In situ conversion of a Ru metathesis catalyst to an isomerization catalyst

Article abstract of DOI:10.1039/b400229f

Addition of alcohols and substoichiometric amounts of a base to a metathesis reaction induces conversion of the metathesis-active carbene catalyst to an isomerization-active hydride species.

Full text of DOI:10.1039/b400229f

In situ conversion of a Ru metathesis catalyst to an isomerization
catalyst†
Bernd Schmidt
Universitaet Dortmund, Fachbereich Chemie – Organische Chemie, Otto-Hahn-Strasse 6, D-44227
Dortmund, Germany. E-mail: bschmidt@chemie.uni-dortmund.de
Received (in Cambridge, UK) 9th January 2004, Accepted 9th February 2004
First published as an Advance Article on the web 23rd February 2004
Addition of alcohols and substoichiometric amounts of a base to
a metathesis reaction induces conversion of the metathesis-
active carbene catalyst to an isomerization-active hydride
species.
poses to the hydride complex [Cl(CO)(PCy3)2Ru–H] (6) upon
heating.9 We planned to exploit this observation by testing ethyl
vinyl ether as an additive in the ring-closing metathesis–isomeriza-
tion sequence. Thus, ring-closing methathesis of 1a was conducted
in the presence of 5 mol% of 4 in toluene at ambient temperature.
After complete conversion of 1a to the primary metathesis product
2a (TLC), a sample of the reaction mixture was analyzed by 31P-
NMR spectroscopy. A small amount of carbene complex 4 could
still be detected [d(31P) 36.6 ppm],10 the major part of 4 was
converted to [Cl2(PCy3)2RuNCH2] (7), which was identified by its
d(31P) value of 43.9 ppm.10 Upon addition of ethyl vinyl ether (30
equiv.), the signal at 43.9 ppm rapidly disappeared and a new signal
at d(31P) 37.0 ppm appeared, which is in good agreement with the
literature value reported for 5.9 The mixture was subsequently
heated to reflux to induce decomposition of 5 to the hydride
complex 6. Compound 6 is indeed formed (as indicated by a 31P
resonance at 47.7 ppm);9 however, less than 10% of the primary
metathesis product 2a was isomerized to 3a after 6 h. It may be
concluded that 6 is probably not an efficient isomerization catalyst
under these conditions and for the substrates in question. Never-
theless, we investigated an alternative method for the generation of
6 in situ that was inspired by a study recently published by Dinger
and Mol.11 These authors reported that ruthenium carbene complex
4 reacts with primary alcohols in the presence of a base to yield the
same Ru hydride complex obtained by Louie and Grubbs via
thermolysis of 5. In a typical experiment, ethanol was added as a co-
solvent after completion of the metathesis reaction, followed by 50
mol% of solid NaOH. After 4 h at 110 °C, a 1 : 1 mixture of 2a and
the desired isomerization product 3a was obtained. Upon heating in
the presence of the additives for 3 h, a 31P-NMR resonance at 53.5
ppm was observed, along with several minor signals. It appears
likely from the spectroscopic evidence and the significantly
enhanced catalytic activity that under these conditions a different
isomerization catalyst is formed than with ethyl vinyl ether. In order
to exclude that the isomerization observed with ethanol–NaOH is a
base-induced process, dihydropyran 2a was isolated, purified by
distillation and then subjected to the reaction conditions (prolonged
heating in toluene–ethanol in the presence of 50 mol% of NaOH).
At the end of the reaction, no isomerization was observed and 2a
was recovered unchanged.
The fact that the nature of the reactive functional group is not
altered in the course of an olefin metathesis reaction makes this
transformation ideally suited for the construction of catalyzed
reaction sequences.1 For instance, cascades consisting of ring-
opening, ring-closing and cross-metathesis steps have been found
to be extremely useful in target molecule synthesis.2a,b The
individual steps of these reaction sequences are mediated by the
same catalytically active metal carbene species. Sequences that
combine a metathesis step and a subsequent non-metathesis
functionalization2c of the C–C double bond are conceptually
different. These require either the use of two different compatible
catalysts3 or the selective conversion of the metal carbene catalyst
to a different catalytically active species after completion of the
metathesis reaction. An example of the latter class of reactions is
the metathesis–hydrogenation sequence, where the C–C double
bond formed in the metathesis step is subsequently hydrogenated
by exchanging the inert gas atmosphere for hydrogen.4 More
recently, a metathesis–isomerization sequence has been independ-
ently developed by Snapper et al.5a and ourselves (Scheme 1).5b
The synthetic value of this sequence is very high, as it makes cyclic
enol ethers such as 3a conveniently available from allyl homoallyl
ether 1a without isolation of the primary metathesis product 2a.
Snapper et al. achieved the conversion of the metathesis catalyst to
an isomerization catalyst by applying a dilute hydrogen atmos-
phere,5a while our method involves the addition of substoichio-
metric amounts of inorganic hydrides (e.g. NaH, NaBH4).5b
Metathesis–hydrogenation as well as metathesis–isomerization
sequences seem to rely on the conversion of a (metathesis-active)
ruthenium carbene to a (hydrogenation-/isomerization-active) ru-
thenium hydride6 species in situ.7,8 The development of novel
methods for the in situ formation of ruthenium hydrides from
ruthenium carbenes may therefore lead to a significant improve-
ment in these synthetically valuable reaction sequences. Fur-
thermore, alternative methods for in situ generation of Ru hydride
from Ru carbene species might open up the pathway to the
development of novel metathesis–non-metathesis sequences that
rely on Ru hydrides as catalysts.
The observation that ruthenium carbene complexes show activity
in transfer hydrogenation–dehydrogenation reactions4,12 prompted
us to investigate secondary rather than primary alcohols as
additives. Ruthenium-catalyzed transfer hydrogenation and de-
hydrogenation reactions are commonly assumed to proceed via
ruthenium hydrides as catalytically active species. These are
generated by substitution of a ruthenium-bound chlorine by an
alkoxide, followed by b-hydride elimination.13 Gratifyingly, addi-
tion of isopropanol and a trace amount of solid NaOH to a
metathesis reaction induces conversion of the metathesis catalyst to
a highly active isomerization catalyst. For instance, conversion of
substrates 1a–c to enol ethers 3a–c (Table 1 and Scheme 1), which
requires 5–7 h using NaH or NaBH4 as additives, can be achieved
within 2 h or less using this method.‡
Recently, Louie and Grubbs reported that the Fischer-type
ruthenium carbene complex [Cl2(PCy3)2RuNCHOEt] (5) decom-
Scheme 1 The ring-closing metathesis–isomerization sequence.
Having established the superior activity of the isopropanol–
NaOH additive combination, we focused on some substrates that
showed poor or no reactivity in our previous study. 1d and 1e,
which undergo the isomerization step only with incomplete
† Electronic supplementary information (ESI) available: representative
experimental procedure and analytical data for products 3. See http://
www.rsc.org/suppdata/cc/b4/b400229f/
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C h e m . C o m m u n . , 2 0 0 4 , 7 4 2 – 7 4 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

View Article Online
Table 1 Products and yields from the ring-closing metathesis–isomerization
Details of the mechanism and the extension of the methodology to
other substrates and its application to target molecule synthesis are
currently under investigation in our laboratory.
Generous financial support of this work by the DFG, the Fonds
der Chemischen Industrie and the Chemistry Department of the
University of Dortmund is gratefully acknowledged.
sequencea
Yield
Entry
1
Starting material (1)
Product (3)
(%)
1a
1b
3a
3b
82
Notes and references
‡ Representative procedure: to 1a (354 mg, 1.9 mmol) dissolved in dry
toluene (8 mL) was added Cl2(PCy3)2RuNCHPh (78 mg, 5 mol%). The
solution was stirred at 20 °C until the starting material was completely
consumed (TLC). 2-Propanol (2 mL) and solid NaOH (40 mg, 1.0 mmol)
were added. The mixture was heated to reflux until the primarily formed 2a
was completely consumed (TLC). Aqueous work-up followed by flash
chromatography gives 1a (250 mg, 82%).
2
3
75b
78
1c
3c
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4
5
1d
1e
3d
3e
78c
70
4 J. Louie, C. W. Bielawski and R. H. Grubbs, J. Am. Chem. Soc., 2001,
123, 11 312.
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6
1f
rac-3f
65d
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2000, 65, 3966; (b) W. A. L. van Otterlo, E. L. Ngidi and C. B. de
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a Refer to Scheme 1. All reactions complete within 2 h, unless otherwise
stated. Reagents and conditions: [Cl2(PCy3)2RuNCHPh] (5 mol%), toluene
(20 °C); then add isopropanol (30% v/v) and NaOH (50 mol%), 110 °C.
b Complete after 1 h. c Complete after 3 h. d Complete after 7 h.
7 (a) B. Alcaide, P. Almendros and J. M. Alonso, Chem. Eur. J., 2003, 9,
5793; (b) C. Cadot, P. I. Dalko and J. Cossy, Tetrahedron Lett., 2002,
43, 1839; (c) M. Arisawa, Y. Terada, M. Nakagawa and A. Nishida,
Angew. Chem., Int. Ed., 2002, 41, 4732.
8 The reaction of Grubbs’ catalyst with hydrogen has been mechanist-
ically investigated: S. D. Drouin, G. P. A. Yap and D. E. Fogg, Inorg.
Chem., 2000, 39, 5412.
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90.
conversion if NaH or NaBH4 are used as additives, are smoothly
converted to 3d and 3e, respectively, under the present conditions.
The result obtained for triene 1f is quite surprising: ring-closing
metathesis is a moderately diastereoselective process (dr = 4 : 1)14
and proceeds in good yields. Attempted isomerization using either
NaH or NaBH4 as additives failed completely. With isopropanol–
NaOH, the isomerization occurs; however, the exocyclic double
bond is selectively hydrogenated. Transfer hydrogenation of
alkenes by alcohols is comparatively rare15 and the factors leading
to the preferred hydrogenation of one double bond in 1f are
currently under investigation. To date, we have not been able to
identify the actual isomerization catalyst. After completion of the
isomerization step, the 31P-NMR spectrum shows a major signal at
51.7 ppm, along with two minor signals at 10.6 and 78.8 ppm. Thus,
it appears likely that a different isomerization catalyst is formed if
isopropanol rather than ethanol is added to the reaction mixture.
C h e m . C o m m u n . , 2 0 0 4 , 7 4 2 – 7 4 3
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