New developments in the Pd-catalysed cyclisation-coupling reaction of alkene-containing carbonucleophiles with organic halides (and triflates). The first examples of asymmetric catalysis

Article abstract of DOI:10.1016/S0022-328X(03)00700-9

The results of our preliminary investigations directed toward asymmetric catalysis of the cyclocarbopalladation of alkenes bearing a proximate nucleophile with organic halides (or triflates) are disclosed. A series of bidentate phosphine ligands were eval

Full text of DOI:10.1016/S0022-328X(03)00700-9

Journal of Organometallic Chemistry 687 (2003) 466ꢂ472
/
www.elsevier.com/locate/jorganchem
New developments in the Pd-catalysed cyclisation-coupling reaction
of alkene-containing carbonucleophiles with organic halides (and
triflates). The first examples of asymmetric catalysis.
Didier Bruye`re, Nuno Monteiro, Didier Bouyssi, Genevie`ve Balme *
Laboratoire de Chimie Organique 1, CNRS UMR 5622, Universite´ Claude Bernard, Lyon 1, CPE. 43, Bd du 11 Novembre 1918, 69622 Villeurbanne,
France
Received 11 June 2003; received in revised form 17 July 2003; accepted 21 July 2003
Dedicated to Professor Jean-Pierre Geneˆt on the occasion of his 60th birthday with regards and best wishes
Abstract
The results of our preliminary investigations directed toward asymmetric catalysis of the cyclocarbopalladation of alkenes bearing
a proximate nucleophile with organic halides (or triflates) are disclosed. A series of bidentate phosphine ligands were evaluated in
intramolecular versions of this reaction using (E)-2-[7-(2-bromophenyl)-hept-4-enyl]-malonic acid dimethyl ester (1) and (Z)-2-[7-(2-
trifluoromethanesulfonyloxy-phenyl)-hept-4-enyl]-malonic acid dimethyl ester (9) as model substrates. The highest enantioselective
induction was obtained with aryl triflate 9 which produced the corresponding cyclopentylindane as a single diastereomer in 54%
chemical yield and 43% ee by using PdCl2[S-(ꢀ/)-TolBINAP] as chiral catalyst and K2CO3 as base.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Asymmetric catalysis; Palladium; P ligands; Carbocyclisations
1. Introduction
complex rather than a palladium salt acts as the
electrophilic promotor. Finally, a reductive elimination
leads to the expected product and regenerates the
catalyst.
The cyclisation of unsaturated substrates bearing a
proximate nucleophile promoted by organopalladium
complexes is now well established as a powerful method
for the one-step synthesis of various carbo- and hetero-
cyclic systems [1,2].
The mechanistic pathway generally considered for this
process is described in Scheme 1. An oxidative addition
of the electrophilic substrate RX to palladium (0) gives a
RPdL2X complex. Displacement of one of the ligands L
or X and coordination to the insaturation activates it
toward the intramolecular attack of the nucleophile
from the side opposite to the palladium. Such a
mechanism is quite similar to that involved in Wacker-
type reactions but in this case an organopalladium
In this context, our group has recently developed
some efficient intramolecular versions of this methodol-
ogy for the construction of tricyclic structures [3]. In
particular, we have demonstrated that the palladium-
mediated cyclisation of linear compounds of type 1 (Z
or E) proceeds with complete retention of the stereo-
chemistry in a stereocontrolled mode since it involves
attack of the carbon nucleophile onto the double bond
electrophilically activated by the organopalladium spe-
cies [4a]. Therefore, the reaction was shown to be
stereospecific with the stereochemical outcome depend-
ing on the geometry of the internal alkene [4b,c].
Moreover, the regiochemistry of the cyclisation (5 exo
vs. 6 endo) can be controlled by the steric bulk of the
nucleophilic part (Scheme 2). This transformation
occurred with the formation of two new contiguous
tertiary carbon stereocenters.
* Corresponding author. Tel.: ꢁ
214.
E-mail address: balme@univ-lyon1.fr (G. Balme).
/
33-47-2431-416; fax: ꢁ33-47-2431-
/
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-328X(03)00700-9

D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ
/
472
467
would like to report herein our preliminary results in
this field.
2. Results and discussion
With regard to the enantioselectivity, the key steps in
the catalytic cycle seems to be complexation of the
organopalladium intermediate to the alkene (identical to
that of the Heck reaction) and attack of the carbon
nucleophile onto this activated alkene. It is not very easy
to determine which of these two elementary steps is the
more important for the resulting enantioselectivity,
however, it appeared to us that to maximize the
asymmetric induction, as for the Heck reaction, both
phosphines of the diphosphine ligand have to be
coordinated to palladium during the enantioselective
step. Cabri and Hayashi have demonstrated that a high
level of asymmetric induction can be obtained in Heck
reactions when aryl or vinyltriflates were used as
substrates 6a,b. In this case, the reaction follows a
cationic pathway and the chiral bidentate ligand is
strongly associated to the palladium atom in the
complexation step (Scheme 1, path a). In marked
contrast, a low enantioselectivity was observed in the
presence of the corresponding halides. This was attrib-
uted to the reaction mechanism involving here a neutral
organopalladium intermediate via a partial dissociation
of the chiral ligand (Scheme 1, path b). However, it was
shown that addition of silver salts regenerates a cationic
pathway by scavenging the halide [7].
2.1. Cyclisation of (E)-2-[7-(2-bromophenyl)-hept-4-
enyl]-malonic acid dimethyl ester (1)
The linear substrate (E)-1 prepared previously [4a]
was selected for our preliminary study of the enantio-
selective intramolecular biscyclisation reaction. The
effect of varying the chiral auxiliary was studied and
1
the enantiomeric purity determined by H-NMR in the
presence of the chiral shift reagent (ꢁ)-Eu(hfc)3. In this
/
case, it is not possible to add silver salts to the reaction
so as to sequestre the halide because they would oxidize
the metal malonate enolates to give homocoupling
products [8].
Scheme 1.
BINAP [2,2?-bis(diphenylphosphino)-1,1?-binaphthyl]
has been used widely as chiral ligand in catalytic Heck
reactions [9] and the asymmetric reaction of linear
substrate (E)-1 was first investigated with this ligand.
Bromide 1 was subjected to the conditions that had been
determined optimum for the cyclisation of the linear
homologous substrates [4]. The reaction was carried out
by heating the substrate in N-methylpyrrolidinone
The synthetic utility of this new process would be
enhanced if optically active products were to be
produced. Indeed, although this new palladium-
mediated cyclisation process has received considerable
attention since its discovery, asymmetric catalysis of this
reaction has not been investigated to date [5]. In this
regard, we envisioned that the use of a palladium
complex containing chiral phosphine ligands would
offer an opportunity for enantioselective induction
when the reaction is applied to alkene substrates. We
(NMP) at 60 8C in the presence of 5 mol% Pd(R-(ꢁ)-
/
BINAP), 1.1 equivalents of KH and 0.2 equivalents of
18-crown-6. These conditions gave the expected regioi-

468
D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ
/
472
Scheme 2.
somer anti 2 in 50% chemical yield but with low
enantioselectivity (7%) (Table 1, entry 1). Other chiral
out these preliminary studies, we decided to prepare the
readily available linear substrate (Z)-9. Indeed, this
cyclisation precursor was accessible in only four steps
from the known 2-(2-iodophenoxy)-tetrahydropyran (4)
[11]. Thus, treatment of 4 with allylic alcohol according
to the procedure published by Jeffery [12] afforded
aldehyde 5 in 62% yield. Wittig olefination of the latter
with the ylide derived from phosphonium salt 6 [13]
proceeded smoothly at 0 8C to provide chloride 7 in 70%
yield. Substitution of chloride group by the sodium salt
of dimethylmalonate and subsequent removal of the
THP protecting group provided the phenolic derivative
8 which was converted to the triflate 9 using standard
conditions (Scheme 3).
phosphines including (ꢀ
2,3-dihydroxy-1,4-bis(diphenylphosphino)butane) and
(ꢀ)-CHIRAPHOS [(2S,3S)-bis(diphenylphosphi-
/
)-DIOP (2,3-O-isopropylidene-
/
no)butane] resulted in an increase of the optical yield
of the reaction to 16 and 21% ee, respectively (Table 1,
entries 2 and 3). When S-(ꢀ)TolBINAP [2,2?-bis(di-p-
/
tolylphosphino)-1,1?-binaphtyl] was used as asymmetric
ligand, more satisfactory results were obtained. The
expected product was formed in 42% chemical yield
(73% conversion) and in 35% ee (Table 1, entry 4).
2.2. Cyclisation of (Z)-2-[7-(2-
trifluoromethanesulfonyloxy-phenyl)-hept-4-enyl]-
malonic acid dimethyl ester (9)
Initial attempts to effect the palladium-catalysed
cyclisation of the triflate 9 under conditions similar to
those reported for bromide 1 (Pd(OAc)2, dppe, KH,
758C) proved disappointing, the desired tricyclic com-
This last result encouraged us to develop the same
reaction on the corresponding aryltriflate. However,
aryltriflates are reported to be ineffective substrates for
similar intermolecular palladium-mediated cyclisation
processes [10]. Therefore, it was necessary to first
investigate their utilisation in this intramolecular cycli-
sation reaction in the racemic version. In order to carry
pound syn 2 being formed in poor yields (B20%).
/
Several reaction parameters were varied such as the
nature of the base (t-BuOK and KH), the solvent
(DMF, THF, DMSO), but no improvement in the yield
of syn 2 was observed. The best results were obtained by
using 5 mol% Pd(OAc)2 as the palladium source with 10
Table 1
Cyclisation of aryl bromide 1
Entry
Phosphine
R-(ꢁ)-BINAP
Solvent
T (8C)
Time (h)
Yield (%) a
Ee (%) b
1
2
3
4
5
6
/
NMP
NMP
NMP
NMP
60
60
60
60
60
60
16
3
50
50
48
42
50
50
7
16
21
35 c
0
(ꢀ/)-DIOP
(ꢀ/)-Chiraphos
3
S-(ꢀ
R-(ꢁ)-BINAP
S-(ꢀ)-TolBINAP
/)-TolBINAP
3
/
NMPꢂ/toluene
16
16
/
NMPꢂ/toluene
0
All reactions were run in the presence of 5 mol% Pd(OAc)2, 1.1 equivalents KH, 0.2 equivalents 18-crown-6 and 10 mol% of the ligand.
a
Isolated yield.
Determined by 1H-NMR using (ꢁ
b
/
)-Eu(hfc)3 as shift reagent.
c
[a]2D0ꢃ
/
ꢀ/
16.7 (cꢃ
/
2.4 10ꢀ3, CHCl3).

D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ
/
472
469
Scheme 3.
mol% of dppb or dppf [14] as ligand in DMSO at room
temperature. These conditions afforded syn 2 in 52 and
53% yield, respectively (Scheme 4).
Having established satisfactory conditions for the
palladium-mediated intramolecular cyclisation of the
linear triflate (Z)-9, we turned our attention to the
asymmetric version using different chiral ligands and the
results of these studies are reported in Table 2. With
according to the procedure reported by Hayashi and
coworkers [16]. To our delight, when the reaction was
performed in DMSO at 35 8C, a remarkable improve-
ment was achieved since syn 2 was isolated in 62%
chemical yield and 37% ee (Table 2, entry 5). When
the same reaction was performed in the presence of
BINAPAs
(2-diphenylarsino-2?-diphenylphosphino-
1,1?binaphtyl) as an asymmetric ligand [17], a low
enantioselectivity was observed and the chemical yield
dropped to 36% (Table 2, entry 6).
chiral biphosphine such as (ꢀ)-BPPFA ((R)-N,N-
/
dimethyl-1-[(S)-1?,2-bis(diphenylphosphino)ferrocenyl]
ethylamine), cyclisation of 9 afforded the desired adduct
in 45% yield and in 17% ee (Table 2, entry 1). When
DIOP ligand was used, improved yields were observed
(64%) but enantioselectivities were not improved (16%)
(Table 2, entry 2). When Pd(OAc)2 was used as a
precursor of the catalyst, the highest enantiomeric excess
observed (26%) was obtained with BINAP as chiral
ligand but the chemical yield was rather modeste (Table
2, entry 3). As the palladium(0) catalyst generated in situ
by reduction of PdCl2(PPh3)2 with n-BuLi has been
found particularly effective in related carbopalladation
reactions [15] we decided to test the biscyclisation
reaction with the preformed catalyst PdCl2[(S)-TolBI-
NAP] prepared by the reaction of dichlorobis (acetoni-
trile) palladium with one equivalent of [(S)-TolBINAP]
In order to improve the enantioselectivity and the
chemical yield of this palladium-mediated biscyclisation
reaction using PdCl2[(S)-TolBINAP] as catalytic sys-
tem, we further examined the effect of the temperature
and of the nature of the base. The results of this
investigation are compiled in Table 3. When the reaction
was conducted at lower temperature (Table 3, entry 2)
the yield (50%) and ee (18%) were inferior compared to
the value obtained at 35 8C (Table 3, entry 1).
The moderate yields generally observed during the
cyclisation of the triflate substrate when compared to
the same reaction effected on the corresponding bro-
mide (90%) [4c] can be attributed to the cleavage of the
triflate by attack of the strong base. The same problem
was observed by Buchwald during a coupling reaction
between aryl triflates and amines in the presence of t-
BuOK as base [18]. The use of a weaker base such as
Cs2CO3 was a solution to this problem. However, while
strong bases such as KH or t-BuOK had previously
been used to promote this palladium-mediated cyclisa-
tion reaction, a competitive Heck reaction was generally
observed with weaker bases [19]. The cyclisation of 9
was then attempted in the presence of two equivalents of
Cs2CO3 as base in place of t-BuOK. Remarkably, the
isolated yield of syn 2 was noticeably improved to 85%
Scheme 4.

470
D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ472
/
Table 2
Cyclisation of aryl triflate 9
Entry
Phosphine
T (8C)
Time (h)
Yield (%) b
Ee (%) c
[a]2D0 d
1
(ꢀ
/
)-BPPFA
25
25
25
25
35
40
20
22
20
23
3
45
64
48
53
62
36
17
16
26
11
37
9
ꢀ
ꢀ/
/
8
2
(ꢀ
/
)-DIOP
6
3
R-(ꢁ
S-(ꢀ
PdCl2[S-(ꢀ
PdCl2[R-BINAPAs]
/
)-BINAP
)ꢂTolBINAP
)-TolBINAP]
ꢂ
4.4
/
4
/
/
ꢁ
/
5 a
6 a
/
ꢁ
/
15.8
15
ꢂ
/
All reactions were run in DMSO in the presence of 5 mol% Pd(OAc)2, 1.1 equivalents of base, 0.2 equivalents of 18-crown-6 and 10 mol% of the
ligand or 5 mol% of catalyst (entries 5, 6).
a
In this case the catalyst was reduced with n-BuLi prior to use.
Isolated yield.
b
c
Determined by 1H-NMR using (ꢁ
)-Eu(hfc)3 as shift reagent.
deg, CHCl3.
/
d
and the enantiomeric purity was 21% (Table 3, entry 3).
The best enantioselectivity (43%) was obtained when the
reaction was carried out in the presence of K2CO3 as
base (Table 3, entry 4). Quite surprisingly, while using a
single enantiomer of the TolBINAP ligand, the opposite
enantiomer of syn 2 was obtained by changing the
nature of the inorganic base [20] (Table 3, entries 3 and
4).
opposite enantiomer being formed in 85% chemical yield
and 21% ee.
3. Experimental
In conclusion, enantioenriched cyclopentylindanes
were obtained through asymmetric catalysis of the
palladium-mediated biscyclisation reaction developed
on an aryl bromide or triflate tethered to an alkene
bearing a stabilized carbonucleophile. The best combi-
nation of chemical yields (54%) and enantioselectivity
(43%) was realized on the aryltriflate substrate.
PdCl2[(S)-TolBINAP] prepared from PdCl2(PPh3)2 as
the precatalyst and [(S)-TolBINAP] as the chiral bipho-
sphine was found to be the optimal palladium system,
the reaction beeing performed at 35 8C in DMSO using
K2CO3 as base. Unexpectedly, the enantioselectivity can
be reversed in the cyclisation of this aryl triflate by
simply changing the nature of the inorganic base, the
3.1. General
Infrared spectra were recorded on a Perkinꢂ
/
Elmer
298 or PerkinꢂElmer FT-IR PARAGON 500. Proton
/
magnetic resonance (1H-NMR) and carbon magnetic
resonance (13C-NMR) spectra were measured at 300
MHz with a Bruker AM 300 and ALS 300 spectrometer.
Chemical shifts are reported in parts per million (ppm)
downfield from tetramethylsilane (d scale). The multi-
plicity (sꢃ
/
singlet, dꢃ
/
doublet, tꢃ
/
triplet, qꢃ
/
quartet,
mꢃmultiplet, brꢃ
/
/
broad, number of protons and
coupling constants (reported in Hz)) are indicated in
parentheses.
Table 3
Effect of base in the cyclisation of aryl triflate 9
Entry
Base
Solvent
T (8C)
Time (h)
Yield (%)
Ee (%) a
[a]2D0 b
15.5
1
2
3
4
t-BuOK
t-BuOK
Cs2CO3
K2CO3
DMSO
DMSO
DMSO
DMSO
35
25
40
40
3
24
4
62
50
85
54
37
18
21
43
ꢁ
/
ꢂ/
ꢁ
/
11.4
24
ꢀ/
21.6
All reactions were run using 5% of PdCl2[S-(ꢀ
/
)-TolBINAP] as catalyst
a
Determined by 1H-NMR using (ꢁ
deg, CHCl3.
/
)-Eu(hfc)3 as shift reagent
b

D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ
/
472
471
3.2. Synthesis of triflate 9
warmed to 80 8C and stirred for 6 h. After usual work-
up the crude product was directly treated with amberlyst
IR-15 (0.5 g) in 130 ml of MeOH for 1 h at 45 8C. After
filtration on Celite and evaporation, the crude product
was purified by flash chromatography on silica gel
(eluent: PE:Et2O 80:20) yielding 8 as a yellow oil (1.67
g, 54%).
3.2.1. 3-[2-(Tetrahydropyran-2-yloxy)-phenyl]-
propionaldehyde (5)
2-(2-Iodo-phenoxy)-tetrahydropyran (9.7 g, 32
mmol), allyl alcohol (6.72 g, 96 mmol), Pd(OAc)2 (180
mg, 0.8 mmol), triethylbenzylammonium chloride (7.3 g,
32 mmol), NaHCO3 (6.72 g, 80 mmol) were successively
added to 225 ml of DMF and the resulting solution was
stirred at 65 8C for 22 h. The reaction mixture was
quenched with 300 ml of water and extracted with Et2O
IR (film): 3460, 3000, 2950, 1735, 1610, 1590, 1500,
1460, 1440, 1150, 760 cmꢀ1 1H-NMR (CDCl3, 300
.
MHz): d 1.30 (m, 2H), 1.89 (m, 2H), 2.00 (m, 2H), 2.37
(m, 2H), 2.67 (t, Jꢃ7.5 Hz, 2H), 3.37 (t, Jꢃ7.5 Hz,
1H), 3.75 (s, 6H), 5.3ꢂ5.5 (m, 2H), 6.7ꢂ
7.0 (m, 4H). 13C-
/
/
(2ꢄ/250 ml) and washed with brine (200 ml). The
/
/
organic phase was dried (MgSO4) and concentrated in
vacuo. Purification of the crude product by flash
chromatography on silica gel (eluent: PE:Et2O:Et3N
87:10:3) yielded 5 as a yellow oil (4.8 g, 64%).
NMR (CDCl3, 75 MHz): d 26.7, 27.3, 27.5, 28.5, 30.7,
51.7, 52.6, 115.3, 120.3, 127.1, 128.3, 129.4, 130.0, 130.4,
154.1, 170.2. Microanalysis Found: C, 67.11; H, 7.60.
Calc. for C18H24O5: C, 67.48; H, 7.55%.
IR (film): 3060, 2940, 2880, 2720, 1730, 1680, 1600,
1495, 1240, 1130, 930, 880, 760 cmꢀ1
.
1H-NMR
3.2.3. (Z)-2-[7-(2-Trifluoromethanesulfonyloxy-
phenyl)-hept-4-enyl]-malonic acid dimethyl ester (9)
2,6-Lutidine (0.97 ml, 7.8 mmol) was added slowly to
(CDCl3, 300 MHz): d 1.60ꢂ
2H), 3.00 (t, Jꢃ7 Hz, 2H), 3.63 (m, 1H), 3.87 (m, 1H),
5.43 (t, Jꢃ3 Hz, 1H), 6.91 (t, Jꢃ7.5 Hz, 1H), 7.00ꢂ
/1.90 (m, 6H), 2.77 (m,
/
/
/
/
a cooled solution (ꢀ10 8C) of phenol 8 (5.2 mmol, 1.67
/
7.20 (m, 3H), 9.83 (s, 1H). 13C-NMR (CDCl3, 75 MHz):
d 19.1, 23.7, 30.6, 30.7, 44.2, 62.2, 96.4, 114.3, 121.5,
127.8, 129.1, 130.0, 154.9, 202.4. Microanalysis Found:
C, 71.98; H, 7.78. Calc. for C14H18O3: C, 71.80; H,
7.70%.
g) in CH2Cl2 (10 ml), followed by the addition of Tf2O
(0.98 ml, 5.7 mmol). After 1 h at this temperature, the
reaction mixture was quenched by a solution of sat.
NH4Clꢂ1 N HCl 3/1 (5 ml). The organic phase was
/
separated and the aqueous layer extracted with CH2Cl2
(10 ml). The combined organic phases were washed with
water and brine, dried over Na2SO4, and concentrated
in vacuo. The crude oil was purified by flash chromato-
graphy on silica gel (eluent: PE:Et2O 90:10) yielding 9 as
a yellow oil (2.23 g, 95%).
3.2.2. Synthesis of phenol 8
The phenol was prepared from 5 by a two-step
procedure: Wittig reaction with phosphonium salt 6 as
described in Ref. [4] followed by reaction of the resulting
chloride 7 with dimethyl malonate and subsequent
deprotection of the tetrahydropyranlyloxy protecting
group.
1H-NMR (CDCl3, 300 MHz): d 1.32 (m, 2H), 1.85
(m, 2H), 1.96 (m, 4H), 2.35 (m, 2H), 2.75 (t, Jꢃ
2H), 3.32 (t, Jꢃ7.7 Hz, 1H), 3.75 (s, 6H), 5.3ꢂ
2H), 7.2ꢂ
7.4 (m, 4H). 13C-NMR (CDCl3, 75 MHz): d
/
7.7 Hz,
/
/5.5 (m,
/
3.2.2.1. (Z)-2-[2-(7-Chloro-hept-3-enyl)-phenoxy]-
tetrahydropyran (7). A mixture of (4-chloro-butyl)-
triphenyl phosphonium bromide 6 (7.32 g, 16.8 mmol)
and KHMDS (3.43 g, 16.8 mmol) was dissolved in THF
(72 ml) at 0 8C. The resulting red solution was stirred for
15 min. Aldehyde 5 (1.98 g, 8.46 mmol) in 18 ml of THF
was added to the above solution which was stirred for a
further 15 min at 0 8C and 1 h at 25 8C. The reaction
mixture was poured into 300 ml of petroleum ether, and
filtrated through a pad of silica gel. The filtrate was
concentrated in vacuo and the crude product 7 directly
engaged in the next step.
26.7, 27.2, 27.6, 28.4, 30.0, 51.7, 52.4, 117.0, 121.3,
127.9, 128.3, 128.4, 130.0, 130.4, 131.4, 134.6, 148.1,
169.9. Microanalysis Found: C, 50.47; H, 5.10. Calc. for
C19H23O7SF3: C, 50.50; H, 5.10%.
3.3. Palladium-catalysed cyclisation of bromide 1 or
triflate 9
3.3.1. 2-Indan-1-yl-cyclopentane-1,1-dicarboxylic acid
dimethyl ester (2)
Bromide 1 or triflate 9 (1 equivalent) were treated in
DMSO with the appropriate base (1.1 equivalents or
two equivalents for inorganic bases). The palladium
source was added and the resulting solution heated for
the indicated time (see tables). The crude mixture was
directly purified by flash-chromatography on silica gel
(eluent: PE:Et2O 80:20) yielding the corresponding
cyclisation product anti 2 or syn 2, respectively (yield:
see text).
3.2.2.2. 2-[7-(2-Hydroxy-phenyl)-hept-4-enyl]-malonic
acid dimethyl ester (8). Dimethyl malonate (1.6 ml, 14
mmol) was added slowly to a suspension of sodium
hydride (washed previously by pentane) (288 mg, 12
mmol) in THF (80 ml). The resulting solution was
stirred at room temperature (r.t.) for 30 min at which
time chloride 7 (3 g, 9.7 mmol) in DMF (80 ml) and KI
(161 mg, 0.97 mmol) were added. The solution was
Anti 2 colourless solid. M.p.: 50ꢂ
(300 MHz, CDCl3) d 1.45 (1H, ddd, Jꢃ
/
52 8C. 1H-NMR
3.6, 8.7, 17.5
/

472
D. Bruye`re et al. / Journal of Organometallic Chemistry 687 (2003) 466ꢂ472
/
[3] (a) G. Balme, D. Bouyssi, Tetrahedron 50 (1994) 403;
(b) M. Cavicchioli, S. Decortiat, D. Bouyssi, J. Gore´, G. Balme,
Tetrahedron 52 (1996) 11463;
Hz), 1.65 (1H, ddd, Jꢃ
2.1 (3H, m), 2.56 (1H, dt, Jꢃ
m), 3 (1H, dt, Jꢃ2.8, 10 Hz), 3.1 (1H, ddd, Jꢃ
/
7.9, 11.2, 14.2 Hz), 1.85 (2H, m),
8.1, 13.6 Hz), 2.75 (2H,
7.1, 9.7,
/
/
/
(c) I. Coudanne, G. Balme, Synlett (1998) 998.
[4] (a) D. Bruyere, G. Gaignard, D. Bouyssi, G. Balme, J.-M.
Lancelin, Tetrahedron Lett. 38 (1997) 827;
23.8 Hz), 3.75 (6H, s), 7.1 to 7,53 (4H, m). 13C-NMR (75
MHz, CDCl3) d 23.5, 30.9, 31.6, 31.9, 37.32, 47.6, 49.9,
52.2, 52.6, 63, 124.6, 125.5, 125.6, 126.6, 144.7, 146.6,
172.3, 174. IR (KBr): 3060, 2940, 2840, 1740. Anal.
Calc. for C18H22O4: C, 71.5; H, 7.33. Found: C, 71.29;
H, 7.68%. Syn 2 yellow oil 1H-NMR (CDCl3, 300
MHz): d 1.50 (m, 3H), 1.75 (m, 2H), 2.00 (m, 2H), 2.50
(b) C. Bressy, D. Bruyere, D. Bouyssi, G. Balme, ARKIVOC
(Gainesville, FL, United States) [online computer file] 5 (2002)
127;
(c) D. Bruyere, D. Bouyssi, G. Balme, to be published.
[5] N. Monteiro, Asymmetric catalysis of the intermolecular version
of this process was however briefly investigated in our labora-
tories soon after its discovery but with little success, PhD
dissertation, Lyon, 1992.
(ddd, Jꢃ
Jꢃ2.9, 7.2 Hz, 1H), 3.60 (dt, Jꢃ
(s, 6H), 7.10ꢂ
7.34 (m, 4H). 13C-NMR (CDCl3, 75
/
7.1, 8.5, 13.6 Hz, 1H), 2.85 (m, 2H), 3.0 (dt,
/
/2.9, 10 Hz, 1H), 3.75
[6] (a) W. Cabri, I. Candiani, Acc. Chem. Res. 28 (1995) 2;
(b) F. Ozawa, A. Kubo, T. Hayashi, J. Am. Chem. Soc. 113
(1991) 1417.
/
MHz): d 22.9, 26.4, 29.9, 32.2, 34.8, 44.7, 50.1, 52.6,
62.9, 123.9, 124.3, 126.4, 126.6, 143.7, 146.9, 173.0.
Microanalysis Found: C, 71.45; H, 7.54. Calc. for
C18H22O4: C, 71.50; H, 7.33%.
[7] F. Miyazaki, K. Uotsu, M. Shibasaki, Tetrahedron 54 (1998)
13073.
[8] Z. Wrobel, M. Makosza, Liebigs Ann. Chem. 7 (1990) 619.
[9] (a) M. Shibasaki, F. Miyazaki, in: E-I. Negishi (Ed.), Handbook
of Organopalladium Chemistry for Organic Synthesis, Wiley,
3.4. Determination of enantiomeric excess of 2
New York, 2002, 1283ꢂ1315;
/
(b) For review see: M. Shibasaki, C.D.J. Boden, A. Kojima,
Enantiomeric excesses were measured by adding 1.2
Tetrahedron 53 (1997) 7371.
[10] (a) G. Balme, M. Bottex, D. Bouyssi, T. Lomberget, N. Monteiro,
Unpublished results;
equivalents of (ꢁ
CDCl3 to the NMR tube and the methyl esters at 3.75
ppm split into four singlets (4.2ꢂ4.5 ppm) which could
/
) Eu(hfc)3 to 2 (8ꢂ
/
10 mg) in 1 ml of
(b) A. Arcadi, A. Burini, S. Cacchi, M. Delmastro, F. Marinelli,
B.R. Pietroni, J. Org. Chem. 57 (1992) 976.
/
be integrated.
[11] G.T. Crisp, T.P. Bubner, Tetrahedron 53 (1997) 11881.
[12] T. Jeffery, Tetrahedron Lett. 32 (1991) 2121.
[13] W.H. Pearson, H. Suga, J. Org. Chem. 63 (1998) 9910.
[14] Examples of Heck reactions involving aryl or vinyltriflates and
using dppf, dppb and/or dppp as ligands
Acknowledgements
(a) S. Laschat, F. Narjes, L.E. Overman, Tetrahedron 50 (1994)
347;
The authors gratefully acknowledge professor M.
Shibasaki (University of Tokyo) for a generous gift of
BINAPAs. D. Bruye`re thanks the Ministe`re de l’Educa-
tion Nationale, de la Recherche et de la Technologie for
a fellowship.
(b) W. Cabri., I. Candiani, A. Bedeschi, R. Santi, J. Org. Chem.
57 (1992) 3558.
[15] (a) M. Bottex, M. Cavicchioli, B. Hartmann, N. Monteiro, G.
Balme, J. Org. Chem. 63 (2001) 175;
(b) T. Lomberget, D. Bouyssi, G. Balme, Synlett (2002) 1439.
[16] (a) Y. Matsumoto, T. Hayashi, Y. Ito, Tetrahedron 50 (1994)
335;
References
(b) M. Tinkl, S. Evans, P. Nesvadba, Preparation of 3-arylbenzo-
furanones via carbonylation of arylmethylidenecyclohexadie-
nones, PCT Int. Appl., WO 9967232 A2 19991229 (1999).
[17] Recently BINAPAs was found to be more effective chiral
ligand than BINAP in asymmetric Heck reactions that use aryl
triflates, see: S.Y. Cho, M. Shibasaki, Tetrahedron Lett. 39 (1998)
1773.
[1] For reactions involving carbon nucleophiles see;
(a) G. Balme, D. Bouyssi, T. Lomberget, N. Monteiro, Synthesis,
in press;
(b) G. Balme, N. Monteiro, D. Bouyssi, in: E.-I. Negishi (Ed.),
Handbook of Organopalladium Chemistry for Organic Synthesis,
[18] J. Ahman, S.L. Buchwald, Tetrahedron Lett. 38 (1997) 6363.
[19] I. Coudanne, J. Castro, G. Balme, Synlett (1998) 995.
[20] A similar result was recently reported. In this case, either
WileyNew York, 2002, pp. 2245ꢂ2265
/
[2] For reactions involving oxygen nucleophiles see:
(a) S. Cacchi, A. Arcadi, in: E.-I. Negishi (Ed.), Handbook of
Organopalladium Chemistry for Organic Synthesis, Wiley, New
enantiomer of
a Heck product was formed using a single
enantiomer of the BINAP ligand depending on the presence of
tertiary amine or silver salts in the mixture. see:
York, 2002, pp. 2193ꢂ2210;
/
(b) For reactions involving nitrogen nucleophiles see:
(b) S. Cacchi, F. Marinelli, E.-I. Negishi (Ed.), Handbook of
Organopalladium Chemistry for Organic Synthesis, Wiley, New
(a) A. Ashimori, L.E. Overman, J. Org. Chem. 57 (1992) 4571;
(b) A. Ashimori, B. Bachand, L.E. Overman, D.J. Poon, J. Am.
Chem. Soc. 120 (1998) 6477.
York, 2002, 2227ꢂ2244.
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