Tandem isomerization/Claisen rearrangement of diallyl- and allylhomoallyl-ethers: In situ conversion of Grubbs' catalyst to a Ru-H species

Article abstract of DOI:10.1055/s-2004-829068

Diallyl- and allylhomoallylethers do not undergo the expected ring closing metathesis reaction if ethyl vinyl ether is added to the reaction mixture. Instead, upon heating, a selective isomerization of the substrates to allyl vinyl ethers is induced. These then undergo a Claisen rearrangement to produce pent-4-enals.

Full text of DOI:10.1055/s-2004-829068

LETTER
1541
Tandem Isomerization/Claisen Rearrangement of Diallyl- and Allylhomoallyl-
ethers: In Situ Conversion of Grubbs’ Catalyst to a Ru-H Species
T
andem Isomeriz
e
ation/Clais
r
en
R
earr
n
angement d Schmidt*
Universität Dortmund, Fachbereich Chemie, Organische Chemie I, Otto-Hahn-Straße 6, 44227 Dortmund, Germany
Fax +49(231)7555363; E-mail: bschmidt@chemie.uni-dortmund.de
Received 3 April 2004
tathesis activity of 1 has to be reduced, while the isomer-
Abstract: Diallyl- and allylhomoallylethers do not undergo the ex-
pected ring closing metathesis reaction if ethyl vinyl ether is added
to the reaction mixture. Instead, upon heating, a selective isomeriza-
tion of the substrates to allyl vinyl ethers is induced. These then
undergo a Claisen rearrangement to produce pent-4-enals.
ization activity has to be enhanced (Scheme 1). Olefin
isomerization reactivity (and some other non-metathesis
reactivities) of ruthenium carbene complexes are often
attributed to the formation of ruthenium-hydride species
under the reactions conditions.13
Key words: catalysis, rearrangements, ruthenium, tandem reac-
tions
R
O
The ring closing metathesis1 of diallyl ethers and allyl
homoallylethers2 to unsaturated oxacycles3 is an extraor-
dinarily facile process if ruthenium carbene complexes,
such as Grubbs’ catalyst [Cl2(PCy3)2Ru=CHPh] (1),4 are
used. Undesired non-metathesis side reactions,5 such as
olefin isomerization,6 are normally not observed for these
substrates but are limited to those which undergo olefin
metathesis only slowly or not at all. In these cases the
isomerization reaction may even become the predominant
or exclusive pathway.7 Olefin isomerization and other
non-metathesis activities of ruthenium carbene complexes
would normally be expected to limit the synthetic utility
of these catalysts. Over the past few years, we and others
embarked on the development of novel synthetic method-
ologies based on these non-metathesis reactivity patterns.
Currently, we are investigating synthetic perspectives that
might generally be classified in the following way: (a) re-
action sequences of one olefin metathesis step and a sub-
sequent non-metathesis functionalization of the newly
formed double bond, with both steps being mediated by a
single-site catalyst8 and (b) olefin metathesis and non-
metathesis transformations of a given substrate as com-
peting pathways.9 While the aforementioned reaction se-
quences represent a significant improvement with respect
to the efficiency of the catalytic process, the latter class of
synthetic perspectives addresses an important issue in di-
versity oriented synthesis:10 by chosing different reagents,
one substrate might be converted into structurally diverse
products. In this contribution we report an example for
this principle. Diallylethers and allyl homoallylethers,
which cyclize to dihydrofurans or dihydropyrans under
metathesis conditions, can also undergo a tandem iso-
merization/Claisen-rearrangement sequence to pent-4-
enals.11,12 If one wants to use Grubbs’ catalyst for the
isomerization of ethers 2 to aldehydes 5, the olefin me-
n
3
R
O
Cl2(PCy3)2Ru=CHPh (1)
n
R
O
R
O
2
n = 0: R1 = H
n = 1: R1 = CH3
R1
R1
4
5
Scheme 1 RCM and tandem isomerization/Claisen rearrangement
as branching pathways
Recent studies revealed a variety of pathways leading
from ruthenium-carbene to ruthenium-hydride species.
For instance, Grubbs et al. reported that 1 reacts with elec-
tron rich olefins such as ethyl vinyl ether to Fischer-type
carbene complexes such as [Cl2(PCy3)2Ru=CHOEt] (6),
which upon heating decomposes to the ruthenium–hy-
dride complex [RuHCl(CO)(PCy3)2] (7).14,15 We planned
to exploit this observation by using ruthenium complex 1
to promote selectively the Tandem-isomerization/Claisen
rearrangement. In a first experiment, diallylether 2a and
four equivalents of ethyl vinyl ether (two equivalents per
double bond in the substrate) were dissolved in toluene
and 5 mol% of ruthenium complex 1 was added at ambi-
ent temperature. From previous studies2d it is known that
this substrate is cleanly converted to the corresponding di-
hydrofuran within 15 minutes in the absence of ethyl vinyl
ether. Under the present conditions, olefin metathesis is
inhibited which can be attributed to the rapid formation of
6 by metathetic exchange of the benzylidene ligand
against the ethoxymethylidene ligand. This assumption is
supported by a resonance in the 31P NMR spectrum at d =
35.6 ppm,14a while no resonance arising from
[Cl2(PCy3)2Ru=CH2],4 which is the propagating species
for olefin metathesis, is observed. Heating the reaction
mixture to reflux induces a color change from deep red to
yellow, accompanied by a decrease of the intensity of the
signal at d = 35.6 ppm and a simultaneous appearance of
SYNLETT 2004, No. 9, pp 1541–1544
2
2.
0
7.
2
0
0
4
Advanced online publication: 01.07.2004
DOI: 10.1055/s-2004-829068; Art ID: G10504ST
© Georg Thieme Verlag Stuttgart · New York

1542
B. Schmidt
LETTER
a new signal at d (31P) = 47.4 ppm. This value is in good
agreement with the literature value reported for 7 [(d
(31P) = 47.1 ppm).14a Monitoring the reaction by TLC re-
veals that the starting diene is rapidly consumed once the
hydride complex 7 is formed, resulting in the formation of
a less polar product (the primary isomerization product)
and a more polar product, which is identified as the alde-
hyde 5a. Over a period of a few hours, the enolether is ful-
ly converted to the Claisen rearrangement product. This
protocol was subsequently applied to a variety of other
dienes and the results are summarized in Table 1.
Table 1 Pent-4-enals 5 from Dienes 2a
Entry Diene
1
Pent-4-enal
Yield
78%
O
O
2a
5a
2
53%
OCH3
OCH3
O
O
O
Pent-4-enals resulting from diallyl ethers 2b–d are ob-
tained in mediocre yields, because a variety of by-prod-
ucts are formed in small amounts, making purification by
column chromatography necessary. In the case of 2b, by-
product 6 could be isolated in approximately 10% yield as
a mixture of diastereoisomers, but as a single regioisomer.
Compound 6 results from a cycloisomerization pathway,
which can be promoted by ruthenium-hydrides, as was re-
cently demonstrated by Itoh et al.16 We propose a mecha-
nism for the formation of 6 that involves hydroruthenation
of the less-hindered allyl moiety, followed by insertion of
the remaining C-C double bond into the Ru-C bond and
finally a b-hydride elimination to give 6 (Scheme 2).
2b
2c
5b
5c
3
4
5
60%
52%
91%
OCH3
O
OCH3
O
O
O
O
Ph
Ph
2d
5d
OCH3
OCH3
+[Ru]-H
-[Ru]-H
O
O
O
2b
O
H
6
[Ru]
5e
5f
2e
2f
6
7
84%
70%
OCH3
OCH3
Scheme 2 Proposed mechanism for the formation of byproduct 6
O
O
Compound 5d was obtained as a 2:1 mixture of diastereo-
isomers from diastereomerically pure 2d.6e The configu-
ration of the exocyclic double bond is E for both
diastereoisomers, which was proved by 1D-NOE spec-
troscopy (NOE effect between the =CHCH2- proton and
the CHPh proton, as well as NOE effect between
=CHCH2- protons and -CH=CH-). Significantly better
yields were obtained for allyl homoallylethers. For in-
stance, 5e and 5f are formed in virtually quantitative yield.
Only trace amounts (<5%) of the ring closing metathesis
product could be detected in the 1H NMR spectrum of the
crude reaction mixture. The reduced yield of 5g (70%) can
probably be explained by competing formation of Diels–
Alder adducts. Quite surprising is the clean formation of
5h, because no regioisomers resulting from a double bond
migration subsequent to the Claisen rearrangement step
are observed. This point illustrates that the isomerization
catalyst [RuHCl(CO)(PCy3)2] (7) obviously shows some-
what reduced activity to sterically more hindered double
bonds, leading to a high degree of selectivity for the
isomerization of terminal double bonds. The final exam-
ple, 5i, is obtained in somewhat lower yield, because some
unidentified side products are formed which need to be re-
moved by column chromatography. All pent-4-enals are
O
O
O
O
2g
2h
5g
8
9
82%
O
O
5h
55%
O
O
BnO
BnO
2i
5i
a Reagents and conditions: Toluene (5 mL/mmol of 2), H2C=CHOEt
(4.0 equiv), then add 1 (5 mol%), 110 °C.
Synlett 2004, No. 9, 1541–1544 © Thieme Stuttgart · New York

LETTER
Tandem Isomerization/Claisen Rearrangement
1543
obtained with very high degrees of E-selectivity (with 3J
values typically in the range of 15 to 16 Hz). Isomeriza-
tion/Claisen rearrangement products resulting from allyl
homoallyl ethers are obtained as mixtures of diastereoiso-
mers, typically in a 2:1 ratio. Phenyl substituted derivative
5e has previously been prepared by two Ir-catalyzed se-
quences. Ishii et al.11f use the same starting material 2e as
in the present study and report the formation of a 1:1 mix-
ture of diastereoisomers. Very recently, Nelson et al.11j re-
ported the highly diastereoselective formation of 5e from
E-8 and assigned a (2R*,3R*)-configuration (Scheme 3).
References
(1) Reviews on olefin metathesis: (a)Armstrong, S. K.J. Chem.
Soc., Perkin Trans. 1 1998, 371. (b) Fürstner, A. Top.
Organomet. Chem. 1998, 1, 37. (c) Fürstner, A. Angew.
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Ph
O
Ph
O
[Ir] (cat.)
(3) Review: Elliott, M. C. J. Chem. Soc., Perkin Trans. 1 2002,
2301; and previous reviews cited therein.
dr = 94:6
(4) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100.
(2R*,3R*)-5e
E-8
Scheme 3 Nelson’s Ir-catalyzed tandem isomerization/Claisen
(5) Alcaide, B.; Almendros, P. Chem.–Eur. J. 2003, 9, 1259.
(6) (a) Maynard, H. D.; Grubbs, R. H. Tetrahedron Lett. 1999,
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rearrangement11j
By comparison with Nelson’s results, we assign the oppo-
site relative configuration to the major diastereoisomers
obtained in our study. It is not yet clear if the stereochem-
ical outcome observed in this study results from low E,E-
selectivity in the isomerization of ethers 2 to allyl vinyl
ethers 4, or if the initially formed diastereoisomer of pent-
4-enals 5 equilibrates under the reaction conditions. Fur-
ther studies addressing this issue are currently underway
in our laboratory and will be reported in due course.
(f) Bourgeois, D.; Pancrazi, A.; Nolan, S. P.; Prunet, J. J.
Organomet. Chem. 2002, 643-644, 247.
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Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312.
(b) Borsting, P.; Nielsen, P. Chem. Commun. 2002, 2140.
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1, 2512. (e) RCM/isomerization: Sutton, A. E.; Seigal, B.
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Representative Procedure: To a solution of the appropriate diene
2 (2.2 mmol) in toluene (10 mL) was added ethyl vinyl ether (0.88
mL, 8.8 mmol) under argon. Ruthenium catalyst 1 (80 mg, 4.5
mol%) was added, and the mixture was stirred at ambient tempera-
ture for 10 min. After this period, the deep red solution was heated
to reflux, inducing a color change to yellow. After complete con-
sumption of the starting material and the intermediately formed al-
lyl vinyl ether, the solution was cooled to ambient temperature, the
solvent was evaporated, and the residue was purified by Kugelrohr
distillation or by column chromatography, if necessary. Analytical
data for 5c: 1H NMR (500 MHz, CDCl3): d = 9.71 (s, 1 H, -CHO),
7.41 (d, J = 7.5 Hz, 1 H, Ar), 7.21 (dd, J = 7.5, 7.5 Hz, 1 H, Ar), 6.91
(dd, J = 7.5, 7.5 Hz, 1 H, Ar), 6.86 (d, J = 7.5 Hz, 1 H, Ar), 6.79 (d,
J = 15.7 Hz, 1 H, ArCH=), 6.16 (ddd, J = 15.7, 7.5, 7.5 Hz, 1 H,
ArCH=CH-), 3.85 (s, 3 H, -OCH3), 2.65 (m, 1 H, -CH2-), 2.53
[m, 1 H, CH(CH3)], 2.33 (m, 1 H, -CH2-), 1.16 (d, J = 7.0 Hz, 3 H,
-CH3) ppm. 13C NMR (125 MHz, CDCl3): d = 204.6 (1), 156.3 (0),
128.2 (1), 127.1 (1), 127.1 (1), 126.4 (1), 126.1 (0), 120.5 (1), 110.7
(1), 55.3 (3), 46.3 (1), 34.3 (2), 13.1 (3). IR (film on KBr plates):
n = 1727 (s) cm–1. MS (EI): m/z = 204 (69) [M+], 134 (100). Anal.
Calcd. for C13H16O2 (204.3): C, 76.4; H, 7.9. Found: C, 76.6; H, 8.4.
(f) Higashino, T.; Sakaguchi, S.; Ishii, Y. Org. Lett. 2000, 2,
4193. (g) Le Nôtre, J.; Brissieux, L.; Sémeril, D.; Bruneau,
C.; Dixneuf, P. H. Chem. Commun. 2002, 1772. (h) Ben
Ammar, H.; Le Nôtre, J.; Salem, M.; Kaddachi, M. T.;
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J.; Wang, K. J. Am. Chem. Soc. 2003, 125, 13000.
Acknowledgment
This work was generously supported by the Deutsche Forschungs-
gemeinschaft and the Chemistry Department of the University of
Dortmund.
Synlett 2004, No. 9, 1541–1544 © Thieme Stuttgart · New York

1544
B. Schmidt
LETTER
(12) For an example describing the use of pent-4-enals in target
molecule synthesis, see: Sattelkau, T.; Hollmann, C.;
Eilbracht, P. Synlett 1996, 1221.
(13) Review: Schmidt, B. Eur. J. Org. Chem. 2004, 1865.
(14) (a) Louie, J.; Grubbs, R. H. Organometallics 2002, 21,
2153. (b) Dinger, M. B.; Mol, J. C. Organometallics 2003,
22, 1089.
(15) Hydride-carbonyl complexes of ruthenium were originally
obtained from RuCl3·xH2O, methanol and an appropriate
phosphine ligand: (a) Esteruelas, M. A.; Werner, H. J.
Organomet. Chem. 1986, 303, 221. (b) Esteruelas, M. A.;
Liu, F.; Onate, E.; Sola, E.; Zeier, B. Organometallics 1997,
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18, 5152; the chemistry of some other Ru-H complexes is
discussed in ref. 13.
(16) Yamamoto, Y.; Nakagai, Y.; Ohkoshi, N.; Itoh, K. J. Am.
Chem. Soc. 2001, 123, 6372.
Synlett 2004, No. 9, 1541–1544 © Thieme Stuttgart · New York