Synthesis of 2-arylmaleimides via the Heck reaction

Article abstract of DOI:10.1016/j.mencom.2008.11.016

The Heck reaction of maleimides with aryl iodides in the presence of PdCl₂(MeCN)₂, Bu₄NCl and HCOOK affords the corresponding 2-arylmaleimides in moderate yields.

Full text of DOI:10.1016/j.mencom.2008.11.016

Mendeleev
Communications
Mendeleev Commun., 2008, 18, 332–333
Synthesis of 2-arylmaleimides via the Heck reaction
Alexander I. Roshchin* and Evgeny V. Polunin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: rosc71@yandex.ru
DOI: 10.1016/j.mencom.2008.11.016
The Heck reaction of maleimides with aryl iodides in the presence of PdCl2(MeCN)2, Bu4NCl and HCOOK affords the
corresponding 2-arylmaleimides in moderate yields.
The most usual approach to 2-arylmaleimides is the Meervein
arylation of maleimides with arene diazonium salts, with the
yields ranging from low to moderate.1–4 Palladium-catalyzed
Heck arylation of maleimides is so far unknown, apparently due
to their instability in basic media. Nonetheless, this reaction
provides more and more new opportunities for the synthesis
of olefinic compounds (a recent example is the synthesis of
2-arylmaleic anhydrides from fumaric acid5). Very broad variations
in the nature of catalyst, base and additives are indeed possible.6
Table 1 Yield of 2-(4-fluorophenyl)maleimide from 4-fluoroiodobenzene
and maleimide depending on reaction conditions.
a
Entry HCOOKa Bu4NCla PdCl2(MeCN)2 Time/days Yield (%)b
1
2
3
4
5
6
2.5
KOAc, 2.5
2.5
0.2
0.1
1
1
—
1.5
1.5
1
0.02
0.02
0.02
0.02
0.02
0.05
8
1
14
14
34 (30)
—
c
0
12d
3 at 60 °C 13d
2.5
3
35 (30)
aMoles per 1 mol of maleimide; ArI:maleimide = 1.25. bEstimated from the
1H NMR spectrum of the crude product; yields of the isolated pure product
are given in parentheses. cExtensive formation of deep red resinous matter.
dConsiderable amounts of unreacted ArI and maleimide by TLC.
I
O
O
R2
2–5% PdCl2(MeCN)2
N
+
N
R2
Bu4NCl, HCOOK
catalytic system was introduced to perform reductive arylation
of norbornene,7 in the case of maleimide, we observed only
2-arylmaleimide formation (Table 1). This implies that inter-
mediate A undergoes elimination of H–PdI rather than substitu-
tion of palladium with formate hydrogen, in spite of trans-con-
figuration of the H–C–C–PdI fragment (for mechanistic details
of β-hydride elimination step, see ref. 6).
O
DMF, room temperature
R1
R1
O
Scheme 1
In this work, we found that the PdCl2(MeCN)2–Bu4NCl–
HCOOK system in DMF at ambient temperature effects the
Heck arylation of maleimides in moderate yields (Scheme 1).
An initial study was made for the reaction of maleimide with
4-fluoroiodobenzene; the yields of 2-(4-fluorophenyl)maleimide
under various conditions are given in Table 1.† Although this
O
H
Ar
N
†
General procedure for the reactions of aryl iodides with N-phenyl-
Pd
H
maleimide and maleimide. A mixture of ArI (5 mmol), N-phenylmaleimide
(0.69 g, 4 mmol) or maleimide (0.39 g, 4 mmol), Bu4NCl (1.11 g, 4 mmol),
HCOOK (0.84 g, 10 mmol), PdCl2(MeCN)2 (0.021 g, 0.08 mmol or
0.052 g, 0.20 mmol) in DMF (4 ml) was stirred under argon at room
temperature until the starting imide was consumed. Water (25 ml) was
added and the mixture was extracted with EtOAc (40 + 20 ml). The
extract was washed with water and evaporated in vacuo. The residue
was extracted several times with hot hexane–benzene or toluene; on
cooling the crude product precipitated, containing 5–10% Bu4NI. It was
recrystallized from small amounts of AcOH.
I
O
A
If NaHCO3 or KOAc was used instead of HCOOK (this
system has been thoroughly studied8–10), maleimide deteriorated
rapidly, probably, by anionic polymerization (entry 2). In the
absence of Bu4NCl, no arylation product was found (entry 3),
in agreement with Jeffery’s observations.8 If excess Bu4NCl was
used with only a minimal amount of formate, the reaction had
halted before all starting materials were consumed (entries 4
In reactions of maleimide, the reaction mixture instead of extraction
with EtOAc was concentrated in vacuo, the residue was washed with
water and further extracted as above.
Table 2 Reactions of aryl iodides with maleimide and N-phenylmaleimide.
2-(4-Fluorophenyl)-N-phenylmaleimide (Table 2, entry 1). Yellow
Isolated
Entry R1
R2
PdCl2(MeCN)2
Time/days
1
yield (%)a
crystals, mp 149.5–150.5 °C (from AcOH). H NMR (500 MHz, CDCl3)
3
d: 6.83 (s, 1H, =CH), 7.18 (pseudo-t, 2H, F–C–CH, JHF = 3JHH
=
1
2
3
4
5
6
7
8
4-F
4-F
Ph
H
Ph
H
Ph
Ph
H
0.02
0.05
0.02
0.02
0.02
0.02
0.05
0.05
5
3
6
12
3
6
40
30
30
42
= 8.6 Hz), 7.38 (m, 3H, Ph), 7.49 (t, 2H, Ph, J 7.8 Hz), 8.02 (dd, 2H,
.
3
4
F–C–CH=CH, JHH 8.9 Hz, JHF 7.1 Hz). MS, m/z (%): 267 (47, M +),
238 (14, M – HCO), 211 (14, M – 2CO), 120 (100, M – 2CO – PhN), 91
(36, PhN+). Found (%): C, 71.82; H, 3.81; N, 5.81. Calc. for C16H10FNO2
(%): C, 71.91; H, 3.77; N, 5.24.
4-OMe
4-OMe
4-Cl
4-CO2Me
4-CO2Me
2-NO2
32
(28)b
c
4
5
—
2-(4-Methoxycarbonylphenyl)-N-phenylmaleimide (Table 2, entry 6).
1H NMR (CDCl3, 500 MHz) d: 3.96 (s, 3H, COOMe), 6.99 (s, 1H,
=CH), 7.40 (m, 3H, Ph), 7.50 (t, 2H, Ph, J 7.7 Hz), 8.06 (d, 2H, C6H4,
H
—
aYield of pure 2-arylmaleimide with satisfactory mp and NMR purity of
> 95%. bEstimated from the 1H NMR spectrum of the crude product. c61%
of unreacted ArI was recovered.
.
J 8.4 Hz), 8.15 (d, 2H, C6H4, J 8.4 Hz). MS, m/z (%): 307 (25, M +), 292
(8, M – OMe), 276 (5, M – HCO), 248 (55, M – COOMe), 129 (100).
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© 2008 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2008, 18, 332–333
and 5). Raising temperature or increasing the catalyst load
References
allowed us to shorten the reaction time but not to improve the
yield (entries 5 and 6).
1
2
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The arylation was performed with other combinations of
aryl iodide and maleimide, affording similar isolated yields of
30–40% (Table 2). N-Phenylmaleimide reacted notably faster
than maleimide (cf. entry 1, Table 2 with entry 1, Table 1 or
entry 3 with entry 4 in Table 2). Electron-withdrawing groups
in aryl iodide make the reaction difficult: lower yield was
observed with R1 = 4-CO2Me, R2 = Ph (entry 6), and no aryl-
maleimide was isolated with R1 = 4-CO2Me, R2 = H and R1 =
= 2-NO2 (entries 7, 8). Similar retarding effect was reported10
for the Heck arylation of cinnamonitrile.
3
4
5
6
7
8
9
T. Jeffery, Tetrahedron, 1996, 52, 10113.
R. C. Larock and S. Babu, Tetrahedron Lett., 1987, 28, 5291.
Thus, we discovered the first example of Heck arylation of
maleimides. We are looking forward to increase yields of 2-aryl-
maleimides and also to employ them for the new syntheses of
polycyclic compounds.
10 M. Moreno-Manas, R. Pleixats and A. Roglans, Synlett, 1997, 1157.
Received: 26th June 2008; Com. 08/3160
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