Rhodium N-heterocyclic carbene complexes as effective catalysts for [2+2+2]-cycloaddition reactions

Article abstract of DOI:10.1055/s-0029-1217982

Rhodium complexes of N-heterocyclic carbenes (NHC) [RhCl(cod)(NHC)], [cod = 1,5-cyclooctadiene, NHC = 1,3-diisopropylimidazolin- 2-ylidene, and NHC = 1,3-dimesitylimidazolin- 2-ylidene] are tested for intra- and partially intramolecular [2+2+2]- cycloaddition reactions demonstrating their effectiveness in this kind of process. This is the first use of a rhodium-NHC complex in a [2+2+2]-cycloaddition reaction of three alkynes. ESI-MS has been used to detect oxidative addition intermediates using rhodium NHC as the catalytic system.

Full text of DOI:10.1055/s-0029-1217982

2844
LETTER
Rhodium N-Heterocyclic Carbene Complexes as Effective Catalysts for
[2+2+2]-Cycloaddition Reactions
R
h-NHC
v
C
omplexes
á
a
s
Catalysts
n
for [2+2+2] Cycl
G
Department of Chemistry, University of Girona, Campus de Montilivi, s/n. 17071 Girona, Spain
Fax +34(972)418150; E-mail: anna.roglans@udg.edu
Received 1 July 2009
dehydes and ketones,6 isocyanates,7 nitriles,8 and carbon
dioxide.9 Okamoto et al. described the intramolecular
cyclotrimerization of triynes catalyzed by NHC cobalt
and iron complexes,10 and more recently Aubert, Gandon
Abstract: Rhodium complexes of N-heterocyclic carbenes (NHC)
[RhCl(cod)(NHC)], [cod = 1,5-cyclooctadiene, NHC = 1,3-diiso-
propylimidazolin-2-ylidene, and NHC = 1,3-dimesitylimidazolin-
2-ylidene] are tested for intra- and partially intramolecular [2+2+2]-
cycloaddition reactions demonstrating their effectiveness in this et al. reported a straightforward [2+2+2] cycloaddition of
kind of process. This is the first use of a rhodium-NHC complex in
enediynes mediated by cobalt and an N-heterocyclic car-
bene in the presence of manganese.11
a [2+2+2]-cycloaddition reaction of three alkynes. ESI-MS has
been used to detect oxidative addition intermediates using rhodium
Phosphane ligands, mainly used to stabilize rhodium cat-
alysts in [2+2+2]-cycloaddition reactions, are prone to ox-
idation and so the reactions need to be run in anaerobic
conditions. Furthermore, the corresponding phosphane
oxides formed at the end of the process often hamper
product purification. Therefore, the aim of the present
study was to test the ability of readily available
[RhCl(IPr)(cod)] and [RhCl(IMes)(cod)] complexes to-
wards [2+2+2] carbocyclization of macrocyclic triynes
and enediynes, as well as in intramolecular and partially
intramolecular versions in order to circumvent the draw-
backs of phosphane use.
[RhCl(IPr)(cod)]12 (1) and [RhCl(IMes)(cod)]13 (2)
[cod = 1,5-cyclooctadiene, IPr = 1,3-diisopropylimidazo-
lin-2-ylidene, and IMes = 1,3-dimesitylimidazolin-2-
ylidene] (Figure 1) were prepared by deprotonation of the
corresponding imidazolium salt with potassium tert-
butoxide followed by transmetalation with [RhCl(cod)]2,
as already described in the literature.
NHC as the catalytic system.
Key words: cycloadditions, rhodium, carbenes, homogenous catal-
ysis, polycycles
The development of efficient methods for transition-
metal-catalyzed [2+2+2]-cycloaddition reactions of un-
saturated substrates has attracted considerable attention in
recent decades.1 A number of excellent procedures have
been published using various transition metals. Among
the metals able to promote this atom-economical transfor-
mation, rhodium has been widely used due to its efficient
performance in catalytic conditions.
Phosphane-stabilized rhodium complexes, whether the
Wilkinson catalyst or a combination of [Rh(cod)2]BF4 and
bidentate diphosphine ligands (i.e., BINAP), constitute
the most common source of rhodium for these transforma-
tions. Rhodium complexes stabilized by N-heterocyclic
carbene (NHC) ligands show great electronic versatility,
are easy to handle, readily synthesized, and have applica-
tions in other rhodium-catalyzed transformations (C–H
activation, hydroborylation, hydrosililation, etc.).2 How-
ever, they have been little used in cycloaddition reactions,
and only a few studies have described the use of Rh–NHC
complexes in this kind of process. Evans et al. described a
diastereoselective [4+2+2] cycloaddition3 of 1,6-enynes
and 1,3-butadiene, Chung et al. developed [4+2] and
[5+2] cycloadditions of dienynes and alkyne vinylcyclo-
propanes, respectively, in their intra- and intermolecular
versions,4 and Webster and Li used a quinoline-tethered
NHC to assist rhodium to catalyze a [3+2] cycloaddition
of diphenylcyclopropenone and internal alkynes.5
R
N
1 (R = i-Pr)
N
2 (R = Mes)
Rh
R
Cl
Figure 1 Rhodium–NHC complexes used in the study
Macrocyclic ligands, cycloisomerized in the group using
the Wilkinson catalyst,14 were the first substrates to be
tested. The [2+2+2]-cycloaddition reaction was studied
both on the triyne macrocycle 3a and enediyne macro-
cycle 3b (Table 1). Remarkably, although it took seven
days, it was possible to accomplish the reaction of macro-
cycle 3a using catalyst 1 at room temperature in dichlo-
romethane media (entry 1, Table 1). The reaction time
was considerably decreased by switching to toluene and
heating to 50 °C (entry 2, Table 1). IMes catalyst 2 was
also able to promote the cycloisomerization but needed
more vigorous heating (90 °C, entry 3, Table 1). Enediyne
macrocycle 3b was also cycloisomerized with excellent
yields using catalyst 1 at 50 °C (entry 4, Table 1). The
more vigorous conditions needed for Rh–NHC catalyst 2
The use of transition-metal catalysts of metals other than
rhodium stabilized with NHC for [2+2+2]-cycloaddition
reactions has also been reported by some groups in the last
decade. Louie et al. used Ni–NHC complexes with great
success in [2+2+2] cycloadditions of two alkynes and al-
SYNLETT 2009, No. 17, pp 2844–2848
Advanced online publication: 24.09.2009
DOI: 10.1055/s-0029-1217982; Art ID: G19709ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
9

LETTER
Rh–NHC Complexes as Catalysts for [2+2+2] Cycloadditions
2845
Table 2 [2+2+2] Cycloisomerization of Triyne 5a
to accomplish the cycloisomerization of the triyne macro-
cycle may possibly be explained by the greater steric hin-
drance introduced by the mesityl substituents in the NHC.
H
N
H
N
SO2Ar
HN
ArO2S NH
ArO2S
ArO2S
SO2Ar
SO2Ar
catalyst
toluene
Table 1 [2+2+2] Cycloisomerization of Triyne Macrocycle 3a and
Enediyne Macrocycle 3b
N
N
N
N
SO2Ar
ArO2S
SO2Ar
SO2Ar
5
6
N
N
N
N
Entry
Catalyst
(mol%)
Temp
(°C)
Time (d) Product
Yield (%)
catalyst
toluene
ArO2S
N
ArO2S
N
1
2
1 (5)
2 (4)
90
1
1
6
6
66
76
SO2Ar
SO2Ar
90
3a
3b
4a
4b
C=C
a Ar = 4-methylphenyl.
H
H
C
C
The activity of the Rh–NHC complexes was also exam-
ined in the partially intramolecular version of the [2+2+2]
cycloaddition. Several N-tethered diynes were reacted
with 2-butyne-1,4-diol, propargyl alcohol, or phenylacet-
ylene under rhodium catalysis using either toluene or eth-
anol as the solvent (Table 3).
Entry Substratea Catalyst Temp Time Product
Yield
(%)
(mol%) (°C)
(d)
1b
2
3a
3a
3a
3b
1 (5)
1 (5)
2 (5)
1 (5)
r.t.
50
90
50
7
4a
4a
4a
4b
90
98
97
98
2
3
1
The hindered diyne 7a was reacted with 2-butyne-1,4-diol
8a in toluene with Rh–NHC catalysts. In all cases, the de-
sired benzene product 9 was obtained in moderate yields,
with slightly higher yields being obtained when IPr was
used as the ligand for rhodium (entries 1 and 2, Table 3).
The reaction was then tested in the less hindered 1,6-diyne
7b, resulting from dialkylation of p-methylphenylsulfon-
amide with 1-bromo-2-butyne. The reaction conditions
for the cycloaddition of diyne 7b were optimized to mini-
mize homocoupling of the starting diyne. By conducting
the reaction in refluxing ethanol it was possible to isolate
cycloaddition product 10 with a 65% yield when using a
10 mol% of catalyst 2 (entry 3, Table 3).
4
3
a Ar = 2,4,6-triisopropylphenyl.
b CH2Cl2 was used as the reaction media.
A completely intramolecular version in open-chain ana-
logues of the macrocycles 3 was also tested (Table 2).
Triyne 5 was treated with 5 mol% of the catalyst in tolu-
ene at 90 °C. Using the two NHC catalysts 1 and 2, a good
yield of the cyclotrimerized product 6 was obtained after
one day of reaction (entries 1 and 2, Table 2).
Table 3 [2+2+2] Cycloaddition of Azatethered Diynes 7 with Various Monoynes 8a
X
R1
R2
R1
R2
X
X
8a–c
ArO2SN
ArO2SN
catalyst
9–14
7a–d
X
Entry
7 X
8 R1/R2 (equiv)
8a CH2OH (1.2)
8a CH2OH (1.2)
8a CH2OH (1.2)
8a CH2OH (5)
8a CH2OH (5)
8a CH2OH (5)
8a CH2OH (5)
8a CH2OH (5)
Catalyst (mol%) Solvent
Temp (°C)
65
Time (h) Product
Yield (%)
1b
2b
3
7a CH2NHSO2Ar
7a CH2NHSO2Ar
7b Me
2 (5)
1 (5)
2 (10)
2 (10)
2 (5)
2 (5)
2 (5)
2 (10)
toluene
toluene
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
48
24
30
72
45
48
24
24
9
46
61
65
85
68
78
42
59
90
9
reflux
reflux
reflux
reflux
reflux
reflux
10
10
10
10
11
11
4
7b Me
5
7b Me
6c
7
7b Me
7c H
8
7c H
9
7b Me
8b H/Ph (5)
2 (5)
EtOH
reflux
48
12
64
Synlett 2009, No. 17, 2844–2848 © Thieme Stuttgart · New York

2846
I. González et al.
LETTER
Table 3 [2+2+2] Cycloaddition of Azatethered Diynes 7 with Various Monoynes 8a (continued)
X
R1
R2
R1
R2
X
X
8a–c
ArO2SN
ArO2SN
catalyst
9–14
7a–d
X
Entry
10
7 X
8 R1/R2 (equiv)
Catalyst (mol%) Solvent
Temp (°C)
reflux
Time (h) Product
Yield (%)
7d Me/H
8c H/CH2OH (5)
2 (5)
EtOH
24
13
68 (m/o = 1.27)
11c
7d Me/H
8b H/Ph (5)
2 (5)
EtOH
reflux
24
14
82 (m/o = 1.84)
a Unless otherwise noted, Ar = 4-methylphenyl.
b Ar = 2,4,6-triisopropylphenyl.
c Solvent was taken directly from the bottle without any degassing or drying.
This yield was considerably increased when the number ring at reflux, a sample was injected into the mass spec-
of equivalents of the monoyne was increased from 1.2 to trometer. A new cluster corresponding to the oxidative
5 (compare entries 3 and 4, Table 3). When the catalyst addition intermediate could be detected centered at m/z =
load was decreased to 5 mol%, the yield fell to 68% (entry 790.2 {[Rh(IMes)(cod)(7b)]+}, which retains both the
5, Table 3). Interestingly, when the reaction was carried NHC and cod ligands in the rhodium metal (Figure 2).
out with absolute ethanol taken straight from the bottle The oxidative coupling of the two alkynes in the diyne to
without any additional drying or degassing15 it was found generate a rhoda(III)cyclopentadiene is supported by the
that the yield increased to 78% (entry 6, Table 3). This isolation and characterization of several derivatives18 and
procedure has clear advantages over the use of a phos- is a common intermediate postulated in these Rh-cata-
phane-based catalyst, which requires care to avoid oxi- lyzed cycloaddition reactions. An excess of 2-butyne-1,4-
dation of the phosphanes. The reaction was then tested diol 8a was then added to the reaction mixture. However,
with terminal diyne 7c. A moderate 42% yield of 11 was no further intermediate could be observed involving
obtained after 24 hours at reflux which became 59% when the monoyne reacting partner although a small cluster
the amount of catalyst was increased from 5 to 10% mol at m/z = 384.1 corresponding to [10 + Na]+ was observed
(entries 7 and 8, Table 3). Phenylacetylene 8b was also after 1.5 hours of stirring at reflux, showing that the reac-
checked as a monoyne partner in the Rh–NHC-catalyzed tion does take place (as is also seen by TLC monitoring).
cycloaddition. A 64% yield of the corresponding biphenyl Interestingly, a peak at m/z = 1065.2 was observed
product 12 was obtained after 48 hours at reflux. Asym- (Figure 3) which is assigned to the most advanced inter-
metric 1,6-diyne 7d was reacted with either propargyl al- mediate involving the third alkyne of another diyne mole-
cohol 8c or phenylacetylene 8b in order to evaluate the cule {[Rh(IMes)(cod)(7b)2]+}. This intermediate evolves
regiochemical control of NHC catalyst 2. Good yields of
cycloaddition products 13 and 14 were achieved but only
a poor regioisomeric ratio was obtained for each of the
two acetylenes. In the two cases, the less sterically hin-
dered regioisomer with the two substituents in a relative
meta position is the main compound (entries 10 and 11,
Table 3).
In order to gain further mechanistic information about the
[2+2+2] cycloaddition of alkynes catalyzed by the Rh–
NHC complexes, an electrospray ionization mass spec-
trometry (ESI-MS)16 study was conducted. This technique
has become increasingly popular as a mechanistic tool for
the study of transient intermediates involved in organo-
metallic catalytic reactions.17 The partially intramolecular
cycloaddition reaction between diyne 7b and alkyne 8a
was chosen as the reaction model. First, Rh–NHC com-
plex 2 was dissolved in ethanol and injected into the mass
spectrometer for analysis. A peak corresponding to the
catalyst which is ionized by the loss of the chlorine atom
appeared at m/z = 515.2 {[Rh(IMes)(cod)]+} together with
a smaller peak corresponding to the protonated carbene
Figure 2 ESI(+)-MS spectrum of the reaction mixture: 7b (1 equiv)
and 2 (0.5 equiv) in EtOH at reflux after 0.5 h of reaction
ligand at m/z = 305.1 {[IMes + H]+}. Diyne 7b was then
added to the former solution and, after 30 minutes of stir-
Synlett 2009, No. 17, 2844–2848 © Thieme Stuttgart · New York

LETTER
Rh–NHC Complexes as Catalysts for [2+2+2] Cycloadditions
2847
to the homocoupled product observed in traces in these re-
actions.
References and Notes
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Figure 3 ESI(+)-MS spectrum of the reaction mixture: 7b (1 equiv),
2 (0.5 equiv), and 8a (excess) in EtOH at reflux after 1.5 h of reaction
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It can be concluded from the results obtained that N-het-
erocyclic carbene rhodium complexes 1 and 2 are efficient
catalysts for the [2+2+2]-cycloaddition reaction. They are
able to promote the cycloisomerization of both triyne and
enediyne azamacrocycles as well as the cycloisomeriza-
tion of open-chain triyne substrates. Furthermore, the par-
tially intramolecular version of the [2+2+2] cycloaddition
of three alkynes can be achieved with readily available
Rh–NHC catalysts. It has also been shown that the robust
Rh–NHC catalysts studied here can be run under aerobic
conditions with solvent taken straight from the bottle.
ESI-MS was used to detect the oxidative addition interme-
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[2+2+2] Cycloaddition of Compound 5 with [RhCl(IPr)(cod)]
(1, Entry 1, Table 2) –General Method
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A degassed solution of 1,6,11,16-tetrakis[(4-methylphenyl)sulfo-
nyl]-1,6,11,16-tetraazahexadeca-3,8,13-triyne (5, 0.082 g, 0.098
mmol) and [RhCl(IPr)(cod)] (0.0020 g, 0.0050 mmol) in anhydrous
toluene (15 mL) was heated at 90 °C for 1 d (TLC monitoring). The
solvent was then evaporated, and the residue was purified by col-
umn chromatography on silica gel with mixtures of CH2Cl2 and
EtOAc (polarity from 20:1 to 10:1) to afford 6 (0.054 g, 66%) as a
colorless solid.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
Financial support from the MICINN of Spain (CTQ2008-05409)
and the University of Girona (grant to I.G.) is acknowledged. We
also thank the Research Technical Services of the UdG for analyti-
cal data and Johnson and Matthey for a loan of RhCl3.
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Synlett 2009, No. 17, 2844–2848 © Thieme Stuttgart · New York

2848
I. González et al.
LETTER
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