Catalytic ketone olefination with methyltrioxorhenium

Article abstract of DOI:10.1016/j.tetlet.2005.09.045

Methyltrioxorhenium (MTO) catalyses the olefination of ketones with ethyl diazoacetate in the presence of triphenylphosphane. Unactivated ketones require the addition of 0.5 equiv of benzoic acid to achieve good yields, while trifluoromethyl ketones require no co-catalyst. The optimised system allows the olefination of aromatic, aliphatic, unsaturated, cyclic and trifluoromethyl ketones.

Full text of DOI:10.1016/j.tetlet.2005.09.045

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7777–7779
Catalytic ketone olefination with methyltrioxorhenium
Filipe M. Pedro, Sebastian Hirner 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 24 June 2005; revised 5 September 2005; accepted 7 September 2005
Available online 26 September 2005
Abstract—Methyltrioxorhenium (MTO) catalyses the olefination of ketones with ethyl diazoacetate in the presence of triphenyl-
phosphane. Unactivated ketones require the addition of 0.5 equiv of benzoic acid to achieve good yields, while trifluoromethyl
ketones require no co-catalyst. The optimised system allows the olefination of aromatic, aliphatic, unsaturated, cyclic and trifluoro-
methyl ketones.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
developed method proves to be general and straightfor-
ward to apply for a wide range of ketones.
The olefination of aldehydes and ketones is an impor-
tant transformation in organic synthesis. The Wittig
reaction and its variations provide a highly effective
and general method, but still have several drawbacks.1
The catalytic approach to aldehyde olefination has re-
ceived considerable attention in recent years,2 while
the research on ketone olefination is far less developed
and only a few examples of transition metal complex-
mediated ketone olefination systems are known.3
2. Results and discussion
The olefination of cyclohexanone with triphenylphos-
phane (PPh3) and ethyldiazoacetate (EDA) at 80 °C in
toluene with 5 mol % MTO as catalyst (see Experimen-
tal part for details) proceeds comparatively slowly,
affording less than 10% of olefin after 48 h of reaction
time. The slow progress, being in contrast to the reac-
tion rate of the correspondent aldehyde olefination sys-
tem6 is expected since the ketone carbonyl group is
generally much less electrophilic than the aldehyde car-
bonyl moiety. This difference is also known for the Wit-
tig ketone olefination, which in the absence of other
reactants usually requires harsh reaction conditions to
obtain good results.7
Methyltrioxorhenium (MTO) is an easily accessible
organometallic complex whose stability and high cata-
lytic activity in several processes makes it an attractive
target for new catalytic applications.4 Recently we pub-
lished a detailed study on the catalytic aldehyde olefin-
ation reaction with several organometallic rhenium
complexes and we observed that some MTO derived
complexes are able to catalyse the olefination of ke-
tones.5 Based on the good results obtained with MTO
in the catalytic aldehyde olefination, where it was one
of the first catalysts reported,2,6 we tested its suitability
for the catalytic ketone olefination.
To overcome this problem, ways to enhance the electro-
philicity of the carbonyl group and render it a higher
reactivity were surveyed. It is reasonable to assume that
Lewis or Bro¨nsted acids can form complexes with or
protonate ketoneÕs carbonyl group increasing its electro-
philic character and possibly its reactivity. Therefore,
the olefination of cyclohexanone using Lewis acids
(SbCl5 and Et3OBF4) as co-catalysts for the olefination
of cyclohexanone under the same reaction conditions
was attempted. Along with unreacted ketone, the main
reaction products are the coupling products of EDA
(ca. 35%), as well as the ring extension product 2-oxo-
cycloheptane carboxylic acid ethyl ester (ca. 25%). The
Herein, the results of our research on catalytic ketone
olefination with MTO as catalyst are presented. The
Keywords: Homogeneous catalysis; Ketone olefination; Methyl-
trioxorhenium.
*
Corresponding author. Tel.: +49 089 289 13080; fax: +49 089 289
13473; e-mail: fritz.kuehn@ch.tum.de
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.045

7778
F. M. Pedro et al. / Tetrahedron Letters 46 (2005) 7777–7779
R1
R2
5% MTO, Toluene
R1
R2
H
+ N2 + Ph3P=O
C
O + PPh3 + N2=CHCO2Et
C
C
80 oC, 0.5 eq Benzoic Acid
CO2Et
Scheme 1.
olefin yield remains below 10% showing that strong
Lewis acids do not activate the ketones towards the olef-
ination reaction.
To test the effectiveness of MTO in the olefination of
ketones, we extended the study to a series of other
substrates (entries 8–12), using the optimised reaction
conditions, namely, toluene at 80 °C with a catalyst
loading of 5 mol % and 0.5 equiv of benzoic acid as
co-catalyst.
The Wittig reaction between aldehydes8 or ketones8,9
and Ph3P@CHCO2Et can be strongly accelerated by
sub-molar quantities of benzoic acid, and Zhang et al.
have already successfully applied this Bro¨nsted acid
for catalytic ketone olefination3c,3d applying Fe(TPP)Cl
and Co(TPP) as the catalysts.
This set of results allows drawing the following con-
clusions: activated ketones, that is, electron-deficient
ketones, react well and reach good to excellent yields
within short reaction times (entries 5 and 12). In fact
a,a,a-trifluoro-acetophenone is active enough to be
olefinated with quantitative yield in the absence of any
co-catalyst with a high Z-isomer selectivity.3b
The olefination of cyclohexanone with PPh3 and EDA
at 80 °C in toluene, using 5 mol % MTO and 0.5 equiv
of benzoic acid as co-catalyst (Scheme 1), affords 70%
olefin after a reaction time of 48 h. This remarkable
improvement in activity led us to further explore the
potential of this reaction system.
The olefination of inactivated ketones (entry 8) is also
possible although—as expected—with lower yields and
longer reaction times. This outcome is due to the low
electrophilicity of the unactivated carbonyl group.
The olefination of acetophenone under the same reac-
tion conditions affords 65% of olefin with an E:Z ratio
of 13:87 (Table 1, entry 3) after 48 h of reaction. If only
0.2 equiv of benzoic acid are used in the same reaction,
the olefin yield remains below 15%. Therefore, 0.5 equiv
of co-catalyst was applied throughout all further
experiments.
The ability of MTO to catalyse a wide array of ketones
is noteworthy: aromatic, cyclic, a,b-unsaturated, ali-
phatic and trifluoromethyl ketones can all be success-
fully olefinated by the MTO system, most importantly
with the highest selectivities reported so far.
A comparatively electron-deficient ketone such as 4-nitro-
acetophenone is more reactive than acetophenone and
the olefination reaction is completed after 24 h with
70% olefin yield. Performing the reaction at room tem-
perature causes a significant decrease of the reaction
rate, though it is beneficial for the reactionÕs selectivity
(entries 5 and 6).
In conclusion, a useful process for the olefination of
ketones under non-basic conditions could be developed,
confirming once more that MTO is one of the most
versatile catalysts available.
3. Experimental
Reducing the MTO loading to half (2.5 mol %) requires
a longer time for the olefination of 4-nitroacetophenone
to reach completeness, however, the yield and selectivity
remain quite similar (entries 5 and 7).
3.1. General information
All reactions were carried under an inert gas atmosphere
(Argon), using standard Schlenk techniques. Solvents
Table 1. Performance of MTO in ketone olefination with PPh3 and EDA using 0.5 equiv of benzoic acid as co-catalyst
Entry
Ketone
%MTO
T/°C
Yielda/%
E:Zd
Reaction time
1
2
3
4
5
6
7
8
Cyclohexanone
Cyclohexanone
Acetophenone
Acetophenone
4-Nitro acetophenone
4-Nitro acetophenone
4-Nitro acetophenone
4-Methoxy acetophenone
Cycloheptanone
2-Nonanone
(E)-4-Phenyl-3-buten-2-one
Trifluoro acetophenone
5
5
5
5
5
5
2.5
5
5
80
80
80
80
80
RT
80
80
80
80
80
80
<10b
71
—
—
50
50
50
68
24
48
44
132
72
120
42
65
13:87
42:58
30:70
20:80
31:69
32:68
—
48:52
26:74
11:89
15c
70
40
70
30
40
54
45
93
9
10
11
12
5
5
5
48
a Isolated yields, product authenticity was checked by 1H NMR and 13C NMR.
b No co-catalyst used.
c 0.2 equiv of benzoic acid used as co-catalyst.
d E:Z ratios determined by GC.

F. M. Pedro et al. / Tetrahedron Letters 46 (2005) 7777–7779
7779
Comprehensive Organic Functional Group Transformations;
Katritzky, A. R., Meth-Con, O., Rees, C. W., Eds.;
Pergamon: New York, 1995; Vol. 1, p 589; (g) Gosney, I.;
Lloyd, D. In Comprehensive Organic Functional Group
Transformations; Katritzky, A. R., Meth-Con, O., Rees,
C. W., Eds.; Pergamon: New York, 1995; Vol. 1, p 719.
were dried following standard procedures and kept un-
der Argon. MTO was synthesised following a literature
procedure.10
3.2. General procedure for ketone olefination
2. Kuhn, F. E.; Santos, A. M. Mini-Rev. Org. Chem. 2004, 1,
¨
Ketone (2 mmol), PPh3 (0.577 g, 2.2 mmol), MTO
(0.025 g, 0.1 mmol) and benzoic acid (0.122 g, 1 mmol)
were dissolved in dry toluene (10 cm3) and heated to
80 °C. EDA (0.274 g, 2.4 mmol) dissolved in toluene
(1 cm3) was added dropwise and allowed to react at
80 °C. After the reaction was completed, the solution
was cooled to room temperature and the solvent was
removed under vacuum. The residue was dissolved in
n-hexane/ethyl acetate (5:1) and chromatographed over
silica gel affording the olefin(s).
55, and references cited therein.
3. (a) Cheng, G.; Mirafzal, G. A.; Woo, L. K. Organomet-
allics 2003, 22, 1468; (b) Chen, Y.; Huang, L. Y.; Zhang,
X. P. J. Org. Chem. 2003, 68, 5925; (c) Chen, Y.; Huang,
L.; Zhang, X. P. Org. Lett. 2003, 5, 2493; (d) Lee, M. J.;
Chen, Y.; Zhang, X. P. Organometallics 2003, 22, 4905; (e)
Lebel, H.; Guay, D.; Paquet, V.; Huard, K. Org. Lett.
2004, 6, 3047.
4. (a) Kuhn, F. E.; Scherbaum, A.; Herrmann, W. A. J.
¨
Organomet. Chem. 2004, 689, 4149, and references cited
therein; (b) Romao, C. C.; Kuhn, F. E.; Herrmann, W. A.
˜
¨
Chem. Rev. 1997, 97, 3197.
5. Santos, A. M.; Pedro, F. M.; Jogalekar, A. A.; Lucas, I.
S.; Romao, C. C.; Kuhn, F. E. Chem. Eur. J. 2004, 10,
Acknowledgements
˜
¨
6313.
6. (a) Herrmann, W. A.; Wang, M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 1641; (b) Herrmann, W. A.; Roesky, P. W.;
Wang, M.; Scherer, W. Organometallics 1994, 13, 4531.
7. (a) Fodor, G.; To¨mo¨sko¨zi, I. Tetrahedron Lett. 1961, 16,
579; (b) Isaacs, N. S.; El-Din, G. N. Tetrahedron Lett.
1987, 28, 2191; (c) Spinella, A.; Fortunati, T.; Soriente, A.
Synlett 1997, 1, 93; (d) Wu, J.; Wu, H.; Wei, S.; Dai,
W.-M. Tetrahedron Lett. 2004, 45, 4401.
F. M. Pedro thanks the Fundac¸ao para a Cieˆncia e a
˜
Tecnologia for a PhD grant. The Fonds der Chemischen
Industrie is acknowledged for financial support.
References and notes
8. Ruchardt, C.; Panse, P.; Eichler, S. Chem. Ber. 1967, 100,
1. (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 44,
580; (b) Wittig, G.; Scho¨llkopf, U. Chem. Ber. 1954, 87,
1318; (c) Wittig, G.; Schlosser, M. Tetrahedron 1962, 1023;
(d) Maryanoff, B. E.; Reiz, A. B. Chem. Rev. 1989, 89, 863;
(e) Kelly, S. E. In Comprehensive Organic Synthesis; Trost,
S. E., Fleming, I., Schreiber, S. L., Eds.; Pergamon:
Oxford, 1991; Vol. 1, p 729; (f) Maguire, A. R. In
¨
1144.
9. (a) Ruchardt, C.; Eichler, S.; Panse, P. Angew. Chem.
¨
´
1963, 75, 858; (b) Fliszar, S.; Hudson, R. F.; Salvadori, G.
Helv. Chim. Acta 1964, 47, 159.
10. Herrmann, W. A.; Kratzer, R. M.; Espenson, J. H.; Wang,
W. Inorg. Synth. 2002, 33, 110.