Selective isomerization of a terminal olefin catalyzed by a ruthenium complex: The synthesis of indoles through ring-closing metathesis

Article abstract of DOI:10.1002/anie.200290031

Aruthenium complex, generated from the Grubbs carbene catalyst with vinyloxytrimethylsilane, catalyzed the isomerization of terminal alkenes RCH₂-CH=CH₂ to internal alkenes RCH=CH-CH₃. Application of this olefin isomerization to 2-(N-allylamino)styrene gave the corresponding enamines, which were converted into indoles by a standard ring-closing metathesis, see scheme (Ts = tosyl).

Full text of DOI:10.1002/anie.200290031

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Experimental Section
Selective Isomerization of a Terminal Olefin
Catalyzed by a Ruthenium Complex: The
Synthesis of Indoles through Ring-Closing
Metathesis**
The lanthanide oxide based catalysts were prepared by the incipient
wetness impregnation technique with aqueous solutions of, for example,
lanthanum acetate (Aldrich, > 99.9%) with Al2O3 (Condea, surface area
of 220 m« gꢀ1) as support. La2O3 (99.99%) was purchased from Alfa Aesar.
The catalyst material was dried at 1008C for 1 h, followed by granulation.
The size fraction of 0.25 0.50 mm was loaded into the catalytic reactor.
Catalytic tests were performed in a fixed-bed reactor at atmospheric
pressure. The reactor consisted of a quartz tube, which was loaded
successively with quartz wool, quartz pearls, quartz wool, catalyst (1 g),
quartz wool, quartz pearls, and quartz wool. Before the reaction started, the
catalyst was calcined for 8 h in O2 at 4508C. During reaction, the feed
consisted of a He flow, which was led through a saturator filled with CCl4
(VEL, p.a.) and maintained at 08C in an icebath to preserve the same vapor
pressure of CCl4. All the tubes were made of Vitton, and the total He flow
was set at 0.480 Lhꢀ1. This resulted in a CCl4 loading of 47000 ppm (v/v).
The gaseous hourly space velocity (GHSV) was 800 hꢀ1 (contact time of
4.5 s). The gas flows were controlled with Bronkhorst mass flow controllers,
while H2O was added to the reactor at a rate of 1.2 mLhꢀ1 by a Methrom
dosimeter and evaporated at the inlet of the reactor. The reaction
temperature was controlled using a K-type thermocouple placed in the
reactor. The condensate was trapped after the reactor in an impinger at
room temperature and analyzed by GC-MS. The remaining gases were
guided to a gas chromatograph (HP 4890D with a FID detector and
methanator) and analyzed on a packed Hayesep Q CP column (80 100
mesh, 3 m length). X-ray diffraction patterns of the solids were measured
with a Siemens D5000 Matic instrument, while Raman spectra were
recorded with a Holoprobe Kaiser Optical spectrometer equipped with a
holographic notch filter and CCD camera. XPS measurements were done
with a VG MT 500 spectrometer. FTIR spectra were measured using a
Nicolet 730 spectrometer.
Mitsuhiro Arisawa, Yukiyoshi Terada,
Masako Nakagawa, and Atsushi Nishida*
Isomerization of olefins may proceed under acidic, basic, or
photochemical conditions to give a mixture of olefins that
depends on their thermodynamic stability. Recent advances in
transition-metal chemistry (Fe, Pd, Rh, Pt, Ni, Ir, Ru, Co, and
Cr) have enabled milder conditions for olefin isomerization to
be used to realize selective and synthetically useful trans-
formations, such as the deprotection of an allyl group on
nitrogen and oxygen functionalities.[1] Recently, a few reports
have appeared concerning this olefin isomerization using
ruthenium carbene catalysts, such as the Grubbs catalyst.[1m
o]
This isomerization reaction is limited to substrates which
contain an oxygen or a nitrogen substituent in the olefinic side
chain. In addition, the reaction competes with metathesis.[2]
During the course of our investigation of the synthesis of
nitrogen-containing heterocycles by using ring-closing meta-
thesis (RCM),[3] we found a novel method for synthesizing
substituted quinolines by RCM, which included a metathesis
reaction of a silyl-protected enol ether with an alkene.[3f]
These results prompted us to investigate cross metathesis to
prepare a silyl enol ether. However, unexpectedly, we found
selective isomerization of the terminal olefin to the corre-
sponding internal olefin, which made a novel indole-ring
synthesis possible by RCM. Herein, we report a novel and
selective isomerization of a terminal olefin by combining a
ruthenium carbene catalyst with vinyloxytrimethylsilane, and
its application to the synthesis of an indole ring from 2-(N-
allyl-N-tosylamino)styrene by RCM.
When 1 was heated in CH2Cl2 at 508C with 2 molar
equivalents of silyl enol ether (2a) in the presence of the
Grubbs catalyst (A, 5 mol%),[4] we unexpectedly found that
the terminal double bond of 1 isomerized to the internal
double bond to give 3 in 60% yield, 40% of 1 was recovered
(Table 1, entry 1, full experimental details are given in the
supporting information). The exclusive formation of 3 was
Received: June 24, 2002
Revised: September 23, 2002 [Z19595]
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[*] Prof. A. Nishida, Dr. M. Arisawa, Y. Terada
Graduate School of Pharmaceutical Sciences
Chiba University
1-33 Yayoi-cho, Inage-ku, Chiba 263 8522 (Japan)
Fax: ( þ 81)43-290-2909
E-mail: nishida@p.chiba-u.ac.jp
Prof. M. Nakagawa
Present Address: Faculty of Science
Kanagawa University
[10] M. Wilde, K. Anders, Chem. Tech. 1994, 6, 316.
[11] B. M. Weckhuysen, M. P. Rosynek, J. H. Lunsford, Phys. Chem. Chem.
Phys. 1999, 1, 3157; B. M. Weckhuysen, G. Mestl, M. P. Rosynek, T. R.
Krawietz, J. F. Haw, J. H. Lunsford, J. Phys. Chem. B 1998, 102, 3773.
[12] G. Sinquin, C. Petit, J. P. Hindermann, A. Kiennemann, Catal. Today
2001, 70, 183; G. Sinquin, C. Petit, S. Libs, J. P. Hindermann, A.
Kiennemann, Appl. Catal. B 2000, 27, 105; G. Sinquin, J. P. Hinder-
mann, C. Petit, A. Kiennemann, Catal. Today 1999, 54, 107.
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[14] G. R. Lester, Catal. Today 1999, 53, 407.
[**] We thank Prof. Amir H. Hoveyda at Boston College for his helpful
discussions and for the generous gift of his catalyst. This research was
supported by a Grant-in-Aid for Scientific Research on Priority
Areas (A) ™Exploitation of Multi-Element Cyclic Molecules∫ and a
Grant-in-Aid for Exploratory Research from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan. M.A. is also
grateful for a Takeda Chemical Industries, Ltd. Award in Synthetic
Organic Chemistry, Japan for financial support.
[15] U. Weiss, M. P. Rosynek, J. H. Lunsford, Chem. Commun. 2000, 405.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
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Angew. Chem. Int. Ed. 2002, 41, No. 24

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Table 1. Reaction of 1 with various silyl enol ethers and vinyl ethers in the
presence of a ruthenium carbene catalyst.
X
Y
X
a
N
Y
N
Mes
N
N Mes
Z
Ts
Z
Ts
O
O
O
O
Cl
A
Ru
4h: X = H, Y = H, Z = H
6h: 93%, 6i: 95%
6j: 90%, 6k: 100%
OR
Ph
Cl
O
O
PCy3
4i: X = MeO, Y = H, Z = H
4j: X = MeO, Y = MeO, Z = MeO
4k: X = H, Y = Cl, Z = H
+
(5 mol%)
CH2Cl2
(12.5 mM)
50 °C
b
3
2
1
X
X
c
Entry
R
Equiv
t [h]
Product [%]
60
quantitative
no reaction
12
E/Z Ratio of 3[a]
Y
N
Y
N
1
2
3
4
5
2a
2a
2b
2c
2c
TMS
TMS
Ac
Et
Et
2
10
10
10
10
20
3
23
3
3.2/1
3.5/1
Z
Ts
Z
Ts
5h: quant,
5i, 5j, 5k
7h: 94%, 7i: quant, 2 steps
7j: 83%, 2 steps, 7k: 79%, 2 steps
[b]
24
quantitative
3.2/1
Scheme 1. Selective isomerization of terminal olefins, a) A (5 mol%),
CH2Cl2, 508C, 1 h; b) A (5 mol%), vinyloxytrimethylsilane (1 eq.), CH2Cl2,
508C, 1.5 h; c) for 5h: A (5 mol%), benzene, 808C, 1 h, for 5i: A (5 mol%),
benzene, 808C, 3 h, for 5j: A (5 mol%), toluene, 1108C, 17 h for 5k: A
(5 mol%), toluene, 1108C, 13 h.
[a] The ratios were determined by 1H NMR spectroscopy. [b] Not deter-
mined.
observed in the reaction with 10 equivalents of 2a, again as a
mixture of E and Z isomers (entry 2). However, neither
isomerization nor dimerization of 1 occurred when vinyl
acetate 2b was subjected to similar reaction conditions
(entry 3). On the other hand, the combination of ethylvinyl
ether 2c with catalyst Aunder optimized conditions promoted
the quantative isomerization of 1 (entry 5).[5] Clearly, 2a is the
most favorable enol ether for isomerization.
Several terminal olefins were subjected to the same
reaction conditions (Table 2). All of the monosubstituted
olefins (4a 4g) were isomerized in moderate to excellent
yields, even when the substrate did not have an oxygen
substituent. Therefore, this reaction is quite general and
selective for terminal olefins.
We carried out the isomerization of 4h (Scheme 1) in
competition with RCM. While the reaction of 4h with
ruthenium-catalyst A gave 1,2-dihydroquinoline (6h) in
excellent yield,[3f] the reaction of 4h with catalyst A in the
presence of vinyloxytrimethylsilane (1 equiv is sufficient for
this substrate) gave enamine (5h; Scheme 1) in quantitative
yield, which is inaccessible by conventional methods. Al-
though the use of a ruthenium carbene catalyst in the
isomerization of olefin has been reported,[1m o], to our knowl-
edge, this is the first example of a highly selective isomer-
ization using a ruthenium carbene complexthat proceeds
faster than RCM.
Since this method is quite effective for generating enam-
ines, we applied this reaction to the synthesis of indoles.[6]
Enamine 5h was obtained by the evaporation of volatile
material after the isomerization of 4h and was subjected to
normal RCM conditions using catalyst A at 808C in benzene.
The expected indole (7h) was isolated in 94% yield. Similarly,
4i, 4j, and 4k gave 7i, 7j, and 7k via isomerized enamines 5i,
5j, and 5k, respectively.
The protective group on a nitrogen atom is not limited to
the p-toluenesulfonyl group. 2-(N-Acetyl-N-allylamino)styr-
ene gave N-acetylindole in 96% yield under the same
conditions.
While a detailed mechanism of this isomerization is not
clear, we considered that the new catalyst was formed by the
reaction of A and vinyloxytrimethylsilane. The results of
monitoring the reaction of the Grubbs catalyst A with 2a in
CDCl3 at 508C by 1H and 31P NMR spectroscopy showed that:
1) in the 1H NMR spectrum, the signal arising from the
methyne proton of the Grubbs catalyst (19.1 ppm) disap-
peared and signals associated with styrene appeared; and 2) in
the 31P NMR spectrum, the signal arising from the tricyclo-
hexylphosphane group of the Grubbs catalyst (29.6 ppm)
completely disappeared and a new signal appeared at
33.1 ppm. Furthermore, the IR spectrum of the crude product
showed a new signal at 1935 cmꢀ1.
These results offer an extremely
Table 2. Novel isomerization of various terminal olefins.
facile and selective isomerization of
A
(5 mol%)
terminal olefins by combining
a
OTMS
+
R
R
ruthenium carbene catalyst and vi-
nyloxytrimethylsilane. The utility of
this reaction was demonstrated in a
novel and efficient synthesis of an
indole ring from 2-(N-allylamino)-
styrene using RCM. As a conse-
quence of its simplicity, chemo-selec-
tivity, and the mild reaction condi-
tions, this procedure should lead to
new aspects of olefin metathesis.
CH2Cl2 , 50 °C
2a (10 eq)
4
5
Entry Substrate
t [h] Product
Yield [%][a]
E/Z[b]
¼
¼
1
2
3
4
5
6
7
PhCH2CH CH2 (4a)
1.5 PhCH CHCH3 (5a)
34 (quantitative) 12.8/1
58
¼
¼
Ph(CH2)2CH CH2 (4b)
3.0 PhCH2CH CHCH3 (5b)
2.8/1
8.5/1
¼
¼
pMeOC6H4CH2CH CH2 (4c) 3.0 pMeOC6H4CH CHCH3 (5c) 78
HO(CH2)4CH CH2 (4d)
BnO(CH2)4CH CH2 (4e)
BnOCH2CH CH2 (4 f)
¼
¼
3.0 HO(CH2)3CH CHCH3 (5d) 34 (quantitative) 6.1/1
3.0 BnO(CH2)3CH CHCH3 (5e) 96 (quantitative) 8.2/1
3.0 BnOCH CHCH3 (5 f)
¼
¼
¼
¼
73
1/1.25
¼
¼
BnO(CH2)2C(Me) CH2 (4g) 3.0 BnOCH2CH CMe2 (5g)
no reaction
[a] Isolated yield. Yields in parenthesis were estimated by 1H NMR spectroscopy. [b] Determined by
1H NMR spectroscopy.
Received: July 9, 2002 [Z19690]
Angew. Chem. Int. Ed. 2002, 41, No. 24
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The Structure of the Peroxo Species in the TS-1
Catalyst as Investigated by Resonant Raman
Spectroscopy**
Silvia Bordiga,* Alessandro Damin,
Francesca Bonino, Gabriele Ricchiardi,
Carlo Lamberti, and Adriano Zecchina
Ti-silicalite-1 (TS-1)[1] has exhibited a remarkably high
efficiency and molecular selectivity in oxidation reactions
with H2O2 under mild conditions, such as for olefin epox-
idation, phenol hydroxylation, cyclohexanone ammoxima-
tion, and conversions of ammonia to hydroxylamine, secon-
dary alcohols to ketones, and secondary amines to dialkylhy-
droxylamines[2] (Figure 1). Because of its relevance in indus-
trial applications, it has been one of the most studied materials
[2] Recent reviews: a) T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001,
34, 18 29; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140 3172;
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13]
in heterogeneous catalysis in recent years.[3
[3] a) M. Arisawa, E. Takezawa, A. Nishida, M. Mori, M. Nakagawa,
Synlett 1997, 1179 1180; b) H. Uchida, Y. Torisawa, A. Nishida, M.
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Arisawa, C. Theeraladanon, A. Nishida, M. Nakagawa, Tetrahedron
Lett. 2001, 42, 8029 8033; g) M. Arisawa, H. Kaneko, A. Nishida, M.
Nakagawa, J. Chem. Soc. Perkin Trans. 1 2002, 959 964.
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Org. Lett. 1999, 1, 1751 1753) is an effective catalyst; A phosphane-
free N-heterocyclic carbene complex(d) S. B. Garber, J. S. Kingsbury,
B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 8168 8179;
e) S. Gessler, S. Randl, S. Blechert, Tetrahedron Lett. 2000, 41, 9973
Figure 1. Schematic representation of the most relevant oxidation reac-
tions catalyzed by TS-1.
¼
¼
9976) is also effective. The catalysts, [Cl2Ru(PCy3)2 CHCH Ph] and
¼
[Cl2Ru(PCy3)2 CHPh], were ineffective for this isomerization.
It has been shown that the active species is a TiIV atom
isomorphically inserted into the MFI-type framework.[1] TS-1
is characterized by an increase of the unit cell volume
[5] Grubbs and co-workers found that vinylic ethers were not reactive in
cross-metathesis. He also reported the formation of a new Fischer
carbene species prepared by the reaction of a ruthenium alkylidene
complexwith ethyl vinyl ether. (a) A. K. Chatterjee, J. P. Morgan, M.
Scholl, R. H. Grubbs, J. Am. Chem. Soc. 2000, 122, 3783 3784; b) J.
Louie, R. H. Grubbs, Organometallics 2002, 21, 2153 2164).
proportional to the Ti content[1,5,7,14] and by the presence of a
10,13]
™fingerprint∫ IR absorption component[1,6b,8
centered at
960 cmꢀ1, the intensity of which grows proportionally with
increased Ti content. This band is clearly visible in IR spectra
appearing on the low-energy tail of the very strong absorption
resulting from the nasym(Si-O-Si) modes that appear in the
broad 1250 1030 cmꢀ1 region. In addition to the component at
[6] a) The Chemistry ofHeterocyclic Compounds, Indoles (Ed.: W. J.
Houlihan), Wiley-International, Toronto, 1972; b) G. W. Gribble, J.
Chem. Soc. Perkin Trans. 1 2000, 1045 1075.
[*] Prof. Dr. S. Bordiga,+ A. Damin, F. Bonino, Dr. G. Ricchiardi,
Dr. C. Lamberti,+ Prof. Dr. A. Zecchina
Dipartimento di Chimica IFM and
INSTM Research Unit, Turin University
Via P. Giuria 7, 10125 Torino (Italy)
Fax: ( þ 39)011-670-7855
E-mail: silvia.bordiga@unito.it
[þ] also with INFM UdR di Torino Universit‡ (Italy)
[**] This project has been supported by MURST (Cofin 2000, Area 03):
™Structure and reactivity ofcatalytic centers in zeolitic materials ∫. We
are indebted to R. Tagliapietra, M. Ricci, F. Rivetti, and G. SpanÚ for
fruitful discussions.
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