Palladium-Catalyzed Carbonylative Cyclization of Terminal Alkynes and Anilines to 3-Substituted Maleimides

Article abstract of DOI:10.1002/adsc.201800672

Herein, we describe an interesting palladium-catalyzed protocol for the carbonylative synthesis of 3-substituted maleimides. By annulation of simple anilines with terminal alkynes under carbon monoxide pressure, the desired 3-substituted maleimides can be

Full text of DOI:10.1002/adsc.201800672

Title: Palladium-Catalyzed Carbonylative Cyclization of Terminal
Alkynes and Anilines to 3-Substituted Maleimides
Authors: Xiao-Feng Wu and jian-xing xu
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.2018
Palladium-Catalyzed Carbonylative Cyclization of Terminal
Alkynes and Anilines to 3-Substituted Maleimides
Jian-Xing Xu,a Xiao-Feng Wua,b*
a
Leibniz-Institut für Katalyse an der Universität Rostock e. V., Albert-Einstein-Straße 29a, 18059 Rostock, Germany
Phone: (+49) -0381-1281-343; E-Mail: xiao-feng.wu@catalysis.de
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of
b
China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.2018
Abstract. Herein, we describe an interesting palladium- Additionally, with the addition of phosphine ligand, maleic
catalyzed protocol for the carbonylative synthesis of 3- acid isoimide can be obtained from the same substrates as
substituted maleimides. By annulation of simple anilines well. With the presence of K2S2O8, the obtained maleic acid
with terminal alkynes under carbon monoxide pressure, the isoimide can be completely transformed to the
desired 3-substituted maleimides can be obtained in 50-85% corresponding maleimide.
yields.
Keywords: carbonylation; annulation; heterocycles
synthesis; palladium catalyst; maleimides
can be transformed and the products are limited to
3,4-disubstituted maleimides. More recently, Alper’s
group achieved a procedure on palladium-catalyzed
chemo- and regioselective aminocarbonylation of
alkynes with aminophenols.[11] The desired α,β-
unsaturated amides were obtained in good to
excellent yields. Additionally, Dyson, Liu and co-
Introduction
Maleimide is an important class of nitrogen-
containing heterocycles with many potent
applications in various areas (Figure 1).[1] Among all
the maleimide analogues, 3-substituted maleimides
are even more attractive. For example, biologically
active α-2-adrenoceptor antagonist can be directly
produced from the corresponding 3-substituted
workers
developed
a
palladium-catalyzed
aminocarbonylation procedure for the synthesis of
succinimide derivatives from alkynes and amines in
the presence of p-TsOH.[6p] Inspired by these
achievements and also as our continues interest in
carbonylative synthesis of heterocycles, we describe
here the first example on palladium-catalyzed
carbonylative annulation of simple anilines and
terminal alkynes. 3-Substituted maleimides were
prepared in moderate to good yields.
maleimide
by
asymmetric
hydrogenation.[2]
Additionally, they are ready for further modifications
at the 4th position to produce the corresponding non-
symmetrical 3,4-disubstituted products.[3] Although
their obvious importance, synthetic methodologies
for 3-substituted maleimides construction are still
very limited. The known procedures are mainly based
on the cross-coupling of aryl halides or
aryldiazonium salts with maleimides.[4] Obviously,
special effort should be given to overcome challenges
between conversion and overreaction (give 3,4-
disubstituted product).
On the other hand, transition-metal-catalyzed
carbonylative transformations have found tremendous
applications in organic synthesis. Through CO
incorporation, a wide range of carbonyl-containing
compounds can be prepared easily.[5] By using the
proper substrates, heterocycles can be prepared in an
atom-economical manner as well.[6,7] Among them,
our group recently developed a rhodium-catalyzed
carbonylation procedure for the synthesis of
substituted maleimides.[6h] However, this procedure
failed with terminal alkynes and only internal alkynes
Figure 1. Selected examples of biologically active
molecules featuring maleimides and derivatives.
1
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
Results and Discussion
Interestingly, a 1:1.2 ratio mixture of the two
products 3a and 4a were formed when 2,6-
dimethoxy-1,4-benzoquinone used as the oxidant in
the presence of 10 mol% PPh3, (Table 2, entry 1).
The molecular structure of the product 4a was
confirmed by X-ray diffraction (Figure 2), and known
as maleic acid isoimide which is widely used as
reactive intermediates for polyamides, polymerizable
surfactants, and β-lactams synthesis.[8] They are
usually prepared by condensation reaction.[9] To the
best of our knowledge, this is the first example on
palladium-catalyzed carbonylative annulation of
simple aniline and terminal alkyne to synthesize
maleic acid isoimide.
Initially, phenylacetylene (1a) and aniline (2a)
were selected as the model substrates to establish this
catalytic system (Table 1, also see SI). As shown in
Table 1, the desired 1,3-diphenyl-1H-pyrrole-2,5-
dione (3a) could not be detected with BQ (1,4-
benzoquinone), Ag2CO3, Ag2O, Cu(OAc)2, or DTBP
(di-tert-butyl peroxide) as the oxidant (Table 1,
entries 1-5). To our delight, 45% yield of the desired
product 3a was obtained in the presence of 5 mol% of
PdCl2, 10 mol% of PPh3 and 1.5 equiv. of K2S2O8
under CO gas pressure (20 bar) in 1,4-dioxane at
120 °C for 24 h. Other solvents including toluene,
DMF, DMSO, THF, and CH3CN were tested as well,
and 1,4-dioxane was found to be the most effective
solvent (Table 1, entry 6). To our surprise, 55% yield
of the desired product 3a can be obtained in the
absence of ligand (Table 1, entry 13, SI). Notably,
46% yield of the desired product can still be obtained
with only 2.5 mol% of the catalyst (Table 1, entry 14).
The ratio of the two substrates were checked as well,
and the yield of 3a can be improved to 63% with
slightly excess (1.2 equiv.) of aniline (Table 1, entry
16). Notably, 3a can be obtained in 71% yield by
using 1 mol% of PTSA as the additive (Table 1, entry
17).
Figure 2. ORTEP representation of 4a (CCDC
1843193). Displacement ellipsoids correspond to
30% probability.[12]
In order to improve the chemoselectivity of 4a,
we subsequently screened various ligands. As shown
in Table 2, diphosphine ligands were less effective on
this transformation, in the respect of both reactivity
and selectivity (Table 2, entries 5-7). Monophosphine
with bulky substitution, such as tri-tert-
butylphosphine and L2, facilitated the formation of
3a (Table 2, entries 4 and 11). Remarkably, the yield
of 4a can be improved to 33% when we use 1,3,5,7-
tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha-
Table 1. Screening of Reaction Conditions.[a]
Entry Catalyst Ligand Oxidant
Solvent Yield[b]
1
2
3
4
5
6
7
8
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
-
BQ
Ag2CO3
Ag2O
Cu(OAc)2 dioxane n.r.
DTBP
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
dioxane trace
dioxane n.r.
dioxane n.r.
adamantane[10] (CYTOP 292, L8 here) as the ligand
(Table 2, entry 17). The yield and chemoselectivity
can be further improved with NPh3 (10 mol%) as the
additive (Table 2, entry 21, 3a/4a = 1:3.3, 41% yield
of 4a). Further increase the loading of phosphine
ligand resulted in decreased substrates conversion
(Table 2, entry 25). And the ratio of 3a and 4a did not
change by prolong the reaction time even to 40 hours.
However, we failed to drive the selectivity fully to
produce maleic acid isoimide. Here, it is also
important to mention that maleic acid isoimide 4a can
be completely transformed to 3a with K2S2O8 as the
promotor in 1,4-dioxane at 100°C for 8 h. (Scheme 1).
dioxane n.r.
dioxane 45%
Toluene 13%
DMF
DMSO trace
THF 35%
CH3CN 29%
DME 13%
trace
9
10
11
12
13
14[c]
15[d]
16[e]
dioxane 55%
dioxane 46%
dioxane 56%
dioxane 63%
dioxane 71%
-
-
-
-
17[e,f] PdCl2
[a]
Reaction conditions: phenylacetylene 1a (0.4 mmol),
aniline 2a (0.2 mmol), PdCl2 (5 mol%), PPh3 (10
mol%), oxidant (0.3 mmol), 1,4-dioxane (2 mL), 20 bar
CO at 120 °C, 24 h.
[b] GC yield by using hexadecane as an internal standard.
[c] PdCl2 (2.5 mol%).
[d] PdCl2 (10 mol%).
[e] Phenylacetylene 1a (0.2 mmol), aniline 2a (0.24 mmol).
Scheme 1. The conversion from 4a to 3a. Determined by
GC and TLC after reaction.
[f]
p-Toluenesulfonic acid monohydrate (1 mol%) as the
additive.
2
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
With the optimized conditions in hand (Table 1,
19
20
21
L8
L8
L8
L8
L8
L8
L8
DBU
TBAC
NPh3
NPh3
NPh3
NPh3
NPh3
-
-
5:1
1:3.3
1:1.7
1:1.1
1:4.5
1:3
-
entry 17), a range of substituted alkynes and amines
were investigated. As summarized in Scheme 2, a
series of terminal alkynes and anilines were smoothly
transformed under identical conditions and gave the
desired products in 50-85% yields. For anilines, the
electronic properties of the substituent on the
aromatic ring have little influence on the reaction
outcomes. Both electron-withdrawing and electron-
donating groups were well tolerated. Anilines with
fluoro, chloro, and bromo substituents were also well
tolerated and provide the corresponding products in
moderate to good yields (3d, 3e, and 3f). These
halogen substituents are ready for further
18%
53%
54%
46%
44%
44%
3%
41%
34%
24%
36%
33%
22[d]
23[e]
24[f]
25[g]
[a]
Reaction conditions: phenylacetylene 1a (0.4 mmol),
aniline 2a (0.2 mmol), PdCl2 (5 mol%), PPh3 (10 mol%),
DMBQ (0.3 mmol), 1,4-dioxane (2 mL), 20 bar CO at
120 °C, 20h. DMBQ
benzoquinone, TFP = tri-(2-furyl)-phosphine, DPEPhos
= bis(2-diphenylphosphinophenl)ether, JohnPhos = 2-
(di-tert-butylphosphino)biphenyl,
triphenylphosphine oxide, TBAC
ammonium chloride.
Determined by GC using hexadecane as an internal
standard.
=
2,6-dimethoxy-1,4-
P(O)Ph3
=
=
transformations
by
cross-coupling
reactions.
tetrabutyl
However, our procedure failed when quinolin-5-
amine and 2-methylbenzofuran-5-amine were tested
with phenylacetylene under our standard conditions.
Cyclohexylamine, as an example of aliphatic amine,
was tested under our standard conditions as well.
However, no desired product can be detected but the
phenylacetylene homo-coupling product and together
with a small amount of N1,N2-dicyclohexyloxalamide.
[b]
[c] 10 mol% additive.
[d] Reaction at 100 °C.
[e] 15 bar CO.
[f] 15 mol% L8.
[g] 20 mol% L8.
Table 2. Optimization of reaction conditions using 2,6-
dimethoxy-1,4-benzoquinone as the oxidant in the
presence of ligands.[a]
Scheme 2. Substrates scope of anilines and terminal
alkynes.
Entry Ligand
Add.[c]
Conv.[b] 3a:4a [b] Yield
4a[b]
1
2
3
4
5
6
7
8
PPh3
PCy3
TFP
P(n-Bu)3
DPEPhos
dppp
BINAP
JohnPhos
P(O)Ph3
L1
L2
L3
L4
L5
L6
L7
L8
L8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
48%
30%
48%
51%
34%
22%
44%
13%
67%
54%
42%
44%
50%
41%
42%
31%
49%
11%
1:1.2
3.3:1
2.2:1
9:1
3.8:1
4.5:1
7.8:1
>99:1
8.5:1
1.1:1
6:1
1:1.1
7.3:1
1.2:1
2:1
1.2:1
1:2
26%
7%
15%
5%
7%
4%
5%
-
7%
26%
6%
23%
6%
19%
14%
14%
33%
-
9
10
11
12
13
14
15
16
17
18
-
Reaction conditions: terminal alkynes 1a (0.4 mmol),
anilines 2a (0.48 mmol), PdCl2 (5 mol%), PPh3 (10 mol%),
Et3N
>99:1
3
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
K2S2O8 (0.6 mmol), PTSA (1 mol%), 1,4-dioxane (4 mL),
20 bar CO at 120 °C, 24 h. [b] Terminal alkynes 1a (0.4
mmol), anilines 2a (0.2 mmol), PdCl2 (5 mol%), PPh3 (10
mol%), 2,6-dimethoxy-1,4-benzoquinone (0.6 mmol),
PTSA (10 mol%), 1,4-dioxane (4 mL), 20 bar CO at
120 °C, 24 h.
Subsequently, a series of alkynes were also tested.
Substrates with electron-donating or electron-
withdrawing group were well tolerated and the
corresponding 3-substituted maleimides were
obtained in good yields (3i and 3j). Furthermore,
phenylacetylene bearing substituents with halogen at
the ortho-, para- or meta-position of the phenyl ring
were converted into the corresponding products in
good yields as well (3l, 3m and 3n). 9-
Ethynylphenanthraene substituted with a sterically
hindered group can also gave the desired product in
61% yield (3p). Additionally, aliphatic terminal
alkyne can be successfully applied as well and give
the target product in good yields (3q, 3r).
Additionally, internal alkyne can also be applied and
gave the desired 3,4-disubstituted products in
moderate yield (3s). However, no desired products
could be detected when 3-ethynylpyridine, 3-
ethynylthiophene and 3-methoxyprop-1-yne were
tested with aniline under our best conditions.
Scheme 3. Proposed Mechanism.
Conclusion
In summary, we have developed an interesting
palladium-catalyzed carbonylative annulation
procedure for the synthesis of 3-substituted
maleimides from simple anilines and terminal
alkynes. By modifying the reaction conditions,
maleic acid isoimide can be formed as well which can
be further transformed into the corresponding
maleimides in the presence K2S2O8. Notably, to the
best of our knowledge, this is the first example on
palladium-catalyzed carbonylative synthesis of 3-
substituted maleimides from anilines and terminal
alkynes.
Concerning the reaction pathway, based on our
results and literatures,[11]
a
possible reaction
mechanism is proposed and shown in Scheme 3. The
reaction started with Pd(OTs)2 which was produced
in-situ from PdCl2 and PTSA, after X ligand
exchange with aniline to give the amino-palladium
complex I. Then CO coordinates and inserts to
produce complex II. After interaction with alkyne,
vinyl palladium complex III will be formed. After
rotation and the second CO insertion, the final
maleimide will be eliminated after reductive
elimination.[13] Then the formed Pd(0) will be re-
oxidized and gave the active Pd(II) for the next
catalytic cycle. In the case of using K2S2O8 as the
oxidant, 4a can be transformed into 3a completely.
Experimental Section
General produce of palladium-catalyzed carbonylative
annulation.
A 7 mL screw-cap vial was charged with PdCl2 (3.6 mg,
0.02 mmol, 5 mol%), p-toluenesulfonic acid monohydrate
(0.8 mg, 1 mol%), K2S2O8 (162 mg, 0.6 mmol) and an
oven-dried stirring bar. The vial was closed by Teflon
septum and phenolic cap and connected with atmosphere
with a needle. Then a 1,4-dioxane (4 mL) solution of
phenylacetylene (0.4 mmol) and aniline (0.48 mmol) was
injected by syringe. The vial was fixed in an alloy plate
and put into Paar 4560 series autoclave (300 mL) under
argon atmosphere. At room temperature, the autoclave is
flushed with carbon monoxide for three times and 20 bar
of carbon monoxide was charged. The autoclave was
reacted at 120 °C for 24 hours. After the reaction had
finished, the autoclave was cooled down to room
temperature and the pressure was released carefully. The
reaction mixture was diluted with water and extracted with
EtOAc (20 mL × 3). The combined organic layer was
washed with H2O and brine, dried over anhydrous Na2SO4.
After evaporation of the solvent, the residue was adsorbed
on silica gel and the crude product was purified by column
chromatography using n-pentane/EtOAc as eluent.
However,
transformation.
DMBQ
cannot
promote
such
Acknowledgements
4
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
The authors thank the Chinese Scholarship Council for financial
support. We thank Dr. Anke Spannenberg for the crystal
diffraction support. We also thank the analytical department of
Leibniz-Institute for Catalysis at the University of Rostock for
their excellent analytical service here. We appreciate the general
support from Professor Armin Börner and Professor Matthias
Beller in LIKAT.
Chem. Int. Ed. 2009, 48, 6041-6044; f) S.
Prateeptongkum, K. M. Driller, R. Jackstell, A.
Spannenberg, M. Beller, Chem. Eur. J. 2010, 16, 9606-
9615; g) S. Prateeptongkum, K. M. Driller, R. Jackstell,
M. Beller, Chem. Asian J. 2010, 5, 2173-2176; h) F.
Zhu, Y. Li, Z. Wang, X.-F. Wu, ChemCatChem 2016, 8,
3710-3713; for other related examples, see: i) X. Li, X.
Li, N. Jiao, J. Am. Chem. Soc., 2015, 137, 9246-9249;
j) M. Feng, B. Tang, H.-X. Xu, X. Jiang, Org. Lett.,
2016, 18, 4352-4355; k) Y.-F. Liang, R. Steinbock, A.
Münch, D. Stalke, L. Ackermann, Angew. Chem. Int.
Ed., 2018, 57, 5384-5388; l) F. Zhu, Y. Li, Z. Wang,
X.-F. Wu, Adv. Synth. Catal. 2016, 358, 3350-3354; m)
X. Zhang, H. Liu, Y. Jia, Chem. Commun., 2016, 52,
7665-7667; n) X. Li, J. Pan, H. Wu, N. Jiao, Chem. Sci.,
2017, 8, 6266-6273; o) G. Zhang, H. Yu, G. Qin, H.
Huang, Chem. Commun., 2014, 50, 4331-4334; p) . H.
Liu, G. P. S. Lau, P. J. Dyson, J. Org. Chem. 2015, 80,
386-391.
References
[1] a) N. Matuszak, G. G. Muccioli, G. Labar, D. M.
Lambert, J. Med. Chem. 2009, 52, 7410-7420; b) S. K.
Grant, Cell. Mol. Life. Sci. 2009, 66, 1163-1177; c) A.
A. Panov, A. Y. Simonov, S. N. Lavrenov, S. A.
Lakatosh, A. S. Trenin, Chem. Heterocyclic. Compd.
2018, 54, 103-113.
[2] Z. Han, P. Li, Z. Zhang, C. Chen, Q. Wang, X.-Q.
Dong, X. Zhang, ACS Catal. 2016, 6, 6214-6218.
[3] a) C. I. Manley-King, G. Terre’Blanche, N. Castagnoli,
J. J. Bergh, J. P. Petzer, Bioorg. Med. Chem. 2009, 17,
3104-3110; b) N. P. Argade, A. Kar, Synthesis 2005,
2284-2286; c) T. C. McKenzie, J. W. Epstein, W. J.
Fanshawe, J. S. Dixon, A. C. Osterberg, L. P.
Wennogle, B. A. Regan, M. S. Abel, L. R. Meyerson, J.
Med. Chem. 1984, 27, 628-632; d) S.-C. Chien, M.-L.
Chen, H.-T. Kuo, Y.-C. Tsai, B.-F. Lin, Y.-H. Kuo, J.
Agr. Food. Chem. 2008, 56, 7017-7022; e) E. Conchon,
F. Anizon, B. Aboab, R. M. Golsteyn, S. Léonce, B.
Pfeiffer, M. Prudhomme, Eur. J. Med. Chem. 2008, 43,
282-292; f) W. Lv, B. Banerjee, K. L. Molland, M. N.
Seleem, A. Ghafoor, M. I. Hamed, B. Wan, S. G.
Franzblau, A. D. Mesecar, M. Cushman, Bioorg. Med.
Chem. 2014, 22, 406-418. g) F. Jafarpour, M.
Shamsianpour, RSC Adv. 2016, 6, 103567-103570; h) F.
Jafarpour, M. Shamsianpour, S. Issazadeh, M. Dorrani,
H. Hazrati, Tetrahedron 2017, 73, 1668-1672; i) N.
Argade, P. Deore, Synthesis 2014, 46, 281-289.
[7] a) X.-F. Wu, H. Neumann, ChemCatChem 2012, 4,
447-458; b) X.-F. Wu, X. Fang, L. Wu, R. Jackstell, H.
Neumann, M. Beller, Acc. Chem. Res. 2014, 47, 1041-
1053; c) R. Skoda-Foldes, L. Kollar, Curr. Org. Chem.
2002, 6, 1097-1119; d) G. Bartolo, M. Raffaella, S.
Giuseppe, Eur. J. Org. Chem. 2012, 2012, 6825-6839;
e) S. D. Friis, A. T. Lindhardt, T. Skrydstrup, Acc.
Chem. Res. 2016, 49, 594-605; f) X.-F. Wu, RSC Adv.
2016, 6, 83831-83837.
[8] a) I. Klimenkovs, I. Zhukovska, I. Uzulina, A.
Zicmanis, A. Guyot, C. R. Chimie 2003, 6, 1295-1304;
b) I. Klimenkovs, A. Zicmanis, I. Uzulina, C. Graillat,
A. Guyot, J. Disper. Sci. Tec. 2004, 25, 119-128; c) D.
Ivanov, C. Găină, C. Grigoraş, J. Appl. Polym. Sci.
2004, 91, 779-788; d) S. Rojas-Lima, H. López-Ruiz, A.
Álvarez-Hernández, L. Santillán-Sid, Heterocycles
2007, 71, 531.
[9] a) R. J. Cotter, C. K. Sauers, J. M. Whelan, J. Org.
Chem. 1961, 26, 10-15; b) K. P. Haval, S. B. Mhaske,
N. P. Argade, Tetrahedron 2006, 62, 937-942; c) I.
Klimenkovs, E. Bakis, A. Priksane, Synth. Commun.
2013, 43, 2634-2640.
[4] a) L. H. Lim, J. Zhou, Org. Chem. Front. 2015, 2, 775-
777; b) Z.-H. Yang, Z.-H. Chen, Y.-L. An, S.-Y. Zhao,
RSC Adv. 2016, 6, 23438-23447; c) A. I. Roshchin, E.
V. Polunin, Mendeleev Commun. 2008, 18, 332-333.
[5] a) L. Kollar, Modern Carbonylation Methods; Wiley-
VCH, 2008 ; b) X.-F. Wu, H. Neumann, M. Beller,
Chem. Soc. Rev. 2011, 40, 4986-5009; c) X.-F. Wu, H.
Neumann, M. Beller, ChemSusChem 2013, 6, 229-241;
d) Y.-H. Li, Y.-Y. Hu, X.-F. Wu, Chem. Soc. Rev. 2018,
47, 172-194.
[10] a) M. Amézquita-Valencia, H. Alper, Org. Lett. 2014,
16, 5827-5829; b) M. Amézquita-Valencia, G.
Achonduh, H. Alper, J. Org. Chem. 2015, 80, 6419-
6424.
[11] F. Sha, H. Alper, ACS Catal. 2017, 7, 2220-2229.
[6] For a review on palladium-catalyzed heterocycles
synthesis, see: a) X.-F. Wu, H. Neumann, M. Beller,
Chem. Rev. 2013, 113, 1-35; for examples on
carbonylative synthesis of 3,4-disubstituted maleimides,
see: b) T. Kondo, M. Nomura, Y. Ura, K. Wada, T.
Mitsudo J. Am. Chem. Soc. 2006, 128, 14816-14817; c)
P. Mathur, R. K. Joshi, D. K. Rai, B. Jha, S. M. Mobin,
Dalton Trans. 2012, 41, 5045-5054; d) S. Inoue, Y.
Fukumoto, N. Chatani, J. Org. Chem. 2007, 72, 6588-
6590; e) K. M. Driller, H. Klein, M. Beller, Angew.
[12] CCDC 1843193 (4a) contains the supplementary
crystallographic data for this paper. These data are
provided free of charge by The Cambridge
Crystallographic Data Centre.
[13] a) J. Ni, J. Li, Z. Fan, A. Zhang, Org. Lett. 2016, 18,
5960-5963; b) L. Grigorjeva, O. Daugulis, Org. Lett.
2014, 16, 4688-4690.
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10.1002/adsc.201800672
Advanced Synthesis & Catalysis
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Palladium-Catalyzed Carbonylative Cyclization of
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Adv. Synth. Catal. Year, Volume, Page – Page
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