One-step synthesis of 1-halo-1,3-butadienes via ruthenium-catalysed hydrohalogenative dimerisation of alkynes

Article abstract of DOI:10.1039/c2cc36422k

An efficient, novel and direct access to 1-halo-1,3-butadienes is developed. This stereoselective ruthenium-catalysed reaction proceeds under mild conditions via the head-to-head oxidative coupling of two alkynes and a concomitant hydrohalogenation.

Full text of DOI:10.1039/c2cc36422k

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COMMUNICATION
One-step synthesis of 1-halo-1,3-butadienes via ruthenium-catalysed
hydrohalogenative dimerisation of alkynesw
´
Hubert Klein, Thierry Roisnel, Christian Bruneau and Sylvie Derien*
Received 3rd September 2012, Accepted 24th September 2012
DOI: 10.1039/c2cc36422k
An efficient, novel and direct access to 1-halo-1,3-butadienes is
developed. This stereoselective ruthenium-catalysed reaction
proceeds under mild conditions via the head-to-head oxidative
coupling of two alkynes and a concomitant hydrohalogenation.
also be obtained by addition of alcohols, water or phosphine
oxides.13 Our catalytic reaction involves the formation of a
metallacyclic biscarbene-ruthenium II, with mixed Fischer and
Schrock-type behavior,12 as the key catalytic species, followed
by the stereoselective formal addition of proton and nucleophile
at C1 and C4 carbon atoms resulting in concomitant C–C, C–H
and C–Nu bonds formation in a single step (Scheme 1).
On the basis of this mechanism, we envisioned the catalytic
and selective formation of 1-halo-1,3-dienes under mild conditions
through a hydrohalogenative dimerisation of alkynes in one step
(Scheme 1). Indeed, when 1.0 mmol of phenylacetylene 1a was
reacted with 0.6 equiv. of HCl (2 N in Et2O) in the presence of
5 mol% of [Cp*RuCl(cod)] (I) at room temperature in 0.5 mL of
1,2-dichloroethane (DCE) for 20 h, the dienylchloride 2a was
isolated in 64% yield (Scheme 2).
The direct and efficient preparation of stereodefined and
functionalised conjugated dienes remains an area of current
investigation due to the utilisation of 1,3-diene units in numerous
transformations1–3 such as the Diels–Alder reaction and because
they appear as a recurring structure in natural products and
molecular materials.2 In this respect, halo-1,3-dienes represent an
attractive synthon for the incorporation of the 1,3-diene building
block in more complex structures or for the introduction of new
functionalised groups for the preparation of a wide variety of
linear and cyclic compounds.2,3 Beside some classical synthetic
methods such as Wittig-type reactions, the synthesis of mono- or
dihalo-1,3-dienes essentially involves transition metal-mediated
coupling reactions. The most frequently used approach consists
of halogenation of zircona- or titanacyclopentadienes.4 However,
these methods require the stoichiometric formation of an
organometallic complex from two alkynes. Although the
development of atom-economical single-step routes using a
catalytic amount of metal is of special interest, few reports
have been described. Halogenative couplings of alkynes with
Pd,5 Rh,6 Ir7 or Pt8 catalysts via a halometalation process are
representative examples. Recently, 1-halo-1,3-dienes have
been obtained through a gold-catalysed rearrangement of
propargylic carboxylates containing halogenated alkynes.9
During the course of our studies on the catalytic activity of
the complex [Cp*RuCl(cod)]10 (Cp* = C5Me5) and its ability
to promote the formation of a biscarbene-ruthenium complex
via the head-to-head oxidative coupling of alkynes,11 we found
that addition of carboxylic acids provided a catalytic and
stereoselective access to functional conjugated dienes.12 With
similar ruthenium catalysts, functionalised 1,3-dienes could
The neutral precursor [Cp*RuCl(cod)] appeared to be a
selective catalyst for this reaction whereas the use of the
cationic Ru(II) [Cp*Ru(CH3CN)3]PF6 gave compound 2a in
only 25% yield. A great improvement came from the concentration
of the substrates and the best result was obtained with [1a] =
2 mol Lꢀ1. Further optimization of solvents revealed that DCE
was the best solvent for the stereoselective formation of 2a. One
stereoisomer for 2a was clearly favoured, however, according to
the solvent, a second stereoisomer could be detected by gas
chromatography analysis (ratio 98/2 in DCE). In each case, the
major stereoisomer showed the same NMR footprint and was
assumed to be the (1Z, 3E)-1-chloro-1,4-diphenylbuta-1,3-diene.
´
UMR 6226 CNRS – Universite de Rennes 1, Institut des Sciences
Scheme 1 Key steps of the formation of functional 1,3-dienes.
Chimiques de Rennes, Organometallics: Materials and Catalysis,
Campus de Beaulieu, 35042 Rennes Cedex, France.
E-mail: sylvie.derien@univ-rennes1.fr; Fax: +33 223236939;
Tel: +33 223235003
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for compounds 2–4. CCDC
890488 (2a) and 890489 (2i). For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c2cc36422k
Scheme 2 Ruthenium-catalysed reaction of phenylacetylene 1a with
HCl.
c
11032 Chem. Commun., 2012, 48, 11032–11034
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Table 1 Ruthenium-catalysed reaction of arylacetylenes 1a–j with
HCla
Table 2 Ruthenium-catalysed reaction of phenylacetylene 1a with
chloride and acida
Entry
RSO3H
R0Cl
Yieldb (%)
1
2
3
4
5
6
PTSA, H2O
CSA
CSA
CSA
CSA
CSA
NaCl (1.0 equiv.)
NaCl (1.0 equiv.)
KCl (1.0 equiv.)
[Me4N]Cl (1.0 equiv.)
[BnEt3N]Cl (1.0 equiv.)
[BnEt3N]Cl (0.5 equiv.)
28
48
59
85
92
87c
a
Reaction conditions: 1a (1.0 mmol), RSO3H (0.5 equiv.) and R0Cl in
the presence of cat I (1a/[Ru] in 1/0.05 molar ratio), in 1,2-dichloro-
b
ethane (0.5 mL) at room temperature, 20 h. Isolated yields obtained
c
after purification by silica gel chromatography. 88% yield of 2a was
obtained after 5 h.
X-ray analysis of a suitable crystal of the second isomer of 2i
allowed the assignment of the 1E, 3E structure.14 The major
stereoisomer probably results from the steric hindrance of the
Cp* moiety which induces an anti-addition of H+ and Clꢀ on
the carbene carbons. However electronic effects must play a
role during this addition since the stereoselectivity decreases
with an electron-withdrawing substituent and no (1Z, 3E) -
(1E, 3E) isomerisation seemed to occur after the formation of
1-chlorodienes 2.
a
Reaction conditions: 1 (1.0 mmol) and HCl (2 N in Et2O, 0.6 equiv.)
in the presence of cat I (1a/[Ru] in 1/0.05 molar ratio), in 1,2-
dichloroethane (0.5 mL) at room temperature. Isolated yields obtained
after purification by silica gel chromatography. Ratio 1Z, 3E/1E, 3E in
parentheses.
The undesired formation of byproducts obtained by utilizing
HCl solutions led us to consider another approach to perform
the addition of a proton and a chloride. Thus, we were pleased
to find that the reaction took place when phenylacetylene 1a
was reacted with 0.5 equiv. of p-toluenesulfonic acid (PTSA) as
a source of proton and 1.0 equiv. of NaCl as a source of
chloride although the expected chlorodiene 2a was recovered in
a low 28% yield (Table 2, entry 1). An increase to 48% yield
was performed by changing PTSA for camphorsulfonic acid
(CSA) (entry 2). A screening of different sources of chloride
showed that if the use of KCl gave a better result than NaCl
(entry 3), using ammonium chloride salts significantly improved
the efficiency of the reaction and gave excellent yields (entries
4–6). Indeed, one equivalent of tetramethylammonium chloride
allowed us to obtain an 85% isolated yield (entry 4), and the
use of benzyltriethylammonium chloride led to up to 92% yield
The structure of this major stereoisomer was unequivocally
confirmed by single crystal X-ray diffraction study after successful
crystallization in a dichloromethane–pentane mixture.14 Under
the optimised reaction conditions, we then examined the scope
of this coupling reaction with various arylacetylene derivatives
(Table 1).
Moderate to good yields in 1-chlorodienes 2 were obtained.
The reaction did not proceed with alkylacetylenes, the biscarbene
intermediate II being probably stabilised by the conjugated aryl
substituents.11c It is noteworthy that the reaction proceeded
faster from arylacetylenes containing electron-withdrawing
groups (complete conversion within 2 to 6 h) and better yields
were produced (up to 88%). With electron-donating groups, the
reaction took place more slowly and a reaction time of 40 h
was necessary to achieve complete conversion. Unfortunately,
byproducts were also formed and the yield in diene 2 decreased
(45% with R = OMe). The nature of the substituent of the aryl
group also had an influence on the stereoselectivity. Only one
(entry 5). Interestingly,
a lower amount of [BnEt3N]Cl
(0.5 equiv.) still led to a good yield (87%) in chlorodiene 2a,
thus avoiding the use of an excess of reagent (entry 6).
Particularly notable is the fact that the same yield could be
obtained in only 5 h (instead of 20 h with HCl) clearly showing
that the reaction proceeded faster under these conditions.
We then examined if the system CSA (0.5 equiv.)–[BnEt3N]Cl
(0.5 equiv.) could also improve the efficiency of the reaction with
various arylacetylenes (Table 3). A great improvement was obtained
for the less reactive electron-donating arylacetylenes (entries 2–3).
The reaction proceeded faster (4 h instead of 40 h for completion
for 1d) and became more efficient as the yields increased to up to
90% for 2c or 2d. In the case of arylacetylenes featuring electron-
withdrawing substituents, complete conversion was always obtained
rapidly but the yields in dienes 2 were lower than with the addition
of HCl. In each case, the stereoselectivity remained similar.
1
stereoisomer was observed in H NMR when the reaction was
carried out with electron-donating groups (R = OMe, tBu, Me),
R = H or R = halide (F, Br) whereas for electron-withdrawing
groups at the phenyl para position, a second stereoisomer was
observed, in small amounts (ratio 95/5) for R = CF3 or COMe
or in more important amount (ratio 62/38) for R = p-CN. The
steric hindrance of a substituent at the phenyl ortho position
slowed down the reaction (6 h for o-CN as compared to 2 h for
p-CN) but favoured the formation of one stereoisomer (ratio 93/7).
c
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Table 3 Ruthenium-catalysed reaction of arylacetylenes 1 with chlor-
ide and acida
possible further transformations, to create a variety of functio-
nalised dienes.
The authors are grateful to the CNRS and the Ministere de
la recherche for support, the latter for a PhD grant to HK.
They thank Dr Mathieu Achard for helpful discussions.
Entry
R
t/h
Diene
Yieldb (%) (Z,E/E,E)
Notes and references
1
2
3
4
5
H
5
19
4
3
2
2a
2c
2d
2h
2i
88 (100/0)
91 (100/0)
90 (100/0)
62 (88/12)
62 (65/35)
p-tBu
p-OMe
p-COMe
p-CN
1 (a) F. Fringuelli and A. Taticchi, Dienes in the Diels–Alder Reaction,
Wiley, New York, 1990; (b) W. Carruthers, Cycloaddition Reactions in
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(f) S. Ma and G. Wang, Tetrahedron Lett., 2002, 43, 5723;
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a
Reaction conditions: 1 (1.0 mmol), CSA (0.5 equiv.) and [BnEt3N]Cl
(0.5 equiv.) in the presence of cat I (1a/[Ru] in 1/0.05 molar ratio), in
b
1,2-dichloroethane (0.5 mL) at room temperature. Isolated yields
2 (a) M. Mori, Adv. Synth. Catal., 2007, 349, 121; (b) Z. Rappoport,
The Chemistry of Dienes and Polyenes, John Wiley & Sons,
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Scheme 3 Synthesis of dienylbromide.
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2021.
Scheme 4 Suzuki–Miyaura coupling of dienylchloride.
As bromide derivatives are often more reactive than chlorides
for further transformations, we tried to extend this reaction to the
formation of 1-bromo-1,3-butadienes. Phenylacetylene 1a reacted
with 0.5 equiv. of camphorsulfonic acid and 1.0 equiv. of
benzyltriethylammonium bromide in the presence of 5 mol%
of precatalyst I in 1,2-dichloroethane (0.5 mL) at room
temperature to lead successfully after 2 h to 1-bromo-1,4-
diphenyl-1,3-butadiene 3a in 70% yield with a (1Z, 3E)/
(1E, 3E) ratio of 95/5 (Scheme 3).
9 Y. Wang, B. Lu and L. Zhang, Chem. Commun., 2010, 46, 9179.
10 (a) S. De
689, 1382; (b) C. Vovard-Le Bray, S. De
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´
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C. Bruneau, P. H. Dixneuf, L. Toupet, G. Dazinger and
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¨
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reactions of chlorinated alkenes have been reported recently,15
dienylchlorides can also be regarded as suitable substrates for the
stereoselective preparation of multi-substituted dienes. Our attempt
to perform a Suzuki–Miyaura coupling of phenylboronic acid
and chlorodiene 2a led to 1,1,4-triphenyl-1,3-butadiene 4a in
an excellent yield under mild conditions (Scheme 4).
(c) C. Gemel, A. LaPense
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In conclusion, we have successfully developed a novel and
straightforward access to 1-halo-1,3-dienes via a stereoselective
[Cp*RuCl(cod)]-catalysed reaction. This one-pot catalytic process
proceeds with good yields, under mild conditions, from easily
accessible alkynes, and constitutes a remarkable example of total
atom economy for the addition of HCl. We described also a new
efficient hydrohalogenative system consisting of separate proton
and halide sources. This method provides a novel approach to
the synthesis of conjugated dienes and has potential, by various
14 X-ray structure of compounds 2a and 2i.
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Commun., 2004, 1400; (b) J. Simar-Mercier, A. B. Flynn and
W. W. Ogilvie, Tetrahedron, 2008, 64, 5472.
c
11034 Chem. Commun., 2012, 48, 11032–11034
This journal is The Royal Society of Chemistry 2012