Iron-catalyzed carbonylation: Selective and efficient synthesis of succinimides

Full text of DOI:10.1002/anie.200902078

Angewandte
Chemie
DOI: 10.1002/anie.200902078
Homogeneous Catalysis
Iron-Catalyzed Carbonylation: Selective and Efficient Synthesis of
Succinimides**
Katrin Marie Driller, Holger Klein, Ralf Jackstell, and Matthias Beller*
Dedicated to Professor Hans Jꢀrgen Wernicke on the occasion of his 60th birthday
The development of sustainable, efficient, and selective
catalysis is a fundamental goal in chemistry. During the last
decades, manifold transition metal catalyzed reactions have
been uncovered which have significantly improved organic
synthesis. Notably, most of the applications are based on
complexes of precious metals such as palladium, rhodium,
iridium, and ruthenium. The limited availability of these
metals and their high price makes it highly desirable to search
for more economical and environmentally friendly alterna-
tives.[1] Among the various biorelevant metals, iron is an
especially attractive alternative compared to precious metals.
Iron is the second most abundant metal in the earth’s crust
(4.7 wt%), it is cheap, benign, readily available, and ecolog-
ical friendly.[2] Obviously, numerous iron salts and complexes
are commercially accessible on a large scale[3] or are easy to
synthesize.[4] In contrast to man-made precious-metal cata-
lysts, iron takes part in various biological systems as an
essential key element, for example, in metalloproteins for the
transport or metabolism of small molecules (oxygen, nitro-
gen, methane, etc.) and electron-transfer reactions.[5]
Despite these many advantages, until recently, iron-
catalyzed processes were underrepresented in the field of
organic synthesis. One reason for this might be the fact that
most of the known catalytic reactions with iron are either
limited in scope or do not qualify for practical applications.
In 2004, Bolm et al. summarized the achievements in iron
catalysis until that time.[6] Since then, a number of impressive
examples have demonstrated the increased potential of iron
catalysis in the field of reduction, oxidation, and coupling
reactions.[7,8] However, to the best of our knowledge, there are
no modern examples of iron-catalyzed carbonylation reac-
tions known,[9] even though such reactions would allow for the
most efficient way to prepare carboxylic acid derivatives.[10]
Clearly, the main problem of such catalytic reactions is the
formation of stable iron–carbonyl complexes, which are
kinetically relatively inert. To achieve catalytic carbonyla-
tions based on iron, we started to investigate the reaction of
alkynes with carbon monoxide and different nucleophiles.
Herein, we report the first iron-catalyzed synthesis of
succinimides by carbonylation of different terminal and
internal alkynes with ammonia or amines to give good
selectivity and high activity. This new catalytic reaction is
based on the double carbonylation of alkynes and intra-
molecular nucleophilic attack.
Initially, the carbonylation of 3-hexyne with ammonia was
investigated as a model system. First attempts were per-
formed with and without the use of a metal. Such blank tests
are important when using high pressure equipment in order to
exclude a possible contamination of the autoclave by previous
reactions that were carried out in the presence of precious
metal catalysts. As shown in Table 1, entry 1 no activity was
seen without iron present.
In contrast, when 10 mol% of ironpentacarbonyl
[Fe(CO)5] was used at a CO pressure of 20 bar and 1208C,
Table 1: Iron-catalyzed carbonylation of 3-hexyne: catalysts and
ligands.[a]
Entry
c(Cat.)
[mol%]
Ligand
(Fe/L 1:2)
p(CO)
[bar]
Conv.
[%][b]
Yield
[%][b]
1
–
10
10
10
5
5
2
2
2
2
1
1
0.5
0.5
0.5
0.5
0.5
(tBu)2P(nBu)
–
(tBu)2P(nBu)
PPh3
–
–
–
–
–
–
–
–
–
–
–
–
–
50
50
50
50
50
50
50
25
20
10
20
20
20
20
20
20
20
0
97
46
20
85
79
60
79
100
96
95
19
79
94
93
32
94
0
96
26
15
79
66
40
79
93 (84)
92
92
14
74
85
87
18
36
2[c]
3[c]
4[c]
5[c]
6
7
8
9
10
11
12[d]
13
14[e]
15[f]
16[g]
17[h]
[*] K. M. Driller, Dr. H. Klein, Dr. R. Jackstell, Prof. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
Fax: (+49)381-1281-51113
E-mail: matthias.beller@catalysis.de
Homepage: http://www.catalysis.de
[**] This work was funded by the State of Mecklenburg-Western
Pomerania, the BMBF (Bundesministerium fꢀr Bildung und
Forschung), the Deutsche Forschungsgemeinschaft (Graduierten-
kolleg 1213 and Leibniz Prize). We thank Dr. W. Baumann, Dr. C.
Fischer, S. Buchholz, S. Schareina, and K. Mevius for their excellent
technical and analytical support.
[a] Reaction conditions: 20 mL of THF, 10 mmol of 3-hexyne, Fe
([Fe3(CO)12]), 5 g of NH3, 1208C, 16 h. [b] Determined by GC analysis
with bis(2-methoxyethyl)ether as the internal standard. Yield of isolated
product in parenthesis. [c] Fe(CO)5 as catalyst. [d] T=1008C. [e] T=
1408C. [f] Reaction with 10 g of NH3. [g] Reaction with 2 g of NH3.
[h] Reaction with toluene as solvent.
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almost quantitative conversion along with excellent yield
[Fe2(CO)8] species, which on further reaction with alkynes
leads to complexes 1 or 2. In the presence of an excess amount
of amine the corresponding cyclic imides 6 are obtained via
intermediates 3–5. The order of adding the reagents is
significant. Notably, when the amine is added to the catalyst
solution before the alkyne the yield increases by about 10%.
We assume that double carbonylation and not a stepwise
reaction via acryl amide is responsible because the product
yield decreases upon the addition of acryl amide to the model
system. Obviously, ironpentacarbonyl shows a completely
different reaction behavior compared to [Co2(CO)8], which
reacts with acryl amides to give the corresponding succini-
mides.[13]
Next, the scope of the catalyst system was demonstrated in
the carbonylation of various simple alkynes, including termi-
nal and internal alkynes (Table 2). Terminal alkynes such as
phenylacetylene and 1-hexyne showed lower reactivity com-
pared to 3-hexyne (Table 2, compare entry 1 with entries 2
and 5). However, when the reaction mixture was more diluted
(96%) and selectivity was obtained without any ligand
present (Table 1, entry 2). The addition of basic alkylphos-
phine or triphenylphosphine both significantly decreased the
activity of the catalyst (Table 1, entries 3 and 4). Therefore,
we used no ligand in the following experiments. Next,
different sources of iron were used. Beside ironpentacar-
bonyl, triirondodecacarbonyl [Fe3(CO)12] was used as a
catalyst precursor (Table 1, entries 6–17), which is less toxic
and easier to handle as it is a solid.
The CO pressure had an important influence on the
product yield (Table 1, entries 7–10): When using a CO
pressure of 50 bar only 40% yield of 3,4-diethylsuccinimide
was observed, while the yield increased up to 93% when a CO
pressure of 20 bar was used. Apparently, the metal centre
becomes inaccessible for the substrate as a result of the
increased CO pressure. A further lowering of the pressure led
to decreased yields.
Notably, at a CO pressure of 20 bar the iron concentration
can be as low as 0.5 mol% to still afford good yields (74–
84%) and high selectivity (Table 1, entries 13–15). In addi-
tion, the reaction temperature has a major influence on the
catalysis. At 1008C (Table 1, entry 12) the yield was negli-
gible, whereas at 1208C (Table 1, entry 11) the yield increased
to 92%.
With respect to the mechanism, we believe that our
catalytic reaction proceeds in a similar way to the stoichio-
metric studies reported by Periasamy et al., who worked
intensively on the carbonylation of alkynes.[11,12] The forma-
tion of the cyclic imides can be tentatively explained by the
sequence of reactions and intermediates shown in Scheme 1.
According to Periasamy et al. the amine reacts with
[Fe3(CO)12] to form an “amine–[Fe(CO)4]” and an
Table 2: Carbonylation of various substituted alkynes with ammonia.[a]
Entry Alkyne
Succinimide
Conv. [%] Yield [%][b]
1[c]
1
2
3
100
100
100
84 (93)
68 (79)
68
2[d]
3[d]
4[d]
4
5
100
100
83
5[d]
– (92)
6[d]
6
100
55 (86)
7[d]
7
8
100
100
37 (50)
82 (98)
8
[a] Reaction conditions: 20 mL of THF, 10 mmol of alkyne, 10 mol% of Fe
([Fe3(CO)12]), 5 g of NH3, CO pressure of 20 bar, 1208C, 16 h. [b] Yield of
isolated product. Yield determined by GC analysis, using isooctane as the
internal standard, in parenthesis. [c] Reaction with 2 mol% of Fe. [d] Reac-
tion with 2 mmol of alkyne.
Scheme 1. Proposed mechanism for the iron-catalyzed carbonylation of
alkynes.
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Angewandte
Chemie
in the presence of a higher iron catalyst concentration
products 1–8 were obtained in good to excellent yields (50–
98%). Both symmetrical and nonsymmetrical aliphatic-sub-
stituted (Table 2, entries 1–3) as well as cyclic aliphatic-
substituted succinimides (Table 2, entry 4) were successfully
synthesized. Also, the preparation of aromatic-substituted
succinimides proceeded smoothly in good to very good yields
(Table 2, entries 5–8).
When comparing the reactions of substituted phenyl-
acetylenes it is evident that electron-donating substituents
(Table 2, entry 6) seem to have no influence on the product
yield, whereas electron-withdrawing substituents like the CF3
group (Table 2, entry 7) led to lower yields. This observation
might be explained by the lower nucleophilicity of acceptor-
substituted alkynes. The corresponding symmetrical aromatic
derivative 3,4-diphenylsuccinimide was obtained almost
quantitatively in 98% yield (Table 2, entry 8).
Notably, the concentration of the nucleophilic primary
amines was lower compared to the reactions with ammonia.
In most cases, the corresponding N-substituted succini-
mides were obtained in good to very good yields (Table 3).
Interestingly, when diphenylacetylene was the substrate that
was treated with various amines, the reaction gave N-
substituted maleinimides. This result can be explained by
the facile aromatization of this fully conjugated system
(Table 3, entries 7 and 8).
In conclusion, we have developed a convenient one-pot
method for the synthesis of various substituted succini-
mides.[14] By starting from commercially available amines
(or ammonia) and alkynes a range of interesting succinimides
were obtained selectively in the presence of catalytic amounts
of either [Fe(CO)5] or [Fe3(CO)12]. For this novel environ-
mentally friendly reaction, no expensive catalyst was
required. Currently, we are expanding this chemistry to the
monocarbonylation of alkynes.
Finally, we investigated the use of various amines
(Table 3). Thus, 3-hexyne was carbonylated in the presence
of different amines under the optimized reaction conditions.
Experimental Section
General procedure: [Fe(CO)5] or [Fe3(CO)12] was dissolved in THF
under an argon atmosphere in a 50 mL schlenk flask. The alkyne and
amine were added to this solution before being transferred into an
autoclave. When ammonia was required, it was condensed from a
small bomb into the autoclave. Afterwards the autoclave was
pressurized with carbon monoxide and heated to 1208C. The reaction
was carried out for 16 h before the reaction mixture was cooled to
room temperature. The pressure was then released and isooctane
(internal standard) was subsequently added to the mixture. After
removal of the solvent in vacuo, the crude succinimide product was
purified by column chromatography on silica gel (heptane/ethyl
acetate 10:1!1:1). The yield was measured by GC analysis.
Table 3: Reaction of various substituted alkynes with different amines.[a]
Entry Amine
Succinimide
Conv. [%] Yield [%][b]
1[c]
ammonia
1
9
100
100
84 (93)
56 (63)
44 (48)
79
2
cyclohexylamine
pentylamine
Synthesis of 3,4-diethylsuccinimide (1): Fe3(CO)12 (0.07 mmol,
35 mg, 2 mol% Fe) was dissolved in THF (20 mL) under an argon
atmosphere in an 50 mL schlenk flask before 3-hexyne (10 mmol,
1.15 mL) was added and the mixture was stirred. The solution was
transferred into a 100 mL Parr autoclave, then ammonia (5 g) was
condensed into the ice-cooled autoclave. Afterwards the autoclave
was pressurized with carbon monoxide (20 bar) and heated to 1208C
for 16 h. The reaction mixture was then cooled to room temperature,
the pressure was then released, and isooctane (0.5 mL, internal
standard) was added to the mixture. After removal of the solvent
in vacuo, the crude product was purified by column chromatography
on silica gel (heptane/ethyl acetate 10:1!1:1) to afford 1 in 84% yield
3
10 82
11 95
12 100
4
isopropylamine
phenethylamine
5
88
1
as a colorless solid. H NMR (300 MHz, CDCl3): d = 7.93 (brs, 1H,
6
benzylamine
13 100
14 100
71
NH), 2.54–2.48 (m, 2H, CH), 1.93–1.65 (m, 4H, CH2), 1.02 ppm (t,
3JCH
= 7.5 Hz, 6H, CH3). 13C NMR (175 MHz, CDCl3): d = 179.3
2;CH2
(s, 2 ꢀ CO), 47.5 (s, 2 ꢀ CH), 24.1 (s, 2 ꢀ CH2), 10.9 ppm (s, 2 ꢀ CH3).
MS (GC-MS): 155 (14), 127 (100), 112 (26), 99 (26), 98 (76), 84 (11), 69
(21), 56 (22), 55 (46), 42 (20), 41 (24), 39 (19). HRMS (EI): calcd for
7[d,e] cyclohexylamine
60 (92)
~
C8H13O2N1: 155.09408; found: 155.094054. IR (ATR): n = 3177 (m),
3067 (m), 2964 (m), 2941 (m), 2909 (m), 2879 (m), 2758 (w), 1773 (w),
1693 (s), 1459 (m), 1436 (w), 1385 (m), 1361 (m), 1335 (m), 1313 (m),
1258 (w), 1227 (w), 1183 (s), 11232 (w), 1077 (m), 1053 (w), 1036 (w),
953 (m), 884 (m), 830 (m), 786 (m), 738 (m), 674 cmꢀ1 (m).
8[e]
benzylamine
15 71
48 (66)
Received: April 17, 2009
Published online: July 9, 2009
[a] Reaction conditions: 20 mL of THF, 10 mmol of 3-hexyne, 2 mol% of Fe
([Fe3(CO)12]), 13 equiv of amine, CO pressure of 20 bar, 1208C, 16 h.
[b] ] Yield of isolated product. Yield determined by GC analysis, using
isooctane as the internal standard, in parenthesis. [c] Reaction with 5 g of
NH3. [d] Reaction with 10 mol% of Fe. [e] Reaction with 10 mmol of
diphenylacetylene.
Keywords: carbonylation · homogenous catalysis · iron ·
.
succinimides
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Communications
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6044 www.angewandte.org
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