A family of highly active copper(I)-homoscorpionate catalysts for the alkyne cyclopropenation reaction

Article abstract of DOI:10.1039/b105020f

Equimolar mixtures of ethyl diazoacetate and alkynes can be converted into cyclopropenes in very high yields, at room temperature, through the intermediacy of readily available Cu(I) catalysts containing trispyrazolylborate ligands.

Full text of DOI:10.1039/b105020f

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A family of highly active copper( )–homoscorpionate catalysts for the
I
alkyne cyclopropenation reaction
a
a
a
a
M. Mar Díaz-Requejo, Miguel Angel Mairena, Tomás R. Belderrain, M. Carmen Nicasio,
b
a
Swiatoslaw Trofimenko and Pedro J. Pérez*
a
Departamento de Química y Ciencia de Materiales, Universidad de Huelva, Carretera de Palos de la
Frontera s/n, E-21819 Huelva, Spain. E-mail: perez@dqcm.uhu.es; Fax: +34 959 017414;
Tel: +34 959 017411
b
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
Received (in Cambridge, UK) 7th June 2001, Accepted 1st August 2001
First published as an Advance Article on the web 3rd September 2001
Equimolar mixtures of ethyl diazoacetate and alkynes can be
converted into cyclopropenes in very high yields, at room
temperature, through the intermediacy of readily available
transformations is the formation of diazoacetate-coupling
products: diethyl fumarate and maleate are also formed when
EDA is employed as the carbene source. Usually, this is avoided
by using a large excess of the alkyne with respect to EDA, and
by adding the diazocompound by means of slow-addition
devices onto the alkyne and catalyst-containing solution. As a
consequence of our knowledge on the olefin cyclopropanation
reaction, we have learnt that there is an enormous dependence of
the three-membered ring yields on the reaction design,
particularly the catalyst concentration and the carbene precursor
addition rate. Fig. 1 shows the results of the hex-3-yne
cyclopropenation reaction obtained from three experiments at
three different concentrations of complex 2. The initial hex-
3-yne concentration was fixed at 0.45 M and EDA (0.15 M) was
added with two different addition rates (0.15 and 1.5 mmol
Cu( ) catalysts containing trispyrazolylborate ligands.
I
Carbon–carbon unsaturated bonds can be converted into three-
membered rings by the intermediacy of metal-based catalysts
and the appropriate carbene source.1 Thus, a diazo compound
and an olefin lead to cyclopropanes whereas the same carbene
precursor and alkynes afford cyclopropenes (Scheme 1).
Despite the obvious similarities between both reactions, most
efforts have been devoted to the former transformation, the
catalytic systems reported to date for the cyclopropenation
reaction being reduced to a few, and mainly based on copper
,2
and rhodium. Copper bronze, Cu( ) and Cu(II) salts have been
I
2
1
employed as catalysts for the cyclopropenation reaction, but
h ). The use of initial [2] of 0.0075 M (1+20+60 of [Cu]–
high temperatures (90–140 °C) were required and yields were
[EDA]–[hex-3-yne]) induced the almost quantitative conver-
sion into the corresponding cyclopropene, whereas a third of
that value caused a 50% decrease of the product. As expected,
an increase in the addition rate of EDA diminished the yields,
but the same trend was observed upon varying [Cu]. These
results are in accord with the reaction pathway proposed for the
3
low. At room temperature, Rh
2
(OAc)
4
has been the catalyst of
4
choice for this transformation, as reported by Hubert et al.
Related chiral derivatives of the type Rh (L–L*) have been
2
4
5
developed by Doyle and co-workers, inducing high enantio-
meric excesses. However, there are two major drawbacks to
address in this field. First, those rhodium catalysts do not
operate with internal alkynes, or if so, yields are quite low.
Secondly, and despite the use of high alkyne–EDA (ethyl
diazoacetate) ratios, only moderate to high conversion yields
have been achieved (40–85%), the quantitative conversion
being still elusive.
1
0
related cyclopropanation reaction with this type of catalyst.
With this knowledge, we have tested an array of trispyr-
azolylborate ligands11 (Fig. 2) in which R –R can be modified
1
3
to tune the electronic and steric effects induced to the metal
X
centre. The catalysts of general formula Tp Cu(
I
) were
generated in situ by mixing equimolar amounts of CuI and the
corresponding potassium or thalium salt of the homoscorpio-
nate ligand. These preliminary experiments were run with a
[Cu]–[EDA]–[hex-3-yne] ratio of 1+30+90, that corresponds to
[Cu] 0.005 in Fig. 1. As inferred from data in Table 1, the
3-neopentyl and 3-cyclohexyl derivatives showed excellent,
unprecedented degrees of conversion into ethyl 2,3-diethylcy-
cloprop-1-enecarboxylate (95 and 97%, respectively) therefore
The catalytic capabilities of the homoscorpionate complex
2 4
Tp*Cu(C H ) (1) (Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)-
borate (1), towards the alkyne cyclopropenation reaction were
6
reported a few years ago. Those preliminary results showed
that both internal and alk-1-ynes could be converted into the
corresponding cyclopropenes with moderate yields (40–65%).
7
Complex Tp*Cu (2) displays the same catalytic behaviour,
with the advantage of its higher stability in comparison with 1.
Complexes 1 or 2 also catalyse the conversion of olefins into
8
9
cyclopropanes and epoxides, both under homogeneous and
heterogeneous conditions, as well as the aziridination of
alkenes.6 This remarkable behaviour has been now expanded
to the achievement of higher degrees of alkyne cyclopropen-
ation. It is worth mentioning that the main problem in these
,9
Fig. 1 Dependence of cyclopropene yields (hex-3-yne as alkyne) and the
2
1
amount of catalyst (Tp*Cu, 2). EDA addition rate: : 1.5 mmol h ; - 0.15
2
1
Scheme 1
mmol h
.
1804
Chem. Commun., 2001, 1804–1805
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105020f

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in Table 2, entry 5, in which an equimolar EDA–alkyne ratio
was employed: yields of cyclopropene fall in the range 80–94%.
The lack of alkyne excess in these high-yield transformations
has no precedent in the literature: our system has obviated the
need for an excess of alkyne to achieve noticeable yields, not
only with the cyclohexyl derivative but also with other TpX
ligands (X = alkyl). Thus, the cyclopropenation of hex-3-yne
using an equimolar ratio of the alkyne and ethyl diazoacetate
afforded the corresponding three-membered ring in 75–94%
yield (Table 3).
Fig. 2 TpX ligands.
Table 3 Equimolar EDA–hex-3-yne cyclopropenation experimentsa
X
a
Entry
TpX
Yieldb
Table 1 Cyclopropenation of hex-3-yne with Tp –Cu catalysts
TpX
R1
R2
R3
Yieldb
1
2
3
4
Tp*
75
72
82
94
Entry
tBu
Tp
Tp
Tp
Np
Cy
1
2
3
4
5
6
7
8
9
Tp
Tp*
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
32
82
85
95
97
21
27
31
52
43
49
Me
tBu
t
a
b
Tp
Tp
Tp
Tp
Tp
Tp
Tp
Tp
Tp
Bu
[Cu]–[EDA]–[hex-3-yne] ratio of 1+60+60, 0.1 mmol of Cu employed.
Percentage of cyclopropene determined by GC after total EDA consump-
tion. Diethyl fumarate and maleate accounted for the remaining diazoace-
tate employed.
Np
Np
Cy
Ph
a-Nt
Ms
p-C
p-C
p-C
Cy
Ph
a-Nt
Ms
ClPh
An
In conclusion, we have developed an extraordinarily efficient
cyclopropenation system in which terminal and internal alkynes
can be converted into the corresponding unsaturated rings in
very high yields. In addition, no excess of the alkyne is required
for those yields to be produced. Work aimed to extend these
results to a number of other unsaturated substrates is currently
underway in our laboratory.
6
6
6
H
4
H
4
H
4
Cl
OCH
3
CH
1
1
a
0
1
Tol
3
See footnote† for experimental details. b Percentage of cyclopropene
determined by GC after total EDA consumption. Diethyl fumarate and
maleate accounted for the remaining diazoacetate employed.
minimising the formation of EDA-coupling products (ethyl
fumarate and maleate). We have recently reported12 an
extraordinarily active and diastereoselective (towards the cis
isomer) catalytic system for the olefin cyclopropanation
Notes and references
†
Experimental procedure: CuI and an equimolar amount of the MTpX salt
2 2
were dissolved in CH Cl and the mixture was stirred for 2–3 h. After
filtration volatiles were removed under reduced pressure. The residue was
dissolved in 20 mL of 1,2-dichloroethane, and the resulting solution was
charged with alkyne. A solution of EDA in 1,2-dichloroethane was slowly
added with the aid of an automatic syringe pump. All reactions were
performed at room temperature. After complete addition, the reaction
mixture was analyzed by GC, only cyclopropenes and ethyl fumarate or
maleate being detected. Yields are shown in Tables 1–3.
1
reaction, in which aromatic substituents as R provided the best
results in comparison with the aliphatic groups in this position.
But this situation reverses in the alkyne cyclopropenation
1
reaction, since aliphatic groups as R seem to be required for
high conversions. This constitutes a significant difference
between these two transformations that traditionally have been
described to occur in a similar way.1
,2
1
2
M. P. Doyle, in Comprehensive Organometallic Chemistry II, ed. E. W.
After this initial screening, optimisation of the reaction
conditions and expansion to other alkynes afforded more
interesting features. Table 2 displays the results of the
cyclopropenation reaction of hex-1-yne, 1-phenylprop-1-yne
Abel, F. G. A. Stone and G. Wilkinson, Pergamon Press, Oxford, UK,
1
995, vol 12, p. 387.
M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds, John Wiley & Sons, New
York, 1998.
and hex-3-yne with different [Cu]–[EDA]–[alkyne] ratios using
Cy
the Tp
derivative. The observed yields show dramatic
3 M. N. Protopopova and E. A. Shapiro, Russ. Chem. Rev., 1989, 58,
667.
improvement over any other reported catalytic system in terms
of cyclopropene formation not only for alk-1-yne derivatives,
but also for internal ones: the values for hex-3-yne are > 90% in
all cases and 1-phenylprop-1-yne also undergoes high conver-
sions (73–94%). This remarkable activity is confirmed by data
4
5
N. Petiniot, A. J. Anciaux, A. F. Noels, A. J. Hubert and P. H. Teyssie,
Tetrahedron Lett., 1978, 14, 1239.
M. P. Doyle, M. Protopopova, P. M u¨ ller and E. A. Shapiro, J. Am.
Chem. Soc., 1994, 116, 8492; M. P. Doyle, M. Protopopova, P. Müller
and D. Ene, J. Am. Chem. Soc., 1992, 114, 2755.
P. J. Pérez, M. Brookhart and J. L. Templeton, Organometallics, 1993,
12, 261.
6
7
Table 2 Cyclopropenation of alkynes with TpCyCua
C. Mealli, C. S. Arcus, J. L. Wilkinson, T. J. Marks and J. A. Ibers,
J. Am. Chem. Soc., 1975, 98, 711.
Cu–EDA–
alkyne
1-Phenyl-
b
Hex-1-ynec Hex-3-ynec prop-1-ynec
Entry
8 M. M. Díaz-Requejo, M. C. Nicasio and P. J. Pérez, Organometallics,
1
998, 17, 3051; M. M. Díaz-Requejo, T. R. Belderrain, M. C. Nicasio
1
2
3
4
5
0.05+1.5+7.5
0.05+3+9
0.1+3+9
87
75
80
70
80
97
90
97
95
94
94
84
90
73
85
and P. J. Pérez, Organometallics, 2000, 19, 285.
9 M. M. Díaz-Requejo, T. R. Belderrain and P. J. Pérez, Chem. Commun.,
2000, 1853; M. M. Díaz-Requejo, P. J. Pérez, M. Brookhart and J. L.
Templeton, Organometallics, 1997, 16, 4399.
10 M. M. Díaz-Requejo, T. R. Belderrain, M. C. Nicasio, F. Prieto and P. J.
Pérez, Organometallics, 1999, 14, 2601.
0.1+6+9
0.1+6+6
a
See footnote† for experimental details. b In mmol. c Percentage of
1
1 S. Trofimenko, Scorpionates, The Coordination Chemistry of Poly-
pyrazolylborate ligands, Imperial College Press, London, 1999.
2 M. M. Díaz-Requejo, T. R. Belderrain, S. Trofimenko and P. J. Pérez,
J. Am. Chem. Soc., 2001, 123, 3167.
cyclopropene determined by GC after total EDA consumption. Diethyl
fumarate and maleate accounted for the remaining diazoacetate em-
ployed.
1
Chem. Commun., 2001, 1804–1805
1805