Alkyne metathesis: Toward simplicity and efficiency

Article abstract of DOI:10.1016/j.tetlet.2006.01.120

No catalyst pre-activation, no suicide alkyne, and no additive is required in an extremely simple procedure for the metathesis of alkyl-, alkenyl-, and aryl-propynes: just mix Mo(CO)₆, p-chlorophenol, and the alkyne in 1,2-dichloroethane, heat at 85°C for 9-24 h, and the symmetrical alkyne is produced in ca. 95% yield.

Full text of DOI:10.1016/j.tetlet.2006.01.120

Tetrahedron Letters 47 (2006) 2155–2159
Alkyne metathesis: toward simplicity and efficiency
´
Valerie Maraval, Christine Lepetit, Anne-Marie Caminade,
Jean-Pierre Majoral and Remi Chauvin*
Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 Route de Narbonne, 31077 Toulouse Cedex 4, France
Received 13 December 2005; revised 20 January 2006; accepted 23 January 2006
Available online 10 February 2006
Abstract—No catalyst pre-activation, no suicide alkyne, and no additive is required in an extremely simple procedure for the
metathesis of alkyl-, alkenyl-, and aryl-propynes: just mix Mo(CO)6, p-chlorophenol, and the alkyne in 1,2-dichloroethane, heat
at 85 °C for 9–24 h, and the symmetrical alkyne is produced in ca. 95% yield.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
less, the modified system remains of academic interest:
the turnover frequency is indeed low, and the simplicity
of the original Mortreux’ system has been lost. During
preliminary trials for further optimization, the accelerat-
ing efficiency of several ether co-ligands was compared:
1,2-dimethoxybenzene (veratrole) had no effect, while
anisole was less effective than ethylene diethers (DME,
DPE).4,8 We also observed that replacing chlorobenzene
for o-dichlorobenzene (a commonly used solvent at high
temperature)3,9 killed the catalytic activity at 50 °C.8
Noticing the structural analogy between the ‘solvent
effect’ and ‘ether effect’ (Scheme 1), we may try to
extrapolate this trend: the solvent missing link is here-
after addressed for an exploratory, but representative
set of simple hydrocarbon substrates.
Alkyne metathesis is an equilibrium process devoid of
stereochemical ambiguity. It is attractive for the design
of acetylenic molecules of either kinds: symmetrical, or
disymmetrical (by recourse to the ring-closing trick via
transient coupling of the reactants). Today, highly effi-
cient well-defined catalytic precursors can manage func-
tional substrates at low temperature.1 They however
require fine chemical design under strictly anhydrous
and anaerobic conditions, and thus the know-how of
trained specialists. By contrast, the original in situ
Mortreux’ system can be quickly generated at low cost
and without difficulty,2 but can efficiently manage only
robust hydrocarbon substrates at high temperature.3
Facing this limitation, but aware of the advantage of the
system, we proposed a threefold modification of the ori-
ginal procedure allowing for metathesis of phenyl-
propyne at low temperature (50 °C):4 (i) precatalyst
Phenylpropyne 1a was treated under the modified condi-
tions mentioned above (pre-activation step, DPE, MS)
˚
generation at high temperature; (ii) addition of 4 A
molecular sieves (MS); (iii) addition of an ether co-li-
gand. The beneficial co-ligand effect of dimethoxyethane
(DME) or diphenoxyethane (DPE) had indeed been pre-
viously noticed with other catalytic precursors,5 and was
recently confirmed for a related system using o-fluoro-
phenol instead of p-chlorophenol ligands.6,7 Nonethe-
Scheme 1. Structural correlation of the ether additive and solvent
effects on the metathesis efficiency.8 Phenylpropyne substrate at 50 °C,
after pre-activation at 135 °C, in the presence of 4 A MS. Top: in
Keywords: Alkyne metathesis; In situ catalyst; Molybdenum; Solvent
effect; DFT models.
˚
*
Corresponding author. Tel.: +33 5 61 33 31 13; fax: +33 5 61 55 30
chlorobenzene; bottom: with diphenoxyethane as the co-ligand.
03; e-mail: chauvin@lcc-toulouse.fr
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.120

2156
V. Maraval et al. / Tetrahedron Letters 47 (2006) 2155–2159
in 1,2-dichloroethane (DCE). Since the pre-activation
step cannot be run at a temperature higher than the sol-
vent boiling point, the whole sequence was uniformly
run at 85 °C. We found that the kinetics of the meta-
thesis reaction is strongly accelerated, and that DCE is
indeed the missing link (Scheme 1). Encouraged by this
result, we decided to check whether either of the three
(complicating) modifications were still required in
DCE instead of chlorobenzene as solvent.
confirmed the specific accelerating effect of DCE: after
9 h, the metathesis yield reaches 95% in DCE, while it
remains below 5% in chlorobenzene (Fig. 1).
Nevertheless, the reaction then accelerates in chlorobenz-
ene, and smoothly reaches 60% after 24 h while the
concentration of the tolane product has remained sta-
tionary in DCE. These results were established for a p-
chlorophenol/[Mo] ratio of 3.1:1. No reaction occurs
in the absence of p-chlorophenol, but lowering this ratio
to 2:1 or 1:1, did not markedly affect the initial catalytic
activity. After 7 h, the tolane yield (85%) is almost equal
to the conversion (90%), but then the diphenylacetylene
product (tolan) starts to degrade. Thus, in the absence of
sufficient amount of p-chlorophenol ligand, as the cata-
lytic species is less and less involved in the metathesis
process, the Lewis acidity of the unsaturated molybde-
num centers starts to promote some oligo/polymeriza-
tion processes.
(i) Precatalyst generation step: We were here inspired
by Bunz et al., who proposed a methodological
improvement for difficult substrates by adding an
auxiliary alkyne to efficiently generate the alkyli-
dyne-Mo active species.10 In the simplest version,
the phenylpropyne substrate itself was added as
the ‘suicide’ alkyne, and we observed that the reac-
tion starts to proceed rapidly. A separated pre-
activation step is thus no longer required.
(ii) Co-ligand addition: In the absence of any ether
additive, the catalysis proceeded with the same
efficiency, and even slightly faster. Speculations
about a possible role of DCE as a weak co-ligand
of molybdenum are inviting (see below), but the
main point here is the simplification of the cata-
lytic mixture.
(iii) Molecular sieves addition: In the absence of molec-
ular sieves, the use of distilled DCE resulted in
the same activity. The simplification of the proce-
dure is now extreme: no reaction takes place in the
strict absence of Mo(CO)6 or p-chlorophenol
(Scheme 2).
Since 3 or 1 catalytic equivalents of p-chlorophenol trig-
ger metathesis at the same rate, an efficient Mo active
species might involve a single p-chlorophenolate ligand
(instead of three, as it has long been assumed).2–4
Assuming that this species is a Mo(VI)–carbyne com-
plex,5 the missing X ligands could reasonably be chlo-
ride ligands, which are potentially abundant in our
system and in most related systems based on the Mor-
treux’ catalyst.2–4 The above results suggest that DCE
could be an optimal chlorine donor.11 Before speculat-
ing about the nature of the putative chlorinated species
(see below), the scope of the optimization was tested in
more details concerning the working temperature, the
catalytic ratio, and the substrate compatibility.
A blank experiment using freshly distilled chlorobenzene
at 85 °C, in one step and in the absence of any additive,
Beyond aryl-propyne 1a, an alkyl-propyne 1b (undeca-
2-yne) has been submitted to the novel metathesis condi-
tions using 3 catalytic equivalents of p-chlorophenol
(Table 1). After overnight reaction, the GC yield of
the known octadeca-9-yne 2b is almost quantitative
(96%).12 Finally, a third kind of hydrocarbon propyne
derivative, that is an alkenyl-propyne, has been tested
from enyne 1c. The use of 3 catalytic equivalents of p-
chlorophenol allows to stabilize the known dienyne
product 2c,13 which is produced in 96% GC yield after
24 h. Let us notice that metathesis of a similar enyne
substrate under Mortreux–Bunz’ conditions in o-dichlo-
Scheme 2. Simple Mo-catalyzed alkyne metathesis procedure.
Figure 1. Kinetics of phenylpropyne metathesis. Left: Compared kinetic solvent effect of DCE and chlorobenzene, for a ratio p-chlorophenol/
[Mo] = 3:1. Right: Conversion and metathesis yield curves in DCE for a ratio p-chlorophenol/[Mo] = 1:1. In the three experiments, the simplified
procedure is used (direct mixing of reaction components at 85 °C, catalytic ratio 1a/[Mo] = 1:0.1).

V. Maraval et al. / Tetrahedron Letters 47 (2006) 2155–2159
2157
LANL2DZ*(Mo) level.17 The coordinating properties
of DCE were investigated either in the gas phase or in
the solvent (e = 10.36) through PCM calculations.18 The
geometry of the various isomers of [Cln(OAr)3ꢀnMo„
C–Me](L) complexes (n = 1,2) were first optimized in
the gas phase.19 All but one converged toward flattened
four-coordinate Mo complexes resulting from the
decoordination of the DCE ligand. The latter remains in
the vicinity of the Mo-ethylidyne moiety through weak
Table 1. Alkyne metathesis of substrates 1a–c in 1,2-dichloroethane at
85 °C
Entry Substrate Time Conversion GC
Isolated
(h)
(%)
yield (%)a yield (%)b
1
2
3
1a
1b
1c
9
15
24
95
96
97
94
96
96
96c
91
93
Conditions: 1/Mo(CO)6/p-chlorophenol = 10:1:3.1, DCE, 85 °C.
a Decaline was introduced as the internal standard.
b After column chromatography over silicagel.
c 99% GC yield after 15 h.
˚
hydrogen interactions (H2CHꢁ ꢁ ꢁCl = 2.7–2.9 A, C–Hꢁ ꢁ ꢁ
Cl = 167–170°). In the case of a mer starting structure
bearing a single chlorine ligand, DCE was found to be
retained as a very weak monodentate ligand trans to
˚
robenzene required both high temperature (130 °C) and
a pre-activation step by 3-hexyne.10 The DCE trick
allows to run the reaction under much milder and simpler
conditions.
the carbyne ligand (Moꢁ ꢁ ꢁClCH2CH2Cl = 3.40 A) (Fig.
2a), while the geometry of the Mo-carbyne moiety
remains classical.20 The corresponding five-coordinate
structure is however isoenergetic with a four-coordinate
structure in the non-bonding vicinity of DCE. In this
and all other cases, PCM calculations yielded only
four-coordinate Mo-carbyne species.
Beyond a simple solvent effect, a specific ‘chlorine effect’
is supported by the fact that the catalytic activity on
substrate 1a is totally suppressed by switching to non-
chlorinated polar solvents (DMF, benzonitrile, nitro-
benzene, methylbenzoate, . . .), and in particular to the
isostructural 1,2-dibromoethane (e = 4.75). Along the
same line, we also observed that upon reflux, a colorless
DCE solution of Mo(CO)6 and phenylpropyne 1a
turned to brown-red after a few hours. The correspond-
ing species (possibly quite diluted) could not be charac-
terized, but it might result from an oxidation of the
Mo(0) centers by the chlorinated solvent. In a closely
These results rule out a significant role of DCE through
Mo-coordination or simple dielectric constant effect.
They support experimental suggestions of its chlorinat-
ing effect, and propound that the catalytic precursor
might involve a four-coordinate/two-chloride Mo com-
plex (Fig. 2b).
In conclusion, mild chemical and thermal conditions
were found to give reproducible results for the catalytic
metathesis of all kinds of hydrocarbon alkynes with al-
kyl, aryl, or alkenyl substituents. The dramatic effect
of the DCE solvent has been investigated through con-
trol experiments and DFT calculations. It seems that
the main effect could actually be chemical in nature,
and that an efficient catalytic species might be a
dichloro(monoaryloxy)molybdenum carbyne complex.
This hypothesis of course requires confirmation by
experimental evidences, but calculations are in progress
to compare the reactivity of Cln(OAr)3ꢀnMo„C–Me
species toward alkynes. We indeed considered the resting
state of the catalytic species, but DCE might also play a
decisive role in the stabilization of the transition state. A
more practical prospect is the scope of the substrate
compatibility of the DCE system. Aware of the preli-
minary character of the reported results, we are now
focussing on more challenging substrates such as func-
tional alkynes and/or alkadiynes. According to our latest
investigations, however, the case of functional alkyl-
propynes is more problematic. While single metathesis
related prospect, Furstner and Moore reported on
¨
selective chlorination processes of a molybdenum
complexes in CH2Cl2 solution, which afforded efficient
catalysts for alkyne metathesis.14 Likewise, photochem-
ical chlorination of W(CO)6 in CCl4 solution was also
shown to provide polymerization catalysts.15 In the
present case, several catalyst structures can thus be
envisaged. Although only partial decarbonylation can-
not be ruled out (residual IR CO absorption bands were
detected after the metathesis has started), we may rea-
sonably consider tetracoordinate Cln(ArO)3ꢀnMo„
C–R cores, possibly boosted or stabilized by weak co-
ligands (L = DME, DPE, or DCE). The case n = 2 is
not only supported by our observations (see above),
but also by literature reports on the catalytic activity
of di- and tri-chloro molybdenum(III) moieties.16
To gain insight into the stability and the structure of the
putative chlorinated active species (see above), DFT cal-
culations were carried out at the B3LYP/6-31G*/
Figure 2. DFT-optimized geometries of (a) monochlorinated Mo–carbyne complex weakly retaining a DCE ligand; (b) free dichlorinated Mo–
carbyne complex (see text).

2158
V. Maraval et al. / Tetrahedron Letters 47 (2006) 2155–2159
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of classical x-diynes to medium-size cycloalkynes
(RCAM) has been widely exemplified with other cata-
lytic systems,1a we are specifically interested in exploring
the possibility of sequential metathesis of b-diynes for
the synthesis of ring carbo-mers.21 Sequential metathesis
of non-functional b-diynes X(C„CMe)2 (X = alkylid-
ene, alkenylidene), the feasibility of which has been illus-
trated for X = Ph2Si with the Mo/MS/diether system,4
is being currently investigated with the DCE system.
The results will be communicated in the near future.
´
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2. Typical metathesis procedure
A 25 mL round-bottom flask equipped with a reflux
condenser is filled with Mo(CO)6 (0.100 g, 0.38 mmol),
p-chlorophenol (0.155 g, 1.21 mmol), the substrate
(3.8 mmol), decalin as the internal standard for GPC
(0.3 mL), and 12 mL of distilled DCE. The solution is
stirred under a stream of argon at 85 °C (gentle reflux).
The metathesis is monitored by gas chromatography. At
the end of the reaction, the solvent is removed under
vacuum and the metathesis product is purified by silica
gel chromatography.
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11. A possible stoichiometry for the chlorination process
might be:
Cl
Acknowledgments
+ (3–n) HCl
ClnMo(OAr)3– n + 6 CO + 3/2
3/2
+ Mo(CO)6 + (3–n) Ar–OH
Cl
.
`
The CNRS, the french Ministere de l’Enseignement
12. Pawlowski, N. E.; Lee, D. J.; Sinnhuber, R. O. J. Org.
Chem. 1972, 37, 3245.
´
Superieur de la Recherche et de la Technologie, and
the European Social Fundings are gratefully acknowl-
edged for financial support. The authors also wish to
13. Kuznetsov, M. A.; Dorofeeva, Yu. V.; Semenovskii, V. V.;
Gindin, V. A.; Studenikov, A. N. Tetrahedron 1992, 48,
1269.
´ ´
thank CALMIP (Calcul Intensif en Midi-Pyrenees,
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¨
CICT, Toulouse) and CINES (Centre Informatique de
Chem. Soc. 1999, 121, 9453; (b) Furstner, A.; Mathes, C.;
¨
´
l’Enseignement Superieur, Montpellier, France) for
Lehmann, C. W. Chem. Eur. J. 2001, 7, 5299; (c) Zhang,
W.; Kraft, S.; Moore, J. S. Chem. Commun. 2003, 832.
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nomet. Chem. 2000, 601, 16.
16. Keller, A.; Matusiak, R.; Glowiak, T. J. Mol. Catal. A:
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computing facilities.
Supplementary data
GC analyses of the final reaction products correspond-
ing to entries 1–3 in Table 1, preparation and 13C and
1H NMR spectra of substrate 1c, cartesian coordinates
and total energy of optimized structures a and b are
shown in Figure 2. Supplementary data associated with
this article can be found, in the online version at
doi:10.1016/j.tetlet.2006.01.120.
17. Geometries were fully optimized at the B3LYP/6-31G*/
LANL2DZ*(Mo)
level
using
Gaussian03.18
LANL2DZ*(Mo) means that f-polarization functions for
Mo have been added to the LANL2DZ(Mo) basis set:
Ehlers, A. W.; Bo¨hme, M.; Dapprich, S.; Gobbi, A.;
Ho¨llwarth, A.; Jonas, V.; Ko¨hler, K. F.; Stegmann, R.;
Veldkamp, A.; Frenking, G. Chem. Phys. Lett. 1993, 208,
111. Vibrational analysis was performed at the same level
in order to check that a minimum was obtained on the
potential energy surface.
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and trans manner. Nevertheless, fac/mer and cis/trans
isomerisms disappear in the final tetrahedral or bipyra-
mid-trigonal structures.
20. In the case of the triaryloxy/DME carbyne complex, the
DME acted as a bidentate ligand, but the Mo–OMe
˚
interaction was also very weak: Mo–O = 2.64 A: see
Ref. 4.
19. The starting structures of the optimization were built from
either fac or mer isomers of the optimized
ðDMEÞðArOÞ3MoBC–Me complex (Ref. 4) by replacing
DME for DCE and OAr ligands for the suitable number
21. Chauvin, R.; Lepetit, C. In Modern Acetylene Chemistry.
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