Palladium-catalyzed pseudo-domino cyclizations: An easy entry toward polycondensed pyrrolidone derivatives

Article abstract of DOI:10.1016/S0022-328X(03)00621-1

A new type I palladium-catalyzed pseudo-domino process is developed, in which a single Pd-based catalytic system promotes two mechanistically unrelated, sequential catalytic cycles in chronologically distinct order. Suitable precursors undergo an allylic

Full text of DOI:10.1016/S0022-328X(03)00621-1

Journal of Organometallic Chemistry 687 (2003) 291ꢀ300
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www.elsevier.com/locate/jorganchem
Palladium-catalyzed pseudo-domino cyclizations
An easy entry toward polycondensed pyrrolidone derivatives
Se´bastien Lemaire a, Guillaume Prestat a, Giuliano Giambastiani b, David Madec a,
Barbara Pacini a,1, Giovanni Poli a,*
a Laboratoire de Chimie Organique, UMR 7611 CNRS, Universite´ Pierre et Marie Curie, 4, Place Jussieu, Boˆıte 183, F-75252 Paris, France
b CNR, Institute of Chemistry of Organometallic Compounds ICCOM, Florence Research Area, Via Madonna del Piano, I-50019 Sesto Fiorentino,
Firenze, Italy
Received 13 May 2003; accepted 20 June 2003
Dedicated to Professor Jean-Pierre Geneˆt on the occasion of his 60th birthday
Abstract
A new type I palladium-catalyzed pseudo-domino process is developed, in which a single Pd-based catalytic system promotes two
mechanistically unrelated, sequential catalytic cycles in chronologically distinct order. Suitable precursors undergo an allylic
alkylation and a Heck coupling in sequence, affording polycondensed pyrrolidone derivatives. Depending on the starting precursors,
intra/inter or doubly intramolecular processes can be obtained. The allylic alkylation process takes place always very smoothly. On
the other hand, the Heck coupling turns out to be rather difficult either when the process is intermolecular, or when an
intramolecular process generates polycondensed structures featuring three fused bonds connected to a common carbon atom. In
such difficult cases, use of the Herrmannꢀ
that allylic alkylations can be catalyzed by the Herrmannꢀ
# 2003 Elsevier B.V. All rights reserved.
/
Beller phosphapalladacycle allowed to catalyze the coupling. This study demonstrates also
/
Beller phosphapalladacycle.
Keywords: Palladium; Pseudo-domino cyclizations; Pyrrolidone; Heck coupling; HerrmannꢀBellar phosphapalladacycle
/
1. Introduction
On the other hand, multistep palladium-catalyzed
processes featuring sequential and mechanistically in-
dependent catalytic cycles have been so far much less
studied [3]. Albeit synthetically interesting and mechan-
istically intriguing, their success cannot be given for
granted owing to possible undesired sequential enchain-
ing or incompatibilities among the different catalytic
cycles. In order to better appreciate these processes, we
recently proposed to conceptually differentiate these
transformations from the more traditional domino
transformations, by classifying them as ‘‘transition
metal-catalyzed pseudo-domino’’ processes (TM-
PDOM). Further subdivision into type I or type II
process is also possible, if a single multipurpose catalytic
system (‘‘M’’), or mutually compatible catalytic systems
of different nature (‘‘M1, M2, etc.’’) are respectively
involved (Fig. 1).
The research in the field of domino reactions is
attracting considerable attention in synthetic organic
chemistry since it enables the rapid assembly of complex
molecules in one-pot processes [1]. In this context, very
elegant examples of transition metal-catalyzed domino
processes wherein a single catalytic cycle entails several
sequential bond transformations have been recently
reviewed [2].
* Corresponding author. Tel.: ꢁ
7567.
E-mail address: poli@ccr.jussieu.fr (G. Poli).
/
33-1-4427-5572; fax: ꢁ33-1-4427-
/
1
Present address: IRBM, Biotechnology Department, via Pontina
km. 30.600, 00040 Pomezia, Rome, Italy.
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-328X(03)00621-1

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Fig. 1. Classification of domino transition metal-catalyzed processes.
Scheme 2. Construction of o-haloarylated precursor
expected doubly intramolecular Pd-PDOM transformation.
B and its
2. Results and discussion
2.2. The doubly intramolecular process
2.1. The intra/inter-molecular process
As an extension of the above study, we decided to
investigate next a doubly intramolecular variant of the
Pd-PDOM process. We judged, in fact, that such a
modification could enable the one-pot construction of
synthetically interesting complex polycyclic structures.
In particular, we envisaged to convert amide A into the
o-haloaryl derivative B, in the hope that the transiently
generated 3-vinyl pyrrolidone C could directly undergo
an unimolecular Heck process, to generate the poly-
cyclic structure D (Scheme 2).
Indeed, such a strategy has been successfully exploited
by us in the synthesis of an aza-analogue of epiisopi-
cropodophyllin, the C-3 epimer of podophyllotoxin
(Scheme 3) [9].
In order to gain more information on the scope of
above Pd-PDOM process, we then decided to study the
double cyclization sequence as a function of the nature
of the group stabilizing the a-amide anion, as well as of
the structure of the allylic moiety in the precursor.
Accordingly, amide 1a was alkylated with o-bromo-
benzyl bromide, and the newly generated amide 3a was
submitted to cyclization (Scheme 4). In contrast to the
intra/inter-molecular version, we soon realized that the
We started our investigations in multistep one-pot
palladium-catalyzed processes by studying the behavior
of mixtures of amide 1 and aryl bromides in the presence
of palladium catalysts. After considerable experimenta-
tion, we could observe the expected allylic alkylation [4]/
Heck coupling pseudo-domino sequence (Pd-PDOM
type I), which led to (E)-3-b-styryl pyrrolidone deriva-
tives 2aꢀ
acceptable results for the latter step were obtained only
when the HerrmannꢀBeller phosphapalladacycle [6,7]
/2e [5]. Despite the overall positive outcome,
/
was used as the catalyst. Such a result was mechan-
istically very interesting, since it demonstrated for the
first time that allylic alkylations can be efficiently
catalyzed by this palladacycle, a catalyst whose mechan-
ism in the Heck coupling has been long debated [8]. On
the other hand, complete arylation of the vinyl chain
was never achieved, and the high temperature required
brought about demethoxycarbonylation of the product
(Scheme 1).
HerrmannꢀBeller phosphapalladacycle was no more
/
essential for the Heck process. Indeed, deprotonation
Scheme 1. Pd-PDOM intramolecular allylic alkylation/intermolecular
Heck coupling.
Scheme 3. Doubly intramolecular Pd-PDOM process affording an
epiisopicropodophyllin aza-analogue.

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293
of amide 3a with NaH in DMF, followed by treatment
with (Pd(OAc)2/1,2-bis-(diphenylphosphino)ethane
(dppe)) and appropriate heating gave rise smoothly to
the trans and cis double cyclization products trans-4
and cis-4 in a 38:62 ratio.
Interesting to note, this double intramolecular process
is much faster than the previously described intra/inter-
molecular approach. Such a result suggests that the rate-
determining step of the catalytic cycle associated with
the intermolecular Heck coupling is likely to be the
carbopalladation step, and not the oxidative addition
step [10]. It should also be pointed out that the allylic
alkylation process is the stereodetermining step, and its
selectivity is directly transposed into the diastereomeric
ratio of the final tricyclic product. Furthermore, the
trans/cis ratios observed in this step are expected to
reflect a kinetic control. In fact, the allylation processes
are usually irreversible processes, and, in contrast to
related cyclizations previously studied by us [4,11], the
resulting 2,2-disubstituted-3-vinyl pyrrolidones cannot
undergo equilibration via enolization.
The same cyclization protocol has been successively
applied to the two o-bromobenzylated amides 3b and
3c, having respectively a nitrile and a phenysulfonyl
group as carbanion-stabilizing moieties. In the event, the
cyano derivative afforded the expected tricyclic struc-
tures trans-4b and cis-4b in a 89:11 ratio, whereas the
sulfonylated derivative gave cis-4c as the only detectable
diastereomer.
Fig. 2. ORTEP drawing of the tricyclic amide cis-4c.
spectroscopic trends and the relative configuration of
the ring junction. On the other hand, the X-ray structure
of the crystalline sulfone derivative cis-4c (Fig. 2), which
in turn possessed a nil allylic coupling constant value,
unveiled a cis stereochemistry at the ring junction.
Accordingly, we could tentatively correlate the isomers
4
featuring Jab
Unequivocal assignment of the stereochemistry at the
ring junction was obtained via a combination of
spectroscopic and diffraction methods. Indeed, in all
the three cases studied, only one diastereomer of the
ꢂ
/
0 Hz to the cis configurated products,
and those having J "/0 Hz to the trans ones (Table 1).
Inspection of Table 1 reveals that the trans:cis ratio of
the tricyclic products is directly dependent on the steric
requirements of the carbanion-stabilizing group (EWG).
More precisely, the bigger the stabilizing group, the
higher the resulting cis:trans ratio. Such a trend may be
cautiously rationalized on steric grounds, according
to the differential destabilizing eclipsing interactions
ensuing at the transition state level, between the internal
couple showed a nil allylic coupling constant value
(4Jab
1
0 Hz) in the H-NMR spectrum. Furthermore,
ꢂ
/
the same type of isomer was always associated with a
larger chemical shift difference between the two sets of
peaks pertaining to the N-benzylic AB system, as
compared with the other isomer. Such a behavior clearly
suggested that a correlation exists between the above
Scheme 4. Formation of precursors 3aꢀ3c and their doubly intramolecular Pd-PDOM (allylic alkylation/Heck) transformations.
/

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S. Lemaire et al. / Journal of Organometallic Chemistry 687 (2003) 291ꢀ300
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Table 1
Jab constants and relative ppm differences for diagnostic sets of peak
Entry
EWG
Compound
4Jab (Hz) a
AB system b
1
2
3
4
5
MeO2C
MeO2C
NC
trans-4a
cis-4a
1.85
0
0.24
0.64
0.13
0.61
trans-4b
cis-4b
1.90
0
Scheme 6. Expected Pd-PDOM doubly intramolecular process on the
cyclic precursor F and comparison with lysergic acid structure.
NC
PhO2S
cis-4c
0
ꢀ/
a
Average value.
Relative ppm difference between the two sets of peaks.
b
the polycondensed structure G, a compound featuring
the lysergic acid backbone (Scheme 6).
Cꢀ
/
C portion of the allyl fragment and, either the EWG,
Accordingly, the new o-bromobenzylated amide 6, in
turn obtained from the cyclic precursor 5 [13], was
prepared and tested for cyclization (Scheme 7). Depro-
tonation of 5 with NaH at 0 8C followed by treatment
with o-bromobenzyl bromide in DMF at 100 8C, gave
uneventfully the expected precursor in 95% yield. Then,
treatment of 6 with NaH at 0 8C in DMF, followed by
addition of the catalytic system (Pd(OAc)2/dppe) and
heating at 50 8C, gave the allylic alkylation product 7 in
a 90:10 trans:cis ratio as the only new product (entry 1).
or the bromobenzylic residue [12]. Accordingly, the
stereochemical outcome may be accounted for, assum-
ing that the internal Cꢀ
/C portion of the allyl fragment
will preferentially eclipse the less sterically demanding
group. Hence, the trans product will be favored when
the bromobenzylic residue is bulkier than the EWG
(nitrile derivative), whereas the preference reverts when
the steric requirements of EWG become overwhelming
(sulfone derivative) (see Scheme 5).
With the aim of obtaining synthetically more complex
polycondensed structures, we next envisaged to extend
our cyclization studies to precursors wherein the allylic
moiety is incorporated into a cyclic structure. Thus, for
example, eliciting of the above-described pseudo-dom-
ino process on the new precursor F, obtainable via o-
halobenzylation of amide E, was anticipated to afford
The same result was obtained when the Herrmannꢀ
/
Beller catalyst was used in place of the (Pd(OAc)2/
dppe) system, thereby confirming the ability of this
catalyst to catalyze the allylic alkylation reaction (entry
2). On the other hand, when the latter reaction was
performed at 130 8C, and in the presence of AcOK,
formation of the desired tetracyclic product 8 as the only
Scheme 5. Rationalization of the stereochemical outcome in the Pd(0)-catalyzed intramolecular allylic alkylation of amides 3aꢀ3c.
/

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295
Scheme 7. Preparation of the cyclic precursor 6 and its Pd(0)-catalyzed cyclization.
diastereomer, together with trans-7 and cis-7, was
observed in a 44:48:8 ratio, respectively (entry 3).
Gratifyingly enough, when AcOK was replaced for
Bu4NOAc, so as to mimic Jeffery conditions [14], the
8:trans-7:cis-7 ratio improved to 70:20:10 and the yield
of isolated 8 raised to 60%. The results assembled in
Scheme 7 clearly indicate that tetracycle 8 has to
originate exclusively from the cyclization of trans-7,
the other diastereomer being too strained to do so. An
NOE difference experiment on 8 unequivocally demon-
strated the spatial proximity of the three vicinal methine
hydrogen atoms Ha, Hb, and Hc, thereby confirming the
stereochemical assignment of this compound, and con-
sequently of its precursor (trans-7) and the epimer of the
latter (cis-7).
experimentally observed intramolecular Heck coupling
of the only major isomer. It has also to be pointed out
that while the former Pd-PDOM process features an
achiral precursor (3), which is transformed into 4 with
the concomitant generation of two vicinal stereogenic
centers (internal diastereoselection), the precursor of the
latter process (6) bears a stereogenic center, capable of
governing the allylic alkylation step (diastereofacial
selection). Furthermore, the presence of the pre-existing
ring structure in precursor 6 forces the syn regiospecific
dehydropalladation, during the Heck coupling, so as to
generate an additional stereogenic center in the final
product (Scheme 8, compare sequence 30
/
H0
/
I0
/
L0/4
with 60M0N08).
/
/
/
Coming back to the allylic alkylation step, the same
steric grounds as invoked in the former process may
account for the observed stereochemical result. How-
ever, in this latter case uncertainty on configuration of
the h3-allyl fragment is no more present, owing to its
Attainment of the tetracyclic structure 8 as the only
diastereomer in a satisfactory yield was a remarkable
result, due to the intrinsic high diastereoselectivity of the
intramolecular allylic alkylation in combination with the
Scheme 8. Comparison of the dehydropalladation processes during transformations 30
/
4 and 608. Key for the stereogenic centers: (*) generated
/
during the allylic alkylation; (^) generated during the Heck coupling; (I) pre-existing in the substrate.

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S. Lemaire et al. / Journal of Organometallic Chemistry 687 (2003) 291ꢀ300
/
Scheme 9. Rationalization of the stereochemical outcome in the Pd(0)-catalyzed intramolecular allylic alkylation of amide 6.
incorporation into the six-membered structure. As a
matter of fact, cyclization of 6 appears to be more
selective than that of the corresponding acyclic methox-
ycarbonylated precursor 4a (Scheme 9, compare also
entry 1 in Scheme 4 with entries 1 or 2 in Scheme 7).
isolated as oils unless otherwise specified, and their
purities were determined to be ꢀ95% by NMR analysis.
/
4.2. General procedure for the synthesis 1-benzyl-4-
[(E)-2-(3-methoxy-phenyl)-vinyl]-pyrrolidin-2-one
(2a), 1-benzyl-4-[(E)-2-(4-methoxy-phenyl)-vinyl]-
pyrrolidin-2-one (2b), 1-benzyl-4-[(E)-2-phenyl-vinyl]-
pyrrolidin-2-one (2c), 1-benzyl-4-[(E)-2-(3-acetyl-
phenyl)-vinyl]-pyrrolidin-2-one (2d), 1-benzyl-4-[(E)-2-
(4-acetyl-phenyl)-vinyl]-pyrrolidin-2-one (2e)
3. Concluding remarks
This study has shown a new type I palladium-
catalyzed pseudo-domino process, wherein a single Pd-
based catalytic system is able to promote two mechan-
istically distinct, successive catalytic cycles in a precise
chronological order. Suitable precursors were synthe-
sized and submitted to sequential intra/inter or doubly
intramolecular allylic alkylation/Heck coupling se-
quences, thereby obtaining differently substituted pyr-
rolidone derivatives. While the allylic alkylation step
took place always very easily, the Heck coupling turned
out to be rather hard, either when it was intermolecular,
or when polycondensed structures bearing three fused
bonds connected to a common carbon atom were
To a solution of the acyclic precursor 1 (0.2 mmol) in
dry Me2NAc (5 ml), under nitrogen atmosphere, cooled
in a water-ice bath, NaH (60% dispersion in mineral oil)
(0.24 mmol) was added and the solution was stirred at
r.t. for 20 min. Then, the proper aryl-halide (3-bromoa-
nisole for 2a, 4-bromoanisole for 2b, bromobenzene for
2c, 3-bromoacetophenone for 2d, 4-bromoacetophenone
for 2e) (0.28 mmol), anhydrous AcONa (0.22 mmol) and
trans-di-(m-acetate)-bis[o-(di-o-tolylphosphine)benzyl]-
dipalladium(II) (HerrmannꢀBeller catalyst) (0.02 mmol)
/
were added in this order with stirring. The resulting
mixture was brought to 140 8C for the appropriate time
(2a: 47 h, 2b: 50 h, 2c: 31 h, 2d and 3d: 22 h), then a 25
wt.% aqueous solution of NH4Cl (40 ml) was added and
generated. In such difficult cases, the HerrmannꢀBeller
/
phosphapalladacycle allowed to catalyze the Heck
coupling and, at the same time, the preceding allylic
alkylation step. Further work is currently underway to
explore applications of the above methodology as well
as other TM-PDOM processes.
the aqueous phase was extracted with Et2O (3ꢃ10 ml).
/
The collected organic phases were dried and the solvent
was removed in vacuo. Flash chromatography (hexane-
s:AcOEt) gave the pure compounds as oils (2a, 58%; 2b,
38%; 2c, 54%; 2d, 59%; 2e, 60%). 1-Benzyl-4-vinyl-
pyrrolidin-2-one (see below for the characterization) was
also obtained as an undesired byproduct in 36, 42, and
30% during the preparation of 2a, 2b, and 2c, respec-
tively. 2a: 1H-NMR (CDCl3, 200 MHz): d 2.41 (dd, 1H,
4. Experimental
4.1. General
All reactions were conducted under dried nitrogen or
argon atmosphere using oven-dried glassware. For air-
and/or water-sensitive reactions, glassware was flame-
dried and then allowed cooling under argon or dried
nitrogen atmosphere before use. All solvents were
purified and distilled according to standard methods.
Chromatographic purifications were conducted using
Jꢂ
3.03 (2H), 3.44 (m, 1H), 3.80 (s, 3H), 4.48 (s, 2H), 6.10
(dd, 1H, Jtrans 15.7, 7.3 Hz), 6.38 (d, 1H, Jtrans 15.7
Hz), 6.91ꢀ6.75 (3H), 7.40ꢀ
7.15 (6H) ppm. 13C-NMR
/
16.8, 8.1 Hz), 2.71 (dd, 1H, Jꢂ
/
16.5, 8.1 Hz), 3.22ꢀ
/
ꢂ
/
ꢂ
/
/
/
(CDCl3, 200 MHz): d 35.5, 37.7, 46.5, 52.0, 55.2, 111.5,
113.3, 118.8, 127.6, 127.7, 128.2, 128.8, 129.6, 131.0,
136.3, 138.1, 159.9, 173.4 ppm. IR (CDCl3): 3034, 2930,
1674 cmꢄ1. MS (EI) m/z (%): 307 [22], 186 [2], 173 [15],
160 [39], 159 [46], 158 [9], 91 [100]. Anal. Calcd. for
C20H21NO2: C, 78.15; H, 6.89; N, 4.56. Found: C, 78.06;
40ꢀ
recorded in CDCl3. Elemental analyses were carried out
with accepted tolerance of 90.3 units on carbon (C),
hydrogen (H) and nitrogen (N). All compounds were
/
63 or 15ꢀ40 mm silica gel. All NMR spectra were
/
/
1
H, 6.61; N, 4.47%. 2b: H-NMR (CDCl3, 200 MHz): d

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297
2.39 (dd, 1H, Jꢂ
8.1 Hz), 3.18ꢀ3.05 (2H), 3.43 (m, 1H), 3.79 (s, 3H), 4.47
(s, 2H), 5.96 (dd, 1H, Jtrans 15.8, Jꢂ7.3 Hz), 6.35 (d,
1H, Jtrans 15.8 Hz), 6.83 (d, 2H, Jortho 8.8 Hz), 7.39ꢀ
/
16.5, 8.1 Hz), 2.69 (dd, 1H, Jꢂ
/
16.5,
4.3. General procedure for the synthesis of (9
/
)-(Z)-4-
/
{benzyl-[2-(2-bromo-benzyl)-2-methoxycarbonyl-
acetyl]-amino}-but-2-enyl-acetate (3a), (9)-(Z)-4-
{benzyl-[2-(2-bromo-benzyl)-2-cyano-acetyl]-amino}-
but-2-enyl-acetate (3b), (9)-(Z)-4-{benzyl-[2-(2-
ꢂ
/
/
/
ꢂ
/
ꢂ
/
/
7.18 (7H) ppm. 13C-NMR (CDCl3, 50.3 MHz): d 35.6,
37.9, 46.5, 52.2, 55.3, 114.0, 127.3, 127.7, 127.8, 128.2,
128.7, 129.4, 130.4, 136.4, 159.3, 174.0 ppm. IR
(CDCl3): 3036, 2932, 1673 cmꢄ1. MS (EI) m/z (%):
/
bromo-benzyl)-2-phenylsulfonyl-acetyl]-amino}-but-2-
enyl-acetate (3c)
308 [Mꢁ
/
Hꢁ, 8], 307 [26], 292 [2], 173 [7], 160 [69], 159
To a solution of the acyclic substrate (1a, 1b, or 1c)
(1.50 mmol) in dry DMF (6 ml), under nitrogen atmo-
sphere, cooled in a water-ice bath, NaH (60% dispersion
in mineral oil) (1.80 mmol) was added and the solution
was stirred at r.t. for 20 min. 2-Bromobenzyl bromide
(1.80 mmol) as solution in dry DMF (2 ml) was added
and reaction mixture was heated at 100 8C for 1 h. A 25
wt.% aqueous solution of NH4Cl (50 ml) was added and
[46], 145 [18], 144 [20], 134 [29], 121 [26], 120 [16], 119
1
[5], 91 [100]. 2c: H-NMR (CDCl3, 200 MHz): d 2.40
(dd, 1H, Jꢂ
Hz), 3.22ꢀ3.05 (2H), 3.45 (m, 1H), 4.47 (s, 2H), 6.10 (dd,
1H, Jtrans 15.7, 7.4 Hz), 6.41 (d, 1H, Jtrans 15.7 Hz),
7.39ꢀ
7.17 (10H) ppm. 13C-NMR (CDCl3, 50.3 MHz): d
/
16.9, 8.1 Hz), 2.70 (dd, 1H, Jꢂ16.1, 8.1
/
/
ꢂ
/
ꢂ
/
/
35.9, 37.2, 46.5, 52.0, 115.7, 126.2, 127.7, 128.2, 128.7,
128.8, 130.0, 131.1, 136.6, 138.5, 173.9 ppm. IR
(CDCl3): 3033, 2930, 2858, 1669 cmꢄ1. MS (EI) m/z
(%): 278 [6], 277 [27], 131 [10], 130 [81], 129 [90], 128 [36],
115 [39], 91 [100]. Anal. Calcd. for C19H19NO: C, 82.28;
H, 6.90; N, 5.05. Found: C, 82.16; H, 6.78; N, 4.96%. 2d:
the aqueous phase was extracted with Et2O (3ꢃ10 ml).
/
The collected organic phases were dried and the solvent
was removed in vacuo. Flash chromatography (hexane-
s:AcOEt) gave the pure products as oils (3a, 90%; 3b,
1
64%; and 3c, 86%). 3a: H-NMR (CDCl3, 200 MHz): d
1H-NMR (CDCl3, 200 MHz): d 2.41 (dd, 1H, Jꢂ
8.1 Hz), 2.59 (s, 3H), 2.71 (dd, 1H, Jꢂ16.9, 8.5 Hz),
3.24ꢀ3.07 (2H), 3.45 (m, 1H), 4.48 (s, 2H), 6.20 (dd, 1H,
Jtrans 15.8 Hz, Jꢂ7.4 Hz), 6.45 (d, 1H, Jtrans 15.8
Hz), 7.51ꢀ7.22 (7H), 7.88ꢀ
7.77 (2H) ppm. 13C-NMR
(CDCl3, 50.3 MHz): d 26.7, 35.5, 37.6, 46.6, 51.9, 125.8,
127.5, 127.7, 128.2, 128.8, 128.9, 130.2, 130.7, 131.5,
136.3, 137.1, 137.5, 173.7, 198.1 ppm. IR (CDCl3): 3034,
2928, 1690, 1674 cmꢄ1. MS (EI) m/z (%): 320 [12], 319
[46], 306 [1], 305 [4], 278 [11], 277 [37], 201 [16], 129 [88],
128 [85], 127 [38], 120 [89], 91 [100]. 2e: 1H-NMR
/
16.9,
1.98 (s, 3H, 51%), 2.00 (s, 3H, 49%), 3.53ꢀ
3.69 (s, 3H, 51%), 3.75 (s, 3H, 49%), 3.86 (d, 2H, 49%,
Jꢂ5.8 Hz), 3.98 (d, 2H, 51%, Jꢂ6.6 Hz), 4.17 (m, 1H),
4.63ꢀ4.33 (4H), 5.69ꢀ5.04 (2H), 7.53ꢀ6.86 (9H) ppm.
/
3.29 (2H),
/
/
/
/
ꢂ
/
/
ꢂ
/
/
/
/
/
/
13C-NMR (CDCl3, 50.3 MHz): d 20.8, 35.6, 35.7, 42.9,
44.4, 47.6, 47.7, 48.8, 50.6, 52.6, 59.6, 59.8, 124.5, 124.7,
126.4, 127.0, 127.2, 127.4, 127.6, 127.6, 127.7, 128.0,
128.5, 128.7, 128.8, 129.0, 129.4, 132.5, 132.6, 132.7,
132.8, 135.8, 136.6, 137.3, 137.4, 168.3, 169.5, 169.5,
170.69 ppm. IR (CHCl3): 3005, 2957, 1736, 1642 cmꢄ1
.
MS (EI) m/z (%): 490 [0.2], 488 [0.2], 430 [9], 428 [14],
409 [13], 408 [10], 171 [28], 169 [29], 91 [100]. Anal.
Calcd. for C25H28BrNO5: C, 59.77; H, 5.62; N, 2.79.
Found: C, 59.59; H, 5.47; N, 2.61%. 3b: 1H-NMR
(CDCl3, 200 MHz): d 1.94 (s, 1H, 45%), 1.96 (s, 1H,
(CDCl3, 200 MHz): d 2.42 (dd, 1H, Jꢂ
2.57 (s, 3H), 2.72 (dd, 1H, Jꢂ16.8, 8.1 Hz), 3.25ꢀ
(2H), 3.46 (m, 1H), 4.47 (s, 2H), 6.24 (dd, 1H, Jtrans
16.1 Hz, Jꢂ7.0 Hz), 6.44 (d, 1H, Jtrans 16.1 Hz),
7.41ꢀ7.22 (7H), 7.88 (d, 2H, Jortho
8.4 Hz) ppm. 13C-
/16.5, 8.1 Hz),
/
/
3.06
ꢂ
/
/
ꢂ
/
/
ꢂ
/
55%), 3.53ꢀ
/
3.21 (2H), 4.23ꢀ
/
3.88 (3H), 4.59ꢀ4.37 (4H),
/
NMR (CDCl3, 50.3 MHz): d 26.6, 35.6, 37.6, 46.6, 51.8,
126.3, 127.7, 128.2, 128.7, 128.8, 130.2, 133.0, 136.1,
136.3, 141.2, 173.6, 197.5 ppm. IR (CDCl3): 3035, 2925,
2857, 1690, 1675 cmꢄ1. MS (EI) m/z (%): 320 [8], 319
[40], 318 [5], 304 [1], 172 [11], 146 [9], 130 [11], 129 [84],
128 [65], 120 [46], 104 [13], 91 [100]. Anal. Calcd. for
C21H21NO2: C, 78.97; H, 6.63; N, 4.39. Found: C, 78.84;
H, 6.61; N, 4.27%. 1-Benzyl-4-vinyl-pyrrolidin-2-one:
5.78ꢀ5.23 (2H), 7.54ꢀ
/
/
7.00 (9H) ppm. 13C-NMR
(CDCl3, 50.3 MHz): d 20.7, 20.8, 34.3, 34.4, 36.6,
43.9, 44.6, 49.6, 50.8, 59.3, 59.6, 116.5, 116.7, 124.3,
124.4, 126.2, 127.9, 128.0, 128.0, 128.1, 128.1, 128.2,
128.6, 128.8, 129.2, 129.6, 132.5, 132.9, 135.1, 135.2,
135.3, 136.0, 164.5, 164.6, 170.5, 170.6 ppm. MS (EI) m/
z (%): 397 [27], 395 [30], 343 [10], 341 [12], 261 [100]. IR
(CH2Cl2): 3017, 2957, 2260, 1731, 1668 cmꢄ1. Anal.
Calcd. for C24H25BrN2O3: C, 61.41; H, 5.37; N, 5.97.
Found: C, 61.23; H, 5.19; N, 6.02%. 3c: 1H-NMR
(CDCl3, 200 MHz): d 1.94 (s, 1H, 45%), 1.98 (s, 1H,
1H-NMR (CDCl3, 200 MHz): d 2.32 (dd, 1H, Jꢂ
8.4 Hz), 2.62 (dd, 1H, Jꢂ16.5, 8.4 Hz), 3.07ꢀ2.86 (2H),
3.37 (m, 1H), 4.44 (system AB, 2H), 5.00 (d, 1H, Jcis
2.9 Hz), 5.08 (d, 1H, Jtrans 9.5 Hz), 5.76 (m, 1H),
7.39ꢀ
7.17 (5H) ppm. 13C-NMR (CDCl3, 50.3 MHz): d
/16.5,
/
/
ꢂ
/
ꢂ
/
55%), 3.77ꢀ
4.79ꢀ4.62 (2H), 5.68ꢀ
(11H), 7.97ꢀ
7.81 (2H) ppm. 13C-NMR (CDCl3, 50.3
/
3.21 (3H), 4.29ꢀ
/
3.95 (2H), 4.54ꢀ
/
4.31 (3H),
/
/
/
5.29 (2H), 6.53 (m, 1H), 7.68ꢀ
/6.92
35.9, 37.3, 46.6, 51.8, 115.8, 127.7, 128.2, 128.7, 136.3,
138.5, 174.0 ppm. IR (CDCl3): 3069, 3033, 2929, 2857,
1673 cmꢄ1. MS (EI) m/z (%): 202 [13], 201 [69], 146 [19],
146 [20], 104 [19], 103 [22], 91 [100]. Anal. Calcd. for
C13H15NO: C, 77.58; H, 7.51; N, 6.96. Found: C, 77.48;
H, 7.39; N, 6.79%.
/
MHz): d 20.8, 34.7, 34.9, 43.7, 44.8, 49.6, 50.8, 59.6,
59.7, 65.0, 65.1, 124.4, 124.6, 126.0, 127.1, 127.5, 127.6,
127.8, 128.0, 128.5, 128.9, 129.0, 129.1, 129.1, 129.2,
129.8, 129.9, 132.5, 132.9, 133.1, 134.4, 134.9, 134.9,
135.4, 136.1, 136.8, 163.9, 164.1, 170.5, 170.6 ppm. MS

298
S. Lemaire et al. / Journal of Organometallic Chemistry 687 (2003) 291ꢀ300
/
(EI) m/z (%): 512 [3.6], 510 [5.2], 370 [7.2], 368 [8.4], 91
[100], 77 [40]. IR (CH2Cl2): 3070, 3005, 2946, 1734, 1661
cmꢄ1. Anal. Calcd. for C29H30BrNO5S: C, 59.59; H,
5.17; N, 2.40. Found: C, 59.68; H, 5.23; N, 2.60%.
130.2, 133.9, 135.3, 136.1, 140.2, 169.6, 171.8 ppm. MS
(EI) m/z (%): 347 [13], 288 [38], 155 [70], 91 [100]. IR
(CH2Cl2): 3028, 2946, 1740, 1693 cmꢄ1. m.p. 106ꢀ
/
108 8C. cis-4b: 1H-NMR (CDCl3, 200 MHz): d 2.88
(dd, 1H, Jꢂ9.2, 3.3 Hz), 3.11 (part of AB system, d,
1H), 3.39 (part of AB system, d, 1H), 3.82ꢀ3.63 (2H),
4.05 (part of AB system, d, 1H), 4.66 (part of AB
system, d, 1H), 5.13 (s, 1H), 5.40 (s, 1H), 6.76ꢀ6.65 (m,
1H), 7.39ꢀ
7.16 (8H) ppm. 13C-NMR (CDCl3, 50.3
/
4.4. General procedure for the synthesis of (9
/
)-
/
(9aS,3aS)-2-benzyl-9-methylene-3-oxo-1,2,3,4,9,9a-
hexahydro-benzo[f]isoindole-3a-carboxylic acid methyl
/
ester (cis-4a), (9
oxo-1,2,3,4,9,9a-hexahydro-benzo[f]isoindole-3a-
carboxylic acid methyl ester (trans-4a), (9)-(9aS,3aS)-
2-benzyl-9-methylene-3-oxo-1,2,3,4,9,9a-hexahydro-
benzo[f]isoindole-3a-carbonitrile (cis-4b), (9)-
/)-(9aS,3aR)-2-benzyl-9-methylene-3-
/
MHz): d 29.7, 34.4, 42.8, 47.0, 51.1, 114.2, 119.6,
125.8, 127.5, 127.8, 128.2, 128.6, 128.8, 129.0, 131.8,
134.6, 135.4, 142.4, 167.5 ppm. MS (EI) m/z (%): 314
[23], 166 [7], 91 [100]. IR (CH2Cl2): 3049, 2926, 2854,
2242, 1708 cmꢄ1. trans-4b: 1H-NMR (CDCl3, 200
/
/
(9aS,3aR)-2-benzyl-9-methylene-3-oxo-1,2,3,4,9,9a-
hexahydro-benzo[f]isoindole-3a-carbonitrile (trans-4b),
MHz): d 3.05ꢀ
d, 1H), 3.72ꢀ3.42 (2H), 3.54 (part of AB system, d, 1H),
4.53 (part of AB system, d, 1H), 4.66 (part of AB
system, d, 1H), 4.91 (d, 1H, Jꢂ2.2 Hz), 5.78 (d, 1H,
Jꢂ1.8 Hz), 7.43ꢀ7.16 (8H), 7.73ꢀ
7.64 (1H) ppm. 13C-
/2.96 (m, 1H), 3.23 (part of AB system,
(9
/
)-(9aS,3aS)-9a-benzenesulfonyl-2-benzyl-4-
/
methylene-2,3,3a,4,9,9a-hexahydro-benzo[f]isoindol-1-
one (cis-4c)
/
/
/
/
To a solution of the acyclic substrate (3a, 3b, or 3c)
(0.25 mmol) in dry DMF (2 ml), under argon atmo-
sphere, cooled in a water-ice bath, NaH (60% dispersion
in mineral oil) (0.28 mmol) was added and the solution
was stirred at r.t. for 20 min. In a separate flask,
Pd(OAc)2 (0.013 mmol) and dppe (0.025 mmol) were
dissolved in dry DMF (1 ml). The previously preformed
enolate was transferred under argon atmosphere to the
thus formed palladium(0) complex, and the resulting
mixture was stirred at the proper temperature for the
proper time (see Scheme 4). A 25 wt.% aqueous solution
of NH4Cl (30 ml) was added and the aqueous phase was
NMR (CDCl3, 50.3 MHz): d 34.9, 46.6, 46.6, 46.9, 47.3,
108,9, 116.5, 124.8, 127.5, 128.0, 128.2, 129.1, 129.4,
130.5, 131.6, 133.1, 135.3, 138.5, 167.8 ppm. MS (EI) m/
z (%): 314 [42], 223 [3], 166 [10], 91 [100]. IR (CH2Cl2):
3032, 2929, 2854, 2236, 1709 cmꢄ1. Anal. Calcd. for
C21H18N2O: C, 80.23; H, 5.77; N, 8.91. Found: C, 80.06;
H, 5.63; N, 8.90%. cis-4c: 1H-NMR (CDCl3, 200 MHz):
d 2.75 (part of AB system, 1H), 3.08 (s, 2H), 3.68 (t, 1H,
Jꢂ
AB system, 1H), 4.59 (part of AB system, 1H), 5.23 (s,
7.48
/9.6 Hz), 3.94 (part of AB system, 1H), 4.27 (part of
1H), 5.27 (s, 1H), 6.47 (2H), 7.24ꢀ
/
7.15 (7H), 7.69ꢀ
/
(3H), 8.02 (2H) ppm. 13C-NMR (CDCl3, 50.3 MHz): d
32.4, 39.2, 46.7, 51.6, 74.0, 114.2, 125.9, 127.1, 127.3,
127.8, 128.4, 128.6, 128.7, 131.0, 132.4, 134.5, 134.9,
135.5, 136.5, 144.5, 167.2 ppm. MS (EI) m/z (%): 429 [1],
288 [48], 196 [9], 91 [100]. IR (CH2Cl2): 3068, 2944, 1703
extracted with Et2O (3ꢃ10 ml). The collected organic
/
phases were dried and the solvent removed in vacuo.
Flash chromatography (hexanes:AcOEt) gave the pure
compounds. (cis-4a, 49% and trans-4a, 32%; cis-4b, 9%
and trans-4b, 73%; cis-4c, 82%). cis-4a: 1H-NMR
(CDCl3, 200 MHz): d 2.85 (m, 1H), 3.08 (part of AB
system, d, 1H), 3.36 (part of AB system, d, 1H), 3.73
(2H), 3.80 (s, 3H), 4.00 (part of AB system, d, 1H), 4.64
(part of AB system, d, 1H), 5.04 (s, 1H), 5.25 (s, 1H),
cmꢄ1. m.p. 172ꢀ
174 8C. Anal. Calcd. for C26H23NO3S:
/
C, 72.70; H, 5.40; N, 3.26. Found: C, 72.68; H, 5.36; N,
3.17%.
4.5. (9)-cis-N-(4-Acetoxy-cyclohex-2-enyl)-N-benzyl-
/
6.64ꢀ
/
6.59 (2H), 7.31ꢀ
/
7.10 (7H) ppm. 13C-NMR
2-(2-bromo-benzyl)-malonamic acid methyl ester (6)
(CDCl3, 50.3 MHz): d 32.7, 42.5, 46.5, 52.1, 52.9,
57.1, 112.9, 125.5, 127.3, 128.6, 128.6, 134.5, 135.4,
136.3, 145.1, 171.2, 171.9 ppm. MS (EI) m/z (%): 347
[40], 288 [88], 141 [42], 91 [100]. IR (CH2Cl2): 3030,
2955, 2926, 1739, 1691 cmꢄ1; Anal. Calcd. for
C22H21NO3: C, 76.06; H, 6.09; N, 4.03. Found: C,
Solid NaH (10 mg, 0.25 mmol, 60% dispersion in
mineral oil) was added to a dry DMF (20 ml) stirred
solution of cis-4-acetoxy-1-[benzyl(methylmalonyl)a-
mino]-cyclohex-2-ene 5 [13] (86 mg, 0.25 mmol) at
0 8C. After 10 min stirring at this temperature and
further 20 min at r.t., a dry DMF (1 ml) solution of o-
bromobenzylbromide (63 mg, 0.25) mmol was added to
the thus formed enolate, and the resulting mixture was
heated at 100 8C for 20 min. Water (10 ml) and ether (50
ml) were then added to the cooled mixture, the organic
layer was separated, and the aqueous phase was
1
75.96; H, 6.00; N, 4.12%. trans-4a: H-NMR (CDCl3,
200 MHz): d 3.08 (part of AB system, d, 1H), 3.17 (m,
1H), 3.36 (dd, 1H, Jꢂ
(part of AB system, d, 1H), 3.87 (dd, 1H, Jꢂ
Hz), 4.48 (part of AB system, d, 1H), 4.72 (part of AB
system, d, 1H), 4.79 (d, 1H, Jꢂ1.9 Hz), 5.57 (d, 1H,
Jꢂ1.8 Hz), 7.38ꢀ
7.15 (8H), 7.58 (m, 1H) ppm. 13C-
/8.8, 6.6 Hz), 3.51 (s, 3H), 3.70
/10, 9.1
/
/
/
extracted with ether (3ꢃ
layers were washed with water (3ꢃ
MgSO4 and evaporated under reduced pressure. Flash
/50 ml). The collected organic
NMR (CDCl3, 50.3 MHz): d 29.7, 35.4, 47.0, 41.2, 52.3,
56.6, 106.1, 124.3, 126.3, 127.8, 128.2, 128.6, 128.7,
/
25 ml), dried over

S. Lemaire et al. / Journal of Organometallic Chemistry 687 (2003) 291ꢀ
/300
299
chromatography (hexanes:AcOEt) of the crude product
1
gave the bromobenzylated amide 6 (103 mg, 95%). H-
127.9, 128.6, 128.8, 129.3, 133.0, 133.2, 135.9, 136.3,
171.0, 171.6 ppm. IR (neat): 1740, 1690, 1440, 1220
cmꢄ1. MS (NH3) (%): m/z 454 [100], 456 [100].
NMR (CDCl3, 200 MHz) d 1.40ꢀ
3H), 3.30ꢀ3.47 (m, 2H), 3.60 (s, 1H), 3.64 (s, 1H), 3.70
(s, 1H), 3.80ꢀ3.90 (m, 0.6H), 4.05ꢀ4.36 (m, 1.6H), 4.43ꢀ
4.74 (m, 0.9H), 4.90ꢀ5.4 (m, 2.6H), 5.68ꢀ5.95 (m, 1.3H),
6.90ꢀ7.00 (m, 1.5H), 7.00ꢀ7.30 (m, 6.5H), 7.40ꢀ7.60 (m,
/2.00 (m, 4H), 1.96 (m,
/
/
/
/
4.7. (9)-(3aR,5aR,10bR,10cR)-4-Benzyl-5-oxo-
/
/
/
3a,4,5,6,10b,10c-hexahydro-3H-4-aza-
/
/
/
acephenanthrylene-5a-carboxylic acid methyl ester (8)
1H) ppm. 13C-NMR (CDCl3, 50 MHz) d 20.3, 22.2,
27.8, 30.7, 36.7, 49.5, 53.0, 53.7, 65.4, 66.1, 125.3, 126.6,
126.7, 127.6, 129.5, 133.4, 134.7, 134.9, 138.2, 138.5,
170.4, 170.5, 170.6 ppm. IR (neat): 1740, 1650, 1430,
1230 cmꢄ1. MS (NH3) (%): 516 [70], 514 [70], 456 [100],
454 [100]. Anal. Calcd. for C26H28BrNO5: C, 60.71; H,
5.49; N, 2.72. Found: C, 60.56; H, 5.60; N, 2.56%.
Dry DMF (0.4 ml) was added to n-Bu4NOAc (60 mg,
0.2 mmol) and the resulting mixture was degassed twice.
After addition of the HerrmannꢀBeller catalyst (2 mg,
/
0.0045 mmol), the flask was degassed again and left
under argon atmosphere. In a separate flask, NaH (4
mg, 0.1 mmol, 60% dispersion in mineral oil) was added
to a water-ice cooled, dry and degassed DMF (4 ml)
solution of the precursor 6 (43 mg, 0.1 mmol). After 10
min stirring at 0 8C and further 20 min at r.t., the thus
formed enolate was transferred under argon atmosphere
into the palladium mixture, and heating was immedi-
ately brought to 130 8C. After 1.5 h stirring at 130 8C,
the reaction flask was let it cool to r.t., treated with
water (10 ml) and ether (20 ml), and the phases were
separated. The aqueous layer was extracted with ether
4.6. (9)-trans- and cis-1-Benzyl-3-(2-bromo-benzyl)-2-
/
oxo-2,3,3a,6,7,7a-hexahydro-1H-indole-3-carboxylic acid
methyl ester (trans-7) and (cis-7)
Solid NaH (5 mg, 0.12 mmol, 60% dispersion in
mineral oil) was added to a water-ice cooled dry DMF
(8 ml) solution of 6 (43 mg, 0.1 mmol) under argon
atmosphere, and the resulting suspension was stirred for
10 min at 0 8C and further 20 min at r.t. In a separate
flask, dppe (4 mg, 0.01 mmol) was added to a dry DMF
(2 ml) solution of Pd(OAc)2 (1 mg, 0.005 mmol). The
previously generated enolate was then transferred under
argon atmosphere to the yellow solution containing the
palladium catalyst, and the resulting mixture was heated
at 50 8C for a 20-min period. Water (4 ml) and ether (20
ml) were then added to the cooled mixture and the
phases were separated. The aqueous phase was extracted
(3ꢃ/20 ml), and the collected organic layers were
washed with water (3ꢃ/20 ml), dried over MgSO4 and
evaporated under reduce pressure. Flash chromatogra-
phy (hexanes:AcOEt) of the resulting crude product
gave the pure tetracycle 8 an oil (22 mg, 60%), plus
minor amounts of trans-7 and cis-7. When AcOK was
used instead of n-Bu4NOAc, under otherwise identical
1
conditions, tetracycle 8 was obtained in 40% yield. H-
NMR (CDCl3, 500 MHz) d 1.94 (m, 1H), 2.22 (m, 1H),
with ether (3ꢃ
were washed with water (3ꢃ
/
20 ml), and the collected organic layers
10 ml), dried over MgSO4
3.07 (dd, Jꢂ
1H), 3.32 (part of AB system, 1H), 3.50 (d, Jꢂ
/
7.2, 9.1 Hz, 1H), 3.21 (part of AB system,
/
/6.3 Hz,
and evaporated under reduced pressure. Flash chroma-
tography of the crude product (hexanes:AcOEt) gave
trans-7 and cis-7 (27 mg, 80%). Trans-7: 1H-NMR
1H), 3.76 (s, 3H), 3.96 (part of AB system, 1H), 4.00 (m,
1H), 4.81 (part of AB system, 1H), 6.00 (m, 1H), 6.15
(m, 1H), 7.07 (m, 2H), 7.17ꢀ
7.35 (m, 7H) ppm. 13C-
/
(CDCl3, 200 MHz) d 1.65ꢀ
AB system, Jꢂ17.0 Hz, 1H), 3.52ꢀ
3H), 3.73 (part of AB system, 1H), 3.90 (AB system,
1H), 3.91 (m, 1H), 5.17 (part of AB system, 1H), 5.28ꢀ
5.36 (m, 1H), 5.83ꢀ5.91 (m, 1H), 6.95ꢀ7.40 (m, 8H),
3.9 Hz, 1H) ppm. 13C-NMR (CDCl3, 50
/
2.03 (m, 4H), 3.15 (part of
NMR (CDCl3, 100 MHz) d 4.5, 14.0, 20.5, 26.2, 31.0,
42.5, 46.1, 49.0, 146.9, 149.2,149.3, 150.2, 151.3, 151.7,
156.4, 161.9, 162.2, 164.3 ppm. IR (neat): 1750, 1690,
1450, 1250 cmꢄ1. MS (CH4): m/z 374.1751 (calc.
/
/
3.57 (m, 1H), 3.66 (s,
/
/
/
374.1756) [Mꢁꢁ
/1].
3
7.55 (d, Jꢂ
/
MHz) d 20.0, 23.5, 37.1, 39.9, 44.6, 53.1, 58,5, 123.2,
125.9, 127.6, 127.9, 128.1, 128.8, 128.9, 129.7, 130.6,
133.1, 136.3, 137.6, 127.7, 136.3, 171.3, 171.7 ppm. IR
(neat): 1740, 1690, 1440, 1230 cmꢄ1. MS (CH4): m/z
4.8. Crystal data for cis-4c
C26H23NO3S, Mꢂ/429.51, orthorhombic, space
˚
3
˚
group Pbca, aꢂ16.362(5) A, bꢂ
/
/
12.570(5) A, cꢂ
8, F(0 0 0)ꢂ1808,
1.330 g cmꢄ3. Data set, consist-
1208) reflections, was collected on a
P4 Siemens X-ray diffractometer using the (CuꢀKa)
1.5418 A) for the cell parameter determi-
/
454.1016 (calculated: 454.1018) [Mꢁꢁ
(calculated: 456.1001) [Mꢁꢁ3]. cis-7: 1H-NMR
(CDCl3, 200 MHz) d 1.3ꢀ2.1 (m, 4H), 2.68 (m, 1H),
3.08ꢀ3.15 (m, 1H), 3.51 (part of AB system, 1H), 3.15 (s,
3H), 3.88 (part of AB system, 1H), 3.98 (part of AB
system, 1H), 5.14 (part of AB system, 1H), 5.84ꢀ5.90
/1], 456.1012
20.852(5) A, Vꢂ
mꢂ
1.568 mmꢄ1, Dcꢂ
ing of 3655 (2umax
/
4289(2) A , Zꢂ
/
/
˚
˚
/
/
/
/
ꢂ
/
/
/
˚
radiation (lꢂ
/
/
nation and data collection. The intensities of two
standard reflections were monitored during data collec-
tion to check the stability of the crystal; no loss of
intensity was recognized. The integrated intensities,
(m, 2H), 6.86ꢀ
/
6.90 (m, 2H), 7.00ꢀ
/
7.30 (m, 5H), 7.47ꢀ
/
7.62 (m, 2H) ppm. 13C-NMR (CDCl3, 50 MHz) d 22.6,
23.3, 36.3, 44.4, 52.5, 54.1, 61.9, 124.2, 127,5, 127.7,

300
S. Lemaire et al. / Journal of Organometallic Chemistry 687 (2003) 291ꢀ300
/
Vogtle (Eds.), Stimulating Concepts in Chemistry, WileyꢀVCH,
/
¨
measured at room temperature (293 K) using the u/2u
scan mode, were corrected for Lorentz and polarization
effects [15]. The structure was solved by direct methods
of SIR97 [16] and refined using the full-matrix least-
squares on F2 provided by SHELXL97 [17]. Anisotropic
thermal parameters were used for all the non-hydrogen
atoms. The hydrogen atoms of the phenyl rings were
assigned in calculated positions, while the others were
localized in final difference Fourier map. The final R
Weinheim, 2000, pp. 39ꢀ64.
/
[2] G. Poli, G. Giambastiani, Tetrahedron 56 (2000) 5959.
[3] (a) J.M. Gaudin, Tetrahedron Lett. 32 (1991) 6113;
(b) D. Flubacher, G. Helmchen, Tetrahedron Lett. 40 (1999)
3867;
(c) T. Peglow, S. Blechert, E. Steckhan, Chem. Commun. (1999)
433ꢀ434;
/
(d) B.C. Soderberg, S.R. Rector, S.N. O’Neil, Tetrahedron Lett.
¨
40 (1999) 3657;
(e) L.F. Tietze, R. Ferraccioli, Synlett (1998) 145;
(f) L.F. Tietze, G. Nordmann, Eur. J. Org. Chem. (2001) 3247
[4] G. Giambastiani, B. Pacini, M. Porcelloni, G. Poli, J. Org. Chem.
63 (1998) 804.
index was 0.0422 for reflections having I ꢀ2s(I) and
/
0.0560 for all data.
[5] G. Poli, G. Giambastiani, B. Pacini, Tetrahedron Lett. 42 (2001)
5179.
5. Supplementary material
[6] trans-Di-(m-acetate)-bis[o-(di-o-tolylphosphine)benzyl]-dipalla-
dium(II).
Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic
Data Centre, CCDC No. 209018 for compound cis-4.
Copies of this information may be obtained free of
charge from The Director, CCDC, 12, Union Road,
¨
[7] (a) W.A. Herrmann, C. Brossmer, K. .Ofele, C.-P. Reisinger, T.
Priermeier, M. Beller, H. Fisher, Angew. Chem. Int. Ed. Engl. 34
(1995) 1844;
(b) W.A. Herrmann, C. Brossmer, C.-P. Reisinger, T.H. Rierme-
¨
ier, K. .Ofele, M. Beller, Eur. J. Chem. 3 (1997) 1357;
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(f) W.A. Herrmann, V.P.W. Bohm, C.-P. Reisinger, J. Organo-
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Acknowledgements
¨
(b) W.A. Herrmann, C.-P. Reisinger, K. .Ofele, C. Brossmer, M.
This work was supported by the Centre National de la
Recherche Scientifique and by COST action D-24 (D24/
0002/01) of the European Community. We thank Dr.
Cristina Faggi (University of Florence) for the X-ray
analysis.
Beller, H. Fisher, J. Mol. Catal. A 108 (1996) 51;
(c) B.L. Shaw, New J. Chem. (1998) 77;
(d) C. Amatore, A. Jutand, Acc. Chem. Res. 33 (2000) 314.
[9] G. Poli, G. Giambastiani, J. Org. Chem. 67 (2002) 9456.
[10] A. De Meijere, S. Brase, J. Organomet. Chem. 576 (1999) 88.
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[11] P.-O. Norrby, M.M. Mader, M. Vitale, G. Prestat, G. Poli,
Organometallics 22 (2003) 1849.
[12] Although involvement of the anti-h3-allylpalladium complex is
assumed, owing to the Z configuration of the starting acetate
precursor, possible isomerization to the syn configurated complex
before the cyclization step cannot be completely ruled out.
[13] The synthesis of compound 5 will be described elsewhere: S.
Lemaire, G. Prestat, G. Giambastiani, G. Poli, in preparation.
[14] See for example:
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