The first cobalt catalyzed [2 + 2 + 2] alkyne cyclotrimerization in aqueous medium at room temperature

Article abstract of DOI:10.1039/b207978j

Chelate complex 1 (5 mol%) was found to catalyze the [2 + 2 + 2] cyclization of terminal alkynes in good yields in a 80/20 mixture of water and ethanol at room temperature without further activation.

Full text of DOI:10.1039/b207978j

The first cobalt catalyzed [2 + 2 + 2] alkyne cyclotrimerization in
aqueous medium at room temperature†
Li Yong and Holger Butenschön*
Institut für Organische Chemie, Universität Hannover, Schneiderberg 1B, D-30167 Hannover, Germany.
E-mail: holger.butenschoen@mbox.oci.uni-hannover.de; Fax: +49/(0)511-762-4616
Received (in Cambridge, UK) 14th August 2002, Accepted 11th October 2002
First published as an Advance Article on the web 28th October 2002
Chelate complex 1 (5 mol%) was found to catalyze the [2 +
2 + 2] cyclization of terminal alkynes in good yields in a
80/20 mixture of water and ethanol at room temperature
without further activation.
sponding vinylidene complexes.27,29 In some cases at higher
temperatures a co-dimerization of alkynes or tert-butylphos-
phaethyne was observed leading to the respective cyclobuta-
diene or diphosphete complexes.21,26,28
Here we report on [2+2+2] cyclization reactions of terminal
alkynes in water/ethanol (80+20) at room temperature using 1 as
a catalyst. While 1 is sensitive to air, the complex is stable in
water. Using 10 mol% of 1 the cyclotrimerization of phenyl-
ethyne was complete after 8 h at room temperature giving
regioisomers 2 and 3 (66+34) in 86% yield. Using 5 mol% of 1
caused a slight decrease in yield to 84%, whereas using only 2
mol% of 1 caused a substantial decrease to 74% (Table 1). Thus,
5 mol% of catalyst 1 are regarded as sufficient.
The transition metal facilitated cyclotrimerization of alkynes
and the co-cyclization of alkynes and alkenes as well as of
alkynes and nitriles leading to arenes, cyclohexadienes, and
pyridine derivatives has been recognized as a valuable tool for
organic synthesis during the last three decades.1–6 For the
cyclization of alkynes and nitriles a number of catalysts have
been used, the most prominent ones being cyclopentadienylco-
balt(
) and palladium(0) complexes.1 Although the reaction has
I
widely been explored, still new catalysts and new reaction
conditions are reported. For example, most recently Sugihara
has shown 1–2 mol% of methylidynetricobalt nonacarbonyl to
catalyze the cyclization of terminal as well as internal alkynes to
the respective benzene derivatives in toluene at reflux.7 In some
newer publications the reaction is reported to take place in
aqueous solutions. Heller and co-workers found that co-
cyclizations of alkynes and nitriles in the presence of cyclo-
pentadienylcobalt( ) cyclooctadiene derivatives as catalysts
I
result in the formation of pyridines in water at room temperature
under irradiation with visible light.8–14 Dinjus and co-workers
as well as Parsons and co-workers reported the reaction to take
place in supercritical water.15,16 More recently Eaton and co-
workers reported thermal alkyne cyclotrimerization and alkyne
nitrile co-cyclization in aqueous solvents at elevated tem-
peratures.17–19 These reactions take place with cyclopentadie-
Table 1 Influence of catalyst amount on the 3+4 ratio and on the yield (R =
Ph).
1 [mol %]
3+4a
Yield [%]
10
5
2
66+34
69+31
75+25
86
84
74
nylcobalt( ) catalysts bearing hydrophilic side chains at the
I
a Determined by GC.
cyclopentadienyl ligand. Many of the applied alkynes also have
hydrophilic functional groups such as hydroxy, ketone, ester,
amine, or carboxylic acid functions. In the cases of pyridine
formation the respective nitriles are hydrophilic. The reactions
were usually performed in 70+30 mixtures of water and
methanol at 85 °C for 24 h. Clearly these reports mark some
progress in the field, as the solvent system applied has obvious
advantages in the light of environmental issues and industrial
waste disposal.
The reaction was tested with a number of other alkynes.
Results are summarized in Table 2.
The results demonstrate that the alkyne cyclotrimerization is
possible using 1 as the catalyst in water/ethanol (80+20) at
ambient temperature with no photochemical activation being
necessary. The reaction works in good yield even with alkynes
lacking hydrophilic functional groups (entries 1, 2, 3, 6, 7). In
all cases the symmetric product 3 prevails over 4, presumably
for steric reasons.
Cyclopentadienyl complexes bearing pendant ligands such as
phosphane moieties are gaining increased attention.20 We have
investigated the chemistry of di-tert-butylphosphanylethylcy-
Experiments using internal instead of terminal alkynes
revealed that the yields are, most likely due to steric inter-
clopentadienylcobalt(
) chelate 1 for some time.21–29 Treatment
I
Table 2 Alkyne cyclotrimerization using 5 mol% of 1 in water/ethanol
(80+20) at 25 °C.30
Entry
2
R
3+4a
Yield [%]
1
2
3
4
5
6
7
8
a
b
c
d
e
f
Ph
n-Bu
t-Bu
HOCH2
EtO2C
Cl(CH2)3
n-Decb
p-Tol
69+31
65+35
73+27
61+39
59+41
76+24
77+23
57+43
84
86
74
89
71
77
91
81
of 1 with alkynes in THF at low temperature gave alkyne
complexes.27 The isolation of the phenylethyne complex
required a temperature below 0 °C; terminal alkynes such as
ethyne and 3,3-dimethyl-1-butyne rearranged to the corre-
g
h
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b2/b207978j/
a Determined by GC. b n-Dec = n-Decyl.
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CHEM. COMMUN., 2002, 2852–2853
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Next, some co-cyclization experiments were performed, in
which 1,7-octadiyne was treated with phenylethyne and with
ethyl propionate. Under the usual reaction conditions30 7 and 8
were formed in 44% and 40% yield, respectively. As the co-
cyclization of alkynes and nitriles has been used for the
synthesis of pyridines, 1,7-octadiyne was then treated with
acetonitrile giving tetrahydroisoquinoline 9 in 64% yield.
A closer examination of the reaction revealed that the
reaction mixture is not homogeneous. Upon stirring after
addition of the alkyne and the catalyst apparently an emulsion is
formed, the reaction presumably taking place in the micelles.
Upon alkyne consumption the formed cyclization product
precipitates from the mixture.
We have shown that cobalt chelate 1 serves as a catalyst for
the alkyne trimerization in water/ethanol (80+20) at room
temperature. The use of this medium has obvious advantages
over usual organic solvents in terms of organic solvent
consumption, waste disposal and safety issues.
This work was kindly supported by the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen Industrie
as well as by the Innovations offensive ‘Biologisch aktive
Naturstoffe: Synthetische Diversität’.
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30 Typical experimental procedure: To a 20 mL Schlenk flask, 16.2 mg
(0.05 mmol) of ethene cobalt complex 1, 102 mg (0.11 ml, 1.00 mmol)
of phenylactylene (2a) and 5 ml of degassed water/ethanol (80+20) was
added under argon. The reaction mixture was stirred at room
temperature (25 °C) for 7 h. Then the reaction mixture was extracted
with petroleum ether (3 3 20 mL). The combined organic layers were
dried (MgSO4), filtered, and concentrated in vacuo. The residue was
purified by flash column chromatography (petroleum ether/ethyl acetate
40+1) and gave 86 mg (28.1 mmol, 84%) of 3a/4a.
Notes and references
1 S. Saito and Y. Yamamoto, Chem. Rev., 2000, 100, 2901.
2 A. J. Fletcher and S. D. R. Christie, J. Chem. Soc., Perkin Trans. 1,
2000, 1657–1668.
3 D. B. Grotjahn, in ‘Transition Metal Alkyne Complexes: Transition
Metal-catalyzed Cyclotrimerization’, ed. E. W. Abel, F. G. A. Stone, G.
Wilkinson and L. S. Hegedus, Oxford, 1995.
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