An in situ generated ruthenium catalyst for the Tishchenko reaction

Article abstract of DOI:10.1002/adsc.200900701

A simple and efficient catalytic system for the selective dimerization of aldehydes, the Tishchenko reaction, is described. High yields of symmetrical esters were generally achieved using an in situ generated ruthenium catalyst in association with the electron-rich and hindered cyclohexyl-(diphenyl)phosphane (CyPPh₂) ligand.

Full text of DOI:10.1002/adsc.200900701

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DOI: 10.1002/adsc.200900701
An in situ Generated Ruthenium Catalyst for the Tishchenko
Reaction
Marc-Olivier Simona and Sylvain Darsesa,*
a
Laboratoire Charles Friedel (UMR 7223, CNRS), Ecole Nationale Supꢀrieure de Chimie de Paris, 11 rue P & M Curie,
75231 Paris cedex 05, France
Fax : (+33)-1-4407-1062; e-mail: sylvain-darses@chimie-paristech.fr
Received: October 8, 2009; Revised: November 17, 2009; Published online: January 13, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900701.
Abstract: A simple and efficient catalytic system
for the selective dimerization of aldehydes, the
Tishchenko reaction, is described. High yields of
symmetrical esters were generally achieved using
an in situ generated ruthenium catalyst in associa-
tion with the electron-rich and hindered cyclohexyl-
under highly controlled conditions (glove-box tech-
niques).
In our continuing work on atom-economic reactions
[12,13]
À
involving C H bond functionalization,
we report
here a highly efficient protocol for the dimerization
of aldehydes to the corresponding symmetrical esters,
using an in situ generated active ruthenium catalyst.
The feasibility of the reaction was initially studied
using benzaldehyde (1a) as a model substrate with an
in situ generated ruthenium catalyst made up of di-
ACHTUNGTRENNUNG(diphenyl)phosphane (CyPPh2) ligand.
Keywords: aldehydes; esters; homogeneous cataly-
sis; ruthenium; Tishchenko reaction
meric [RuCl2ACTHNUTRGNE(UNG p-cym)]2 (p-cym=p-cymene) associated
with sodium formate and phosphorus ligands
(Figure 1). We were pleased to find that in the pres-
ence of 1 equivalent of triphenylphosphane compared
Atom-economic reactions have attracted high interest to ruthenium, the dimerization of benzaldehyde pro-
in recent years, allowing the functionalization of more ceeded smoothly at 808C in dioxane to afford ester 2a
easily available starting materials and the reduction of with 84% conversion, along with the formation of 8%
salt amounts (cleaner reactions).[1] Among these, the benzyl alcohol (3a). A screening of ligands revealed
Tishchenko reaction, which has been known for more that the most suited ligands were CyPPh2 (L6) and
than a century,[2,3] involving the dimerization of alde- Cy2PPh (L7), electron-rich and hindered ligands. It
hydes to form the corresponding symmetric esters, is also appeared that in this reaction, electron-poor li-
of industrial importance. For example, the Tishchenko gands L2 or L3 were not really efficient for the dime-
ester of cyclohexanecarboxaldehyde is a precursor in rization of 1a. Moreover, and contrary to the hydroar-
the formation of epoxy resins, benzyl benzoate is used ylation of alkenes using a similar catalyst system,[12]
a
as a dye carrier, and in some countries, ethyl acetate bidentate ligand such as binap (L7) can also be used
is produced from the catalyzed dimerization of acetal- in the reaction. We also evaluated the influence of the
dehyde.[4] Besides the traditional aluminum alkox- number of equivalents of phosphane ligand compared
ides,[5] various other catalysts have been shown to per- to ruthenium, and found that the most active catalyst
form the reaction.[3] Indeed, metal catalysts such as al- was obtained using either 1 or 2 equivalents of phos-
kaline metals,[6] alkaline metal oxides,[7] transition phane; very slow reactions being observed in the ab-
metals[8] and more particularly lanthanides[9] do pro- sence of ligand or with 3 equivalents of phosphane.
mote the reaction more or less efficiently, according Moreover, in the absence of either sodium formate or
to the catalyst employed and the nature of the sub- ruthenium catalyst, no reaction was observed.
strate.[10,11] Noteworthy, even if the dimerization of ar-
To select the most appropriate ligand, we evaluated
omatic aldehydes has been described, only a few cata- the two cyclohexyl-substituted phosphanes L6 and L7
lysts are operating with good efficiency.[6,7b,8e,g,j,10a,c] on a more challenging substrate, the electron-rich 4-
Moreover, most of the catalysts described show low methoxybenzaldehyde (1b). Under identical condi-
efficiency with electron-rich or ortho-substituted sub- tions, and using 1 equivalent of ligand compared to
strates and are expensive or must be manipulated ruthenium, a 95% conversion was achieved using
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305

Marc-Olivier Simon and Sylvain Darses
COMMUNICATIONS
which has been used in liquid crystal preparations,[14]
was obtained in 84% yield (entry 9). ortho-Substituted
aryl aldehydes also underwent dimerization with high
efficiency (entries 3, 7 and 8); a reaction which is gen-
erally difficult to promote using previously published
catalytic systems. Under these conditions, furfural
(1k) was also dimerized into heterocyclic ester 2k, al-
though with lower efficiency (entry 11).
We also evaluated the reactivity of some aliphatic
aldehydes under these conditions. Even if disappoint-
ing results were achieved in the dimerization of hexa-
nal, we found that the use of tris(4-methoxyphenyl)-
phosphane (L5) instead of L6 allowed the dimeriza-
tion of cyclohexanecarboxaldehyde (entries 12) in
good yield. On the other hand, the dimerization of a
benzylic aldehyde (entry 13) was best achieved under
standard conditions, and the symmetrical ester was
obtained as an inseparable mixture of two diastereo-
mers in a 56% yield. Further studies to improve the
reactivity of such substrates are currently underway.
Unsurprisingly, the ruthenium-catalyzed intramo-
lecular Tishchenko reaction of o-phthalaldehyde (1n)
allowed the formation of the corresponding phthalide
2n in high yield and the reaction was very fast
(Scheme 2).
Figure 1. Influence of the ligand on the ruthenium-catalyzed
Tishchenko reaction: GC conversion to 2a (dark gray color)
and to 3a (light gray color).
A probable mechanism for this ruthenium-cata-
lyzed Tishchenko reaction is depicted in Scheme 3.
We have recently shown that the combination of ruth-
enium(II) catalyst precursor and a formate salts al-
CyPPh2 (L6) whereas a moderate conversion of 59% lowed the generation of ruthenium dihydride spe-
was observed using Cy2PPh (L7) for 20 h reaction at cies.[12d] This species A should react with the aldehyde
808C (Scheme 1).
to form either a di
ACHTUNGTNER(NUNG alkoxo)ruthenium species or a
Under these optimized conditions, using CyPPh2 as hydridoACHTUNGTRENNNUG
(alkoxo)ruthenium(II) B (Scheme 3).[15] Com-
ligand for the in situ generated ruthenium catalyst, plexation followed by the insertion of the aldehyde
[16]
À
the scope of this ruthenium-catalyzed Tishchenko re- C=O bond into the Ru O bond in intermediate C,
action was evaluated on a variety of aromatic alde- would result in the formation of intermediate D.
hydes (Table 1). Moderate to good yields were gener- Then, b-hydride elimination would lead to the forma-
ally achieved on a large variety of aromatic aldehydes. tion of the expected symmetrical ester and would re-
More particularly, electron-rich aldehydes, which gen- generate the active ruthenium species A, which can
erally show moderate activity under previously de- be either a ruthenium monohydride or dihydride spe-
scribed conditions, were efficiently dimerized (en- cies.
tries 2 and 3). Interestingly, bromo-substituted aro-
We have thus described a simple and efficient cata-
matic aldehyde 1e also underwent the Tishchenko re- lytic system for the selective dimerization of alde-
action to afford 2e in 74% yield (entry 5); the latter hydes, the so-called Tishchenko reaction. High yields
can be further functionalized by palladium-catalyzed of symmetrical esters were generally achieved using
cross-coupling. In the same way, symmetrical ester 2i, an in situ generated ruthenium catalyst in association
Scheme 1.
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Adv. Synth. Catal. 2010, 352, 305 – 308

An in situ Generated Ruthenium Catalyst for the Tishchenko Reaction
Table 1. Ruthenium-catalyzed Tishchenko reaction.[a]
Entry
1
Aldehyde (1)
Product
Yield[b] [%]
92
Scheme 2. Intramolecular ruthenium-catalyzed Tishchenko
reaction.
2a
2
3
4
5
2b
2c
2d
2e
88
75[d]
87
74[d]
6
7
8
2f
2g
2h
65
82
80
Scheme 3. Proposed reaction mechanism.
with the electron-rich and hindered CyPPh2 ligand.
The reaction conditions are operationaly simple and
use an inexpensive ruthenium catalyst precursor.
9
2i
84
Experimental Section
General Procedure
10
11
12
2j
73
45
A septum-capped vial was charged with [RuCl2ACTHUNTRGNEU(GN p-cymene)]2
(7.7 mg, 12.5 mmol, 2.5 mol% Ru), sodium formate (10.2 mg,
150 mmol, 15 mol%) and cyclohexyldiphenylphosphane
(6.7 mg, 25 mmol, 2.5 mol%). The vial was placed under
vacuum for 15 min then under argon. Degassed dioxane
(1 mL) was added, and then aldehyde (1 mmol) was added.
The vial was placed in a pre-heated oil bath at 808C and the
mixture was stirred until completion of the reaction (fol-
lowed by GC analysis). After concentration under reduced
pressure, the crude mixture was purified by silica gel chro-
matography.
2k
2l
81[c]
56[d]
13
2m
[a]
Reaction conducted on 1 mmol of aldehyde using
1.25 mol% [RuCl2A(p-cym)]2, 2.5 mol% CyPPh2 (L6),
CTHUNGTRENNUNG
15 mol% HCO2Na in dioxane at 808C for 20 h.
Isolated yields.
Using (4-MeOC6H4)3P 2.5 mol% as ligand.
Using 2.5 mol% [RuCl2ACHTNUGTRENUNG(p-cym)]2 and 5 mol% CyPPh2.
Acknowledgements
[b]
[c]
[d]
M.-O. Simon thanks the Ministꢀre de l’Education et de la Re-
cherche for a grant.
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Marc-Olivier Simon and Sylvain Darses
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