Ruthenium-catalysed multiple component transformations: One-step stereoselective synthesis of functional dienes from alkynes and carboxylic acids

Article abstract of DOI:10.1039/a903805a

The precatalyst RuCl(cod)C₅Me₅ allows the head-to-head oxidative dimerization of terminal alkynes and the concommittent 1,4-addition of carboxylic acid to afford (1E,3E)-1-acyloxy-1,3-dienes in one step under mild conditions.

Full text of DOI:10.1039/a903805a

Ruthenium-catalysed multiple component transformations: one-step
stereoselective synthesis of functional dienes from alkynes and carboxylic acids
Jacques Le Paih, Sylvie Dérien and Pierre H. Dixneuf*
UMR 6509 CNRS-Université de Rennes, Organométalliques et Catalyse: Chimie et Electrochimie Moléculaires,
Campus de Beaulieu, 35042 Rennes, France. E-mail: pierre.dixneuf@univ-rennes1.fr
Received (in Liverpool, UK) 7th May 1999, Accepted 22nd June 1999
O2CR1
Ph
The precatalyst RuCl(cod)C5Me5 allows the head-to-head
oxidative dimerization of terminal alkynes and the con-
committent 1,4-addition of carboxylic acid to afford
(1E,3E)-1-acyloxy-1,3-dienes in one step under mild condi-
tions.
[Ru]
R
X
H +
R1CO2H
2
2
(1)
Ph
H
+
MeCO2H
r.t. [Ru]
The development of catalysis towards the selective combination
of several simple substrates to afford in one step a unique
functional molecule in high yield constitutes an important
contribution to the discovery of new synthetic methods for
environmental impact. These reactions require toxic reagents to
be banished, high selectivity and atom economy to avoid costly
separations. Multiple component reactions selectively combin-
ing several molecules into only one1,2 via the formation of more
than two bonds constitute an important challenge for chemists.
Recently, ruthenium catalysts, in particular, have been shown to
promote the one-step addition of three simple substrates.
Representative examples deal with the selective formation of
polycyclic compounds,3 bicyclic phenols,4 tricyclic hydro-
quinones5 or cyclopentenones via the catalytic trifunctional
Pauson–Khand reaction.6 The combination of functional arene
derivatives with alkene and carbon monoxide via the activation
of the inert (sp2)C–H bond has led to aryl ketones.7 1,5-Di-
ketones and (E)-vinyl chlorides can also be obtained in one step
by three component addition of alkyne, unsaturated ketone and
water,8 or NH4Cl,9 respectively. The combination of two
molecules of acetylene and acrylonitrile has just been achieved
by a ruthenium catalyst and affords the heptatrienenitrile.10
We have shown recently that the catalyst precursor RuCl-
(cod)C5Me5 promotes the oxidative coupling of C·C and CNC
bonds of alkynes and allyl alcohol to generate either g,d-
aldehydes11 or performs the three-component synthesis of
methylenetetrahydropyran acetal derivatives.12 We now report
a novel regio- and stereo-selective, three-component catalytic
synthesis of functional 1,3-dienes, by one-step combination of
two molecules of terminal alkynes and one of carboxylic acid to
NOE
[Ru] = RuCl(cod)C5Me5
O2CCH3
(2)
X
X
3a X = H
4 X = OMe
5 X = CN
respectively, at room temperature [eqn. (2)], showing that an
electron-withdrawing group on the phenyl ring drastically
favours the reaction. The reaction also proceeds with alkylace-
tylenes but with a lower efficiency as hex-1-yne and oct-1-yne
are transformed, under the 3a formation conditions, into
(1E,3E)-RCHNCH–CHNC(OAc)R 1 (R = Bun, 20%) and 2
(R = C6H13, 40%).
A variety of carboxylic acids have been added to phenyl-
acetylene in the presence of catalyst A at room temperature and
the corresponding dienes 6 were obtained (Scheme 1). It thus
appears that strong carboxylic acids give a low yield of diene
(6a: 30%), and the weaker acids (pKa > 4) afford quantitative
yields after 16–18 h of catalytic reaction at room temperature
(6d–6f).
It has been shown recently that RuCl(cod)C5R5 precursors
react with terminal alkynes to give, after cod ligand displace-
ment, a complex resulting from the head-to-head, oxidative
coupling of two molecules of alkyne at the ruthenium site10,13,14
to give either a bis-carbene derivative13,14 or, when a phosphine
ligand is coordinated, a ruthenacyclopentadiene.10 Moreover,
we have shown that the addition of two equivalents of
phenylacetylene to precursor A led to the formation and
isolation of the metallacycle B, with a bis-carbene structure
easily
afford
(1E,3E)-1,4-disubstituted-1-acyloxybuta-
1,3-dienes [eqn. 1)].
The reaction of 2.5 mmol phenylacetylene with 1.25 mmol
acetic acid in the presence of 5 mol% of RuCl(cod)C5Me5 (A)
in 1 mL dioxane affords, after 20 h at room temperature 90% of
only the (1E,3E)-1,4-diphenyl-1-acyloxybuta-1,3-diene 3a
stereoisomer [eqn. (2)]. This reaction corresponds to the highly
regioselective head-to-head coupling of terminal alkynes with
stereoselective 1,4-addition of the proton and the carboxylate.
The stereochemistry of 3a was established by NMR and NOE
experiments.† The addition of MeCO2D to 2 equiv. of
phenylacetylene, catalysed by 5% of A, afforded the corre-
sponding PhCDNCH–CHNC(OAc)Ph derivative 3b and showed
the selective 1,4-addition of acetic acid to the conjugated diene
skeleton.
The efficiency of the reaction drastically depends on the
nature of the solvent. After 15 h the previous reaction leading to
3a, performed at room temperature led to 37, 41, 49, 75 and
77% phenylacetylene conversion in toluene, CH2Cl2, MeCN,
THF and dioxane, respectively. The corresponding addition of
acetic acid to p-methoxyphenylacetylene and p-cyanophenyl-
acetylene led to 85% of 4 and 81% of 5, but after 42 and 0.5 h,
O2CR1
[Ru]
Ph
H +
R1CO2H
2
Ph
Ph
6a–f
R1
t/h
Yield (%)
a CHCl2
15
18
20
30
85
62
95
98
91
b CH2CN
c
H
d CH2OMe 18
e Ph
But
16
16
f
Scheme 1 Reaction conditions: alkyne (2.5 mmol), catalyst A (0.125
mmol), acid (1.25 mmol), dioxane (1 ml), stirred at room temperature for
various reaction times (15–20 h ).
Chem. Commun., 1999, 1437–1438
1437

Cp*RuCl(cod) A
tion to the ruthenacycle intermediate resulting from oxidative
coupling of two alkyne molecules at the ruthenium centre.
The authors are grateful to Dr Christian Bruneau for helpful
discussions and MENRT for the award of a thesis grant to
J. L. P.
cod
2
R
H
Cp*
R
H
R
Cl
Ru
Notes and references
† Selected data for 3a Ph–C4HNC3H–C2HNC1(O2CCH3)Ph: dH (CDCl3,
300 MHz) 2.23 (s, 3H, O2CCH3), 6.30 (d, 1H, J 11.2, H2), 6.68 (d, 1H, J
15.6, H4), 6.98 (dd, 1H, J1 11.2, J2 15.6, H3), 7.3–7.5 (m, 10H, Ph).
dH(C6D6, 300 MHz) 1.71 (s, 3H, O2CCH3), 6.31 (d, 1H, J 11.1, H2), 6.49 (d,
1H, J 15.1, H4), 7.00–7.16 (m, 9H, Ph + H3), 7.46–7.54 (m, 2H, Ph). NOE
experiments show the relative cis position of H2 and the O2CCH3 group. In
CDCl3, the irradiation at d 2.23 leads to an increase in 2% of the signal at
d 6.30 (H2). In C6D6, irradiation at d 1.71 leads to an increase in 1.5% of the
signal of the two ortho protons of the phenyl group between d 7.46 and 7.54
and an increase in 2% of the signal at d 6.31 (H2). But the irradiation at d
6.31 (H3) has no influence on the signals at d 7.46 and 7.54 or d 1.71.
R
R1CO2
R
Cp*
R1CO2H
Cl
Ru
R
R
B
2
R
H
–
+ R1CO2
1 I. Ugi, Angew. Chem., 1962, 74, 9; A. Dömling and I. Ugi, Angew.
Chem., Int. Ed. Engl., 1993, 32, 563.
2 L. F. Tietze and U. Beifuss, Angew. Chem., 1993, 105, 137; L. F. Tietze
and U. Beifuss, Angew. Chem., Int. Ed. Engl., 1993, 32, 131; G. H.
Posner, Chem. Rev., 1986, 86, 831 ; B. M. Trost, Angew. Chem., Int. Ed.
Engl., 1995, 34, 259.
3 Y. Yamamoto, H. Kitahara, R. Hattori and K. Itoh, Organometallics,
1998, 17, 1910.
4 N. Chatani, Y. Fukumoto, T. Ida and S. Murai, J. Am. Chem. Soc., 1993,
115, 11 614.
Cp*
Ru
Cp*
Cl
R
Cl
H
Ru
H
R
R
R
R1CO2
E
C
+ R1CO2
–
Cp*
Ru
5 T. Morimoto, N. Chatani, Y. Fukumoto and S. Murai, J. Org. Chem.,
1997, 62, 3762; T. Kondo, N. Suzuki, T. Okada and T. Mitsudo, J. Am.
Chem. Soc., 1997, 119, 6187.
Cl
H
R
R
6 N. Suzuki, T. Kondo and T. Mitsudo, Organometallics, 1998, 17,
766.
D
7 N. Chatani, Y. Ie, F. Kakiuchi and S. Murai, J. Org. Chem., 1997, 62,
2604; E. J. Moore, W. R. Pretzer, T. J. O’Connell, J. Harris, L.
LaBounty, L. Chou and S. S. Grimmer, J. Am. Chem. Soc., 1992, 114,
5888.
8 B. M. Trost, M. Portnoy and H. Kurihara, J. Am. Chem. Soc., 1997, 119,
836.
9 B. M. Trost and A. B. Pinkerton, J. Am. Chem. Soc., 1999, 121,
1988.
10 C. S. Yi, J. R. Torres-Luhian, N. Liu, A. L. Rheingold and I. A. Guzei,
Organometallics, 1998, 17, 1257.
11 S. Dérien, D. Jan and P. H. Dixneuf, Tetrahedron, 1996, 52, 5511.
12 S. Dérien, L. Ropartz, J. Le Paih and P. H. Dixneuf, J. Org. Chem.,
1999, 64, 3524; S. Dérien, B. Gomez-Vicente and P. H. Dixneuf, Chem.
Commun., 1997, 1405.
13 M. O. Albers, D. J. A. de Waal, D. C. Liles, D. J. Robinson, E. Singleton
and M. B. Wiege, J. Chem. Soc., Chem. Commun., 1986, 1680.
14 C. Gemel, A. La Pensée, K. Mauthner, K. Mereiter, R. Schmid and K.
Kirchner, Monatsh. Chem., 1997, 128, 1189.
Scheme 2
(Scheme 2) which was previously obtained via a different
route.14 Consequently, Scheme 2 provides a possible mecha-
nism leading to the formation of dienes 3–6. Protonation of bis-
carbene intermediate B can lead to the species D, via known
carbene ligand insertion into a M–H bond.15 The direct
protonation of the carbene atom of B to afford D in one step
cannot be ruled out. The species E arising from carboxylate
addition to D is expected to generate (1E,3E)-dienes 3–6. In
support of this mechanism we have shown that the isolated
complex B catalyses the formation of 3a under conditions
reported in Scheme 1 and that the substitution of acetic acid by
NaO2CMe in THF does not lead to any transformation of either
phenylacetylene or complex B.
15 H. Le Bozec, J.-L. Fillaut and P. H. Dixneuf, J. Chem. Soc., Chem.
Commun., 1986, 1182; V. A. Osborn, A. Craig and M. J. Winter,
J. Chem. Soc., Chem. Commun., 1986, 1185.
The above catalytic reaction represents a new example of
multiple component addition of type 2A + B ? C, performed
under mild conditions with atom economy. It offers potential for
the stereoselective preparation of functional dienes by 1,4-addi-
Communication 9/03805A
1438
Chem. Commun., 1999, 1437–1438