Efficient aldehyde olefination reactions catalyzed by an iron porphyrin complex in an ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2004.08.070

The commercially available complex Fe(TPP)Cl is an active and highly (E)-selective catalyst for the olefination of a variety of aldehydes in the presence of PPh₃ and diazoacetate in the ionic liquid (bmim)(PF ₆). Dependent on the reactivity of the applied aldehyde, the reaction can be carried out at a reaction temperature of 50-80°C. After 0.5-24 h quantitative olefin yields are reached with a broad variety of different aldehydes. Due to the application of an ionic liquid as reaction medium the products can be easily removed from the catalyst by a simple extraction and the catalyst is conveniently reusable without significant activity loss. Spectroscopic investigations indicate that the reaction mechanism includes the quantitative formation of a phosphorus ylide, which then reacts further in a Wittig reaction under formation of an olefin.

Full text of DOI:10.1016/j.tetlet.2004.08.070

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7415–7418
Efficient aldehyde olefination reactions catalyzed by an iron
porphyrin complex in an ionic liquid
Wei Sun and Fritz E. Kuhn*
¨
Lehrstuhl fu¨r Anorganische Chemie der Technischen Universita¨t Mu¨nchen, Lichtenbergstrasse 4,
D-85747 Garching bei Mu¨nchen, Germany
Received 17 June 2004; revised 12 August 2004; accepted 13 August 2004
Available online 27 August 2004
Abstract—The commercially available complex Fe(TPP)Cl is an active and highly (E)-selective catalyst for the olefination of a vari-
ety of aldehydes in the presence of PPh3 and diazoacetate in the ionic liquid (bmim)(PF6). Dependent on the reactivity of the applied
aldehyde, the reaction can be carried out at a reaction temperature of 50–80°C. After 0.5–24h quantitative olefin yields are reached
with a broad variety of different aldehydes. Due to the application of an ionic liquid as reaction medium the products can be easily
removed from the catalyst by a simple extraction and the catalyst is conveniently reusable without significant activity loss. Spectro-
scopic investigations indicate that the reaction mechanism includes the quantitative formation of a phosphorus ylide, which then
reacts further in a Wittig reaction under formation of an olefin.
Ó 2004 Elsevier Ltd. All rights reserved.
One of the classic approaches for constructing carbon–
carbon double bonds in organic synthesis involves the
Wittig reaction and its numerous variants.1 Despite
being broadly applicable methods, they still have some
noteworthy drawbacks, most prominently the require-
ment of stepwise synthesis of ylide precursors under
basic conditions.1 Accordingly, growing research inter-
est arose in the development of new methods that can
directly use easily accessible diazo compounds for in situ
generation of ylides under neutral conditions.2 Several
transition metal complexes, among them Mo, Re, Rh,
Fe, Co and Cu have been shown to catalyze the olefina-
tion of aldehydes with diazo compounds in the presence
of tertiary phosphines (Eq. 1).3
velocity due to blocking of the active site of the catalyst
in several cases.4 Even more importantly, the separation
procedures necessary to obtain the products often lead
to significant catalyst losses.3 In order to minimize these
problems we applied the iron porphyrin complex
Fe(TPP)Cl, which does not directly bind phosphines
and
the
PF6ꢀ-salt
of
1-butyl,3-methylimide
((bmim)(PF6))5 as reaction medium. Fe(TPP)Cl (for-
mula see Chart 1) has been shown to be one of the most
active aldehyde olefination catalysts,3n particularly in
low catalyst concentrations in THF and toluene.
(Bmim)(PF6) (formula see Chart 1) is a room tempera-
ture ionic liquid, which should allow an extraction of
the olefins without (significant) catalyst loss.5,6
Usually the catalysts are employed in ratios between 1
and 5mol%, sometimes even 10mol% (with respect to
diazo compound) in order to avoid unwanted side reac-
tions such as the formation of azines.4 The reactions are
usually performed in toluene or tetrahydrofurane
(THF). The (necessary) excess of tertiary phosphines
as well as the increasing amount of the reaction product
phosphine oxide are able to slow down the reaction
Cl
N
N
N
N
Fe
N
N
PF6
(bmim)(PF6)
Keywords: Aldehyde olefination; Catalysis; Diazo compounds; Iron
porphyrin.
Fe(TPP)Cl
*
Corresponding author. Tel.: +49 89 289 13108; fax: +49 89 289
13473; e-mail: fritz.kuehn@ch.tum.de
Chart 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.070

7416
W. Sun, F. E. Ku¨hn / Tetrahedron Letters 45 (2004) 7415–7418
In this work we present our finding that the commer-
cially available, stable compound Fe(TPP)Cl can be
successfully applied as catalyst together with the
commercially available (as well as easy to synthesize)5
room temperature ionic liquid (bmim)(PF6). The combi-
nation Fe(TPP)Cl/(bmim)(PF6) fulfils the demand
described above for a commercially available, active,
stable and reusable catalyst/solvent system.
steric bulk of the aldehyde. If electronic reasons would
dominate, the meta derivative should be the easiest of
the three methylbenzaldehydes to be transformed to
the olefin. The deactivated p-methoxybenzaldehyde
and p-(dimethyl)aminobenzaldehyde require higher
reaction temperatures to be quantitatively transformed
to olefins. The reaction with the least activated alde-
hyde, p-(dimethyl)aminobenzaldehyde is completed
after 1day at 80°C.
The catalyst Fe(TPP)Cl was applied in 1:100 molar rela-
tionship (1mol%) to all examined aldehydes. Triphenyl-
phosphine was applied in a 1.2-fold molar excess with
respect to the aldehyde and ethyl diazoacetate (EDA)
was used as diazo compound (for more details see Table
1 and Ref. 7). The products can be separated from the
catalyst/ionic liquid system by simple extraction with
diethyl ether in all examined cases. When the ionic liquid
containing the catalyst is reused for several runs, the
activity of the reaction system does not decrease to a sig-
nificant extent. It is not necessary to re-isolate the cata-
lyst after each run. Spectroscopic examinations confirm
a complete separation of the reaction products from the
catalyst containing system by extraction. This is a clear
and remarkable advantage of the reaction system
described here in comparison to the application of
Fe(TPP)Cl in conventional organic solvents, such as
the previously applied toluene and THF, where the
workup procedure (to obtain the olefin) does not often
allow an easy reuse of the catalyst.3 Furthermore, in
the case of other catalysts such as ReO(Cl)3(PPh3)2,
which can react with O@PPh3, the reaction in conven-
tional organic solvents, which do not allow easy prod-
uct/by-product removal is increasingly slowed down
due to by-product (O@PPh3) formation, particularly
when several catalytic runs are performed with the same
solvent/catalyst system.3
Aliphatic aldehydes as well as aromatic aldehydes can be
used as substrates. In the case of aliphatic aldehydes,
higher reaction temperatures (80°C) are recommended
to shorten the reaction time. The (E)-selectivities are
quite good in all examined cases, ranging from ca. 11-
fold to 30-fold excess of the (E)-product (see Table 1).
Reduction of the reaction temperature to 20°C leads
to very similar (E)-selectivities but significantly pro-
longed reaction times.
These results, summarized in Table 1 clearly indicate
that not only activated (electron poor) but also deacti-
vated (electron rich) aldehydes as well as sterically
hindered aldehydes can be transferred in good to
quantitative yields to the corresponding olefins. Not
unexpectedly, the isolated yields are usually somewhat
lower than the GC-yields due to losses in the workup
procedure. These losses decrease, however, when the
reactions are performed in larger scale. Scaling up the
reaction, for example, from 0.5 to 5mmol p-methylbenz-
aldehyde (see Table 1, all other reactants are, of course,
also used in a larger scale) leads to approximately the
same isolated yield, while further increase leads to
higher isolated yields. Furthermore, the selectivity to-
wards olefins in ionic liquids seems to be even higher
than in common organic solvents, where azines are usu-
ally formed as by-products in amounts mainly depend-
ent on the applied catalyst, the reaction velocity and
the catalyst:substrate ratio.
Benzaldehyde needs 2h to be transformed quantitatively
to the corresponding olefin. Among the methylbenzalde-
hydes, the para derivative is the easiest one to be olefi-
nated, the ortho derivative the most difficult one. This
shows that the olefination is strongly influenced by the
The reaction mechanism (Scheme 1) presumably con-
sists—as it does in common organic solvents—of the
Table 1. Aldehyde olefination catalyzed by 1mol% Fe(TPP)Cl in (bmim)(BF6)7
Aldehyde
T (°C)
t (h)
GC-yield (%)
Isolated yield (%)
91
E/Z-ratio
Benzaldehyde
Benzaldehyde
Benzaldehyde
80
80
50
50
50
50
50d
80
80
80
80
80
1
1
95
95a
100
100
100
18.9
18.8a,b
18.9
13.2
17.7
18.3
18.4d
16.6
15.8
10.6
29.6
12.5
88a
c
2
c
c
o-Methylbenzaldehyde
m-Methylbenzaldehyde
p-Methylbenzaldehyde
p-Methylbenzaldehyded
p-Methoxybenzaldehyde
1-Naphthyl aldehyde
3-Benzyl propionaldehyde
Cyclohexyl aldehyde
p-(Dimethyl)amino benzaldehyde
3
2
1
100
80
81d
92
89
88
80
95
1d
1
e
100
e
1
e
e
1
1
20
100
a Second run (reuse of the catalyst).
b The E/Z-ratio may vary slightly.
c No isolated yield determined.
d 5mmol p-methylbenzaldehyde, 6mmol PPh3 and EDA, 2mol% cat., 5mL BmimPF6 and CH2Cl2.
e No GC-yield determined.

W. Sun, F. E. Ku¨hn / Tetrahedron Letters 45 (2004) 7415–7418
7417
Acknowledgements
R
R
W.S. thanks the Alexander von Humboldt foundation
for a postdoctoral research fellowship. The authors are
grateful to the Fonds der Chemischen Industrie for
financial support and to Prof. Dr. Dr. h. c. mult. W.
A. Herrmann for continuous support.
Cl
N
N
N
N
N
N
N
N
red.
Fe
R
Fe
R
R
R
R
R
R
N2
H
N
N2CHR'
R'
R
References and notes
N
N
N
N
N
Fe
1. (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 44,
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R
Fe
R
R
R
(ionic liquid)
N
N
PPh3
Ph3P=CHR'
PhCH=O
R
R
2. (a) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091; (b)
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PhCH=CHR'
+
Ph3P=O
R'HC=PPh3
+
R = Ph, R' = COOEt
Scheme 1.
reaction of EDA with the catalyst under formation of a
metal carbene species and nitrogen extrusion, which suc-
cessively reacts with triphenylphosphine under ylide for-
mation. The ylide then reacts with aldehyde in a classical
Wittig reaction. If no aldehyde is present, ylide is the
only reaction product and can be easily identified by
31P NMR spectroscopy. We did, however, not attempt
to observe the carbene intermediate by NMR spectros-
copy. As the postulated reduction of iron(III) to iron(II)
in common organic solvents3n this still hypothetic reac-
tion needs closer examination. Anyway, the main
advantage of the aldehyde olefination described here is
the straightforward and clean ylide formation without
the involvement of multistep syntheses or the applica-
tion of basic reaction conditions.
Roma˜o, C. C.; Kuhn, F. E. J. Am. Chem. Soc. 2003, 125,
¨
2414; (j) Zhang, X.; Chen, P. Chem. Eur. J. 2003, 9, 1852;
(k) Chen, X. P.; Zhang, X. Y.; Chen, P. Angew. Chem., Int.
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tallics 2003, 22, 4905; (p) Lebel, H.; Paquet, V. J. Am.
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A. M.; Jogalekar, A. A.; Pedro, F. M.; Rigo, P.; Baratta,
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4. For a recent review see: Kuhn, F. E.; Santos, A. M. Mini
ð1Þ
¨
Rev. Org. Chem. 2004, 1, 54.
5. For the preparation see: Huddleston, J. G.; Visser, A. E.;
Reichert, W. M.; Willauer, H. D.; Broker, G. A.; Roger, R.
D. Green Chem. 2001, 3, 156.
Ylides, however, which do not undergo the Wittig
reaction, such as ylides derived from diazomalonate
are not activated under the reaction conditions
described here. Other types of catalysts would have to
be applied.4
6. About ionic liquids see, for example: (a) Forsyth, S. A.;
Pringle, J. M.; MacFarlane, P. R. Aust. J. Chem. 2004, 57,
125; (b) Jastorff, B.; Stormann, R.; Molter, K.; Stock, F.;
Oberheitmann, B.; Hoffmann, W.; Hoffmann, J.; Nuchter,
M.; Ondruschka, B.; Filser J. Green Chem. 2003, 5, 136; (c)
Leitner, W. Nature 2003, 423, 930; (d) Seddon, K. R. Nat.
Mater. 2003, 2, 363; (e) Dupont, J.; de Souza, R. F.; Suarez,
P. A. Z. Chem. Rev. 2002, 102, 3667; (f) Bo¨hm, V. P. W. In
Appl. Homogen. Catal. with Organomet. Comp.; 2nd ed.;
Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH: Wein-
heim, 2002; (g) Wasserscheid, P.; Keim, W. Angew. Chem.,
Int. Ed. 2000, 39, 3772; (h) Welton, T. Chem. Rev. 1999, 99,
2071.
In summary the application of Fe(TPP)Cl as catalyst for
the aldehyde olefination in the ionic liquid (bmim)(PF6)
leads to a particularly easy, clean and selective way of
synthesizing olefins starting from aldehydes, triphenyl-
phosphine and ethyl diazoacetate (EDA). The applica-
tion of an ionic liquid as reaction medium for the
catalytic aldehyde olefination, here reported for the first
time, obviously is a convenient way to obtain the desired
olefins in quantitative yields and to preserve the catalyst
for further catalytic runs. We are currently examining
other, even more (E)-selective aldehyde olefination cata-
lysts under similar reaction conditions and with other
ionic liquids.
7. Typical procedure for the aldehyde olefination: To a
solution of Fe(TPP)Cl (3.5mg, 0.005mmol) and PPh3
(157.4mg, 0.6mmol) in 1mL of (bmim)(PF6) the corre-
sponding amount of aldehyde (0.5mmol) and ethyl diazo-
acetate (0.6mmol) in 1mL of CH2Cl2 is added. The

7418
W. Sun, F. E. Ku¨hn / Tetrahedron Letters 45 (2004) 7415–7418
reaction mixture is stirred at a constant reaction temper-
products from the catalyst containing ionic liquid. The
catalyst stays in the ionic liquid and can be used for the next
reaction. The yield and the E/Z-ratio where determined by
GC. In the case of the determination of isolated yields the
products were purified by flash silica gel chromatography.
ature in an oil bath until the reaction is completed,
according to the GC/MS results. After the reaction is
finished, the mixture is cooled to room temperature and
extracted with diethyl ether in order to separate the