Indenylidene complexes of ruthenium: Optimized synthesis, structure elucidation, and performance as catalysts for Olefin metathesis - Application to the synthesis of the ADE-ring system of nakadomarin A

Article abstract of DOI:10.1002/1521-3765(20011119)7:22<4811::AID-CHEM4811>3.0.CO;2-P

An optimized and large scale adaptable synthesis of the ruthenium phenylindenylidene complex 3 is described which employs commercially available diphenyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual

Full text of DOI:10.1002/1521-3765(20011119)7:22<4811::AID-CHEM4811>3.0.CO;2-P

FULL PAPER
Indenylidene Complexes of Ruthenium: Optimized Synthesis, Structure
Elucidation, and Performance as Catalysts for Olefin MetathesisÐ
Application to the Synthesis of the ADE-Ring System of Nakadomarin A
Alois Fürstner,* Oliver Guth, Arno Düffels, Günter Seidel, Monika Liebl, Barbara Gabor,
and Richard Mynott[a]
Abstract: An optimized and large scale
adaptable synthesis of the ruthenium
phenylindenylidene complex 3 is de-
scribed which employs commercially
available diphenyl propargyl alcohol 5
as a stable and convenient carbene
source. Previous ambiguities as to the
actual structure of the complex have
been ruled out by a full analysis of its
NMR spectra. A series of applications to
ring closing metathesis (RCM) reactions
shows that complex 3 is as good as or
even superior to the classical Grubbs
carbene 1 in terms of yield, reaction rate,
and tolerance towards polar functional
groups. Complex 3 turns out to be the
catalyst of choice for the synthesis of the
enantiopure core segment 77 of the
marine alkaloid nakadomarin A 60 com-
prising the ADE rings of this target.
Together with a series of other examples,
this particular application illustrates that
catalyst 3 is particularly well suited for
the cyclization of medium-sized rings by
RCM. Other key steps en route to
nakadomarin A are a highly selective
intramolecular Michael addition setting
the quaternary center at the juncture of
the A and D rings and a Takai ± Nozaki
olefination of aldehyde 73 with CH2I2,
Ti(OiPr)4 and activated zinc dust.
Keywords: alkenes
´
carbenes
´
´
metathesis
ruthenium
´ natural products
Introduction
The advent of well-defined catalysts for alkene metathesis has
revolutionized the field within the last few years.[1] Ruthenium
carbene complexes of the general type 1 pioneered by Grubbs
are most prominent of these;[2, 3] they have found widespread
applications in organic synthesis and polymer chemistry,
because they combine reasonable activity and catalyst dura-
bility with an excellent tolerance towards many polar func-
tional groups. As has been outlined recently, replacement of
one PCy3 ligand by an N-heterocyclic carbene moiety (e.g. 2)
improves their excellent application profile even further.[4]
At the beginning of this groundbreaking development, the
rather cumbersome preparation of 1a as the first compound
of this series constituted a certain handicap in practical terms
[Scheme 1, Eq. (1)].[2] A much better access to this family of
metathesis (pre)catalysts was achieved by using diazoalkanes
as carbene sources. Specifically, the phenylcarbene complex
1b formed by reaction of [RuCl2(PPh3)3] with phenyldiazo-
methane followed by an exchange of the PPh3 ligands for PCy3
[Eq. (2)] became the standard and is now commercially
available.[3] The hazards associated with the use of diazoal-
kenes on a large scale, however, should not be underesti-
mated. Therefore, alternative routes to Grubbs-type carbenes
have been investigated, leading to the large scale adaptable
syntheses of 1c, d depicted in Equations (3) and (4), respec-
tively.[5, 6]
Described below is a full account of our work on a further
compound of this series, the indenylidene complex 3, which is
particularly easy to make and exhibits catalytic activity equal
[a] Prof. A. Fürstner, Dr. O. Guth, Dr. A. Düffels, G. Seidel,
Dr. M. Liebl, B. Gabor, Dr. R. Mynott
Max-Planck-Institut für Kohlenforschung
45470 Mülheim/Ruhr (Germany)
Fax : (‡49)208-3 06 29 94
E-mail: fuerstner@mpi-muelheim.mpg.de
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A. Fürstner et al.
FULL PAPER
carbon atoms which had been reported at d ˆ 210.0 and
174.1,[7] could not be found irrespective of whether directly
observed 13C NMR spectra or HMBC spectra were recorded
on a high-field NMR spectrometer (14.1 T, 1H resonance
frequency 600.2 MHz). This holds true for an original sample
of the complex kindly provided by Hill as well as for all the
samples prepared in our laboratory by the optimized proce-
dure described in the Experimental Section. Furthermore, the
1
aromatic region in the H NMR spectra was found to be far
more complicated than that expected for the proposed
structure 6, for which just three signals are to be expected
for the two equivalent phenyl groups.
Therefore, two-dimensional NMR techniques were used to
determine the connectivities in the organic ligand of the
material prepared according to Scheme 2. COSY and C,H-
correlated spectra (HSQC and HMBC) showed unambigu-
ously the presence of a phenylindenylidene moiety. These
conclusions were also supported by NOESY data. The H-2
resonance (arbitrary numbering as shown) is a sharp singlet at
d ˆ 7.39. The signal due to C-2 is observed at d ˆ 139.1 (1JC,H
ˆ
175 Hz). In the HMBC spectrum, cross peaks are observed
between C-3 and H-2, H-5 and H-11. All the chemical shifts
and coupling constants (JH,H as well as JC,H) are consistent with
structure 3b and all signals are accounted for (for the full set
of data see the Experimental Section). Since a single
resonance is observed for the phosphorous ligands in the 31P
NMR spectrum of 3b, the PCy3 ligands must be placed
symmetrically above and below a plane defined by the organic
ligand, the Ru center and the chlorine atoms.
Scheme 1. Established methods for the synthesis of Grubbs-type ruthe-
nium carbene complexes.
to or even better than that of 1. It can be prepared safely on a
large scale using only commercial reagents which are com-
pletely stable in the air. An optimized procedure yielding
multigram quantities of 3 is presented together with a detailed
study of its structure and catalytic performance.
Moreover, our NMR studies confirm that the triphenyl-
phosphine complex 3a formed as the primary product of the
reaction of [RuCl2(PPh3)3] with propargyl alcohol 5 also bears
a phenylindenylidene substituent. Therefore, it must be
concluded that no allenylidene complex is formed as a stable
entity at any stage of the synthesis.[10] We cannot help but
ascribe the signals reported at dC ˆ 210.0 and 174.1 in support
of the allenylidene structure[7] to have arisen from impurities,
artifacts, or accidental noise excursions. Our data, however,
leave open as to whether 3 originated from a rearrangement
of a transient allenylidene 6 or whether it is formed directly.[11]
After we had communicated our findings on the unexpect-
ed constitution of these complexes,[9] Nolan et al. reported the
X-ray structure of complex 4 (R ˆ 2,6-di(isopropyl)phenyl)
derived from 3b by replacement of one of the PCy3 ligands by
a N-heterocyclic carbene.[12] In this particular compound, the
phenylindenylidene moiety occupies the apical site of a
distorted square pyramidal complex.
Results and Discussion
Synthesis and structure: Complex 3b is obtained on treatment
of [RuCl2(PPh3)3] with propargyl alcohol 5 in refluxing THF,
followed by routine exchange of PPh3 for PCy3 (Scheme 2).
Ring closing metathesis reactions: Irrespective of the actual
structure of the complex derived from [RuCl2(PPh3)3] and
propargyl alcohol 5, the excellent catalytic activity of this
material was very quickly recognized.[8, 9, 13±17] When applied
to bis(allyl)tosylamide 9, the presence of only 1 mol% of 3b is
sufficient to form the cyclized product 10 in essentially
quantitative yield after 2 h reaction time at ambient temper-
ature. The homo-bimetallic complex 7, prepared from 3b
according to Scheme 3, is similarly effective but requires
longer reaction times to reach complete conversion of 9. In
both cases, CH2Cl2 turned out to be the solvent of choice.
Scheme 2. Synthesis of the phenylindenylidene complexes 3a,b.
This reaction was originally performed by Hill et al. and was
believed to provide the allenylidene species 6.[7] However,
shortly after the discovery of the promising catalytic activity
of the material thus formed,[8] our group recognized that the
analytical and spectroscopic data of this complex are not in
agreement with the proposed structure 6.[9] Although a
13C NMR signal was observed at d ˆ 293.9 (originally ascribed
to Ca of the allenylidene unit), the signals for the b- and g-
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Indenylidene Complexes of Ruthenium
4811±4820
Table 1. RCM reactions catalyzed by the ruthenium indenylidene com-
plexes 3b and 7. Optimization of the reaction conditions.
Complexes 3b and 7 have been applied to a representative
set of RCM reactions in order to study their scope and
compatibility with functional groups (Table 2). For compar-
ison, the results obtained with the Grubbs carbene 1 are also
included, where available. These data show that 3b and 1 are
roughly equipotent in terms of yield, reaction rate, and
tolerance towards an array of polar substituents including
ethers, esters, amides, silyl ethers, acetals, ammonium salts,
aryl halides, nitro groups, sulfonamides, ketones, urethanes,
free hydroxy groups, furan and pyrrole rings. As expected, the
phenylindenylidene catalyst 3b provides access to all ring
sizes ꢀ5, including several medium and macrocyclic deriva-
tives. Particularly noteworthy among them are the high
yielding cyclizations of the eight- and nine-membered rings
37, 39 and 41, the ten-membered lactones 43, 45, and 47, and
the macrocyclic musk 51 which upon hydrogenation converts
into exaltolide, a valuable perfume ingredient.[19] Entries 23 ±
26 depict the high yielding formation of even larger ring sizes.
A few other examples compiled in Table 2 deserve further
comment. Thus, cyclization of diene 32 to product 33
constitutes the key step of an unprecedentedly short synthesis
of balanol, a potent protein kinase C inhibitor.[13] In this
particular case, the phenylindenylidene complex 3b gives
significantly better results than the standard Grubbs carbene
1b. The same holds true for the formation of the heterocyclic
compound 53, which on hydrogenation affords the strongly
immunosuppressive alkaloid nonylprodigiosin.[9] Again, the
indenylidene complex 3b is superior to complex 1a serving as
the calibration point. This is ascribed to the somewhat higher
stability of 3b in solution, which is beneficial in RCM
reactions requiring longer reaction times. Further noteworthy
applications pertain to the synthesis of 49, which upon
N-deprotection converts into the insect repellent azamacro-
lide epilachnene.[19b] Similarly efficient is the cyclization of the
nonenolide 45, a precursor to the potent herbicidal agent
herbarumin I.[16] In this case, RCM catalyzed by 3b delivers
only the desired (E)-configurated product, whereas in all
other macrocyclization reactions reported here mixtures of
both geometrical isomers are obtained. The stereoselective
course of this reaction is probably due to the preexisting ring
in vicinity of the olefins which restricts the available
conformational space of diene 44 and favorably aligns the
reacting sites during the metathetic ring closure.[20, 21]
Catalyst
Mol%
Solvent
t [h]
T [8C]
Yield [%]
1
2
3
4
5
3b
3b
3b
7
10
10
1
8
1
toluene
CH2Cl2
CH2Cl2
toluene
CH2Cl2
1
1
2
1
17
80
20
20
80
20
85
93
98
90
99
7
Scheme 3. Synthesis of the homobimetallic phenylindenylidene complex 7.
The cyclization of diene 11 to the trisubstituted cycloalkene
12 was investigated in more detail. This example shows again
that the monometallic species 3b is superior to its bimetallic
congener 7, as evident from the kinetic data shown in Figure 1.
Synthesis of the spirotricyclic core of nakadomarin A: The
structurally unique alkaloid nakadomarin A 60 which was
isolated from Amphimedon sp. (SS-264) collected off the
Kerama islands, Okinawa, shows promising and diverse
physiological activities, including cytotoxicity against L 1210
murine lymphoma cells.[22] Moreover, nakadomarin A is
biogenetically related to the potent antitumor agent manza-
mine A 61.[23]
Figure 1. Kinetic of ring closure (GC) of diene 11 to cyclopentene 12
~
catalyzed by the phenylindenylidene complex 3b ( ) and the homobime-
*
tallic analogue 7 ( ); E ˆ COOEt.
While with the former catalyst the cyclization is essentially
complete after 1 h at ambient temperature, the latter effects a
steady but much slower reaction, reaching only 35% con-
version after 6 h. It is noteworthy that this trend is in contrast
to a report of Grubbs claiming that the analogous bimetallic
complex 8 is more reactive in prototype metathesis reactions
than the parent catalyst 1.[18]
The intricate hexacyclic skeleton of 60 poses considerable
challenges in preparative terms. One of them relates to the
stereoselective synthesis of the (Z)-configurated double bond
within the macrocyclic tether; a viable synthetic route to this
structural element has recently been found.[41] Other yet
unsolved problems pertain to the enantioselective formation
of the quaternary center at the juncture of the ABD rings as
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A. Fürstner et al.
FULL PAPER
Table 2. RCM reactions catalyzed by the ruthenium indenylidene com-
plexes 3b and 7 (1 ± 5 mol%) and comparison with the results reported in
the literature for complex 1; E ˆ COOEt.
Table 2 (cont.)
Substrate
Product
Yield [%]
3b
7
1
Substrate
Product
Yield [%]
3b
7
1
Ts
N
Ts
N
16
70 72 68[42]
38
Ts
39
1
2
98 99 93[36]
Ts
N
N
E
E
E
E
E
E
17
61
40
93 91
41
13
14
E
E
O
18
19
56
69
3
92 89
O
15
O
14
O
43
42
E
E
E
E
O
O
4
5
83 75 93[37]
O
O
O
11
O
12
O
E
E
E
E
O
45
92 94
44
16
O
O
17
O
O
20
21
86
88[43]
6
77
46
O
O
47
19
O
O
18
Br
Br
O
O
N
N
82 81 89[19b]
Fmoc
Fmoc
7
8
94 60 99[38]
O
O
48
20
21
49
O2N
O2N
O
O
97 71 97[38]
O
O
O
O
23
OSiEt3
22
22
23
24
89 69 79[19]
OSiEt3
9
79 81 95[39]
51
24
25
50
E
E
E E
NH
N.HCl
10
94 94
NH
N.HCl
26
42[9]
27
MeO
65
64
MeO
H
H
N
N
O
O
52
11
12
79 81
53
28
29
Si
Si
NH
N.HCl
NH
N.HCl
O
O
97 87 91[40]
Ph
Ph
MeO
MeO
30
31
O
O
OBn
OBn
OH
OH
55
54
13
87
93
64[13]
N
N
O
O
O
32
OtBu
OtBu
O
NH
NH
33
25
26
82 85 83[19]
O
O
N
N
O
O
14
15
97
57
56
H
H
O
O
35
34
O
O
O
O
N
87 83 71[19]
N
O
O
74 76 74[41]
59
H
H
58
36
37
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Indenylidene Complexes of Ruthenium
4811±4820
well as to the efficient cyclization of the eight-membered E
ring of this target. The latter aspect deserves particular
attention as the formation of the analogous ring in manzami-
ne A 61 by RCM was very low yielding (26%) and constituted
the major obstacle in a recent total synthesis of this
alkaloid.[24] Therefore we were prompted to explore in detail
whether RCM should be employed as a strategic transforma-
tion en route to 60 to close the rather strained and congested
E ring. Described below is an efficient synthesis of the fully
functional ADE-ring system of nakadomarin A in which the
quaternary center is set with the correct absolute stereo-
chemistry and the E ring is formed in almost quantitative yield
by using the newly developed phenylindenylidene catalyst 3b;
this route can be used to prepare multigram quantities as
required for our total synthesis project.
Scheme 5. [a] LHMDS, THF, 788C, then ClC(O)SEt, 788C, 96%.
[b] Amine 65, AgOTf, (iPr)2NEt, CH3CN, RT, 73%. [c] (iPr)2NEt, CH3CN,
reflux. [d] H2 (1 atm), Pd/C, MeOH, 80% (over two steps). [e] Mg(ClO4)2
(25 mol%), CH3CN, 508C, 99%. [f] LiBH4, THF, RT, 82%. [g] Dess ±
Martin periodinane, H2O (1 equiv), CH2Cl2, RT, 78%. [h] CH2I2,
Ti(OiPr)4, Zn, THF, RT, 84%. [i] NaH, DMF, 08C, then 6-iodo-1-hexene,
RT, 88%. [j] Catalyst 3b (5 mol%), CH2Cl2, reflux, 98%. [k] i) F3CCOOH,
reflux; ii) Me3SiCHN2, toluene/MeOH 3.5:1, 85%.
Scheme 4. [a] Mesyl chloride, Et3N, Et2O, RT. [b] p-Methoxybenzylamine
(PMB-NH2), Et3N, THF, reflux, 68% (over two steps). [c] (Boc)2O, Et3N,
DMAP, CH2Cl2, RT, 86%. [d] i) nBuLi, Et2O,
788C; ii) (Boc)2O,
788C ! RT, 96%. [e] i) pTsOH, Et2O/tBuOH 20:1, RT. ii) aq. NaOH
(2n), 73%.
(R)-(‡)-Pyroglutaminic ester [(R)-(‡)-66] was chosen as a
convenient starting material which is converted into thioester
67 by reacting its lithium enolate with ClC(O)SEt
(Scheme 5).[25] Exposure of this product to amine 65 (pre-
pared according to Scheme 4), AgOTf and (iPr)2NEt in
CH3CN provides b-ketoamide 68 as a mixture of diastereo-
isomers. Following a recent example reported by Brands
et al.,[26] this compound undergoes an intramolecular Michael
addition on treatment with (iPr)2NEt (2 equiv) in refluxing
CH3CN delivering an inseparable mixture of three isomeric
alkenes 69. Subsequent hydrogenation of this material over
palladium on charcoal in MeOH, however, converges this
morass of stereoisomers into a single product 70 which is
isolated by flash chromatography in 80% yield on a multi-
gram scale.[27] Inspection of the recorded NOE effects and
comparison with literature data[26] allow unambiguously to
assign the absolute stereochemistry of the newly formed
quaternary C atom (cf. Figure 2). Moreover, we have secured
the enantiopurity of product 70 thus formed by carrying out
the same sequence of reactions starting from (S)-( )-66 and
comparison of both samples by HPLC on a chiral column
Figure 2. NOE effects recorded in a one-dimensional NOESY experiment
relevant for the assignment of the stereochemistry of the quaternary center
in compound 70.
(Shimadzu LC-10A: Chiralpak AD Æ250 Â 4.5 mm column,
1
eluent: n-heptane/2-propanol 75:25, 0.5 mLmin ).
After deprotection of the N-Boc group in 70 by means of
Mg(ClO4)2,[28] it was possible to achieve a selective reduction
of the methyl ester function in 71 using LiBH4. Oxidation of
the resulting primary alcohol 72 with Dess ± Martin period-
inane according to the optimized procedure described by
Schreiber et al.[29] proceeded uneventfully, delivering the
required aldehyde 73 without any detectable epimerization
of the adjacent chiral center. The envisaged methylenation of
this material, however, required significant optimization. Best
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A. Fürstner et al.
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was charged with [RuCl2(PPh3)3] (10.37 g, 10.8 mmol). THF (600 mL) and
diphenylpropargyl alcohol 5 (3.37 g, 16.2 mmol) were introduced and the
resulting mixture was refluxed under Ar for 2.5 h. During this period, the
mixture turned dark-red. For work-up, the solvent was evaporated in vacuo
(12 mbar), the residue was suspended in hexane (400 mL) and the
suspension stirred for about 3 h until the solid was finely ground and had
a homogeneous appearance. The powdered solid was filtered off and dried
in vacuo, affording complex 3a in quantitative yield. The NMR data are
compiled below.
results were achieved by means of the Takai ± Nozaki protocol
using CH2I2 as the methylene source in combination with
Ti(OiPr)4 and activated zinc dust.[30] Under these conditions,
alkene 74 was obtained in 84% isolated yield. Subsequent
N-alkylation of the sodium salt derived thereof with 6-iodo-1-
hexene readily provides diene 75 and sets the stage for the
envisaged cyclization of the eight-membered ring by RCM.
We were pleased to see that this key transformation
proceeds with essentially quantitative yield (98%) if a dilute
solution of diene 75 (0.002m) in CH2Cl2 is refluxed in the
presence of 5 mol% of the phenylindenylidene catalyst 3b for
18 h. For comparison, the standard Grubbs catalyst 1b was
also tested, delivering only 82% yield of 76 under otherwise
identical conditions; as discussed above, we ascribe the better
performance of 3b to the higher stability of this complex in
solution. Even more surprising is the fact that the ªsecond-
generationº NHC-carbene complex 2, which is generally
believed to be an even more powerful catalyst than the parent
species 1b, is significantly less efficient in this particular case,
affording only 63% of product 76. Trace amounts of various
by-products are detected by TLC which detract from the yield
of the desired hexahydroazocine ring.
Attempted cleavage of the N-PMB group in 76 by means of
cerium ammonium nitrate led to the rapid destruction of this
compound. Fortunately, however, the deprotection is ach-
ieved by refluxing product 76 in neat trifluoroacetic acid for
18 h. Since the tert-butyl ester is concomitantly cleaved under
these vigorous conditions, the crude product was treated with
(trimethylsilyl)diazomethane, affording methyl ester 77 in
excellent overall yield. Based on this high yielding, large scale
adaptable and virtually diastereospecific synthesis of com-
pound 77, which represents a fully functional synthon for the
ADE segment of nakadomarin A 60, we are presently
pursuing the completion of a total synthesis of this challenging
target.
PCy3 (9.39 g, 33.5 mmol) was added to a solution of complex 3a in CH2Cl2
(250 mL) and the resulting mixture was stirred for 2 h at ambient
temperature under Ar. The solvent was evaporated, the crude product
suspended in hexane (400 mL). The suspension was stirred for about 3 h at
ambient temperature, the finely powdered complex was filtered off and
carefully washed with hexane (100 mL) in several portions. Drying of the
product in vacuo afforded complex 3b as an analytically pure, orange
powder (7.90 g, 80%).
Complex 3b: 1H NMR (600.2 MHz, CD2Cl2, 308C): d ˆ 8.67 (dd, J(H-7,H-
8) ˆ 7.5 Hz, 1H, H-8), 7.75 (d, 2H, H-11), 7.52 (d, 1H, H-13), 7.40 (dd, 2H,
H-12), 7.39 (s, 1H, H-2), 7.38 (td, J(H-5,H-6) ˆ J(H-6,H-7) ˆ 7.3 Hz, 1H,
H-6), 7.29 (td, J(H-6,H-7) ˆ J(H-7,H-8) ˆ 7.5 Hz, 1H, H-7), 7.27 (dd, J(H-
5,H-6) ˆ 7.3 Hz, 1H, H-5); cyclohexyl signals: d ˆ 2.60, 1.77, 1.73, 1.66, 1.65,
1.52, 1.50, 1.47, 1.21, 1.19, 1.18; 13C NMR (150.9 MHz, CD2Cl2, 308C): d ˆ
293.9 (s, J ˆ 8.1 Hz (t), J(P,C), C-1), 145.0 (s, C-9), 141.4 (s, C-4), 139.8 (s,
C-3), 139.1 (d, 1J(C,H) ˆ 175 Hz, C-2), 136.8 (s, C-10), 129.41 (d, 1J(C,H) ˆ
163 Hz, C-8), 129.40 (2C, d, C-12), 129.2 (d, C-7), 128.7 (d, C-6), 128.4 (d,
C-13), 126.6 (2C, d, C-11), 117.6 (d, 1J(C,H) ˆ 157 Hz, C-5); cyclohexyl
signals: d ˆ 33.1 (CH), 30.21, 30.16, 28.3, 28.1, 26.9 (all CH2); 31P NMR
(243.0 MHz, CD2Cl2, 308C, rel. ext. H3PO4): d ˆ 32.6.
Complex 3a: 1H NMR (600.2 MHz, CD2Cl2, 308C): d ˆ 7.54 (d, 1H, H-13),
7.50 (d, 2H, H-11), 7.34 (dd, 2H, H-12), 7.31 (td, J(H-5,H-6) ˆ J(H-6,H-7) ˆ
7.5 Hz, 1H, H-6), 7.25 (dd, J(H-5,H-6) ˆ 7.5 Hz, 1H, H-5), 7.08 (dd, J(H-
7,H-8) ˆ 7.3 Hz, 1H, H-8), 6.67 (td, J(H-6,H-7) ˆ J(H-7,H-8) ˆ 7.4 Hz, 1H,
H-7), 6.38 (s, 1H, H-2); phenyl group: d ˆ 7.54, 7.46 (para), 7.33; 13C NMR
(150.9 MHz, CD2Cl2, 308C): d ˆ 301.0 (s, J(P,C) ˆ 12.9 Hz (t), C-1), 145.4 (s,
C-3), 141.8 (s, J(P,C) ˆ 2.7 Hz (t), C-9), 139.8 (s, C-4), 139.4 (d, J(P,C) ˆ
5.2 Hz (t), 1J(C,H) ˆ 175.4 Hz, C-2), 135.6 (s, C-10), 130.1 (d, C-6), 130.1 (d,
C-7), 129.41 (d, 2C, C-12), 129.36 (d, C-13), 129.33 (d, 1J(C,H) ˆ 165 Hz,
C-8), 127.1 (d, 2C, C-11), 118.6 (d, 1J(C,H) ˆ 160 Hz, C-5); phenyl signals:
X part of ABX spin systems (A, B ˆ 31P, X ˆ 13C): d ˆ 135.2 (d, [J(P,C) ‡
J(P',C)] ˆ 11.2 Hz, C-ortho), 131.2 (s, [J(P,C) ‡ J(P',C)] ˆ 42.8 Hz, C-ipso)
130.6 (d, C-para), 128.4 (d, [J(P,C) ‡ J(P',C)] ˆ 9.6 Hz, C-meta); 31P NMR
(243.0 MHz, CD2Cl2, 308C, rel. ext. H3PO4): d ˆ 28.7.
Representative procedure for RCM catalyzed by complex 3b. Synthesis of
2,5-dihydro-benzo[b]oxepine (29): A solution of allyl-(2-allylphenyl)ether
(28; 167 mg, 0.96 mmol) and complex 3b (7 mg, 0.01 mmol) in CH2Cl2
(50 mL) was stirred at ambient temperature until TLC showed complete
conversion of the substrate (ca. 2 h). For work-up, the solvent was
evaporated and the residue was purified by flash chromatography affording
Experimental Section
General remarks: The NMR spectra of 3a,b were measured on a Bruker
DMX 600 NMR spectrometer using a 5 mm TXI triple probe with a z-
gradient coil. Measurement techniques used include COSY (phase
1
compound 29 as a colorless syrup. H NMR (300 MHz, CDCl3): d ˆ 7.19 ±
1
sensitive DQ-filtered), HSQC (optimized for JC,H ˆ 160 Hz), HMBC
7.01 (m, 5H), 5.86 ± 5.83 (m, 1H), 5.49 ± 5.43 (m, 1H), 4.58 (dt, J ˆ 2.3,
5.2 Hz, 2H), 3.50 ± 3.46 (m, 2H); 13C NMR (75 MHz, CDCl3): d ˆ 158.7,
136.1, 128.8, 127.8, 127.3, 125.7, 124.0, 121.4, 71.2, 31.8; IR (film): nÄ ˆ 2931,
2882, 1724, 1602, 1583, 1489, 1455, 1230, 1062, 761 cm 1; MS: m/z (%): 146
(optimized for JC,H ˆ 10 Hz), NOESY, 13C (cpd-decoupled), and DEPT.
n
The C,H coupling constants were taken from the proton coupled 13C NMR
spectrum or a high resolution HSQC spectrum. All reactions were carried
out under Ar. The solvents used were purified by distillation over the
drying agents indicated and were transferred under Ar: THF, Et2O (Mg/
anthracene), CH2Cl2 (P4O10), CH3CN, Et3N (CaH2), MeOH (Mg), DMF
(Desmodur, dibutyltin dilaurate), hexane, toluene (Na/K). Flash chroma-
tography: Merck silica gel 60 (230 ± 400 mesh). NMR: Spectra of organic
compounds were recorded on a DPX 300 or DMX 600 spectrometer
(Bruker) in the solvents indicated; chemical shifts (d) are given in ppm
relative to TMS, coupling constants (J) in Hz. IR: Nicolet FT-7199
spectrometer, wavenumbers in cm 1. MS (EI): Finnigan MAT 8200 (70 eV),
HRMS: Finnigan MAT 95, MALDI: Bruker ICR. Melting points:
Gallenkamp melting point apparatus (uncorrected). Optical rotation:
Perkin Elmer 343 at l ˆ 589 nm (Na D-line). Elemental analyses: Kolbe,
Mülheim/Ruhr. All commercially available compounds (Lancaster, Al-
drich) were used as received.
‡
(100) [M] , 131 (59), 127 (32), 115 (34), 103 (10), 91 (25), 89 (13), 77 (17), 72
(4), 63 (17), 51 (22), 39 (23), 27 (7). The analytical data were in agreement
with those reported in the literature.[31]
Eleven other compounds displayed in Table 2 have been prepared
analogously. Their analytical and spectroscopic data were in agreement
with those reported in the literature: 10,[32] 12,[33] 14,[34] 17,[35] 21,[38] 23,[38]
25,[39] 31,[40] 33,[13] 39,[42] 45,[16] 47,[43] 49,[19] 51,[19] 53,[9] 55,[15] 57,[19] 59.[19] The
data of new compounds are compiled below.
Cyclohept-4-ene-1,1-diethyldicarboxylate (27): 1H NMR (300 MHz,
CDCl3): d ˆ 5.85 (dt, J ˆ 6.1, 10.6 Hz, 1H), 5.68 (dt, J ˆ 6.4, 10.7 Hz, 1H),
4.17 (q, J ˆ 7.0 Hz, 4H), 2.67 (d, J ˆ 6.4 Hz, 2H), 2.26 ± 2.22 (m, 2H), 2.19 ±
2.13 (m, 2H), 1.68 ± 1.61 (m, 2H), 1.24 (t, J ˆ 7.1 Hz, 6H); 13C NMR
(75 MHz, CDCl3): d ˆ 171.7, 134.0, 127.1, 61.0, 56.1, 36.6, 32.3, 28.2, 22.7,
14.0; IR (film): nÄ ˆ 3029, 2981, 2937, 1732, 1656, 1312, 1238, 1213, 1183, 853,
Optimized synthesis of the phenylindenylidene complexes 3a, b: A two-
necked flask equipped with a reflux condenser, a magnetic stirring bar, and
an Ar supply was evacuated, flame dried, and flushed with Ar. The flask
‡
703 cm 1; MS: m/z (%): 240 (8) [M] , 195 (16), 173 (100), 166 (57), 138 (12),
127 (28), 121 (14), 99 (7), 93 (60), 79 (14), 67 (6), 55 (6), 41 (9), 29 (31);
4816
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0722-4816 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 22

Indenylidene Complexes of Ruthenium
4811±4820
‡
elemental analysis calcd (%) for C13H20O4: C 64.98, H 8.39; found: C 64.86,
H 8.31.
82.5, 69.5, 55.2, 52.7, 47.2, 19.5; MS: m/z (%): 189 (6) [M] , 150 (20), 121
(100); IR (film): nÄ ˆ 3291, 3061, 3031, 2952, 2933, 2912, 2835, 2116, 1612,
1585, 1513, 1463, 1301, 1247, 1176, 1109, 1035, 815, 638 cm 1; HRMS
(C12H15NO): calcd 189.11536; found 189.11525; elemental analysis calcd
(%) for C12H15NO: C 76.16, H 7.99, N 7.40; found: C 75.93, H 8.06, N 7.45.
1
(R)-1,3-Dimethyl-cyclohexene (19): H NMR (300 MHz, CDCl3): d ˆ 5.24
(s, 1H), 2.20 ± 2.05 (m, 1H), 1.90 ± 1.83 (m, 2H), 1.80 ± 1.66 (m, 2H), 1.65 ±
1.62 (m, 3H), 1.58 ± 1.43 (m, 1H), 1.15 ± 1.10 (m, 1H), 0.94 (d, J ˆ 7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): d ˆ 133.3, 127.8, 31.2, 30.3, 30.0, 23.8,
22.0, 21.9; IR (film): nÄ ˆ 3038, 2950, 1671, 1454, 1376, 1133, 966, 867,
N-(tert-Butoxycarbonyl)-N-(4-methoxybenzyl)-5-amino-1-pent-2-ynoic
tert-butyl ester (64): Di-tert-butyldicarbonate (55.8 g, 0.256 mol) was slowly
added to a solution of amine 63 (44.0 g, 0.233 mmol), DMAP (2.80 g,
23.2 mmol) and Et3N (35.0 mL, 0.256 mol) in CH2Cl2 (500 mL) at 08C and
the resulting mixture was stirred at ambient temperature for 72 h. Standard
extractive work-up followed by flash chromatography (silica gel, hexane/
ethyl acetate 15:1) provided N-(tert-butoxycarbonyl)-N-(4-methoxyben-
zyl)-4-amino-1-butyne (58.1 g, 86%) as a pale yellow syrup. 1H NMR
(300 MHz, CDCl3, rotamers): d ˆ 7.17 (brs, 2H), 6.86 (d, J ˆ 8.7 Hz, 2H),
4.45 (s, 2H), 3.80 (s, 3H), 3.32 (brs, 2H), 2.34 (brs, 2H), 1.96 (t, J ˆ 2.7 Hz,
1H), 1.50 (brs, 9H); 13C NMR [75 MHz, CDCl3, (resolved signals of
rotamers)]: d ˆ 158.8, 155.3, 130.2, 129.1 [128.5] (2C), 113.9 (2C), [82.0]
81.8, 79.9, 69.5, 55.2, [50.6] 49.8, 45.2, 28.4 (3C), 18.2 [18.0]; MS (EI): m/z
‡
809 cm 1; MS (EI): m/z (%): 110 (27) [M] , 95 (100), 82 (16), 67 (46), 55
(15), 41 (14).
(S)-5-Methyl-1-aza-9-oxa-bicyclo[5.3.0]dec-5-en-10-one (35): 1H NMR
(300 MHz, CDCl3): d ˆ 5.18 ± 5.14 (m, 1H), 4.48 ± 4.41 (m, 1H), 4.36 (t,
J ˆ 7.8 Hz, 1H), 3.93 (dd, J ˆ 7.8, 5.6 Hz, 1H), 3.85 ± 3.76 (m, 1H), 3.22 ±
3.15 (m, 1H), 2.23 ± 2.19 (m, 2H), 1.92 ± 1.75 (m, 2H), 1.72 (s, 3H); 13C NMR
(75 MHz, CDCl3): d ˆ 158.1, 141.9, 123.7, 68.8, 54.2, 45.1, 33.2, 26.2, 25.3;
‡
MS (EI): m/z (%): 167 (29) [M] , 152 (100), 108 (20), 94 (12), 81 (26), 80
(11), 79 (11), 67 (13), 53 (10), 41 (20), 39 (16), 27 (11); IR (film): nÄ ˆ 3496,
2931, 1745, 1425, 1378, 1315, 1218, 1046, 761 cm 1; HRMS (C9H13NO2):
calcd 167.09463; found 167.09435.
‡
(%): 289 (4) [M] , 233 (23), 159 (19), 121 (100), 57 (36); IR (film): nÄ ˆ 3294,
(S)-1-Aza-10-oxa-bicyclo[6.3.0]undec-6-en-11-one (37): [a]D20
ˆ
84.88
3064, 3002, 2975, 2933, 2836, 2119, 1692, 1612, 1586, 1513, 1465, 1411, 1366,
1248, 1166, 1121, 1036, 882, 818, 774, 638 cm 1; HRMS (C17H23NO3): calcd
289.16779; found 289.16786; elemental analysis calcd (%) for C17H23NO3: C
70.56, H 8.01, N 4.84; found: C 70.41, H 8.09, N 4.88.
(c ˆ 0.70, CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 5.91 ± 5.81 (m, 1H),
5.39 (dd, J ˆ 10.9, 5.8 Hz, 1H), 4.47 ± 4.37 (m, 2H), 3.96 ± 3.88 (m, 1H),
3.39 ± 3.30 (m, 2H), 2.39 ± 2.28 (m, 1H), 2.17 ± 2.05 (m, 1H), 1.84 ± 1.73 (m,
1H), 1.67 ± 1.43 (m, 3H); 13C NMR (75 MHz, CDCl3): d ˆ 157.6, 134.3,
nBuLi (43.6 mL, 69.7 mmol, 1.60m in hexane) was slowly added at 788C
to a solution of the compound obtained above (16.8 g, 58.1 mmol) in Et2O
(300 mL). After the mixture had been stirred for 30 min at that temper-
ature, di-tert-butyldicarbonate (17.7 g, 81.3 mmol) was introduced, and
stirring was continued for another 15 min at 788C before the mixture was
allowed to reach ambient temperature. After 1 h, the reaction was
quenched with sat. aq. NH4Cl, the aqueous layer was extracted with ethyl
acetate, and the combined organic phases were dried over Na2SO4.
Evaporation of the solvent followed by flash chromatography of the
residue (silica gel, hexane/ethyl acetate 10:1!4:1) afforded the title
compound 64 (21.7 g, 96%) as a colorless liquid. 1H NMR (300 MHz,
CDCl3, rotamers): d ˆ 7.17 (brs, 2H), 6.86 (d, J ˆ 8.6 Hz, 2H), 4.44 (s, 2H),
3.81 (s, 3H), 3.33 (brs, 2H), 2.46 (brs, 2H), 1.49 (s, 18H); 13C NMR [75 Hz,
CDCl3, (resolved signals of rotamers)]: d ˆ 158.9, 158.8, 152.6, 130.2, 129.2
[128.6] (2C), 113.9 (2C), 84.7, 83.2, 80.2, 75.3, 55.2, [50.8] 49.7, 44.4, 28.4
‡
127.0, 68.1, 53.7, 43.1, 27.0, 25.6, 25.4; MS (EI): m/z (%): 167 (70) [M] , 152
(77), 140 (14), 139 (17), 138 (39), 125 (20), 122 (25), 109 (16), 108 (32), 96
(14), 95 (27), 94 (51), 91 (12), 86 (11), 83 (13), 82 (31), 81 (49), 80 (85), 79
(37), 77 (14), 69 (13), 68 (36), 67 (75), 66 (13), 65 (13), 56 (22), 55 (65), 54
(55), 53 (33), 51 (10), 42 (25), 41 (100), 40 (11), 39 (60), 30 (14), 29 (16), 28
(32), 27 (35); IR (film): nÄ ˆ 3017, 2930, 2859, 1747, 1652, 1420, 1247, 1222,
1183, 1053, 1029, 1005, 842, 778, 761, 739, 709, 689 cm 1; elemental analysis
calcd (%) for C9H13NO2: C 64.65, H 7.84, N 8.38; found: C 64.55, H 7.92, N
8.44.
1-(Toluene-4-sulfonyl)-2,3,4,7,8,9-hexahydro-1H-azonine (41): m.p. 103 ±
1048C; 1H NMR (300 MHz, CDCl3): d ˆ 7.74 ± 7.70 (m, 2H), 7.34 ± 7.30
(m, 2H), 5.57 ± 5.46 (m, 2H), 2.97 (t, J ˆ 6.3 Hz, 4H), 2.47 ± 2.41 (m, 4H),
2.43 (s, 3H), 1.90 ± 1.81 (m, 4H); 13C NMR (75 MHz, CDCl3): d ˆ 143.1,
134.2, 130.0, 129.4, 127.5, 53.3, 28.2, 22.2, 21.4; IR (KBr): nÄ ˆ 3005, 2966,
1
2922, 2857, 1661, 1595, 1490, 1462, 1330, 1156, 1095, 973, 808, 688, 549 cm
;
‡
(3C), 27.9 (3C), 18.5; MS (EI): m/z (%): 389 (<1) [M] , 277 (29), 232 (41),
‡
MS: m/z (%): 279 (1) [M] , 250 (1), 215 (1), 155 (3), 124 (100), 96 (18),
41(12); elemental analysis calcd (%) for C15H21NO2S: C 64.48, H 7.58;
found: C 64.48, H 7.58.
169 (10), 121 (100), 57 (52), 41 (10); IR (film): nÄ ˆ 3063, 3002, 2978, 2934,
2837, 2241, 1704, 1612, 1586, 1513, 1468, 1410, 1368, 1282, 1251, 1163, 1121,
1074, 1036, 887, 845, 755 cm 1; elemental analysis calcd (%) for C22H31NO5:
C 67.84, H 8.02, N 3.69; found: C 67.92, H 8.08, N 3.66.
Benzo[2,1-i]3,4,5,8-tetrahydrooxecin-2-one (43): Mixture of isomers:
E:Z ˆ 1:6.4; 1H NMR (300 MHz, CD2Cl2): d ˆ 7.21 ± 7.05 (m, 2H), 6.93 ±
6.90 (m, 1H), 5.25 ± 5.11 (m, 2H), 2.45 ± 2.21 (m, 4H), 2.05 ± 1.18 (m, 4H);
13C NMR (75 MHz, CD2Cl2): E-isomer (resolved signals): d ˆ 174.1, 149.5,
131.8, 131.5, 131.1, 129.4, 126.9, 125.9, 124.0, 36.2, 34.3, 32.7, 26.6; Z-isomer
(resolved signals): d ˆ 171.7, 149.8, 132.3, 130.2, 130.0, 127.3, 126.9, 126.1,
123.4, 34.7, 30.2, 25.7, 25.1; IR (KBr): nÄ ˆ 3062, 3037, 2941, 2923, 1752, 1656,
N-(4-Methoxybenzyl)-5-amino-1-pent-2-ynoic tert-butyl ester (65): A solu-
tion of compound 64 (17.8 g, 45.7 mmol) in Et2O (100 mL) and tBuOH
(5 mL) was treated with pTsOH ´ H2O (17.4 g, 91.4 mmol) and the mixture
was vigorously stirred (mechanical stirrer) for 16 h at ambient temperature.
The precipitate formed was dissolved by addition of 2n NaOH (100 mL)
and the resulting solution was repeatedly extracted with tert-butyl methyl
ether. The combined organic layers were dried over Na2SO4, the solvent
was evaporated and the residue purified by flash chromatography (silica
gel, ethyl acetate) affording product 65 (9.70 g, 73%) as a pale yellow oil.
1H NMR (300 MHz, CDCl3): d ˆ 7.25 (d, J ˆ 8.6 Hz, 2H), 6.87 (d, J ˆ
8.6 Hz, 2H), 3.81 (s, 3H), 3.75 (s, 2H), 2.84 (t, J ˆ 6.7 Hz, 2H), 2.51 (t,
J ˆ 6.7 Hz, 2H), 1.60 (brs, 1H), 1.50 (s, 9H); 13C NMR (75 MHz, CDCl3):
d ˆ 158.7, 152.7, 132.0, 129.2 (2C), 113.8 (2C), 84.7, 83.1, 75.4, 55.2, 52.6,
‡
1491, 1448, 1208, 1171, 1131, 753, 707, 545 cm 1; MS: m/z (%): 202 (9) [M] ,
173 (19), 145 (11), 131 (11), 118 (47), 107 (11), 91 (10), 84 (100), 55 (23);
elemental analysis calcd (%) for C13H14O2: C 77.20, H 6.98; found: C 77.06,
H 6.87.
Synthesis of the ADE-Ring Segment of Nakadomarin A
N-(4-Methoxybenzyl)-4-amino-1-butyne (63): Methanesulfonyl chloride
(41.6 mL, 0.535 mol) was added at 08C to a solution of 3-butyn-1-ol (62)
(25.0 g, 0.357 mol) in Et2O (500 mL) followed by dropwise addition of Et3N
(74.6 mL, 0.535 mol) over a period of 60 min. The resulting solution was
stirred for 12 h at ambient temperature. The precipitate was then dissolved
by addition of water and the aqueous phase was repeatedly extracted with
tert-butyl methyl ether. The combined organic layers were subsequently
washed with sat. aq. NH4Cl and brine and finally dried over Na2SO4.
Evaporation of the solvent afforded a pale yellow syrup which was
dissolved in THF (500 mL). Et3N (101 mL, 0.725 mol) and p-methoxyben-
zylamine (100 mL, 0.759 mmol) were added and the resulting solution was
‡
46.4, 28.0 (3C), 19.9; MS (EI): m/z (%): 289 (< 1) [M] , 232 (20), 150 (17),
122 (11), 121 (100); IR (film): nÄ ˆ 2978, 2934, 2835, 2237, 1705, 1612, 1570,
1
1513, 1461, 1369, 1279, 1249, 1161, 1129, 1074, 1035, 844, 754 cm
;
elemental analysis calcd (%) for C17H23NO3: C 70.56, H 8.01, N 4.84; found:
C 70.50, H 7.93, N 4.76.
(3rac, 5R)-1-(tert-Butoxycarbonyl)-3-(thioethoxycarbonyl)-2-pyrrolidinon-
5-carboxylic methyl ester (67): Bis-(trimethylsilyl)-lithiumamide (14.3 g,
85.5 mmol) was slowly added to a solution of (R)-66 (10.4 g, 42.7 mmol) in
THF (250 mL) at 788C. The resulting yellow solution was stirred for 1 h
at that temperature before (chloro)thioformic ethyl ester (6.38 g,
51.2 mmol) was introduced and stirring was continued for another
60 min. The reaction was quenched by adding sat. aq. NH4Cl at 788C.
The mixture was extracted with tert-butyl methyl ether and water, the
combined organic layers were washed with sat. aq. NH4Cl and brine, dried
over Na2SO4, and the solvent was evaporated. Flash chromatography of the
refluxed for 14 h.
A standard extractive work-up followed by flash
chromatography (silica gel, ethyl acetate) afforded amine 63 (58.3 g,
68%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3): d ˆ 7.25 (d, J ˆ
8.7 Hz, 2H), 6.87 (d, J ˆ 8.7 Hz, 2H), 3.81 (s, 3H), 3.76 (s, 2H), 2.80 (t, J ˆ
6.6 Hz, 2H), 2.41 (dt, J ˆ 6.6, 2.6 Hz, 2H), 2.00 (t, J ˆ 2.6 Hz, 1H), 1.68 (brs,
1H); 13C NMR (75 MHz, CDCl3): d ˆ 158.6, 132.2, 129.3 (2C), 113.8 (2C),
Chem. Eur. J. 2001, 7, No. 22
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0722-4817 $ 17.50+.50/0
4817

A. Fürstner et al.
FULL PAPER
crude product (silica gel, hexane/ethyl acetate 2:1 ! 1:1) afforded
thioester 67 (13.5 g, 95%) as a colorless solid (mixture of diastereoisom-
ers): m.p. 105 ± 1068C; [a]2D0 ˆ ‡4.688 (c ˆ 1.18, CHCl3); 1H NMR
(300 MHz, CDCl3): d ˆ 4.66 (dd, J ˆ 9.4, 3.0 Hz), 4.61 (dd, J ˆ 9.4, 4.2 Hz)
[1H], 3.78 (s), 3.77 (s) [3H], 2.99 ± 2.70 (m, 3H), 2.62 ± 2.47 (m, 1H), 2.21
(ddd, J ˆ 9.0, 3.0 Hz), 2.16 (dd, J ˆ 9.0, 3.0 Hz) [1H], 1.48 (s, 9H), 1.30 ± 1.23
(m, 3H); 13C NMR [75 MHz, CDCl3, (resolved signals of the diastereo-
isomer)]: d ˆ 194.2 [193.1], 171.4 [170.6], 167.5 [167.4], 149.0, 84.3 [84.1],
[57.5] 57.0, [56.5] 55.7, [52.7] 52.6, 27.8 (3C), 25.2 [24.4], [24.3] 24.1, [15.5]
14.2; MS: m/z (%): 231 (23), 172 (16), 170 (22), 143 (26), 142 (15), 110 (14),
57 (100), 41 (12); IR (film): nÄ ˆ 3449, 3343, 2978, 2934, 2877, 1793, 1753,
1724, 1677, 1599, 1455, 1439, 1371, 1314, 1288, 1254, 1212, 1152, 1071, 1017,
975, 844, 774 cm 1; HRMS (C14H21NO6S‡H): calcd 332.11678; found
332.11667; elemental analysis calcd (%) for C14H21NO6S: C 50.74, H 6.30, N
4.23; found: C 50.60, H 6.43, N 4.28.
(751 mg, 3.37 mmol) was added to a solution of compound 70 (7.55 g,
13.5 mmol) in CH3CN (100 mL) and the resulting mixture was stirred for
2 h at 508C. Standard extractive work-up followed by flash chromatog-
raphy of the crude product (silica gel, hexane/ethyl acetate, 1:1 ! 1:2)
afforded title compound 71 (6.15 g, 99%) as a colorless foam: m.p. 66-
678C; [a]2D0 ˆ ‡49.68 (c ˆ 1.05, CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ
7.15 (d, J ˆ 8.7 Hz, 2H), 6.85 (d, J ˆ 8.7 Hz, 2H), 6.21 (s, 1H), 4.71 (d, J ˆ
14.6 Hz, 1H), 4.37 (d, J ˆ 14.6 Hz, 1H), 4.18 (dd, J ˆ 10.0, 3.3 Hz, 1H), 3.83
(s, 3H), 3.79 (s, 3H), 3.25 ± 3.21 (m, 2H), 3.10 (dd, J ˆ 13.9, 3.3 Hz, 1H),
2.50 ± 2.25 (m, 5H), 1.79 ± 1.71 (m, 1H), 1.43 (s, 9H); 13C NMR (75 MHz,
CDCl3): d ˆ 175.0, 171.6, 171.3, 168.9, 158.9, 129.1 (2C), 128.6, 114.0 (2C),
81.1, 55.2, 53.4, 53.3, 52.7, 50.0, 45.8, 38.1, 36.3, 34.9, 28.0 (3C), 24.3; MS
‡
(EI): m/z (%): 460 (16) [M] , 432 (13), 404 (24), 403 (48), 387 (18), 376 (25),
317 (38), 163 (26), 162 (17), 136 (10), 122 (14), 121 (100), 57 (12); IR (KBr):
nÄ ˆ 3396, 2975, 2953, 2934, 1712, 1639, 1513, 1439, 1368, 1248, 1153, 1033,
957, 845, 816 cm 1; HRMS (C24H32N2O7): calcd 460.22095; found 460.22077;
elemental analysis calcd (%) for C24H32N2O7: C 62.59, H 7.00, N 6.08;
found: C 62.65, H 6.88, N 6.03.
(3rac, 5R)-1-(tert-Butoxycarbonyl)-3-{[(N-tert-butoxycarbonyl-N-(4-meth-
oxy-benzyl)-but-3-yn-1-yl]-carbamoyl}-2-pyrrolidinon-5-carboxylic methyl
ester (68): Silver trifluoromethanesulfonate (6.27 g, 24.4 mmol) was slowly
added to a solution of thioester 67 (7.36 g, 22.2 mmol), amine 65 (8.03 g,
27.8 mmol) and (iPr)2NEt (6.89 g, 53.3 mmol) in CH3CN (150 mL) and the
reaction mixture was stirred for 14 h in the dark. The resulting suspension
was filtered through a pad of Celite and the insoluble residues were
thoroughly washed with ethyl acetate. Evaporation of the combined
filtrates followed by flash chromatography of the residue (silica gel,
hexane/ethyl acetate 2:1 ! 1:1) afforded 68 as a mixture of diastereoisom-
(3R, 5S, 10R)-10-(tert-Butoxycarbonylmethyl)-3-(2-hydroxymethyl)-7-(4-
methoxy-benzyl)-1,6-dioxa-2,7-diaza-spiro[4.5]decane
(72):
LiBH4
(48.0 mg, 2.19 mmol) was added to a solution of methyl ester 71 (504 mg,
1.09 mmol) in THF (50 mL) at 208C, the cooling bath was removed after
5 min, and the mixture was stirred for 30 min at ambient temperature. The
reaction was quenched by addition of aq. sat. NH4Cl (20 mL), the aqueous
phase was repeatedly extracted with ethyl acetate, the combined organic
layers were dried over Na2SO4 and evaporated, and the residue was
purified by flash chromatography (silica gel, ethyl acetate) affording
ers. Pale yellow foam (9.01 g, 73%): m.p. 120 ± 1238C; [a]D20
ˆ
10.08 (c ˆ
1.15, CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 7.20 ± 7.11 (m, 2H), 6.91 ±
6.83 (m, 2H), 5.03 ± 4.54 (m, 2H), 4.48 ± 3.83 (m, 2H), 3.80 (s), 3.789 (s),
3.785 (s), 3.78 (s), 3.75 (s) [6H], 3.41 ± 3.27 (m, 1H), 3.20 ± 2.97 (m, 1H),
2.83 ± 2.37 (m, 2H), 2.30 ± 2.23 (m), 2.07 ± 1.98 (m) [1H], 1.80 (brs, 1H), 1.50
(s), 1.494 (s), 1.487 (s), 1.48 (s), 1.47 (s), 1.46 (s) [18H]; 13C NMR (75 MHz,
CDCl3): d ˆ 171.8, 170.6, 169.7, 169.5, 169.2, 167.3, 167.2, 166.74, 166.70,
159.3, 159.0, 152.5, 152.0, 148.8, 129.3, 129.0, 128.8, 128.3, 128.2, 128.1, 128.0,
127.9, 127.7, 114.3, 114.2, 114.1, 84.2, 84.0, 83.52, 83.48, 83.2, 82.5, 76.7, 75.5,
62.0, 57.9, 57.8, 57.5, 57.3, 55.3, 55.2, 52.60, 52.58, 52.53, 52.48, 51.5, 50.5, 48.1,
46.2, 46.0, 45.5, 45.0, 44.9, 44.1, 28.1, 27.91, 27.88, 27.8, 25.2, 25.1, 18.6, 17.4;
alcohol 72 as a colorless foam (388 mg, 82%); m.p. 65 ± 688C; [a]D20
ˆ
‡36.48 (c ˆ 0.470, CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 7.18 (d, J ˆ
8.7 Hz, 2H), 6.86 (d, J ˆ 8.7 Hz, 2H), 6.68 (s, 1H), 4.72 (s, 1H), 4.63 (d, J ˆ
14.6 Hz, 1H), 4.50 (d, J ˆ 14.6 Hz, 1H), 3.79 (s, 3H), 3.78 ± 3.76 (m, 2H),
3.32 ± 3.22 (m, 2H), 2.68 (dd, J ˆ 14.2, 4.1 Hz, 1H), 2.49 ± 2.12 (m, 5H),
1.77 ± 1.73 (m, 2H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 175.3,
171.3, 170.9, 159.0, 129.1 (2C), 128.2, 114.1 (2C), 81.1, 65.8, 55.3, 54.4, 53.1,
‡
50.6, 46.3, 39.5, 36.6, 34.6, 28.1 (3C), 24.1; MS (EI): m/z (%): 432 (9) [M] ,
404 (11), 376 (17), 375 (34), 359 (17), 348 (21), 289 (29), 163 (25), 162 (13),
136 (10), 122 (13), 121 (100), 57 (11); IR (KBr): nÄ ˆ 3398, 2974, 2932, 1725,
1698, 1617, 1514, 1456, 1439, 1368, 1248, 1154, 1033, 970, 945, 845, 814,
760 cm 1; HRMS (C23H32N2O6): calcd 432.22604; found 432.22628; ele-
mental analysis calcd (%) for C23H32N2O6: C 63.87, H 7.46, N 6.41; found: C
63.94, H 7.45, N 6.48.
‡
MS (EI): m/z (%): 558 (<1) [M] , 232 (27), 216 (22), 215 (29), 172 (13), 121
(100), 57 (24), 41 (11); IR (KBr): nÄ ˆ 2980, 2240, 1790, 1751, 1706, 1651,
1
1613, 1514, 1457, 1370, 1285, 1252, 1153, 1075, 1033, 845, 755, 641 cm
;
HRMS (C29H38N2O9‡H): calcd 559.26555; found 559.26617; elemental
analysis calcd (%) for C29H38N2O9: C 62.35, H 6.86, N 5.01; found: C 62.19,
H 6.95, N 4.88.
(3R, 5S, 10R)-10-(tert-Butoxycarbonylmethyl)-7-(4-methoxybenzyl)-1,6-
dioxa-2,7-diaza-spiro[4.5]decane-3-carboxaldehyde (73): Dess ± Martin pe-
riodinane (868 mg, 2.05 mmol) was added to a solution of alcohol 72
(590 mg, 1.36 mmol) in CH2Cl2 (10 mL). A solution of H2O (28.0 mL,
1.56 mmol) in CH2Cl2 (28 mL) was then added dropwise over a period of
30 min during which the mixture became turbid and a colorless precipitate
started to form. After stirring for another 30 min at ambient temperature,
Na2S2O3 (10% in H2O)/sat. aq. NH4Cl (30 mL, 1:1) and tert-butyl methyl
ether (50 mL) were added, the aqueous layer was extracted with ethyl
acetate in several portions, the combined organic layers were dried over
Na2SO4, the solvent was evaporated, and the residue was rapidly passed
through a short column of silica gel using ethyl acetate as the eluent. This
afforded aldehyde 73 (459 mg, 78%) as a colorless foam: m.p. 62 ± 648C;
(3R, 5R, 10R)-10-(tert-Butoxycarbonylmethyl)-7-(4-methoxybenzyl)-
1,6-dioxa-2,7-diaza-spiro[4.5]decane-2,3-dicarboxylic 2-tert-butyl ester-3-
methyl ester (70): A solution of amide 68 (9.01 g, 16.1 mmol) and (iPr)2NEt
(4.16 g, 32.2 mmol) in CH3CN (300 mL) was refluxed for 16 h. The reaction
mixture was extracted with tert-butyl methyl ether and sat. aq. NH4Cl, and
the combined organic layers were dried over Na2SO4. After evaporation of
the solvent, the residue was dissolved in MeOH (250 mL), Pd on charcoal
was added (4.50 g, 10% Pd) and the resulting mixture was stirred for 16 h
under an atmosphere of H2 (1 atm, introduced after three freeze ± thaw
cycles). For work-up, the catalyst was filtered off, the insoluble residues
were carefully rinsed with ethyl acetate, the combined filtrates were
evaporated, and the residue was purified by flash chromatography
affording the spriocycle 70 as a colorless foam (7.22 g, 80%): m.p. 132 ±
1338C; [a]2D0 ˆ ‡39.18 (c ˆ 1.30, CHCl3); 1H NMR (600 MHz, CDCl3): d ˆ
7.12 (d, J ˆ 8.7 Hz, 2H), 6.82 (d, J ˆ 8.7 Hz, 2H), 4.67 (d, J ˆ 14.2 Hz, 1H),
4.65 (dd, J ˆ 10.5, 3.8 Hz, 1H), 4.32 (d, J ˆ 14.6 Hz, 1H), 3.79 (s, 3H), 3.76
(s, 3H), 3.25 ± 3.14 (m, 2H), 2.87 (dd, J ˆ 13.8, 3.8 Hz, 1H), 2.46 ± 2.37 (m,
1H), 2.33 ± 2.21 (m, 4H), 1.72 ± 1.68 (m, 1H), 1.49 (s, 9H), 1.41 (s, 9H);
13C NMR (150 MHz, CDCl3): d ˆ 171.2, 171.0, 170.8, 167.8, 159.0, 149.1,
129.2, 128.4 (2C), 114.0 (2C), 83.8, 81.3, 57.2, 55.7, 55.2, 52.6, 50.1, 45.6, 39.0,
1
[a]2D0 ˆ ‡37.78 (c ˆ 1.60, CHCl3); H NMR (300 MHz, CDCl3): d ˆ 9.73 (s,
1H), 7.19 ± 7.09 (m, 3H), 6.84 (d, J ˆ 8.7 Hz, 2H), 4.62 (d, J ˆ 14.6 Hz, 1H),
4.40 (d, J ˆ 14.6 Hz, 1H), 3.90 (d, J ˆ 10.2 Hz, 1H), 3.78 (s, 3H), 3.25 ± 3.22
(m, 2H), 2.86 (dd, J ˆ 13.7, 2.0 Hz, 1H), 2.52 ± 2.18 (m, 5H), 1.79 ± 1.61 (m,
1H), 1.43 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 200.2, 176.1, 171.3, 169.5,
159.0, 129.1 (2C), 128.3, 114.0 (2C), 81.0, 58.8, 55.2, 52.7, 50.0, 46.0, 37.6,
‡
36.5, 33.8, 28.0 (3C), 24.4; MS (EI): m/z (%): 432 (9) [M] , 404 (11), 376
(17), 375 (34), 359 (17), 348 (21), 289 (29), 163 (25), 162 (13), 136 (10), 122
‡
36.6, 32.0, 28.0 (3C), 27.8 (3C), 24.1; MS (EI): m/z (%): 560 (<1) [M] , 460
(13), 121 (100), 57 (11); IR (KBr): nÄ ˆ 3398, 2974, 2932, 1725, 1698, 1617,
1
(14), 432 (10), 404 (16), 403 (34), 387 (11), 376 (19), 359 (12), 317 (21), 163
(15), 122 (12), 121 (100), 57 (18), 41 (14); IR (film): nÄ ˆ 2979, 2934, 2254,
1789, 1727, 1643, 1612, 1513, 1457, 1438, 1393, 1369, 1308, 1248, 1154, 1035,
992, 947, 913, 844, 815, 733, 647 cm 1; MALDI (C29H40N2O9‡Na): calcd
583.2626; found 583.2624; elemental analysis calcd (%) for C29H40N2O9: C
62.13, H 7.19, N 5.08; found: C 62.10, H 7.26, N 4.92.
1514, 1456, 1439, 1368, 1248, 1154, 1033, 970, 945, 845, 814, 760 cm
;
HRMS (C23H30N2O6): calcd 432.22604; found 432.22628; elemental analysis
calcd (%) for C23H30N2O6: C 63.87, H 7.46, N 6.41; found: C 63.94, H 7.45, N
6.48.
(3R, 5S, 10R)-10-(tert-Butoxycarbonylmethyl)-7-(4-methoxybenzyl)-3-
vinyl-1,6-dioxa-2,7-diaza-spiro[4.5]decane
(74):
CH2I2
(2.20 mL,
(3R, 5S, 10R)-10-(tert-Butoxycarbonylmethyl)-7-(4-methoxybenzyl)-1,6-
dioxa-2,7-diaza-spiro[4.5]decane-3-carboxylic methyl ester (71): Mg(ClO4)2
27.3 mmol) was added to a suspension of zinc dust (3.20 g, 49.3 mmol;
previously activated by washing with 2n HCl and diethyl ether, followed by
4818
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0722-4818 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 22

Indenylidene Complexes of Ruthenium
4811±4820
drying in high vacuum) in THF (100 mL). After the quite exothermic
reaction had ceased after 30 min, Ti(OiPr)4 (16.4 mL, 16.4 mmol, 1.00m in
THF) was introduced and stirring was continued at ambient temperature
for another 30 min. Aldehyde 73 (1.18 g, 2.73 mmol) was then added and
the mixture was stirred for 14 h. The reaction was quenched with sat. aq.
NH4Cl (50 mL), the aqueous layer was extracted with tert-butyl methyl
ether and ethyl acetate, the combined organic layers were washed with aq.
Na2S2O3 (10% w/w) and brine, and were dried over Na2SO4. Evaporation
of the solvent followed by flash chromatography of the residue (silica gel,
hexane/ethyl acetate 2:1 ! 1:2) provided 74 (985 mg, 84%) as a colorless
foam: m.p. 78 ± 818C; [a]2D0 ˆ ‡42.68 (c ˆ 1.11, CHCl3); 1H NMR
(300 MHz, CDCl3): d ˆ 7.19 (d, J ˆ 8.7 Hz, 2H), 6.84 (d, J ˆ 8.7 Hz, 2H),
6.07 (ddd, J ˆ 18.0, 10.0, 8.2 Hz, 1H), 5.90 (s, 1H), 5.17 ± 5.12 (m, 2H), 4.71
(d, J ˆ 14.6 Hz, 1H), 4.43 (d, J ˆ 14.6 Hz, 1H), 4.08 (ddd, J ˆ 8.4, 8.4,
5.8 Hz, 1H), 3.79 (s, 3H), 3.29 ± 3.25 (m, 2H), 2.86 (dd, J ˆ 13.8, 5.8 Hz,
1H), 2.46 ± 2.21 (m, 5H), 1.80 ± 1.71 (m, 1H), 1.44 (s, 9H); 13C NMR
(75 MHz, CDCl3): d ˆ 175.1, 171.3, 169.4, 158.9, 139.5, 129.1 (2C), 128.7,
116.6, 114.0 (2C), 81.0, 55.22, 55.19, 54.9, 50.4, 46.0, 39.2, 38.9, 36.8, 28.0
2931, 2868, 1727, 1677, 1638, 1513, 1491, 1456, 1438, 1420, 1366, 1354, 1248,
1
1153, 1109, 1095, 1032, 962, 925, 845, 811, 760, 710, 663, 610, 549 cm
;
HRMS (C28H38N2O5): calcd 482.27807; found 482.27816; elemental analysis
calcd (%) for C28H38N2O5: C 69.68, H 7.94, N 5.80; found: C 69.76, H 8.03, N
5.69.
(8'R, 3S, 4R)-4-(Methoxycarbonylmethyl)-spiro[(2-piperidone)-3,12'-(1'-
aza-bicyclo-[6.3.0]undec-6'-en-11'-one)] (77): Compound 76 (2.07 g,
4.29 mmol) was dissolved in trifluoroacetic acid (50 mL) and the solution
was refluxed for 18 h. The acid was then removed in vacuo and the residue
was dried at <10 3 Torr. To a solution of the crude product thus formed in
toluene/MeOH (3.5:1, 100 mL) was slowly added a solution of (trimethyl-
silyl)diazomethane (2.00m in hexane) until a pale yellow color persisted
and no further evolution of gas could be detected. Stirring was continued
for 30 min before so much HOAc was added dropwise that the yellow color
completely disappeared. Evaporation of the solvent followed by purifica-
tion of the crude product by flash chromatography (silica gel, ethyl acetate/
methanol 20:1) delivered title compound 77 as a pale yellow foam (1.17 g,
85%). M.p. 103 ± 1068C; [a]2D0 ˆ ‡19.48 (c ˆ 0.825, CHCl3); 1H NMR
(300 MHz, CDCl3): d ˆ 6.68 (brs, 1H), 5.90 (dt, J ˆ 10.2, 8.5 Hz, 1H), 5.49
(dd, J ˆ 10.2, 7.7 Hz, 1H), 4.29 (quart, J ˆ 7.5 Hz, 1H), 3.70 ± 3.57 (m, 1H),
3.66 (s, 3H), 3.40 ± 3.31 (m, 2H), 3.01 (dd, J ˆ 13.8, 7.0 Hz, 1H), 2.70 (dd,
J ˆ 13.4, 7.0 Hz, 1H), 2.49 ± 2.08 (m, 7H), 2.02 ± 1.93 (m, 1H), 1.76 ± 1.64 (m,
2H), 1.45 ± 1.30 (m, 2H); 13C NMR (75 MHz, CDCl3): d ˆ 172.5, 171.6,
170.9, 134.3, 129.4, 55.5, 53.3, 51.7, 41.0, 40.7, 38.6, 36.8, 35.1, 27.7, 26.9, 26.2,
‡
(3C), 24.2; MS (EI): m/z (%): 428 (8) [M] , 400 (13), 372 (13), 371 (48), 355
(21), 344 (30), 285 (39), 163 (28), 162 (13), 136 (11), 122 (13), 121 (100), 57
(12); IR (KBr): nÄ ˆ 3265, 3080, 2978, 2935, 2837, 1727, 1697, 1638, 1513,
1491, 1456, 1434, 1368, 1292, 1248, 1152, 1033, 996, 969, 925, 844, 814, 759,
1
662, 614, 515 cm
; HRMS (C24H32N2O5): calcd 428.23118; found
428.23093; elemental analysis calcd (%) for C24H32N2O5: C 67.27, H 7.53,
N 6.54; found: C 67.34, H 7.51, N 6.44.
‡
24.4; MS (EI): m/z (%): 321 (20), 320 (100) [M] , 289 (24), 260 (15), 253
(12), 250 (11), 247 (29), 220 (20), 219 (24), 192 (13), 191 (24), 190 (25), 189
(23), 163 (12), 124 (15), 123 (14), 108 (10), 81 (11), 80 (16), 67 (12), 53 (11),
41 (18), 30 (10); IR (KBr): nÄ ˆ 3442, 3090, 3020, 2931, 2867, 1736, 1666, 1491,
1438, 1345, 1285, 1254, 1171, 1086, 999, 948, 922, 862, 841, 783, 668, 570,
539 cm 1; HRMS (C17H24N2O4): calcd 320.17361; found 320.17353; ele-
mental analysis calcd (%) for C17H24N2O4: C 63.73, H 7.55, N 8.74; found: C
63.65, H 7.59, N 8.79.
(3R, 5S, 10R)-10-(tert-Butoxycarbonylmethyl)-2-(5-hexenyl)-7-(4-meth-
oxy-benzyl)-3-vinyl-1,6-dioxa-2,7-diaza-spiro[4.5]decane
(75):
NaH
(130 mg, 5.42 mmol) was added in portions to a stirred solution of
compound 74 (2.11 g, 4.92 mmol) in DMF (150 mL) at 08C and the
mixture was stirred at ambient temperature for 60 min until the evolution
of H2 had ceased. 6-Iodo-1-hexene (1.55 g, 7.38 mmol) was then introduced
at 08C and stirring was continued at ambient temperature for another
60 min. For work-up, sat. aq. NH4Cl (50 mL) and tert-butyl methyl ether
(200 mL) were added, the aqueous layer was repeatedly extracted with
ethyl acetate, the combined organic phases were washed with aq. HCl (1n)
and brine, dried over Na2SO4 and evaporated. Flash chromatography of the
crude product (silica gel, hexane/ethyl acetate 2:1) afforded diene 75 as a
colorless foam (2.21 g, 88%): m.p. 84 ± 878C; [a]2D0 ˆ ‡33.28 (c ˆ 1.09,
CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 7.19 (d, J ˆ 8.7 Hz, 2H), 6.86 (d,
J ˆ 8.7 Hz, 2H), 6.05 (dt, J ˆ 17.0, 9.6 Hz, 1H), 5.86 ± 5.73 (m, 1H), 5.29 ±
5.21 (m, 2H), 5.05 ± 4.93 (m, 2H), 4.74 (d, J ˆ 14.7 Hz, 1H), 4.41 (d, J ˆ
14.7 Hz, 1H), 4.01 (dt, J ˆ 9.1, 5.2 Hz, 1H), 3.79 (s, 3H), 3.56 (ddd, J ˆ 13.6,
8.7, 6.7 Hz, 1H), 3.29 ± 3.25 (m, 2H), 2.93 (ddd, J ˆ 13.6, 8.3, 5.2 Hz, 1H),
2.70 (dd, J ˆ 13.9, 5.2 Hz, 1H), 2.56 ± 2.48 (m, 1H), 2.32 ± 2.04 (m, 6H),
1.73 ± 1.33 (m, 5H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 172.0,
171.4, 169.9, 158.9, 139.2, 138.4, 128.9 (2C), 128.7, 118.2, 114.7, 114.1 (2C),
81.0, 60.1, 55.2, 55.1, 50.3, 46.2, 40.7, 39.8, 36.8, 36.4, 33.2, 28.0 (3C), 26.3,
Acknowledgement
Generous financial support by the Deutsche Forschungsgemeinschaft
(Leibniz award to A.F.) and the Fonds der Chemischen Industrie is
gratefully acknowledged. We thank J. E. Grabowski, K. Radkowski, I.
Storch de Gracia and O. R. Thiel for performing some of the RCM
reactions shown in Table 2, and Mrs. C. Wirtz for recording the NOE data.
Thanks also go to Dr. A. F. Hill, Imperial College, for providing an
authentic sample of the catalyst for initial screenings and for structure
elucidation purposes.
[1] a) T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18 ± 29; b) A.
Fürstner, Angew. Chem. 2000, 112, 3140 ± 3172; Angew. Chem. Int. Ed.
2000, 39, 3012 ± 3043; c) R. H. Grubbs, S. Chang, Tetrahedron 1998, 54,
4413 ± 4450; d) M. Schuster, S. Blechert, Angew. Chem. 1997, 109,
2124 ± 2144; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037 ± 2056; e) A.
Fürstner, Top. Catal. 1997, 4, 285 ± 299; f) S. K. Armstrong, J. Chem.
Soc. Perkin Trans. 1 1998, 371 ± 388; g) K. J. Ivin, J. Mol. Catal. A:
Chem. 1998, 133, 1 ± 16; h) M. L. Randall, M. L. Snapper, J. Mol.
Catal. A: Chem. 1998, 133, 29 ± 40; i) R. R. Schrock, Tetrahedron 1999,
55, 8141 ± 8153; j) M. E. Maier, Angew. Chem. 2000, 112, 2153 ± 2157;
Angew. Chem. Int. Ed. 2000, 39, 2073 ± 2077.
[2] a) S. T. Nguyen, L. K. Johnson, R. H. Grubbs, J. W. Ziller, J. Am.
Chem. Soc. 1992, 114, 3974 ± 3975; b) S. T. Nguyen, R. H. Grubbs,
J. W. Ziller, J. Am. Chem. Soc. 1993, 115, 9858 ± 9859; c) Z. Wu, S. T.
Nguyen, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1995, 117,
5503 ± 5511.
[3] a) P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew. Chem.
1995, 107, 2179 ± 2181; Angew. Chem. Int. Ed. Engl. 1995, 34, 2039 ±
2041; b) P. Schwab, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1996,
118, 100 ± 110.
[4] a) J. Huang, E. D. Stevens, S. P. Nolan, J. L. Petersen, J. Am. Chem.
Soc. 1999, 121, 2674 ± 2678; b) M. Scholl, T. M. Trnka, J. P. Morgan,
R. H. Grubbs, Tetrahedron Lett. 1999, 40, 2247 ± 2250; c) M. Scholl, S.
Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953 ± 956; d) L.
Ackermann, A. Fürstner, T. Weskamp, F. J. Kohl, W. A. Herrmann,
‡
26.2, 24.3; MS (EI): m/z (%): 510 (10) [M] , 482 (16), 454 (22), 453 (43), 426
(32), 367 (36), 163 (31), 162 (15), 122 (11), 121 (100); IR (KBr): nÄ ˆ 3076,
2981, 2926, 1732, 1671, 1635, 1513, 1489, 1426, 1366, 1261, 1251, 1178, 1153,
1101, 1035, 996, 924, 848, 812, 758 cm 1; HRMS (C30H42N2O5): calcd
510.30937; found 510.30975; elemental analysis calcd (%) for C30H42N2O5:
C 70.56, H 8.29, N 5.49; found: C 70.39, H 8.22, N 5.38.
(8'R, 3S, 4R)-1-(4-Methoxybenzyl)-4-(tert-butoxycarbonylmethyl)-spi-
ro[(2-piperidone)-3,12'-(1'-aza-bicyclo[6.3.0]undec-6'-en-11'-one)] (76): A
solution of diene 75 (446 mg, 0.873 mmol) and complex 3b (40.3 mg,
43.7 mmol) in CH2Cl2 (450 mL) was refluxed for 18 h. The reaction mixture
was passed through a short pad of silica, the filtrate was evaporated and the
crude product was purified by flash chromatography (silica gel, hexane/
ethyl acetate 2:1 ! 1:1) affording compound 76 as a colorless foam
(413 mg, 98%): m.p. 84 ± 868C; [a]2D0 ˆ ‡28.98 (c ˆ 0.875, CHCl3); 1H NMR
(300 MHz, CDCl3): d ˆ 7.20 (d, J ˆ 8.7 Hz, 2H), 6.86 (d, J ˆ 8.7 Hz, 2H),
5.93 (dt, J ˆ 10.5, 8.5 Hz, 1H), 5.59 (dd, J ˆ 10.6, 7.5 Hz, 1H), 4.67 (d, J ˆ
14.6 Hz, 1H), 4.49 (d, J ˆ 14.6 Hz, 1H), 4.34 (q, J ˆ 7.5 Hz, 1H), 3.78 (s,
3H), 3.77 ± 3.66 (m, 1H), 3.27 ± 3.12 (m, 2H), 3.14 (dd, J ˆ 13.8, 6.8 Hz,
1H), 2.82 (dd, J ˆ 13.4, 6.8 Hz, 1H), 2.44 ± 2.00 (m, 8H), 1.73 ± 1.63 (m, 2H),
1.54 ± 1.40 (m, 2H), 1.43 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 171.5,
171.4, 169.9, 158.8, 134.1, 129.8, 129.1 (2C), 128.8, 114.0 (2C), 80.9, 56.1,
55.2, 53.6, 50.4, 45.3, 41.2, 39.5, 37.4, 36.8, 28.0 (3C), 27.8, 27.0, 26.1, 24.5; MS
‡
(EI): m/z (%): 482 (11) [M] , 454 (13), 426 (25), 425 (35), 409 (18), 398 (25),
339 (35), 163 (29), 162 (13), 122 (11), 121 (100); IR (KBr): nÄ ˆ 3062, 2963,
Chem. Eur. J. 2001, 7, No. 22
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FULL PAPER
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Received: May 15, 2001 [F3266]
4820
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