M. Beller et al.
doles, -pyrroles,[23] and -imidazoles[24] and demonstrated
their applicability in cross-coupling reactions of aryl chlo-
desired succinimides but also minor amounts of the mono-
carbonylation products (Table 1, entries 2, 16). This mono-
carbonylation reaction is more pronounced if primary
amines are used as the nucleophile instead of ammonia, due
to the increased steric bulk of the amine. For example, treat-
ment of 3-alkynylindole 3a with cyclohexylamine gave de-
sired product 5 in 47% yield, but treatment with ammonia
gave the corresponding product 4a in 70% yield. In addi-
tion to 5, the monocarbonylation product (E)-2-(1-benzyl-
1H-indol-3-yl)-N-cyclohexyl-3-phenylacrylamide is obtained
in 47% yield (Scheme 4).
ACHTUNGTRENNUNG
K CHTUNGTRENNUNG
the catalytic system proceeded smoothly in N,N,N’,N’-tetra-
methylethane-1,2-diamine (TMEDA) at 808C. By using dif-
ferent palladium sources (K
[PdCl4]) at comparably low catalyst loading (0.5 mol%), the
2ACHTUNGTNERNUG[PdCl4], PdACHTUNTGRNE(NUGN OAc)2, and Na2-
ACHTUNGTRENNUNG
Sonogashira product is obtained in high yield (80–86%).
Next, this procedure was applied to the Sonogashira reac-
tion of six different aryl and heteroaryl bromides with five
different terminal arylalkynes (Table 1). In all cases, desired
1,2-diarylalkynes 3 were obtained in good to excellent yields
(78–99%; Table 1). Electronic effects of substituents on the
aryl and heteroaryl bromides did not seem to be important
for the reaction. Thus, electron-rich indole, naphthalene,
and benzo[b]thiophene derivatives were successfully cou-
pled with aromatic alkynes (Table 1, entries 1–4, 16–20).
Similarly, the desired products were obtained in excellent
yields in the presence of electron-deficient pyridines and
pyrimidine derivatives (Table 1, entries 5–15). Additionally,
substituents appeared to have no effect on this reaction for
phenylacetylene derivatives. On the other hand, the position
of the substituent slightly influenced the reaction outcome;
generally, ortho-substituted arylalkynes gave slightly lower
yields of the 1,2-diarylalkyne (Table 1, entries 5, 6 and 8, 9).
Next, 1,2-diarylalkynes 3 were subjected to the iron-cata-
lyzed carbonylation with ammonia to generate the corre-
sponding 3,4-diarylsuccinimides 4. After some optimization,
the double-carbonylation reactions were carried out in THF
at 1208C for 20 h in the presence of excess ammonia and
10 mol% [Fe3(CO)12] under CO (20 bar). When 3-alkynyl-
indoles 3a–d were employed, desired succinimides 4a–d
were obtained in moderate to good yields (48–75%; Table 1,
entries 1–4). It is worth noting that in case of N-benzyl-3-
[(2-methoxyphenyl)ethynyl]-indole (3b), the mono-carbon-
Scheme 4. Fe-catalyzed carbonylation with cyclohexylamine.
The stereochemistry of 4b and 5 was unambiguously de-
termined by single-crystal X-ray crystallographic analysis,
which showed that the relative stereochemistry at C3 and
C4 is trans (Figure 1). Based on this observation, the stereo-
chemistry of the other succinimides was established by using
NMR spectroscopy. In general, the vicinal coupling con-
stants between the succinimide methine protons were ob-
served in the range of 5.8–8.6 Hz. This is in agreement with
the NMR spectroscopic data of other reported trans-disub-
stituted succinimides.[13b,26]
Concerning the mechanism of the iron-catalyzed double-
aminocarbonylation reaction we propose the initial forma-
A
R
tion of an ironACTHUNGETRNNU(G carbonyl)–alkyne complex, although the de-
A
E
tails are not yet fully understood. According to Periasamy
et al., who studied stoichiometric reactions of alkynes with
[Fe3(CO)12] in the presence of primary amines in detail, an
amine Fe(CO)4 and a Fe2(CO)8 species were formed, which
on further reaction led to complexes A and B.[27] Nucleophil-
ic attack of ammonia on one of the carbonyl groups in B
gives C. Subsequent intramolecular amidation and reduction
forms the cyclic imide (Scheme 5). Under catalytic condi-
tions, the involvement of bi- or trimetallic complexes cannot
yet be excluded. Notably, if the amine is added before the
alkyne to the catalyst solution, the product yield is increased
by about 10%. To prepare 3,4-diarylmaleimides E from cor-
responding succinimides C and D, we envisioned an oxida-
tive dehydrogenation reaction. Indeed, in the presence of
one equivalent of the known dehydrogenating reagent 2,3-
dichloro-5,6-dicyano-1,4 benzoquinone (DDQ), seven select-
ed succinimides were oxidatively transformed into 6a–g
under mild conditions.[30] As shown in Table 2, 3-aryl-4-indo-
lylsuccinimides 5, 4b, 4d, and 3-aryl-4-naphthylsuccinimide
yield (Table 1, entry 2); 2- and 3-alkynylpyridines 3e–k and
3-alkynylbenzo[b]thiophenes 3q–t gave the corresponding
succinimides in good yield without problems (Table 1, en-
tries 5–11, 17–20). When 2-alkynyl-6-methoxynaphthalene
3p was employed, the carbonylation gave succinimide 4p in
76% yield along with a trace of the monocarbonylation
product, which was detected by GC–MS (Table 1, entry 16).
The carbonylation of 5-alkynylpyrimidines 3l–o gave biolog-
ically interesting succinimides 4l–o (Table 1, entries 12–15).
In general, the substituent pattern of the phenyl ring of
the initially employed alkyne has an influence on the prod-
uct yield. For example, 4-fluorophenyl-substituted alkynes
led to lower yields compared with electron-rich 1,2-diarylal-
kynes, except in the case of 3k (Table 1, entries 11). In the
double-carbonylation reaction of more sterically crowded
1,2-diaryl- or 1-aryl-2-heteroarylalkynes with, for example,
ortho substituents on the aryl moiety, the selectivity of the
carbonylation reaction is affected and affords not only the
9608
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 9606 – 9615