An olefin metathesis/double bond isomerization sequence catalyzed by an in situ generated ruthenium hydride species

Article abstract of DOI:10.1002/ejoc.200390124

The direct conversion of allyl ethers to cyclic enol ethers using an olefin metathesis/double bond migration sequence is described. Ruthenium carbene complexes were activated to catalyze the double bond migration step by addition of hydride sources, such

Full text of DOI:10.1002/ejoc.200390124

SHORT COMMUNICATION
An Olefin Metathesis/Double Bond Isomerization Sequence Catalyzed by an
In Situ Generated Ruthenium Hydride Species
Bernd Schmidt[a]
Keywords: Homogeneous catalysis / Isomerization / Metathesis / Oxacycles / Rearrangement
The direct conversion of allyl ethers to cyclic enol ethers us-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ing an olefin metathesis/double bond migration sequence is Germany, 2003)
described. Ruthenium carbene complexes were activated to
catalyze the double bond migration step by addition of hy-
dride sources, such as NaH or NaBH4.
The combination of transition metal-catalyzed reactions of complex target molecules rely on the selective func-
into a sequence is an attractive concept in organic syn- tionalization of these substrates.[8] In Scheme 1 two routes
thesis.[1] In the field of olefin metathesis[2] several sequences to cyclic enol ethers based on ring closing metathesis are
of ring closing (RCM), ring opening (ROM) and cross illustrated for dihydropyrans: The enolether metathesis
metathesis (CM) reactions have been developed and applied pathway (A Ǟ B Ǟ C)[9] and the allyl ether metathesis/
to the synthesis of target molecules over the past few double-bond migration pathway (A Ǟ D Ǟ E Ǟ F).[10] The
years.[3] In contrast, comparatively little work has been pub- former route is a single-step procedure that requires only
lished on the sequential catalysis of an olefin metathesis re- one catalyst, but the reactivity of enol ethers B is signific-
action and a non-metathesis reaction. Recently, Grubbs et antly lower than allyl ethers E. The latter route has the ad-
al. discovered that ruthenium carbene complexes, after me- vantages of using a smooth allyl ether metathesis[11] and
diating an olefin metathesis reaction, catalyze the hydro- homoallylic alcohols F as starting materials, which are, in
genation of the C-C double bond formed in the metathesis contrast to pentenols C, available in enantiomerically pure
step if the reaction vessel is pressured with hydrogen.[4a] form by numerous methods, for example well-established
Fogg et al. have obtained unusual polyolefins via a ruth- allylboration strategies.[12] The disadvantage is obviously
enium-catalyzed ring opening metathesis polymerization the additional double-bond migration step (A Ǟ D), which
(ROMP)/hydrogenation sequence.[4b] The reactivity of ruth- can be mediated by stoichiometric amounts of strong
enium carbene complexes such as I[5a] or II[5b] (Figure 1) in bases or catalytic amounts of various transition metal
hydrogenation reactions originates from a hydrogenolysis of complexes of rhodium,[13a] iridium,[13b] nickel[13c] and
the carbene complex to a ruthenium hydride species, a pro- ruthenium.[13dϪ13f] In most reports describing the isomeriz-
cess that has been investigated mechanistically.[6]
ation of allyl ethers to enol ethers this transformation is
used to remove the allyl protecting group.[14] Frauenrath et
Figure 1. First (I) and second (II) generation Grubbs’ catalyst
In the course of our studies directed towards the stereo-
selective synthesis of 2,6-difunctionalized di- and tetrahy-
dropyrans[7] we required a short and efficient synthesis of
six-membered cyclic enol ethers. Cyclic enol ethers are ver-
satile substrates in organic synthesis, and several syntheses
[a]
Universität Dortmund, FB Chemie Ϫ Organische Chemie
Otto-Hahn-Straße 6, 44227 Dortmund, Germany
Scheme 1
816
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0305Ϫ0816 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 816Ϫ819

An Olefin Metathesis/Double Bond Isomerization Sequence
SHORT COMMUNICATION
al. have demonstrated that the regio- and stereoselective
double-bond migration in 1,3-dioxepines gives useful build-
ing blocks for polyether synthesis.[15] In-situ-generated ruth-
enium-hydride species are particularly active catalysts for
the conversion of these substrates.[16]
Table 1. Sequential RCM/Double-bond migration reaction
In this contribution we report a novel sequential reaction
that combines an olefin metathesis-based formation of cyc-
lic allyl ethers with a subsequent isomerization to the cor-
responding cyclic enol ether (route A Ǟ E in Scheme 1). It
has previously been noted that olefin isomerization reac-
tions may interfere with olefin metathesis reactions, norm-
ally as an undesired side-reaction.[17] During preparation of
this manuscript a paper by Snapper et al. was published
that describes an olefin metathesis-double bond migration
sequence, presumably proceeding via ruthenium hydride in-
termediates. The metathesis catalyst was activated to pro-
mote the isomerization step by treatment with molecular
hydrogen diluted with nitrogen.[18]
Ruthenium carbene complexes were activated to catalyze
the double-bond migration by addition of a hydride donor,
such as NaBH4 or NaH, after complete consumption of
the starting materials 1 (monitored by TLC). Ring-closing
metathesis of these substrates is a very smooth process;
complete consumption of 1 is observed in the presence of
five mol % of ruthenium catalysts I or II (Figure 1) within
one hour at ambient temperature. Formation of the cyclic
enol ethers 2 requires elevated temperatures and is complete
within two to five hours (Scheme 2).
Scheme 2
As shown in Table 1, the five-, six- and seven-membered
oxacycles 2 were obtained in good to excellent yields and
selectivities following this sequence. Only in the case of di-
hydrofurans 2aϪc (entries 1Ϫ3) were significant amounts
of the alternative regioisomer with a triply substituted
double bond observed. These products were easily removed
by column chromatography, thus the yield given in these
cases refers to a single isomer of 2. Dihydropyrans 2dϪk
(entries 4Ϫ11) are generally formed in excellent yields and
regioselectivities (better than 10:1), with the exception of 2h
(entry 8). Ring-closing metathesis of 1h is a fast and clean
process, giving 3h in 90% isolated yield. The alternative cyc-
lization mode, leading to a dihydrofuran and styrene, was
not observed (Scheme 3).
[a]
Conditions: 1) Toluene, I (5 mol %), 20 °C, then NaH (30
mol %), 100 °C. 2) Toluene, I (5 mol %), 20 °C, then NaBH4 (30
mol %), 100 °C. 3) Toluene, II (10 mol %), 20 °C, then NaH (50
[b]
[c]
mol %), 100 °C.
Ratio of regioisomers given in parentheses.
Subsequent isomerization of the intermediate 3h to 2h is
extremely slow and stops at 70% conversion, even if 10
Reaction stops at 70% conversion. Yield refers to a 3.0:1 mixture
of 2h and 3h.
Eur. J. Org. Chem. 2003, 816Ϫ819
817

B. Schmidt
SHORT COMMUNICATION
the selective double-bond migration in the seven-membered
ring is due to steric effects. Fastest conversion into the cyclic
enol ethers was observed in the five-membered series (be-
tween one and two hours), while six- and seven-membered
rings appear to have similar reactivity (approximately five
hours are required for full conversion). The geminally di-
substituted compound 1e requires significantly longer reac-
tion times for full conversion (ca. seven hours). We have
chosen one of the most reactive examples to check if addi-
tion of the hydride donor is necessary to activate ruthenium
carbene complexes for double bond migration reactions. If
1a is heated in refluxing toluene in the presence of 5 mol %
of ruthenium complex I, only the olefin metathesis product
3a and no rearrangement product 2a is formed. If, however,
a substoichiometric amount of NaBH4 is added after this
time, clean and rapid conversion into 2a is observed. If
NaH is used as an additive, a base-promoted rather than a
ruthenium-catalysed rearrangement might be possible. To
rule this out, the cyclic allyl ether 3a was isolated and puri-
fied by flash chromatography and distillation, in order to
remove all ruthenium species. Compound 3a was then
treated with an equimolar amount of NaH in refluxing
toluene for four hours. After this time, no rearrangement
product 2a could be detected by TLC or NMR spectro-
scopy. These observations strongly suggest that a ruthenium
hydride species is indeed formed upon addition of a hydride
donor reagent to the reaction, and that this ruthenium hy-
dride species catalyzes the double-bond migration step.
Scheme 3. i, CH2Cl2, 20 °C, I (5 mol %) (90%)
mol % of catalyst II is used. One might speculate that the
exocyclic C-C double bond coordinates intramolecularly to
the ruthenium, leading to a significant retardation of the
double-bond migration step. All structurally related ex-
amples without a double bond in this position (entries 7, 9
and 10) are smoothly converted under the conditions given
in Scheme 2. The 2-furyl-substituted derivative 2f (entry 6)
is obtained in 90% yield, which is particularly remarkable
as we have previously investigated various methods to syn-
thesize 2f from 3f without success. While ring-closing meta-
thesis of 1f gives 3f in good yield, several established
methods for the double-bond migration failed (Scheme 4).
Treatment with KOtBu in DMSO at elevated temperatures
gives exclusively the conjugated regioisomer 4. With Wilkin-
son’s catalyst and DBU a 1:1 mixture of regioisomers 2f
and 4 results, while the use of in situ generated ruthenium
hydride species in methanol[16] yields a 2:1 mixture of the
desired 2f and tetrahydropyran 5.
Experimental Section
The ruthenium complex I (82 mg, 5 mol %) or the ruthenium com-
plex II (85 mg, 5 mol %) was added to a solution of the correspond-
ing metathesis precursor 1 (2.0 mmol) in toluene (10 mL). After
complete conversion of the starting material to the intermediate
RCM product 3 (TLC, between 20 min and 1 hour), NaBH4
(20 mg, 30 mol %) or NaH (25 mg of a 60% dispersion in mineral
oil, 30 mol %) was added and the mixture heated to 110 °C. After
complete conversion (TLC) the reaction mixture was cooled to am-
bient temperature and washed with water. The aqueous layer was
extracted with ether, the combined organic extracts were dried with
MgSO4, filtered and the solvents were evaporated. The residue was
purified by flash chromatography on silica.
2a: 1H NMR (500 MHz, C6D6, 25 °C, TMS): δ ϭ 2.43 (dddd, J ϭ
15.2, 8.2, 2.3, 2.3 Hz, 1 H, -CHH-), 3.09 (dddd, J ϭ 15.2, 10.7, 2.3,
2.3 Hz, 1 H, -CHH-), 3.25 (s, 3 H, -OCH3), 4.73 (ddd, J ϭ 2.5,
2.3, 2.3 Hz, 1 H, -OCHϭCH-), 6.02 (dd, J ϭ 10.7, 8.2 Hz, 1 H, -
Scheme 4. i, KOtBu, DMSO, 100 °C (75%); ii, [RhCl(PPh3)3] (5
mol %), DBU (1.5 equiv.), EtOH, 78 °C (90% of 2f and 4); iii, OCHCH2-), 6.39 (ddd, J ϭ 2.5, 2.3, 2.3 Hz, 1 H, -OCHϭCH-),
[RuCl2(PPh3)3] (2.6 mol %), NaBH4 (25 mol %), MeOH, 65 °C
(40% of 2f and 21% of 5)
6.53 (d, J ϭ 8.2 Hz, 1 H, Ar), 6.95 (dd, J ϭ 7.5, 7.5 Hz, 1 H, Ar),
7.10 (ddd, J ϭ 8.2, 7.5, 1.7 Hz, 1 H, Ar), 7.68 (dd, J ϭ 7.5, 1.2 Hz,
1 H, Ar) ppm. 13C NMR (125 MHz, C6D6, 25 °C, TMS): δ ϭ
156.1, 145.7, 132.4, 128.3, 125.9, 120.9, 110.4, 99.1, 78.0, 54.8,
37.7 ppm. IR (film, KBr plates): ν˜ ϭ 1621 cmϪ1. C11H12O2 (176.2):
calcd. C 75.0, H 6.9; found C 74.9, H 6.6.
Seven-membered cyclic enol ethers are formed in lower
yields, although in these cases the RCM step seems to be a
limitation due to competing acyclic diene metathesis (ent-
ries 12Ϫ14). Product 2m is obtained by a double ring-clos-
ing metathesis/double-bond migration sequence. The
double ring-closing metathesis reaction of 1m yields the spi-
2g: 1H NMR (400 MHz, C6D6, 25 °C, TMS): δ ϭ 1.45Ϫ1.39 (2
H, -CH2-), 1.58 (dddd, J ϭ 13.8, 10.8, 7.0, 4.3 Hz, 1 H, -CH2-),
1.92Ϫ1.68 (3 H, -CH2-), 2.64 (ddd, J ϭ 13.8, 9.5, 7.0 Hz, 1 H, -
OCHϭCHCHH-), 2.78 (ddd, J ϭ 13.8, 9.8, 5.3 Hz, 1 H, -OCHϭ
CHCHH-), 3.63 (m, 1 H, -OCH-), 4.59 (ddd, J ϭ 6.3, 5.5, 2.5 Hz,
rocycle 3m in a moderate yield of 50%.[7c] It is likely that 1 H, -OCHϭCH-), 6.48 (d, J ϭ 6.3 Hz, 1 H, -OCHϭH-),
818 Eur. J. Org. Chem. 2003, 816Ϫ819

An Olefin Metathesis/Double Bond Isomerization Sequence
SHORT COMMUNICATION
7.22Ϫ7.07 (5 H, Ph) ppm. 13C NMR (125 MHz, C6D6, 25 °C,
TMS): δ ϭ 144.3, 142.4, 128.8, 128.6, 126.1, 100.2, 74.1, 37.5, 31.9,
28.2, 20.1 ppm. IR (film, KBr plates): ν˜ ϭ 1650 cmϪ1. C13H16O
(188.3): calcd. C 82.9, H 8.6; found C 82.9, H 8.4.
issner, M. A. Rizzacasa, J. Am. Chem. Soc. 1993, 115,
7152Ϫ7165. [8b] S. J. Danishefsky, S. DeNinno, P. Lartey, J. Am.
Chem. Soc. 1987, 109, 2082Ϫ2089. [8c] P. J. Kocienski, R. C. D.
Brown, A. Pommier, M. Procter, B. Schmidt, J. Chem. Soc.,
[8d]
Perkin Trans. 1 1998, 9Ϫ39.
K. A. Parker, A. T. Georges,
R. W. Friesen, R. W. Loo, C.
[8e]
Org. Lett. 2000, 2, 497Ϫ499.
F. Sturino, Can. J. Chem. 1994, 72, 1262Ϫ1272.
[9] [9a]
C. F. Sturino, J. C. Y. Wong, Tetrahedron Lett. 1998, 39,
Acknowledgments
This work was generously supported by the Deutsche Forschungs-
gemeinschaft, the Fonds der Chemischen Industrie and the Fach-
bereich Chemie der Universität Dortmund.
9623Ϫ9626. [9b] D. Calimente, M. H. D. Postema, J. Org. Chem.
[9c]
1999, 64, 1770Ϫ1771.
D. R. Williams, G. S. Cortez, S. L.
Bogen, C. M. Rojas, Angew. Chem. 2000, 112, 4750Ϫ4753; An-
[9d]
gew. Chem. Int. Ed. 2000, 39, 4612Ϫ4615.
J. M. Cox, J. D.
Rainier, Org. Lett. 2001, 3, 2919Ϫ2922. [9e] A. K. Chatterjee, J.
P. Morgan, M. Scholl, R. H. Grubbs, J. Am. Chem. Soc. 2000,
122, 3783Ϫ3784.
[1] [1a]
A. de Meijere, S. Bräse, J. Organomet. Chem. 1999, 576,
88Ϫ110. [1b] R. Grigg, V. Sridharan, J. Organomet. Chem. 1999,
[10]
H. Oguri, S. Tanaka, T. Oishi, M. Hirama, Tetrahedron Lett.
2000, 41, 975Ϫ978.
M. E. Maier, M. Bugl, Synlett 1998, 1390Ϫ1392.
P. V. Ramachandran, J. S. Chandra, M. V. R. Reddy, J. Org.
Chem. 2002, 67, 7547Ϫ7550.
[1c]
576, 65Ϫ87.
L. F. Tietze, Chem. Rev. 1996, 96, 115Ϫ136.
[2] [2a]
[11]
[12]
S. K. Armstrong, J. Chem. Soc., Perkin Trans. 1 1998,
[2b]
371Ϫ388.
4413Ϫ4450.
109, 2124Ϫ2145; Angew. Chem. Int. Ed. Engl. 1997, 36,
R. H. Grubbs, S. Chang, Tetrahedron 1998, 54,
[2c]
M. Schuster, S. Blechert, Angew. Chem. 1997,
[13] [13a]
[13b]
E. J. Corey, J. W. Suggs, J. Org. Chem. 1973, 38, 3224.
J. J. Oltvoort, C. A. A. van Boeckel, J. H. De Koning, J. H.
[2d]
2036Ϫ2055.
A. Fürstner, Angew. Chem. 2000, 112,
[13c]
3140Ϫ3172; Angew. Chem. Int. Ed. 2000, 39, 3013Ϫ3043.
van Boom, Synthesis 1981, 305Ϫ308.
H. Frauenrath, Synthesis 1998, 305Ϫ308.
A. Wille, S. Tomm,
[3] [3a]
[3b]
[13d]
R. Stragies, S. Blechert, Synlett 1998, 169Ϫ170.
R.
H. Frauenrath,
Stragies, S. Blechert, J. Am. Chem. Soc. 2000, 122, 9584Ϫ9591.
T. Philips, Angew. Chem. 1986, 98, 261Ϫ262; Angew. Chem. Int.
[3c]
[13e]
A. Rückert, D. Eisele, S. Blechert, Tetrahedron Lett. 2001,
Ed. Engl. 1986, 25, 274Ϫ275.
H. Brunner, M. Prommes-
[13f]
42, 5245Ϫ5247.
berger, Tetrahedron: Asymmetry 1998, 9, 3231Ϫ3239.
J. Le
[4]
[4a] J. Louie, C. W. Bielawski, R. H. Grubbs, J. Am. Chem. Soc.
2001, 123, 11312Ϫ11313. [4b] S. D. Drouin, F. Zamanian, D. E.
Fogg, Organometallics 2001, 20, 5495Ϫ5497.
ˆ
Notre, L. Brissieux, D. Semeril, C. Bruneau, P. H. Dixneuf,
Chem. Commun. 2002, 1772Ϫ1773.
[14]
[15]
P. J. Kocienski, Protecting Groups, Georg Thieme Verlag,
Stuttgart, 1994.
[5] [5a]
P. Schwab, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc.
[5b]
1996, 118, 100Ϫ110.
M. Scholl, S. Ding, C. W. Lee, R. H.
H. Frauenrath, D. Brethauer, S. Reim, M. Maurer, G. Raabe,
Angew. Chem. 2001, 113, 176Ϫ178; Angew. Chem. Int. Ed.
2001, 40, 177Ϫ179.
Grubbs, Org. Lett. 1999, 1, 953Ϫ956.
[6]
[6a] T. E. Wilhelm, T. R. Belderrain, S. N. Brown, R. H. Grubbs,
[6b]
[16]
Organometallics 1997, 16, 3867Ϫ3869.
S. D. Drouin, G. P.
H. Frauenrath, J. Runsink, J. Org. Chem. 1987, 52, 2707Ϫ2712.
[6c]
[17] [17a]
A. Yap, D. E. Fogg, Inorg. Chem. 2000, 39, 5412Ϫ5414.
J.
D. Joe, L. E. Overman, Tetrahedron Lett. 1997, 38,
[17b]
Wolf, W. Stüer, C. Grünwald, H. Werner, P. Schwab, M. Schulz,
8635Ϫ8638.
1123Ϫ1125.
T. R. Hoye, H. Zhao, Org. Lett. 1999, 1,
[17c]
Angew. Chem. 1998, 110, 1165Ϫ1167; Angew. Chem. Int. Ed.
A. Fürstner, O. R. Thiel, L. Ackermann, H.-
[6d]
1998, 110, 1124Ϫ1126.
M. Olivan, K. G. Caulton, Inorg.
J. Schanz, S. P. Nolan, J. Org. Chem. 2000, 65, 2204Ϫ2207.
[17d]
Chem. 1999, 38, 566Ϫ570.
C. Cadot, P. I. Dalko, J. Cossy, Tetrahedron Lett. 2002,
[7] [7a]
[7b]
B. Schmidt, Org. Lett. 2000, 2, 791Ϫ794.
B. Schmidt,
43, 1839Ϫ1841.
[7c]
[18]
H. Wildemann, Eur. J. Org. Chem. 2000, 3145Ϫ3163.
B.
A. E. Sutton, B. A. Seigal, D. F. Finnegan, M. L. Snapper, J.
Am. Chem. Soc. 2002, 124, 13390Ϫ13391.
Received November 21, 2002
[O02692]
Schmidt, H. Wildemann, J. Chem. Soc., Perkin Trans. 1 2000,
2916Ϫ2925.
[8] [8a]
R. E. Ireland, I. Armstrong, J. D. J. Lebreton, R. S. Me-
Eur. J. Org. Chem. 2003, 816Ϫ819
819