.7 mg): mp 213ꢁ214 ꢀC, Rf ¼ 0.7
125 MHz) d (ppm) 167.1, 167.0, 165.0, 134.3, 131.7, 129.0, 127.9, 126.5,
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.83 (d,
125.4, 123.5, 120.4, 108.1, 56.1. HRMS (ESI) m/z: calculated for
15H11NO3, [MþNa] 276.0637; found: 276.0629.
J ¼ 7.64 Hz, 1H), 7.76 (s, 1H), 7.58 (d, J ¼ 7.64 Hz, 1H), 7.52e7.47 (m,
C
2H), 7.44e7.38 (m, 3H), 2.55 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 167.5, 167.4, 145.8, 135.0, 132.1, 131.7, 129.13, 129.09, 128.0,
5-Methoxy-2-phenylisoindoline-1,3-dione (3j0) [17]
126.6, 124.2, 123.7, 22.1. HRMS (ESI) m/z: calculated for C15H11NO2,
[MþNa] 260.0687; found: 260.0677.
White solid (35% yield, 17.7 mg): mp 182ꢁ183 ꢀC, Rf ¼ 0.4 (n-
hexane/dichloroethane ¼ 1:2); 1H NMR (CDCl3, 300 MHz)
d (ppm)
7.73 (dd, J ¼ 8.34 Hz, 7.35 Hz, 1H), 7.55e7.38 (m, 6H), 7.26 (d,
5-Methyl-2-phenylisoindoline-1,3-dione (3d) [21]
J ¼ 8.4 Hz, 1H), 4.04 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d (ppm)
White solid (43% yield, 20.3 mg): mp 213ꢁ214 ꢀC, Rf ¼ 0.7
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.83 (d,
167.0, 165.8, 157.0, 136.5, 133.8, 131.6, 129.0, 127.9, 126.6, 117.7, 116.9,
115.8, 56.3. HRMS (ESI) m/z: calculated for C15H11NO3, [MþNa]
276.0637; found: 276.0642.
J ¼ 7.64 Hz, 1H), 7.76 (s, 1H), 7.58 (d, J ¼ 7.64 Hz, 1H), 7.52e7.47 (m,
2H), 7.44e7.38 (m, 3H), 2.55 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 167.5, 167.4, 145.8, 135.0, 132.1, 131.7, 129.13, 129.09, 128.0,
6-Phenyl-5H-[1,3]dioxolo [4,5-f]isoindole-5,7(6H)-dione (3k) [17]
White solid (45% yield, 24.0 mg): mp 80ꢁ82 ꢀC, Rf ¼ 0.7
126.6, 124.2, 123.7, 22.1. HRMS (ESI) m/z: calculated for C15H11NO2,
[MþNa] 260.0687; found: 260.0677.
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.51e7.47 (m,
2H), 7.42e7.36 (m, 3H), 7.31 (s, 2H), 6.20 (s, 2H); 13C NMR (CDCl3,
125 MHz) (ppm) 166.7, 153.0, 131.8, 129.0, 127.9, 127.3, 126.4,
5,6-Dimethyl-2-phenylisoindoline-1,3-dione (3e) [10a]
White solid (52% yield, 26.1 mg): mp 196ꢁ197 ꢀC, Rf ¼ 0.6
d
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d (ppm) 7.61 (s, 2H),
104.0, 103.1. HRMS (ESI) m/z: calculated for C15H9NO4, [MþH]
7.44e7.30 (m, 5H), 2.35 (s, 6H); 13C NMR (CDCl3, 100 MHz)
d (ppm)
268.0610; found: 268.0597.
167.6, 144.1, 132.0, 129.7, 129.0, 127.8, 126.5, 124.6, 20.6. HRMS (ESI)
m/z: calculated for C16H13NO2, [MþNa] 274.0844; found: 274.2747.
7-Phenyl-6H-[1,3]dioxolo [4,5-e]isoindole-6,8(7H)-dione (3k0) [17]
White solid (25% yield, 13.4 mg): mp 245ꢁ247 ꢀC, Rf ¼ 0.6
4,6-Dimethyl-2-phenylisoindoline-1,3-dione (3f) [17]
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d (ppm) 7.53e7.47 (m,
White solid (56% yield, 28.1 mg): mp 122ꢁ123 ꢀC, Rf ¼ 0.8
3H), 7.43e7.37 (m, 3H), 7.10 (d, J ¼ 7.76 Hz, 1H); 6.28 (s, 2H); 13C
(dichloroethane); 1H NMR (CDCl3, 400 MHz)
d
(ppm) 7.59 (s, 1H),
NMR (CDCl3, 125 MHz) d (ppm) 166.3, 164.3, 154.4, 144.0, 131.6,
7.51e7.48 (m, 2H), 7.43e7.37 (m, 3H), 7.33 (s, 1H), 2.70 (s, 3H), 2.49
129.1, 128.1, 126.6, 124.9, 119.3, 112.2, 111.7, 104.0. HRMS (ESI) m/z:
calculated for C15H9NO4, [MþH] 268.0610; found: 268.0598.
(s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 168.0, 167.5, 145.1, 138.2,

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X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
tert-Butyl(1,3-dioxo-2-phenylisoindolin-5-yl)carbamate (3l) [17]
White solid (67% yield, 45.3 mg): mp 181ꢁ183 ꢀC, Rf ¼ 0.3
2-(3-Chlorophenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3q)
White solid (62% yield, 43.0 mg): mp 164ꢁ166 ꢀC, Rf ¼ 0.2
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d
(ppm) 7.99 (d,
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d (ppm) 7.48e7.46 (m,
J ¼ 1.83 Hz, 1H), 7.85 (d, J ¼ 8.19 Hz, 1H), 7.75 (dd, J ¼ 8.22 Hz,
1H), 7.34e7.31 (m, 2H), 7.36e7.25 (m, 1H), 7.20 (s, 1H), 4.11 (s, 3H),
1.92 Hz, 1H), 7.52e7.36 (m, 5H), 6.96 (s, 1H), 1.55 (s, 9H); 13C NMR
3.91 (s, 3H), 3.87 (s, 3H); 13C NMR (CDCl3, 150 MHz)
d
(ppm) 166.2,
(CDCl3, 125 MHz)
d
(ppm) 166.9, 166.88, 151.9, 144.5, 133.5, 131.8,
164.7, 159.0, 152.0, 146.6, 133.3, 130.8, 130.5, 130.4, 129.8, 128.6,
129.0, 128.0, 126.5, 125.3, 124.9, 122.6, 112.9, 82.0, 28.2. HRMS (ESI)
127.7, 114.7, 102.9, 62.7, 61.5, 56.8. HRMS (ESI) m/z: calculated for
m/z: calculated for C19H18N2O4, [MꢁH] 337.1188; found: 337.1192.
C17H14ClNO5, [MþNa] 370.0458; found: 370.0469.
tert-Butyl(1,3-dioxo-2-phenylisoindolin-4-yl)carbamate (3l0) [17]
Yellow solid (10% yield, 6.8 mg): mp 125ꢁ127 ꢀC, Rf ¼ 0.7
2-(4-Chlorophenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3r) [17]
White solid (80% yield, 55.5 mg): mp 187ꢁ188 ꢀC, Rf ¼ 0.4
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d
(ppm) 8.91 (s, 1H),
(dichloroethane); 1H NMR (CDCl3, 500 MHz)
d (ppm) 7.44 (d,
8.58 (d, J ¼ 8.46 Hz, 1H), 7.73e7.68 (m, 1H), 7.55e7.53 (m, 3H),
J ¼ 8.8 Hz, 2H), 7.37 (d, J ¼ 8.8 Hz, 2H), 7.24 (s, 1H), 4.17 (s, 3H), 3.99
7.43e7.41 (m, 3H), 1.54 (s, 9H); 13C NMR (CDCl3, 125 MHz)
d
(ppm)
(s, 3H), 3.94 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 166.5,164.9,
169.0, 166.8, 152.2, 138.6, 136.1, 131.30, 131.27, 129.1, 128.1, 126.3,
123.5, 117.2, 114.5, 81.8, 28.2. HRMS (ESI) m/z: calculated for
159.1, 151.8, 146.6, 133.5, 130.3, 129.1, 128.2, 127.6, 114.5, 102.8, 62.5,
61.5, 56.8. HRMS (ESI) m/z: calculated for C17H14ClNO5, [MþH]
348.0639; found: 348.0636.
C
19H18N2O4, [MþH] 339.1345; found: 339.1335.
2-Phenyl-1H-benzo[f]isoindole-1,3(2H)-dione (3m) [17]
2-(2-Chlorophenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3s)
White solid (73% yield, 50.7 mg): mp 137ꢁ139 ꢀC, Rf ¼ 0.4
Yellow solid (22% yield, 12.0 mg): mp 285ꢁ287 ꢀC, Rf ¼ 0.6
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d
(ppm) 8.46 (s, 2H),
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d (ppm) 7.54e7.53 (m,
8.10e8.09 (m, 2H), 7.74e7.72 (m, 2H), 7.54e7.493 (m, 5H); 13C NMR
(DMSO-d6, 125 MHz) (ppm) 167.2, 135.6, 132.4, 130.8, 129.9, 129.3,
128.8, 127.84, 127.76, 125.3. HRMS (ESI) m/z: calculated for
18H11NO2, [MþH] 274.0868; found: 274.0862.
1H), 7.41e7.37 (m, 2H) 7.33e7.31 (m, 1H), 7.26 (s, 1H), 4.18 (s, 3H),
d
3.98 (s, 3H), 3.94 (s, 3H); 13C NMR (CDCl3, 150 MHz)
d
(ppm) 166.1,
164.6, 158.9, 151.9, 146.4, 133.2, 130.7, 130.4, 130.2, 129.7, 128.5,
127.6, 114.6, 102.8, 62.5, 61.4, 56.7. HRMS (ESI) m/z: calculated for
C
C17H14ClNO5, [MþNa] 370.0458; found: 370.0453.
2-Phenyl-1H-benzo[e]isoindole-1,3(2H)-dione (3m0) [17]
Yellow solid (30% yield, 16.4 mg): mp 170ꢁ171 ꢀC, Rf ¼ 0.8
2-(4-Bromophenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3t)
White solid (63% yield 49.3 mg): mp 158ꢁ159 ꢀC, Rf ¼ 0.5
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d (ppm) 9.01 (d,
J ¼ 8.28 Hz, 1H), 8.24 (d, J ¼ 8.24 Hz, 1H), 8.01e7.95 (m, 2H),
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d (ppm) 7.61 (d,
7.79e7.67 (m, 2H), 7.56e7.49 (m, 4H), 7.45e7.40 (m, 1H); 13C NMR
J ¼ 8.58 Hz, 2H), 7.32 (d, J ¼ 8.58 Hz, 2H), 7.25 (s, 1H), 4.17 (s, 3H),
(CDCl3, 125 MHz)
d
(ppm) 168.5, 167.8, 136.8, 135.4, 131.3, 131.0,
4.00 (s, 3H), 3.95 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm) 166.4,
129.7, 129.1, 128.9, 128.8, 128.1, 127.9, 126.9, 126.6, 125.1, 118.7.
HRMS (ESI) m/z: calculated for C18H11NO2, [MþH] 274.0868; found:
274.0859.
164.9, 159.1, 151.9, 146.7, 132.1, 130.9, 128.3, 127.9, 121.5, 114.6, 102.8,
62.6, 61.5, 56.8. HRMS (ESI) m/z: calculated for C17H14BrNO5, [MþH]
392.0134; found: 392.0128.
4,5,6-Trimethoxy-2-(m-tolyl)isoindoline-1,3-dione (3n)
2-(3,5-Dimethylphenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3u)
White solid (55% yield, 37.5 mg): mp 152ꢁ153 ꢀC, Rf ¼ 0.5
White solid (70% yield, 45.8 mg): mp 139ꢁ140 ꢀC, Rf ¼ 0.5
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d
(ppm) 7.37 (t,
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d (ppm) 7.25 (s, 1H),
J ¼ 7.68 Hz, 1H), 7.25 (s, 1H), 7.20e7.18 (m, 3H), 4.18 (s, 3H), 3.99 (s,
7.02 (s,1H), 6.99 (s, 2H), 4.18 (s, 3H), 3.99 (s, 3H), 3.94 (s, 3H), 2.36 (s,
3H), 3.94 (s, 3H), 2.40 (s, 3H); 13C NMR (CDCl3, 150 MHz)
d
(ppm)
6H); 13C NMR (CDCl3, 150 MHz)
d
(ppm) 167.0, 165.5, 158.9, 151.8,
166.8, 165.4, 158.9, 151.8, 146.5, 138.9, 131.6, 128.8, 128.5, 127.2,
123.7, 114.6, 102.7, 62.6, 61.5, 56.7, 21.3. HRMS (ESI) m/z: calculated
for C18H17NO5, [MþH] 328.1185; found: 328.1187.
146.5, 138.8, 131.5, 129.9, 128.6, 124.5, 114.7, 102.7, 62.6, 61.5, 56.8,
21.3. HRMS (ESI) m/z: calculated for C19H19NO5, [MþNa] 364.1161;
found: 364.1155.
4,5,6-Trimethoxy-2-(p-tolyl)isoindoline-1,3-dione (3o) [17]
2-(3,4-Dichlorophenyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3v)
White solid (68% yield, 51.8 mg): mp 226ꢁ228 ꢀC, Rf ¼ 0.4
White solid (64% yield, 41.9 mg): mp 169ꢁ170 ꢀC, Rf ¼ 0.4
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d
(ppm) 7.27 (s, 4H),
(dichloroethane); 1H NMR (CDCl3, 600 MHz)
d (ppm) 7.61 (d,
7.24 (s, 1H), 4.17 (s, 3H), 3.98 (s, 3H), 3.93 (s, 3H), 2.38 (s, 3H); 13C
NMR (CDCl3, 125 MHz) (ppm) 166.9, 165.4, 158.8, 151.7, 146.4,
J ¼ 2.10 Hz, 1H), 7.56 (d, J ¼ 8.58 Hz, 1H) 7.34 (dd, J ¼ 8.58 Hz,
d
2.16 Hz, 1H), 7.26 (s, 1H), 4.18 (s, 3H), 4.02 (s, 3H), 3.96 (s, 3H); 13C
137.9, 129.6, 129.0, 128.5, 126.4, 114.6, 102.6, 62.5, 61.4, 56.7, 21.1.
HRMS (ESI) m/z: calculated for C18H17NO5, [MþH] 328.1185; found:
328.1177.
NMR (CDCl3, 150 MHz) d (ppm) 166.2, 164.6, 159.3, 152.0, 146.9,
132.9, 131.8, 131.2, 130.6, 128.2, 125.5, 114.4, 102.9, 62.6, 61.6, 56.9.
HRMS (ESI) m/z: calculated for C17H13Cl2NO5, [MþNa] 404.0068;
found: 404.0073.
4,5,6-Trimethoxy-2-(4-methoxyphenyl)isoindoline-1,3-dione (3p)
[17]
2-Butyl-4,5,6-trimethoxyisoindoline-1,3-dione (3w) [17]
White solid (52% yield, 35.7 mg): mp 163ꢁ164 ꢀC, Rf ¼ 0.17
Yellow oil (33% yield, 19.3 mg): Rf ¼ 0.2 (dichloroethane); 1H
(dichloroethane); 1H NMR (CDCl3, 500 MHz)
d
(ppm) 7.30 (d,
NMR (CDCl3, 600 MHz) d (ppm) 7.14 (s, 1H), 4.14 (s, 3H), 3.95 (s, 3H),
J ¼ 9.0 Hz, 2H), 7.25 (s, 1H), 7.00 (d, J ¼ 9.0 Hz, 2H), 4.18 (s, 3H), 3.99
3.89 (s, 3H), 3.60 (t, J ¼ 7.26 Hz, 2H), 1.63e1.58 (m, 2H), 1.36e1.30
(s, 3H), 3.94 (s, 3H), 3.83 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d
(ppm)
(m, 2H), 0.92 (t, J ¼ 7.32 Hz, 3H); 13C NMR (CDCl3, 150 MHz)
d (ppm)
167.0, 165.6, 159.1, 158.8, 151.8, 146.4,128.5,127.9, 124.4, 114.6, 114.4,
102.7, 62.6, 61.5, 56.8, 55.5. HRMS (ESI) m/z: calculated for
167.9, 166.5, 158.5, 157.4, 146.0, 128.9, 114.9, 102.3, 62.4, 61.4, 56.6,
37.7, 30.6, 20.0, 13.6. HRMS (ESI) m/z: calculated for C15H19NO5,
[MþNa] 316.1161; found: 316.1155.
C
18H17NO6, [MþH] 344.1134; found: 344.1136.

X.-F. Dong et al. / Journal of Organometallic Chemistry 779 (2015) 55e61
61
(d) Z.-G. Le, Z.-C. Chen, Y. Hu, Q.-G. Zheng, J. Heterocycl. Chem. 42 (2005)
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Catal. 353 (2011) 3415e3422;
2-(2-Chloroethyl)-4,5,6-trimethoxyisoindoline-1,3-dione (3x)
White solid (27% yield, 16.1 mg): mp 124ꢁ126 ꢀC, Rf ¼ 0.4
(dichloroethane); 1H NMR (CDCl3, 300 MHz)
d (ppm) 7.18 (s, 1H),
4.17 (s, 3H), 4.01e3.98 (m, 5H), 3.92 (s, 3H), 3.74 (t, J ¼ 6.33 Hz, 2H);
13C NMR (CDCl3, 150 MHz) (ppm) 13C NMR (150 MHz, CDCl3)
(ppm) 167.4, 165.9, 158.8, 151.6, 146.3, 128.5, 114.6, 102.6, 62.5,
(b) A. Takacs, P. Acs, L. Kollar, Tetrahedron 64 (2008) 983e987;
(c) H. Cao, H. Alper, Org. Lett. 12 (2010) 4126e4129;
(d) S.A. Worlikar, R.C. Larock, J. Org. Chem. 73 (2008) 7175e7180;
(e) J.R. Martinelli, D.A. Watson, D.M.M. Freckmann, T.E. Barder, S.L. Buchwald,
J. Org. Chem. 73 (2008) 7102e7107.
d
d
61.4, 56.7, 40.8, 39.3. HRMS (ESI) m/z: calculated for C13H14ClNO5,
[MþNa] 322.0429; found: 322.0455.
[11] D.N. Sawant, Y.S. Wagh, K.D. Bhatte, B.M. Bhanage, Eur. J. Org. Chem. (2011)
6719e6724.
Acknowledgements
[12] J. Zhang, M. Senthilkumar, S. Ghosh, S. Hong, Angew. Chem., Int. Ed. 49 (2010)
6391e6395.
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The authors are grateful to the National Natural Science Foun-
dation of China (Grant No. 20906059 and 21272145), the Funda-
mental Research Funds for the Central Universities (Grant
GK201102005 and GK261001095), Shaanxi Innovative Team of Key
Science and Technology (2013KCT-17) for providing financial sup-
port for this research.
(b) J.L. Bras, J. Muzart, Chem. Rev. 111 (2011) 1170e1214;
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