Nickel-catalyzed coupling of isocyanates with 1,3-iodoesters and halobenzenes: A novel method for the synthesis of imide and amide derivatives

Article abstract of DOI:10.1039/b506903c

Substituted imide and amide derivatives were conveniently prepared from the reaction of isocyanates with o-iodobenzoates and haloarenes catalyzed by the NiBr₂(dppe)/dppe/Zn system in moderate to good yields with excellent tolerance of functional groups. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b506903c

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COMMUNICATION
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Nickel-catalyzed coupling of isocyanates with 1,3-iodoesters and
halobenzenes: a novel method for the synthesis of imide and amide
derivatives{
Jen-Chieh Hsieh and Chien-Hong Cheng*
Received (in Cambridge, UK) 16th May 2005, Accepted 5th July 2005
First published as an Advance Article on the web 12th August 2005
DOI: 10.1039/b506903c
Substituted imide and amide derivatives were conveniently
prepared from the reaction of isocyanates with o-iodobenzoates
and haloarenes catalyzed by the NiBr2(dppe)/dppe/Zn system in
moderate to good yields with excellent tolerance of functional
groups.
Isocyanate derivatives are very reactive species, but the application
of isocyanates is mostly limited to the synthesis of urethane or urea
derivatives.1 Only recently, transition metal-mediated cycloaddi-
tion of isocyanates with alkynes to form pyridones has attracted
considerable attention.2 On the other hand, imides are important
industrial, biological and medicinal chemicals.3,4 A common
Scheme 1
method for the preparation of imides is via condensation of amine
with anhydride or phthalic acid derivatives.5,6 Another general
method is the palladium-catalyzed reaction of phthalimide with
iodocompound.7 While there are several synthetic procedures for
preparing these compounds, limitations as noted below were
found. (1) Most of the known procedures for phthalimide forma-
Scheme 2
tion are compatible only with simple alkyl or aryl substituents on
the nitrogen atom. (2) It is difficult to introduce a functional
and 43% yields, respectively. The use of Ni(PPh3)2Cl2 as the
group, especially an electron-donating group, on the phenyl ring of
catalyst afforded only the reductive dimerization product 4 (see
phthalimides. (3) The formation of imide usually requires high reac-
Scheme 3) of iodobenzoate without any desired cyclization
tion temperatures. Thus, a simple and efficient method that can be
product. Ni(dppe)Br2 was found to be the best catalyst giving
applied to the synthesis of a wide range of imide derivatives should
product 3a in 88% yield and a small quantity of reductive
be attractive. Our interest in nickel-catalyzed cyclization reactions8
dimerization product 4. The solvent used for the catalytic reaction
prompted us to explore the possibility of using o-iodobenzoates
is also critical. No desired product was found in Et2O and 1,2-
and b-iodoacrylates for cyclization with isocyanates. Herein, we
wish to report for the first time a nickel-catalyzed cyclization of
dichloroethane at ambient temperature, whereas THF afforded
predominately dimerization product 4 and a trace of the desired
1,3-iodoesters with isocyanates, providing an efficient method for
product 3a at 65 uC. Acetonitrile appears to be the best choice of
solvent when Ni(dppe)Br2 was used as the catalyst. The presence
the synthesis of imide derivatives (Schemes 1–2).
Treatment of methyl 2-iodobenzoate (1a) with cyclohexyl-
of extra dppe diminished the reductive dimerization of iodobenzo-
isocyanate (2a) in the presence of Ni(dppe)Br2, dppe (bis(diphenyl-
ate. Without additional dppe, the reaction provided 3a in only 65%
phosphino)ethane), zinc powder and triethylamine in acetonitrile
yield and the reductive dimer 4 in 24% yield. Triethylamine
at 80 uC for 36 h afforded 2-cyclohexylisoindoline-1,3-dione (3a) in
increased the rate of the catalytic reaction, but the role of this
88% yield. The structure of 3a was confirmed by its 1H NMR, 13
C
species is not yet understood. No desired product was observed
below 60 uC, and the best temperature for this reaction was 80 uC.
Most of the extra isocyanate in the catalytic reaction was
converted to the corresponding isocyanurate 5. Similar to 1a,
NMR and mass data. In the absence of either the nickel complex
or zinc powder, product 3a was not observed.
To understand the nature of this nickel-catalyzed cyclization, the
effect of solvent and nickel complex used on the reaction of 1a with
2a was investigated. Ni(PPh3)2Br2, and Ni(dppm)Br2 were inactive
for the reaction, while Pd(PPh3)4 and Ni(dppb)Br2 gave 3a in trace
Department of Chemistry, National Tsing Hua University, Hsinchu,
30013 Taiwan. E-mail: chcheng@mx.nthu.edu.tw; Fax: 886-3-5724698;
Tel: 886-3-5721454
{ Electronic supplementary information (ESI) available: Preparation and
characterization. See http://dx.doi.org/10.1039/b506903c
Scheme 3
4554 | Chem. Commun., 2005, 4554–4556
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Table 1 Results of cyclization of 1,3-iodoesters with isocyanates
catalyzed by nickel complex Ni(dppe)Br2
methyl o-bromobenzoate also reacted with isocyanate 2a to give
product 3a, but in lower yield (60%); a substantial amount of the
bromobenzoate remained unreacted.
a
Entry
1
1
2
Product
Yield (%)b
88
This nickel-catalyzed cyclization reaction was successfully
extended to various substituted benzoate and b-iodoacrylate and
the results are listed in Table 1. Thus, 1a reacts with n-butyl-
isocyanate (2b) and benzylisocyanate (2c) to give the correspond-
ing cyclization products 3b and 3c in 82 and 79% yield. Similarly,
aryl isocyanates with various substituents on the aryl rings (2d–i)
underwent cyclization with 1a to provide the corresponding imide
derivatives 3d–i in moderate to good yields (entries 4–9). The
results show that the yields of product 3 also depends greatly on
these functional groups. An isocyanate with an electron-donating
group on the aryl ring affords a higher product yield compared to
that with an electron-withdrawing substituent. Consistent with this
notion, the product yield of imide 3 is generally higher for
alkylisocyanates than for arylisocyanates. As shown in entry 10,
the catalytic reaction is also compatible with a siloxane group on
the isocyanate providing product 3j in 79% yield.
1a
2a
2
3
4
1a
1a
1a
2b
2c
2d
82
79
61
5
6
7
1a
1a
1a
2e
2f
66
71
53
Under similar reaction conditions, substituted iodobenzoate 1b
bearing two methoxy moieties on the aryl ring also underwent
cyclization with isocyanates 2a and 2e to give products 3k–3l in 92
and 75% yields, respectively. The observed higher product yields
with substrate 1b reflects that increasing electron density on the
aryl ring of o-iodobenzoate also enhances the formation of the
corresponding imide product. The reductive dimerization product
of dimethoxyiodobenzoate in these three reactions was not clearly
observed. However, iodobenzoate 1c bearing an electron with-
drawing chloro group reacted with 2a (entry 13) to form product
3m in lower yield (51%).
2g
8
1a
2h
44
9
1a
1a
2i
2j
41
79
The present method can also be applied to the cyclization of
b-iodoacrylate. Treatment of (Z)-ethyl-3-iodoacrylate (1d) with
cyclohexylisocyanate under similar reaction conditions furnished
maleimides 3n–o in yields of 47 and 37%, respectively. The low
product yields were accompanied by the formation of a large
quantity of the homo reductive dimerization product of iodoacryl-
ate 1d.
10
11
12
1b
1b
2a
2e
92
75
The foregoing results reveal that the present catalytic reaction
can tolerate most of the functional groups on the isocyanates and
1,3-iodoesters tested. Primary and secondary alkyl isocyanates
were most reactive and gave high yields of the cyclization products.
Aryl isocyanate consisting of electron-donating groups also pro-
vided good yields. Aryl isocyanate bearing electron-withdrawing
groups also underwent cyclization but with lower yields. For the
reaction of dimethoxy iodobenzoate 1b, both alkyl and aryl
isocyanates gave the expected products in high yields. For
iodoacrylate 1d, the cyclization gave only low to moderate yields
of the expected imide products.
13
14
1c
1d
2a
2a
51
47
Based on the above results and the known organometallic
chemistry, a plausible mechanism is proposed to account for the
formation of the imide products (Scheme 4). The catalytic reaction
is probably initiated by the reduction of Ni(II) species to Ni(0)
species by zinc powder. The iodo compound then undergoes
oxidative addition to the Ni(0) complex to form intermediate 6.
Insertion of an isocyanate molecule into 6 provided intermediate 7.
Subsequent imidation leads to product 3 and the regeneration of
the Ni(II) species.
15
1d
2d
37
a
Unless stated otherwise, all reactions were carried out using
iodoester (1) (1.0 mmol), isocyanate (2) (5.0 mmol), Ni(dppe)Br2
(10 mol%), dppe (10 mol%), triethylamine (10 mol%) and Zn
(2.0 mmol) in CH3CN (2.0 ml) at 80 uC under N2 for 36 h.
b
This proposed mechanism gains strong support from the
formation of homo reductive coupling of the iodoester as a side
Isolated yields based on iodoester used.
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Table 2 Results of amide formation from aryl halides with isocya-
nates catalyzed by Ni(dppe)Br2
a
Entry
1
1
2
Product
Yield (%)b
34
8a
2a
2
8c
2a
71
3
4
8c
8b
2e
2e
64
61
Scheme 4
5
8d
8e
2e
2e
59
51
6
a
Unless stated otherwise, all reactions were carried out using
aryliodides or arylbromide (8) (1.0 mmol), isocyanate (2) (2.0 mmol),
Ni(dppe)Br2 (10.0 mol%), dppe (10.0 mol%) and Zn (2.0 mmol) in
CH3CN (2.0 ml) at 80 uC under N2 for 16 h. Isolated yields based
on arylhalides used.
Scheme 5
b
product that can only be formed from intermediate 6. The
observations that electron-donating groups on the aromatic ring of
o-iodobenzoates and on the isocyanates enhance the yields of
phthalimide products indicates that the increase of nucleophilicity
of intermediates 6 and 7 to facilitate the insertion of isocyanate and
the imidation are critical for the present catalytic reaction.
The catalyst system Ni(dppe)Br2/Zn was further tested for the
amidation of aryl iodide and aryl bromide with isocyanates
(Scheme 5 and Table 2). A slight modification of reaction con-
ditions was made. The amidation was better carried out in the
absence of triethylamine. The reaction of aryliodides with
isocyanates gave moderate yields of the expected products. Thus,
iodobenzene 8a reacted with 2a (Table 2, entry 1) to afford amide
derivative 9a in 34% yield, while 3-methyliodobenzene reacted
with p-tolyl isocyanate 2e (entry 4) giving product 9c in higher
yield (61%).
by nickel complexes to form the imide and amide derivatives. This
is the first report that isocyanates can undergo cyclization
with 1-3-iodoesters with good tolerance of functional groups.
Further studies to extend the scope of the catalytic reactions and
determine the mechanistic pathway for these reactions are
currently underway.
We thank the National Science Council of the Republic of
China (NSC-93-2113-M-007-033) for the support of this research.
Notes and references
1 Review papers: S. Ozaki, Chem. Rev., 1972, 72, 457.
2 (a) D. A. Huang, M. J. Cross and J. Louie, J. Am. Chem. Soc., 2004, 126,
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B. E. Maryanoff, Org. Lett., 2003, 5, 4537; (c) Y. Yamamoto,
H. Takagishi and K. Itoh, Org. Lett., 2001, 3, 2117.
3 M. E. El-Araby, R. J. Bernacki, G. M. Makara, P. J. Pera and
W. K. Anderson, Bioorg. Med. Chem., 2002, 12, 2867.
Bromo-substituted arenes generally provided higher yields of the
amidation products relative to the corresponding iodoarenes.
Thus, bromobenzene (8c) reacted with 2a and 2e to afford amide
derivatives in 71 and 64% yields, respectively (entries 2 and 3).
Biphenyl bromide (8d) and bromonaphthalene (8e) also underwent
amidation with p-tolyl isocyanate (2e) (entries 5–6) to form the
corresponding products 9d-e in 59 and 51% yields. Under the
present catalytic reaction conditions, all of these catalytic
amidation reactions were accompanied with homo reductive
dimerization of the aryl halides. The dimerization product is
substantially reduced when aryl iodide is replaced by aryl bromide
and this likely accounts for the higher yields of the amidation
products when bromoarenes were employed.
4 J. A. Kreuz, A. L. Endery, F. P. Gay and C. E. Sroog, J. Polym. Sci.,
Part A, 1966, 4, 26607.
5 (a) J. W. Verbicky, Jr. and L. Williams, J.Org. Chem., 1981, 46, 175; (b)
F. J. Williams and P. E. Donahue, J.Org. Chem., 1977, 42, 3414; (c)
J. A. Moore and J. H. Kim, Tetrahedron Lett., 1991, 32, 3449.
6 (a) P. J. Christopher and Z. Parveen, J. Chem. Soc., Perkin Trans. 2,
2001, 4, 512; (b) B. M. Barchin, A. M. Cuadro and A.-B. Julio, Synlett,
2002, 2, 343; (c) M.-Y. Zhou, Y.-Q. Li and X.-M. Xu, Synth. Commun.,
2003, 33, 3777.
7 (a) M. Sato, S. Ebine and S. Akabori, Synthesis, 1981, 6, 472; (b)
T. Yamamoto, Synth. Commun., 1979, 9, 219.
8 (a) K.-J. Chang, D. K. Rayabarapu and C.-H. Cheng, Org. Lett., 2003, 5,
3963; (b) D. K. Rayabarapu, P. Shukla and C.-H. Cheng, Org. Lett.,
2003, 5, 4903; (c) K.-J. Chang, D. K. Rayabarapu and C.-H. Cheng,
J. Org. Chem., 2004, 69, 4781.
In conclusion, we have developed a new methodology for the
cyclization of isocyanates with iodoesters and haloarenes catalyzed
4556 | Chem. Commun., 2005, 4554–4556
This journal is ß The Royal Society of Chemistry 2005