Ruthenium-catalyzed synthesis of functionalized dienes from propargylic esters: Formal cross-coupling of two carbenes

Article abstract of DOI:10.1002/anie.200805031

Cross-coupling carbenes: The coupling of a propargylic ester with a diazoalkane in the presence of [RuCl(cod)Cp*] catalyst leads to the formation of functionalized conjugated dienes with high stereoselectivity. The reactioninvolves the cross-coupling of a

Full text of DOI:10.1002/anie.200805031

Angewandte
Chemie
DOI: 10.1002/anie.200805031
Synthetic Methods
Ruthenium-Catalyzed Synthesis of Functionalized Dienes from
Propargylic Esters: Formal Cross-Coupling of Two Carbenes**
Chloꢀ Vovard-Le Bray, Sylvie Dꢀrien, and Pierre H. Dixneuf*
The in situ creation of reactive metal carbene intermediates,
especially on interaction of alkyne, enyne, or dienyne
substrates with electrophilic catalysts, such as [RuX2Ln],[1–3]
PtX2,[1,4] or AuX,[5] has recently led to novel skeletal
rearrangements and synthetic methods for the building of
complex molecules and polycylic motifs.[6] The potential of
alkenylcarbene–metal intermediates generated by the Rau-
tenstrauch rearrangement of propargylic esters [Eq. (1a)],
catalyzed by PdII systems,[7] or, more recently, by RuII,[3]
PtII,[4d-f,5g] or Au[5g,8–10] catalysts, has been demonstrated by
the direct synthesis of functional cyclopropane deriva-
tives,[1–3,8b,c] cyclopentanones,[7,8a] terpenoids,[9] trienes,[3c] and
indenes.[3e,4f,10]
the latter with another source of carbene would then be
possible [Eq. (1b)].
We report herein that the reaction of propargylic esters
with diazoalkanes in the presence of [RuCl(cod)Cp*] (cod =
cyclooctadiene) generates functional dienes by the coupling
of a vinylcarbene fragment, arising from the rearranged
propargylic ester, with the diazoalkane carbene [Eq. (2)].
This catalytic reaction constitutes a formal “cross-coupling”
=
C C bond formation from two different carbene sources.
The Rautenstrauch rearrangement promoted by ruthe-
nium catalysts was detected initially with [{RuCl2(CO)3}n] by
Ohe, Uemura, and co-workers. The resulting unsaturated
carbene added to olefins to form vinylcyclopropanes.[3a,b] By
contrast, when we attempted the reaction of propargyl acetate
1a with styrene in the presence of a catalytic amount of
[RuCl(cod)Cp*], it did not lead to the cyclopropanation
product but to compound 2a, resulting from the dimerization
of the rearranged vinylcarbene, along with a small amount of
enyne 3a [Eq. (3)]. Both the decrease in reaction temperature
and the use of toluene rather than dioxane had a positive
effect on the formation of 2a, which was obtained in
moderate yields (35%, E:Z 65:35).[15]
Although Group 6 Fischer-type metal carbene complexes
are known to dimerize the carbene ligands into symmetrical
alkenes by carbene transfer to a palladium catalyst,[11] the
coupling of a vinylcarbene with a different carbene source, to
create a double bond and to generate functional conjugated
dienes, has not been reported [Eq. (1b)]. However, the enyne
metathesis, performed with Grubbs catalyst and leading to
alkenylcycloalkenes, can be formally considered as the
trapping of the vinylcarbene intermediate by the alkene
bond to create the new intracyclic double bond.[12] By
contrast, complexes containing the {Ru(X)Cp*} moiety
(Cp* = C5Me5), which inhibit enyne metathesis,[13] are
known to stabilize the formation of cis bis(carbene) ruthe-
nium complexes.[14] If a catalyst of the form [RuX(C5R5)]
could underwent the Rautenstrauch rearrangement of a
propargylic derivative into a vinylcarbene, the coupling of
[*] C. Vovard-Le Bray, S. Dꢀrien, P. H. Dixneuf
Laboratoire “Catalyse et Organomꢀtalliques”
Institut Sciences Chimiques de Rennes, UMR 6226
CNRS-Universitꢀ de Rennes
Campus de Beaulieu, 35042 Rennes (France)
Fax: (+33)2-2323-6939
E-mail: pierre.dixneuf@univ-rennes1.fr
As compound 2a contains two rearranged propargylic
groups, and as the {RuXCp*} moiety stabilizes cis bis-
(carbene) ruthenium complexes,[14] it seems possible that 2a
arises from a bis(vinylcarbene) ruthenium moiety, rather than
from dimerization of the free vinylcarbene, or by the reaction
of the vinylcarbene ruthenium complex with 1, accompanied
by acetate shift.[3d] We have thus investigated the coupling of
the in situ rearranged vinylcarbene with a diazoalkane which
[**] We are grateful to CNRS and Ministꢁre de la recherche for support,
the latter for a PhD grant to C.V.-L.B., the European Union through
network IDECAT, the Institut Universitaire de France for member-
ship (P.H.D.) and to Christian Bruneau for helpful discussions.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200805031.
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Table 1: Catalytic formation of dienes from propargylic esters and TMS diazomethane.[a]
[Eq. (4)]. The two major isomers,
4 f’ with E configuration of the ace-
tate-substituted double bond (4 f’1
(EZ)/4 f’2 (EE): 80/20), and the
two minor ones, 4 f (4 f1 (ZZ)/4 f2
(ZE): 80/20), were obtained in the
ratio 85:15. The major products
have a silylalkenyl bond with E con-
figuration, in contrast to disubsti-
tuted derivatives 4a–4e.
The desilylation of compounds 4
was not easy to perform. Thus, the
reaction was carried out with
in situ-generated diazomethane, by
using trimethylsilyldiazomethane in
methanol as solvent with 1a in the
presence of styrene (5 equivalents).
After only 15 min of reaction at
608C, the corresponding desilylated
diene 5 was isolated with a good
yield (91%) [Eq. (5)].
Substrate 1 Reaction
Diene 4
Yield
[%][b]
Stereoselectivity
time
(E:Z)
5 min
5 min
4 h
99
–
–
–
99
68[c]
2 h
2 h
89
99
65:35
65:35
Other diazoalkanes proved less
reactive than N2CHTMS for the
formation of dienes. The reaction
of 1a with phenyldiazomethane in
the presence of styrene (5 equiva-
lents) at 608C after 16 h led to the
corresponding conjugated diene 6
in moderate yield (51%). However,
[a] Reaction conditions: propargylic carboxylate (1.2 mmol, 1 equiv), styrene (5 equiv), trimethylsilyl-
diazomethane 2m in diethyl ether (1.1 equiv), [RuCl(cod)Cp*] ( 5 mol%), 608C in 1 mL of dioxane.
[b] Yield of compound isolated by chromatography on silica gel. [c] Conversion of 70%.
easily generates a ruthenium carbene on reaction with
[RuCl(cod)Cp*].[13,17]
The reaction of propargylic acetate 1a (1.2 mmol) with
N2CHTMS (1.1 equiv 2m in Et2O, TMS = trimethylsilyl),
styrene (5 equivalents) and [RuCl(cod)Cp*] (5 mol%) in
dioxane for 5 min at 608C led to the formation of the
conjugated diene 4a, which was isolated in 99% yield
(Table 1).
The propargylic esters 1b–e, with two substituents at the
propargylic position, reacted under the same reaction con-
ditions and gave the products 4b–e in times of 5 min–2 h, in
good yields (89–99%) that were not influenced by the
substituent bulkiness (Table 1).
As for the vinylcarbene dimerization [Eq. (3)], the
presence of styrene was beneficial: without 5 equivalents of
styrene, dienes 4d and 4d’ were obtained in only 50% yield.
Coordination of styrene to the ruthenium intermediate may
temporarily protect the coordinatively unsaturated ruthe-
nium carbene species.
With disubstituted propargylic carboxylates 1a–e, the
formation of the TMS-substituted double bond in dienes 4
was highly stereoselective (100% Z) Table 1. When the two
substituents on 1 were different (1d–e), a mixture of two
isomers in 65:35 ratio was obtained, arising from the Z and
E configurations of the tetrasubstituted double bond, as
shown by NOESY experiments.
The monosubstituted propargylic carboxylate 1 f led to a
mixture of four isomers of type 4 with a 99% total yield
the phenyl-substituted double bond in 6 has the E configura-
tion [Eq. (6)].
At this stage, the reaction mechanism has not been
elucidated as the initial adduct of [RuCl(cod)Cp*] with 1a or
N2CHTMS could not be detected. Two possible approaches
can be considered (Scheme 1). The first potential mechanism
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Experimental Section
Typical procedure for ruthenium-catalyzed cross-coupling of car-
benes: [RuCl(cod)Cp*] (5 mol%) was added as a solid to a solution
of propargyl acetate 1a–1e (1.2 mmol), styrene (5 equiv) and
trimethylsilyldiazomethane (1.1 equiv, 2m solution in diethyl ether)
in dioxane (1 mL) at 608C under an inert atmosphere. The reaction
mixture was stirred for 5 min–2 h. The solvent was removed under
vacuum, and the products were isolated by column chromatography
on silica gel, eluted with mixed solvent (pentane/diethyl ether).
Full experimental details and characterization data are given in
the Supporting Information.
Received: October 14, 2008
Revised: November 20, 2008
Published online: January 19, 2009
Keywords: carbenes · catalysis · cross-coupling · dienes ·
.
ruthenium
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Communications
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