.
Angewandte
Communications
In the search for a specific catalyst and the optimum
experimental conditions for this challenging cyclization, we
initially used ruthenium, rhodium, and platinum catalysts with
N-(2-ethynylphenethyl)propane-1-amine (1a) as a model
substrate (Table 1). We began with the complex [CpRuCl-
reactions.[15] Five years ago, we showed that the complex
[CpOs(py)3]PF6 (3) is a more efficient catalyst than tungsten,
ruthenium, and rhodium complexes for the regioselective 7-
endo heterocyclization of aromatic alkynols to give benzox-
epines.[16] Beller and co-workers recently reported a highly
regioselective and general osmium-
Table 1: Optimization of the reaction.[a]
mediated hydroformylation of ole-
fins to afford aldehydes.[17] These
reactions prompted us to employ
osmium complexes as catalysts, in
view of the low efficiency of the
tested ruthenium complexes. Grat-
ifyingly, when the cyclization of 1a
Entry
Catalyst
Solvent
Yield [%][b]
was performed in the presence of
a catalytic amount of complex 3, the
3-benzazepine 2a was formed in
fairly good yield (Table 1, entry 10).
Similar results were observed with
the more electron rich catalyst
1
2
3
4
5
6
7
8
9
[CpRuCl(PPh3)2]
[Cp*RuCl(PPh3)2]
[CpRuCl(PPh3)2]
[CpRuCl(PPh3)2]
[CpRuCl(PPh3)2]
pyridine
pyridine
toluene
toluene/pyridine (1 equiv)
toluene/2-picoline (1 equiv)
pyridine
DMF
pyridine
DCE
pyridine
pyridine
24
20
–
20
13
5
[CpRu(py)3]PF6
[CpRu(CH3CN)3]PF6/ligand[c]
[{Rh(cod)Cl}2]/(4-FC6H4)3P
PtCl2
–
[d]
[CpOs(CH3CN)2(PiPr3)]PF6
(4;
–
[e]
Table 1, entry 11). Hence, the reac-
tion conditions shown in entry 10 of
Table 1 were chosen for subsequent
examination of the scope of this
transformation.
We first examined the electronic
effect of substituents, which are
typically important for dopaminer-
gic properties, on the efficiency of
the method. The heterocyclization
generally proceeded in fairly good
–
10
11
[CpOs(py)3]PF6 (3)
[CpOs(CH3CN)2(PiPr3)]PF6 (4)
57 (51)[f]
52
[a] Typical reaction conditions: 908C, 24 h, [1a]=0.05m. [b] The yield was calculated by 1H NMR
spectroscopy by using trimethoxybenzene as an internal standard. [c] 5,5’-Bis(trifluoromethyl)-2,2’-
bipyridine was used as a ligand. [d] Starting material was recovered. [e] A complex mixture was obtained.
[f] The yield of the isolated product is given in parenthesis. cod=1,5-cyclooctadiene, Cp*=1,2,3,4,5-
pentamethylcyclopentadienyl, DCE=1,2-dichloroethene, DMF=N,N-dimethylformamide, py=pyri-
dine.
(PPh3)2], which was found be the optimal catalyst for the 5-
and 6-endo cyclization of aromatic homo- and bis-homoprop-
argylic amines and amides to give indoles, dihydroisoquino-
lines, and dihydroquinolines.[3c] Encouragingly, the regiose-
lective 7-endo cyclization of 1a in pyridine occurred to give
the desired 3-benzazepine 2a, albeit in low yield (Table 1,
entry 1). A similar result was found with the bulkier and more
electron rich catalyst [Cp*RuCl(PPh3)2] (Table 1, entry 2).
The presence of pyridine is mandatory; its removal was
detrimental for the reaction (Table 1, entry 3), even though
a stoichiometric amount was sufficient (entry 4). The reaction
yield decreased when the bulkier derivative 2-picoline was
used (Table 1, entry 5), thus showing the importance of
pyridine as both a base and a ligand.[11] Modification of the
electronic nature of the catalyst by using the ruthenium salt
[CpRu(py)3]PF6 or the combination [CpRu(CH3CN)3]PF6/
bipyridine, recently used for the anti-Markovnikov hydration
of alkynes,[12] were detrimental to the reaction (Table 1,
entries 6 and 7). Finally, reactions performed with [{RhCl-
(cod)}2]/(4-FC6H4)3P (Table 1, entry 8) and PtCl2 (entry 9)
were unsuccessful.
yield with monosubstituted electron-rich and electron-poor
substrates (with a substituent para or meta to the alkyne) to
give 3-benzazepines 2b–e (Scheme 2). To our delight, the
dialkoxy-substituted derivatives 1 f–h smoothly and cleanly
underwent the 7-endo heterocyclization to give the corre-
sponding 3-benzazepines 2 f–h in good to excellent yield. The
higher yields as compared to those observed for the mono-
alkoxy derivatives are most likely due to the higher stability of
the products under the reaction conditions.[18] By contrast, the
less electron rich dimethyl phenethylamine 1i was converted
into the dialkyl-substituted 3-benzazepine 2i in moderate
yield.
We subsequently evaluated the influence of different
substituents on the amine to favor future manipulation of the
3-benzazepines. Thus, whereas N-benzyl derivatives 1j and 1k
of the parent phenethylamine or a dimethoxy analogue gave
the corresponding 3-benzazepines 2j,k in moderate yield, the
more electron rich N-(3,4-dimethoxy)benzyl or N-(3,4-dime-
thoxy)phenethyl derivatives 1l and 1m of the parent phen-
ethylamine underwent smooth cyclization to the correspond-
ing 3-benzazepines 2l,m in fairly good yield. Phenethylamines
1n–p bearing bulkier secondary N-alkyl substituents also
cyclized to the corresponding 3-benzazepines 2n–p, although
in low to moderate yield.
Osmium has received little attention in catalysis, although
its stoichiometric chemistry is very rich.[13] Traditionally, it has
been used to stabilize models of reactive intermediates
proposed for reactions catalyzed by ruthenium and other
metals.[14] However, recent findings have demonstrated that it
is a promising alternative to classical metal catalysts, in
particular for promoting some environmentally friendly
Pyridine plays a major role in the catalysis. To isolate
some reaction intermediates from which we could obtain
information about the reaction mechanism, we decided to
study the stoichiometric reaction of the phosphine catalyst 4
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 13357 –13361
álvarez-Pérez, Andrea
