Switching from dimerization to cyclotrimerization selectivity by FeCl 3 in the Y[N(TMS)2]3-catalyzed transformation of terminal alkynes: A new strategy for controlling the selectivity of organolanthanide-based catalysis

Article abstract of DOI:10.1021/om100402h

Y[N(TMS)₂]₃/FeCl₃ has been found to be an efficient bimetallic catalyst system for the cyclotrimerization of terminal alkynes, which cannot be achieved by either trivalent iron or trivalent lanthanide catalysts. Furthermore, this reaction also occurs efficiently in the presence of Fe[N(TMS)₂]₃ and YCl₃. Both aromatic and aliphatic alkynes are compatible with this catalytic system. It is postulated that the catalytic cyclotrimerization proceeds through a tandem intermolecular diinsertion of alkynes into the yttrium-alkynyl bond and intramolecular electrophilic addition of a π-coordinated alkyne moiety, and the π-coordination of Fe³⁺ to alkyne may play an important role in controlling the insertion degree of advancement and selectivity. The observed catalytic reaction is sharply in contrast with the cyclotrimerization of alkynes, known to proceed through a typical metallacyclopentadiene intermediate.

Full text of DOI:10.1021/om100402h

3530 Organometallics 2010, 29, 3530–3534
DOI: 10.1021/om100402h
Switching from Dimerization to Cyclotrimerization Selectivity by FeCl3 in
the Y[N(TMS)2]3-Catalyzed Transformation of Terminal Alkynes: A New
Strategy for Controlling the Selectivity of Organolanthanide-Based Catalysis
Xiuli Bu,† Zhengxing Zhang,† and Xigeng Zhou*,†,‡
†Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials,
Fudan University, Shanghai 200433, People’s Republic of China, and ‡State Key Laboratory of
Organometallic Chemistry, Shanghai 200032, People’s Republic of China
Received May 1, 2010
Y[N(TMS)2]3/FeCl3 has been found to be an efficient bimetallic catalyst system for the cyclotrimer-
ization of terminal alkynes, which cannot be achieved by either trivalent iron or trivalent lanthanide
catalysts. Furthermore, this reaction also occurs efficiently in the presence of Fe[N(TMS)2]3 and YCl3.
Both aromatic and aliphatic alkynes are compatible with this catalytic system. It is postulated that the
catalytic cyclotrimerization proceeds through a tandem intermolecular diinsertion of alkynes into the
yttrium-alkynyl bond and intramolecular electrophilic addition of a π-coordinated alkyne moiety, and
the π-coordination of Fe3þ to alkyne may play an important role in controlling the insertion degree of
advancement and selectivity. The observed catalytic reaction is sharply in contrast with the cyclotrimer-
ization of alkynes, known to proceed through a typical metallacyclopentadiene intermediate.
Introduction
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pubs.acs.org/Organometallics
Published on Web 07/27/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 16, 2010 3531
been used. The major limitation of these processes is that the
metallic catalysts employed are often expensive and/or not
easily available. Meanwhile, most of the catalysts used are
limited to low-valent metal complexes or a mixture of
high-valent transition metal complexes and metal reduc-
tants.4b,8b,11a,12 For a long time, the use of lanthanides was
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The insertion chemistry of organolanthanide complexes is an
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efficient construction of complex cycles through the choice of
appropriate intra- and intermolecular di- or polyinsertion
reactions of organolanthanides as key steps, because of their
high bond-forming efficiency, mild reaction conditions, and
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of terminal alkynes have been investigated extensively, only
dimers and/or oligomers were obtained.16 The major reason can
be attributed to the similar reactivity toward the triple bond
of alkynes between monoinsertion species and diinsertion ones.
If a coordination insertion process is viable for a monoinsertion
intermediate, it usually has a tendency for multiple insertions
to further take place. As a result, less active organolanthanide
catalytic systems preferentially give rise to dimers, whereas the
more active ones lead to the formation of oligomers. We have
recently shownthat organolanthanide complexes can undergo
diinsertion reactions with isocyanates17 and nitriles.18 As part
of a continuing effort in our laboratory toward the develop-
ment of new insertions of organolanthanide compounds and
their applications in organic synthesis,19 we became interested
in the possibility of controlling the chemo- and regioselective
triinsertion of alkynes into the lanthanide-carbon bond and
thus developing a new method for synthesis of trisubstituted
benzenes from alkynes.
It is well known that cooperative or successive interaction
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nide-acetylide bond and subsequent cyclization by the
additional π-coordination of transition metal Lewis acids
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lanthanides and transition metals might lead to the develop-
ment of catalyst design for cyclotrimerization of alkynes. As
a preliminary testing of the concept, we herein report an
unprecedented Y(III)/Fe(III) bimetallic catalyst system for
cyclotrimerization of terminal alkynes, in which the Fe3þ ion
most probably acts as a π-coordinative Lewis acid. The
present work demonstrates that completely different beha-
vior in the Ln[N(TMS)2]3-catalyzed transformation of term-
inal alkynes can be expected depending on the presence of
trivalent iron salts and opens the way toward new develop-
ments in catalytic organolanthanide chemistry.
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Results and Discussion
Readily available homoleptic bis(trimethylsilyl)amides of
yttrium and lanthanide metals are currently attracting consider-
able attention as highly efficient catalysts for various organic
transformations. In the past decade, systematic exploration of
Ln[N(TMS)2]3 chemistry has offered a wide range of useful
methods for organic synthesis. Particular emphasis has been fo-
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hydrogen bonds. Successful transformations now include the
Tishchenko reaction,21 cross-Aldol reactions,22 coupling reac-
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dimerization of terminal alkynes,16 guanylation of amines,24
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3532 Organometallics, Vol. 29, No. 16, 2010
Bu et al.
Table 2. Cyclotrimerization of Various Terminal Alkynes
Table 1. Optimization of the Cyclotrimerizationa
a
Catalyzed by Y[N(TMS)2]3/FeCl3
Ln
entry (mol %)
cocatalyst
(mol %)
yield
T (°C) time (h) (%)b 2a:3ac
isolated
yield (%)
entry
R
2:3
1
Y(10)
FeCl3(10)
100
100
100
100
100
100
100
70
70
50
50
50
50
50
50
25
25
50
50
24
14
24
24
24
24
24
24
24
24
24
12
24
24
24
24
48
24
24
99
0
98:2
1
2
3
4
5
6
7
8
Ph (1a)
99
98
94
78
80
74
98
64
60
68
62
98:2c
97:3d
99:1c
96:4c
97:3b
92:8b
88:12b
53:47c
52:48c
52:48c
95:5b
2
FeCl3(10)
FeCl3(5)
FeCl3(2.5)
p-ClC6H4 (1b)
p-F, m-MeC6H3 (1c)
p-MeC6H4 (1d)
p-(C5H11)C6H4 (1e)
p-MeOC6H4 (1f)
p-tBuC6H4OCH2 (1g)
n-butyl (1h)
n-hexyl (1i)
cyclohexyl (1k)
Me3Si (1j)
3
4
Y(10)
Y(10)
97
93
36
66
79
90
94
99
21
91
89
20
58
80
99
0
98:2
98:2
96:4
98:2
5
6
La(10) FeCl3(2.5)
Sm(10) FeCl3(2.5)
7
8
9
Y(5)
Y(10)
Y(5)
Y(5)
Y(1)
Y(5)
Y(5)
Y(5)
Y(5)
Y(5)
Y(5)
Y(5)
Y(5)
Y(5)
FeCl3(10)
FeCl3(10)
FeCl3(5)
FeCl3(5)
FeCl3(1)
FeCl3(5)
FeCl3 (5)
FeCl3(5)
Fe(acac)3(5)
FeCl3(5)
FeCl3(5)
InCl3(5)
98:2
98:2
9
10
11
10
11
12
13d
14e
15
16
17
18e
19f
20g
21
95:5
93:7
90:10
a Conditions: 5 mL of toluene; 50 °C; 24 h, 0.8 mmol of alkynes, 5 mol
% Y[N(TMS)2]3, and 5 mol % FeCl3. b Determined by 1H NMR.
c Determined by GC. d Determined by HPLC.
Scheme 1. Cyclotrimerization of 1,6-Heptadiyne
ZnCl2(5)
0
0
Fe[N(TMS)2]3 (5)
50
24
0
a Reaction conditions: 5 mL of toluene; phenylacetylene (0.2 mL, 1.82
mmol). b Isolated yield. c Determined by GC. d DCE was used as solvent.
e THFwas used as solvent. f Only oligomers were obtained. g Only linear
dimers were obtained; see ref 16b.
Among rare-earth metals tested, yttrium afforded the best
result, giving 99% combined yield (Table 1, entries 4-6).
These results demonstrate that both the lanthanide ion and the
iron ion are essential, and their cooperative effects play a key
role in the catalytic cyclotrimerization. Toluene was the best
solvent for this reaction (Table 1, entries 10, 13, and 14). The
ratio of Y[N(TMS)2]3 and FeCl3 was found to be important
for the reaction, and the best result was achieved in the molar
ratio of 1:1 (Table 1, entries 1 and 10). Notably, the cyclo-
trimerization reaction also proceeded quite smoothly at room
temperature, although longer reaction time was required
(Table 1, entry 17). When the catalysts were reduced to
1 mol %, only 21% yield was obtained (Table 1, entry 11).
Next, we explored the cyclotrimerization of various substi-
tuted terminal alkynes under optimized conditions, and the
results are summarized in Table 2. The reactivity of alkynes is
controlled by the steric and electronic properties of the sub-
stituents. Aromatic acetylenes with electron-withdrawing sub-
stituents, such as p-chlorophenylacetylene and 4-fluoro-
3-(methylphenyl)acetylene, reacted smoothly to afford the
corresponding 1,2,4-trisubstituted benzenes in high yield and
with excellent regioselectivity (Table 2, entries 2 and 3). At the
same time, electron-donating groups, like alkyls and methoxyl
in the para position of benzene rings, seem to negatively affect
the yield, but the regioselectivity remained essentially constant
(Table 2, entries 4-6). Propargyl ether also worked well under
this condition, yielding the corresponding product in almost
quantitative yield with good selectivity (Table 2, entry 7).
Remarkably, this heterobimetallic catalyst system also worked
for aliphatic alkynes, albeit with low regioselectivities. The
reaction of substrates 1h-k afforded a nearly 1:1 mixture of 2
and 3in moderate combined yields (Table 2, entries 8-10). The
absence of regioselectivity is presumably due to steric and
unsaturated carbon-carbon bonds, and so on. Thus, with
the aim of establishing whether some form of transition metal
additives would govern the selectivity of organolanthanide-cata-
lyzed reaction, we decided to use the Ln[N(TMS)2]3-catalyzed
transformation of terminal alkynes as a model reaction, since it
has proven to be impossible to form trisubstituted benzenes.
Considering that iron salts are readily available, inexpensive,
and environmentally benign,28 initial investigations were carried
out in the presence of various iron salts in toluene to obtain
the optimum reaction conditions. The results are summarized
in Table 1.
In contrast to the previously reported Y[N(TMS)2]3-cata-
lyzed dimerization of phenylacetylene (1a),16b treatment of 1a
with Y[N(TMS)2]3 in the presence of a catalytic amount of iron
salts in toluene gave the unexpected cyclotrimerization pro-
ducts. Among the Lewis acids screened, FeCl3 gave the best
result (Table 1, entry 1). Both yield and selectivity dropped
significantly when Fe(acac)3 was used instead of FeCl3 (Table 1,
entry 15). Meanwhile, no cyclization product was obtained
when InCl3 and ZnCl2 were used as an additive (Table 1, entries
18 and 19). Additionally, FeCl3 and Fe[N(TMS)2]3 by them-
selves were ineffective for this reaction (Table 1, entries 2 and 21).
€
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Article
Organometallics, Vol. 29, No. 16, 2010 3533
Scheme 2
Scheme 3. Cross-Cyclotrimerization of 1a with Diphenylacetylene
electronic reasons. Consequently, excellent regioselectivity was
obtained when more sterically bulky trimethylsilylacetylene
was used (Table 2, entry 11).
When 1,6-heptadiyne was used under the optimized reac-
tion conditions, the double cyclization product (2l) was
obtained in 72% yield with excellent chemo- and regioselec-
tivity (Scheme 1).
products in addition to 2a and 3a. However, treatment of a
mixture of 1a and 1l with Y[N(TMS)2]3/FeCl3 gave only 2a and
2l without the isolation of the cross-cyclotrimerization product.
This could be a proof for our hypothesis.
Based on the results described above, a plausible reaction
pathway for Y[N(TMS)2]3/FeCl3 cocatalyzed cyclotrimeriza-
tion of terminal alkynes is shown in Scheme 4. Terminal alkyne
C-H bond activation leads to the formation of lanthanide
acetylides (A) together with liberation of amine. Coordination
and subsequent insertion of one alkyne molecule into the
Ln-C bond of A gives key alkynyl-substituted alkenyl lan-
thanide intermediates (B and B0).16b A second alkyne mole-
cule insertion of B and B0 gives C and C0, respectively. Sub-
sequently, the intramolecular nucleophilic attack of alkenyl to
the Fe-coordinated alkyne moiety would lead to the formation
of aryliron species.29 Finally, protonation of aryl iron com-
plexes with alkyne followed by transmetalation affords the
cyclotrimerization products (2 and 3) and regenerates the
lanthanide acetylides (A) and FeCl3.
Consistent with this, the coordination of Fe3þ to the CtC
bond should play an important role in adjusting the selec-
tivity. The presence of a coordinative iron ion should reduce
the basicity of the alkynyl-substituted alkenyl ligand and
thus prevent the occurrence of protonation of alkynyl-
substituted alkenyl lanthanide intermediates with terminal
alkynes, instead, which would be favorable to the insertion of
the second alkyne molecule into the resulting yttrium-
alkenyl bond. Moreover, the iron coordination also en-
hances the electrophilic reactivity of the related CtC group
and promotes the occurrence of the cyclization in the cata-
lytic cycle. If FeCl3 is absent, the alkynyl-substituted alkenyl
lanthanide complexes B and B0 would undergo protonation
rather than insertion of the second terminal alkyne to give
the enynes I and II, as observed previously.16b
Iron-mediated cyclotrimerization of alkynes has been
known for a long time, but such reactions proceed through
a metallacyclopentadiene intermediate. In all cases the iron
must be in a low-valent oxidation state.8 If trivalent iron salts
are used as precatalysts, it should require the presence of a
strong reductant. In any case, no cyclotrimerization product
could be detected when only one of the two metals (Fe3þ or
Y3þ) was present. Furthermore, treatment of a suspension of
YCl3 in toluene with (TMS)2NLi followed by reacting with
excessive 1a did not give the cyclotrimerization product too.
Obviously, in the present case the cyclotrimerization is likely to
operate through another mechanistic pathway involving the
concerted effect between the rare-earth metal complex and the
iron salt. To gain a better understanding of how the cyclotri-
merization occurs under these conditions, we further examined
the reaction of 1a withFe[N(TMS)2]3 and YCl3. Interestingly, the
combination of Fe[N(TMS)2]3 (5 mol %) and YCl3 (5 mol %)
could also catalyze cyclotrimerization of 1a, with a ratio
of 97:3 of 2a and 3a in 97% total yield (Scheme 2). Moreover,
the combination of Fe[N(TMS)2]3 and Y[N(TMS)2]3 could
also catalyze cyclotrimerization of 1a, giving the cyclization
product in 99% combined yield with a ratio of 2a:3a of 95:5
(Scheme 2). These results indicate that both trivalent iron and
yttrium are an integral part of the whole catalytic system.
It is noteworthy that the combination of FeCl3 and YCl3 was
inefficient for the catalytic cyclotrimerization of terminal al-
kynes. Moreover, internal alkynes such as 1-phenyl-1-propyne
could not form benzene derivatives under the same conditions.
These results indicate that the yttrium alkynyl might be the
active species in the catalytic cyclotrimerization. In order to
obtain further insight into the cyclization process, we conducted
cross-cyclotrimerization of 1a with 4 equiv of diphenylacetylene
(Scheme 3). To our delight, we got the cross-cyclotrimerization
In conclusion, the yttrium(III) and iron(III)-cocatalyzed
cyclotrimerization of terminal alkynes exhibits a fascinating
(29) (a) Huang, W.; Zheng, P. Z.; Zhang, Z. X.; Liu, R. T.; Chen,
Z. X.; Zhou, X. G. J. Org. Chem. 2008, 73, 6845–6848. (b) Li, R. S.; Wang,
S. R.; Lu, W. J. Org. Lett. 2007, 9, 2219–2222.

3534 Organometallics, Vol. 29, No. 16, 2010
Scheme 4. Proposed Mechanism for Y[N(TMS)2]3/FeCl3 Cocatalyzed Cyclotrimerization of Terminal Alkynes
Bu et al.
variation in selectivity compared to the sole organolantha-
nide(III)-catalyzed dimerization of terminal alkynes. To the
best of our knowledge, the above-described cooperative
effect in catalytic cyclotrimerization is an unprecedented
phenomenon, demonstrating that the introduction of a
transition metal additive into the trivalent lanthanide bis-
(trimethylsilyl)amide system has a high potential to enhance
catalytic activities as well as to change the catalytic selec-
tivity, leading to the occurrence of new reactions that cannot
be achieved by the corresponding monometallic catalyst
systems. The present work opens the way toward new
developments in catalytic organolanthanide chemistry.
(m, 3H), 7.10-7.01 (m, 7H), 2.66-2.54 (m, 6H), 1.67-1.55 (m,
6H), 1.38-1.25 (m, 12H), 0.92-0.87 (m, 9H). 13C NMR
(CDCl3, 100 MHz): δ 142.29, 141.21, 141.13, 141.02, 140.15,
139.37, 139.09, 138.69, 138.17, 131.13, 129.88, 129.84, 129.34,
129.01, 128.99, 128.05, 128.01, 127.07, 125.82, 35.76, 35.68,
31.73, 31.64, 31.62, 31.33, 31.15, 31.14, 22.73, 22.70, 14.22,
14.20. HRMS-ESI: calcd for C39H48 516.3756, found 516.3758.
1,2,4-Tris(4-tert-butylphenoxymethyl)benzene (2g). 1H NMR
(CDCl3, 400 MHz): δ 7.66 (s, 1H), 7.59 (d, J = 7.4 Hz, 1H), 7.49
(d, J = 7.4 Hz), 7.38-7.35 (m, 6H), 6.99-6.96 (m, 6H), 5.21 (s,
4H), 5.12 (s, 2H), 1.37 (s, 27H). 13C NMR (CDCl3, 100 MHz): δ
156.65, 156.56, 156.53, 143.92, 143.88, 143.83, 143.79, 138.25,
137.64, 135.78, 135.18, 129.28, 128.04, 127.40, 126.40, 114.46,
114.44, 114.43, 69.75, 68.10, 67.89, 34.22, 31.67. HRMS-ESI:
calcd for C39H48O3 564.3603, found 564.3600.
Experimental Section
1,2,4-Tris(cyclohexylphenyl)benzene (2k) and 1,3,5- Tris-
(cyclohexylphenyl)benzene (3k). 1H NMR (CDCl3, 400 MHz)
of the mixture of the two products: δ 7.16 (d, J = 8 Hz, 1H), 7.08
(d, J = 2 Hz, 1H), 7.01 (dd, J = 8.0, 1.6 Hz, 1H), 6.89 (s, 3H),
2.81-2.76 (m, 2H), 2.51-2.44 (m, 4H), 1.91-1.74 (m, 24H),
1.50-1.25 (m, 36H). 13C NMR (CDCl3, 100 MHz) of the mixture
of the two products: δ 147.93, 145.16, 144.63, 142.19, 125.72,
124.60, 123.99, 123.05, 44.96, 44.46, 39.42, 39.15, 34.88, 34.85,
34.73, 34.65, 27.47, 27.46, 27.19, 27.18, 26.52, 26.42, 26.41.
HRMS-ESI: calcd for C24H36 324.2817, found 324.2825.
General Experimental Details. All reactions were carried out
under a nitrogen atmosphere using standard Schlenk techni-
ques. The solvents were refluxed and distilled over sodium
benzophenone ketyl under nitrogen. All substrates were com-
mercially available and purified by standard procedures. 1H
NMR and 13C NMR spectra were recorded on a Bruker 400
MHz using CDCl3 as solvent. GC-MS were obtained on a
Hewlett-Packard 6890/5973 instrument. High-resolution mass
spectra (HRMS) were recorded using ESI ionization sources.
General Procedure for the Cyclotrimerization. To a mixture of
Y[N(TMS)2]3 (23 mg, 0.04 mmol) and FeCl3 (6 mg, 0.04 mmol) in
5 mL of toluene was added 0.8 mmol of alkyne. The mixture was
stirred at 50 °C for 24 h. Then the reaction was quenched with
water, andthe aqueous layer was extractedwith ether(3 ꢀ 10mL)
and then ethyl acetate (3 ꢀ 10 mL). The combined organic layer
was dried over Na2SO4. After filtration and removal of solvents
under vacuum, the crude product was purified with flash chro-
matography using petroleum ether as eluent.
Acknowledgment. We thank the NNSF of China, 973
Program (2009CB825300), Shanghai Science and Tech-
nology Committee (No. 08dj1400100), the Research
Fund for the Doctoral Program of Higher Education of
China, and Shanghai Leading Academic Discipline Pro-
ject for financial support (B108).
1,2,4-Tris(4-amyllphenyl)benzene (2e). 1H NMR (CDCl3, 400
MHz): δ 7.64-7.57 (m, 4H), 7.47 (d, J = 8.4 Hz, 1H), 7.27-7.25
Supporting Information Available: This material is available
free of charge via the Internet at http://pubs.acs.org.