Investigation of the aqueous transmetalation of π-allylpalladium with indium salt: The use of the Pd(OAc)2-TPPTS catalyst

Article abstract of DOI:10.1039/b419231c

π-Allylpalladium complexes could be generated in water by the palladium(0) water soluble catalyst prepared in situ from palladium acetate and TPPTS. These complexes were transmetalated with indium to react with benzaldehyde. The aqueous solution of Pd(0)(TPPTS)_n could be reused without deterioration of the catalyst in the first and second recycling. The system proved to be efficient with primary and secondary allylic substrates. The stereochemical outcome of the allylation through umpolung of allylpalladium, was also studied using models with a restraint conformation. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b419231c

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A R T I C L E
Investigation of the aqueous transmetalation of p-allylpalladium with
indium salt: the use of the Pd(OAc)2–TPPTS catalyst
Gianfranco Fontana,† Andre´ Lubineau and Marie-Christine Scherrmann*
Laboratoire de Chimie Organique Multifonctionnelle, UMR 8164, ICMMO, Baˆtiment 420,
Universite´ de Paris-Sud, 91405, Orsay Cedex, France. E-mail: mcscherr@icmo.u-psud.fr;
Fax: +33 1 69154715; Tel: +33 1 69154719
Received 22nd December 2004, Accepted 16th February 2005
First published as an Advance Article on the web 10th March 2005
p-Allylpalladium complexes could be generated in water by the palladium(0) water soluble catalyst prepared in situ
from palladium acetate and TPPTS. These complexes were transmetalated with indium to react with benzaldehyde.
The aqueous solution of Pd(0)(TPPTS)n could be reused without deterioration of the catalyst in the first and second
recycling. The system proved to be efficient with primary and secondary allylic substrates. The stereochemical
outcome of the allylation through umpolung of allylpalladium, was also studied using models with a restraint
conformation.
Introduction
Since the pioneering work of Li and Chan1 in 1991, indium
promoted reactions leading to the formation of carbon–carbon
bonds has been the subject of great interest and several reviews
have been devoted to this topic.2 Among these reactions,
the condensation of allyl indium species and carbonyl com-
pounds in water has been widely studied from a mechanistic
point of view3 and has also been used for various synthetic
applications. In particular, higher carbon sugars have been
synthesised by using this reaction as a key step,4 as well
as C-disaccharides as illustrated by recent works from this
laboratory.5 The organoindium species used in the above cited
works were generated from allylic halides and indium powder or
indium halides. Interestingly, Marshall and Grant showed that
allenylindium halides can be generated through transmetalation
of a transient allenylpalladium complex with InI.6 This concept
was extended to the preparation of allylindium reagents by Araki
and coworkers.7 They reported the preparation of allylic indium
reagents by reductive transmetalation of p-allylpalladium(II)
complexes obtained from a large variety of allylic substrates
with indium salts in various solvents. Later on, this umpolung
methodology was also applied to vinyloxiranes,8 vinylaziridines,9
acylnitroso-derived hetero Diels–Alder cycloadducts,10 or p-
allylpalladium species obtained from aryl iodides and allene in
the presence of Pd.11 Recently, a paper from the group of Kim
described the Pd-catalyzed allylation of carbonyl compounds
with allylic derivatives using In–InCl3 in aqueous media.12 On
the other hand, a palladium(0) water soluble catalyst prepared
from palladium acetate and the sulfonated triphenylphosphine
TPPTS13 has proven to be very efficient in many applications14
including industrial hydrodimerisation, hydrogenation, C–C
bond formation and hydroformylation.15 This prompted us to
examine the use of this catalyst in the umpolung process with
water as the solvent.
Scheme 1 Reagents and conditions: see Table 1.
Table 1 Yields and reaction times for the coupling between allylic
substrates and benzaldehyde in water at rt. [InBr] : [1] : [PhCHO]: 0.2 :
0.2 : 0.1 M and Pd(OAc)2 0.01 M–TPPTS 0.05 M
Entry
Substrate
Time/h
Yield (%)a
1
2
3
1a
1b
1c
4.5
0.5
0.4
100 (0)b
100 (2)b
100c(38)b
a Yields were determined by RP-HPLC with anisole as internal standard.
b Yield obtained without TPPTS after 24 h. c Isolated yield.
All the allylic derivatives gave the homoallylic alcohol in
quantitative yields. As expected, the time needed for the reaction
to go to completion was in good agreement with the leaving
group power of OR on the substrate 1. The influence of
this leaving group was even more important in the reactions
conducted without TPPTS as the palladium ligand since,
after 24 h, 38% of 2 was observed with allyltrifluoroacetate
whereas no product was formed starting from the corresponding
alcohol, and only 2% when the acetate derivative was the
substrate. Furthermore, the result obtained with the acetate
confirmed the power of the Pd–TPPTS catalyst in this process
since the reaction was completed in 30 min and needed 5 h
when tetrakis(triphenylphosphine)palladium(0) was used.7 This
reaction rate enhancement is presumably due to the easier
formation of the p-allylpalladium intermediate when a water-
soluble catalyst is used. The three substrates were also tested in
the same reaction with indium powder as the reductant (Table 2).
Once again, the trifluoroacetate allylic derivatives proved to be
the more reactive in this system since the reaction was complete
after 1.7 h and the corresponding acetate gave only 11% of the
product after 24 h, whereas no product was detected starting
from the alcohol. When zero-valent indium was generated in
situ by aluminium reduction of indium(III) chloride, the reaction
time was longer (Table 2, entry 3b) compared to the same
allylation carried out using indium powder (Table 2, entry 3a).
Results and discussion
Reaction of primary allylic compounds
We first addressed the issue of condensation of allylic derivatives
1 and benzaldehyde in a Barbier-type procedure with indium
bromide in the presence of palladium(II) acetate and TPPTS
(Scheme 1, Table 1). Reactions were also carried out without
TPPTS as a comparison.
† Visiting researcher from University of Palermo, Italy.
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0
1 3 7 5
©

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Table 2 Yields and reaction times for the coupling between allylic
substrates and benzaldehyde in water at rt. [In] : [1] : [PhCHO]: 0.2 :
0.2 : 0.1 M and Pd(OAc)2 0.01 M–TPPTS 0.05 M
Table 4 Yields and reaction times for the recycling in Pd(0)-TPPTS
[InBr] : [1c] : [PhCHO]: 0.2 : 0.2 : 0.1 M
Entrya
Pd(OAc)2/TPPTSb (mol%)
5
Time/h Isolated yield (%)
Entry
Substrate
Time/h
Yield (%)a
1
0.5
2.8
3.2
3.5
100
60
52
41
22
1
2
1a
1b
1c
1c
24
24
1.7
24
0 (0)b
11 (1)b
100c (6)b
100
1a
1b
1c
1d
2
2a
2b
2c
2d
3a
3bd
10
10
0.5
0.5
0.7
1
100
100
100
82
a Yields were determined by RP-HPLC with anisole as internal standard.
b Yield obtained without TPPTS after 24 h. c Isolated yield. d InCl3 : Al
1 : 10.
4
78
a Entries a, b, c, and d are the first, second, third, and fourth recycling.
b 1 : 5 Ratio.
Furthermore, we have shown that only one electron is given
by one indium atom and therefore, two equiv. of In are needed
to reduce one equiv. of allylpalladium 3 into the allylindium(I)
4 (Scheme 2).
procedure in the coupling between allyltrifluoroacetate and
benzaldehyde with InBr and TPPTS–Pd(OAc)2 (Table 4).
Two set of experiments were carried out with 5 and 10%
Pd(OAc)2–TPPTS (1 : 5) (Table 4). At the end of each cycle,
the homoallylic alcohol and the remaining allyltrifluoroacetate
were extracted with Et2O and the aqueous phase was reused
by adding the substrates and InBr. With 5% Pd(OAc)2–TPPTS
(1 : 5) (Table 4, entries 1–1d), the yield decreased significantly
and the reaction times increased from the second run. With 10%
Pd(OAc)2–TPPTS (1 : 5) (Table 4, entries 2–2d) the reaction
time increased from the second recycling. The yield remained
quantitative for the second recycling but decreased in the two
following cycles (82 and 78%, respectively). In both cases (5 or
10% catalyst), the extraction became difficult due to precipitates
from the third run so that a filtration (over Celite) was necessary
and therefore, some catalyst may be lost during this operation.
Scheme 2 Formation of 2 through the transmetalation process.
In fact, the conversion of the reaction conducted with one
equiv. of allyltrifluoroacetate and one equiv. of indium, with
respect to benzaldehyde, did not exceed 50%, even after 48 h
(Table 3, entry 1) whereas a 70% yield was obtained with 2
equiv. of indium (Table 3, entry 2). Indeed, whereas the reaction
using In(I) salts leads to the formation of allylindium(III) species7
so that only one equiv. of indium salt is required to reduce
Pd(II) intermediate, the coupling with In(0) in water should
involve allylindium(I). Actually, Chan and Yang demonstrated3a
the formation of indium(I) instead of indium(III) compounds in
the reactions of indium metal with allyl bromide. We have also
observed that the reaction was faster and the yield higher when
an excess of allyltrifluoroacetate (Table 2, entry 3) or indium
(Table 3, entry 3) was used. The reaction rate dependence of
the indium amount in the reaction could be an indication that
the limiting step of the process is the Pd–In transmetalation.
Furthermore, the In(I) species 5 formed during the second step
together with allylindium(I) 4 should be unreactive (Scheme 2).
We then focussed our attention upon the recycling of the
catalyst. Indeed, since the homoallylic alcohol was soluble in
organic solvents, it could be easily extracted and the aqueous
phase containing, amongst other products, Pd(0)(TPPTS)n,
could be reused for another cycle of reaction. Repeated use of the
aqueous layer has proved to be valuable in hydroformylation of
olefins or hydrogenation. In the case of palladium(0)–TPPTS
catalysed reactions of allylic substrates with nucleophiles, a
decrease in the activity of the aqueous phase has been observed
from the third recycling, certainly due to the accumulation
of side-products in the aqueous phase.16 We have tested this
Reaction of secondary allylic compounds
We then studied the reaction involving a secondary allylic
derivative and chose cyclohexyl derivatives 6a–c as models
(Scheme 3).
Scheme 3 Reagents and conditions: see Table 5.
In the case of the alcohol 6a, no product was observed even
after 72 h whatever the conditions. With the acetate 6b,17 a 40%
isolated yield was obtained after 17 h with 10% Pd(OAc)2 and In
as the metal (Table 5, entry 3). The ratio of syn and anti isomers
was 95 : 5 as judged by1H NMR. This selectivity is comparable to
that obtained by Khan and Prabhudas for the indium-mediated
coupling between 3-bromocyclohexene and benzaldehyde.18
This diastereoselectivity is explained satisfactorily considering
the currently accepted six-membered cycling transition state
between the carbonyl compound and the allylindium cyclohexyl
moiety with the phenyl group in an equatorial position. The
trifluoroacetate 6c19 only gave hydrolysis so that 6a was obtained
in all the conditions we tried (Table 5, entries 7 and 8). Use of a
co-solvent was then tested in the condensation reaction involving
6b. This reaction was carried out in a 2 : 1 H2O–EtOH mixture.
Compound 718 was obtained with a 88 : 12 diastereoselectivity
in 70% or 87% isolated yield after 20 h at rt or 50 ◦C, respectively
(Table 5, entries 5 and 6).
Table 3 Isolated yields and reaction times for the coupling between
1c and benzaldehyde in water at rt in the presence of In and Pd(OAc)2
0.01 M–TPPTS 0.05 M
Entry
1c (equiv.)
In (equiv.)
Time/h
Yield (%)
1
2
3
1
1
2
1
2
4
48
24
1
50
70
100
Aiming to determine if the transmetalation was also the
limiting step in the case of secondary substrates, we have carried
1 3 7 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0

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Table 5 Conditions, isolated yields and reaction times for the coupling between 6 and benzaldehyde in the presence of Pd(OAc)2 0.01 M–TPPTS
0.05 M [InBr] or [In] : [6] : [PhCHO]: 0.2 : 0.2 : 0.1 M
Entry
Substrate
Metal
Conditions
Time/h
Isolated yield (%) (syn : anti)
1
2
3
4
5
6
7
8
6a
6a
6b
6b
6b
6b
6c
6c
In
InBr
In
InBr
In
In
H2O, rt
H2O, rt
H2O, rt
H2O, rt
H2O : EtOH, (2 : 1), rt
H2O : EtOH (2 : 1), 50 ◦
H2O, rt
72
72
17
24
20
20
24
24
0
0
40 (95 : 5)
25 (90 : 10)
70 (88 : 12)
87 (88 : 12)
0
C
In
InBr
H2O, rt
0
Table 6 Isolated yields for the coupling between 6c and benzaldehyde
in H2O–EtOH (2 : 1) at 50 ◦C after 15 h in the presence of In and
Pd(OAc)2 0.01 M–TPPTS 0.05 M
coupling products syn-12a and syn-12b were obtained after 24 h
in a 95 : 5 ratio in 58% overall yield (Scheme 5).
Entry
In (equiv.)
7 (Yield %)
Other isolated products (%)
1
2
3
2
3
4
70
86
40
PhCHO (20)
—
PhCH2OH (20)
out experiments using 2, 3, and 4 equiv. of indium (Table 6). The
reaction was faster using 3 equiv. since, in this case, 86% of the
alcohol 7 was isolated after 15 h while, in the same time, when
2 equiv. of indium were used 7 was obtained in 70% yield and
20% unreacted benzaldehyde was recovered. In the presence of 4
equiv. of indium we obtained only 40% of the coupling product
7 and 20% of benzylic alcohol. We checked that the reduction of
benzaldehyde took place only when both palladium acetate and
indium were present but we did not investigate further this side-
reaction. Since the reaction rate dependance on the amount of
indium is not as significant as in the case of the primary substrate
1c, it is difficult to establish if the limiting step is the formation
of the allylpalladium intermediate or the transmetalation.
In order to study the stereochemical outcome of the allylation
through umpolung of allylpalladium, we have prepared 11a20
and 11b,21 models with a restraint conformation (Scheme 4).
Scheme 5 Reagents and conditions: Pd(OAc)2 0.01 M–TPPTS 0.05 M,
[In] : [11a] : [PhCHO]: 0.2 : 0.2 : 0.1 M, EtOH–H2O 2 : 1, 50 ◦C, 24 h.
In comparison, the cis acetate 11a (2 equiv.) was also allowed
to react with benzaldehyde in THF with Pd(PPh3)4 (10%) and
InBr (2 equiv.). After 24 h syn-12a and syn-12b were obtained
in a 90 : 10 ratio in only 20% yield showing that the reaction is
much faster in aqueous medium using a water-soluble catalyst,
the selectivity being comparable.
The relative syn orientation of the C1ꢀ–OH and C1–C6 bonds
1
in syn 12a and syn-12b was deduced from comparison of H
NMR spectra with those reported in the literature for 7.18 The
trans orientation of the two cyclohexenyl substituents (phenyl
and 1ꢀ-hydroxybenzyl) in syn-12a was also established on the
basis of 1H NMR data. In fact, the axial H6 (d 1.84 ppm)
exhibits a large coupling constant of 11.5 Hz with H5 and a small
coupling constant of 6.0 Hz with H1, in addition to the large
gem-coupling (17.5 Hz) with equatorial H6. This deduction was
confirmed by the observation of a NOE between H1ꢀ and H5.
In the spectrum of syn-12b, the signal of axial H6 (d 1.70 ppm)
is a ddd with three large identical coupling constants of 12.0 Hz
consistent with an equatorial and quasi-equatorial position for
the 5-phenyl and the 1-(1ꢀ-hydroxybenzyl) respectively.
In the same conditions, the trans isomer 11b afforded a
mixture of the coupling products 12a and 12b in a 1.3 : 1
ratio with 38% yield, together with ethoxy and hydroxy-allylic
compounds 1325 and 10 as 4.5 : 1 trans : cis mixtures in 10 and
20% yield, respectively (Scheme 6).
When the reaction was carried out in THF with Pd(PPh3)4
and InBr, no product was formed and the trans acetate 11b
was recovered without epimerisation suggesting that the p-
allylpalladium was not formed in these conditions.
The most plausible explanation for the results obtained in
aqueous medium comes from the examination of the transition
states of the involved reactions (Scheme 7). In the first step, the
p-allylpalladium(II) 15a and 15b are formed through a transition
state resembling 14a and 14b. The transition state 14b should
Scheme 4 Reagents and conditions: (a) i) 2-methyl-1-propanol, APTS,
benzene, Dean–Stark apparatus, ii) LiAlH4·Et2O, iii) aq. HCl; (b)
CeCl3·7H2O, NaBH4, MeOH; (c) Ac2O, pyridine; (d) PPh3, DIAD,
AcOH, THF.
Phenyldione 8 was transformed into enone 922 using a method
described for the methyl or tert-butyldione.23 Luche reduction
of 9 afforded the racemic cis-allylic alcohol 10a24 with an 86%
yield and a very high diastereoselection (de > 99%) as judged
1
by H NMR. Acetylation of the cis-alcohol 10a with pyridine
and acetic anhydride afforded quantitatively the cis-acetate 11a.
Reacting 10a in the Mitsunobu conditions afforded the trans-
acetate 11b as described.21
When 11a was allowed to react with benzaldehyde in the
umpolung process under the conditions giving the bes◦t results
for cyclohexyl derivative 6b (EtOH–H2O 2 : 1, In, 50 C), the
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0
1 3 7 7

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Table 7 Yields for the reaction of cis-11a and trans-11b with Pd(OAc)2
0.01 M–TPPTS 0.05 M in H2O–EtOH (2 : 1) at 50 ◦
C
13
10
Substrate
Yield%
trans : cis
Yield (%)
trans : cis
cis-11a
trans-11b
28
34
1.2 : 1
3.2 : 1
55
51
1 : 1
2.5 : 1
was obtained in 4.5 : 1 trans : cis mixture showing that the
Tsuji–Trost reaction is faster than the isomerisation of 11b. The
formation of the alcohol 10 can be the result of the hydrolysis
of the starting acetate. In fact, while 11a or 11b were stable in
EtOH–H2O at 50 ◦C for 48 h, in the presence of TPPTS, 10% of
alcohol 10 was obtained without epimerisation in both cases. We
have also treated the two acetates with the Pd–TPPTS catalyst in
the same conditions (EtOH–H2O 2 : 1, 50 ◦C) and isolated, after
72 h, compounds 13 and 10 with 28 and 55% yield respectively,
without cis : trans selectivity from the cis-substrate 11a, whereas
the trans isomer 11b afforded 13 and 10 in 34 and 51% yield with
an excess of the trans-alkoxy or hydroxy product (Table 7).
The lack of selectivity in the case of the cis-substrate 11a
could be explained by the isomerisation of 11a into 11b
through the allylpalladium intermediate 15a, the rate of the
isomerisation being faster than both the Tsuji–Trost reaction
and the hydrolysis, whereas the Tsuji–Trost reaction and the
hydrolysis are slightly faster than the isomerisation of 11b
into 11a. Furthermore, as no alkoxy or hydroxy products were
observed from 11a in the reaction with benzaldehyde it should
be deduced that the transmetalation Pd–In is faster in the case
of 15a than the Tsuji–Trost reaction and the hydrolysis and thus
than the isomerisation.
Scheme 6 Reagents and conditions: Pd(OAc)2 0.01 M–TPPTS 0.05 M,
[In] : [11b] : [PhCHO]: 0.2 : 0.2 : 0.1 M, EtOH–H2O, 50 ◦C, 24 h.
be of lower energy than 14a because of steric repulsions in 14a
where both the acetate leaving group and the phenyl group are
in an axial position.26 Transmetalation of 15a or 15b with In(0)
gave allyl indium(I) 16a or 16b with retention of configuration as
observed for transmetalation with other metals.27 From the two
possible six-membered transition states in each case, those with
the phenyl group from benzaldehyde in the equatorial position is
more favourable, thus syn-12a is obtained from 18a and syn-12b
is obtained from 18b. Considering the transition states 18a and
18b, it becomes clear that the reaction with the aldehyde is easier
in the case of the cis-acetate 11a since in 18a, the phenyl group,
substituent from the cyclohexene, is in an equatorial position,
while it is in an axial position in 18b formed through multiple
steps from the trans-acetate 11b.
The formation of syn-12a from 11b can be explained by an
isomerisation of the starting acetate 11b into 11a. In fact, when
we isolated unreacted 11 from an incomplete reaction of 11b
(after 7 h), we obtained a mixture of cis and trans acetates
11a and 11b in a 1 : 1 ratio as judged by 1H NMR. Such
an isomerisation of cyclohexenyl derivatives in a palladium-
catalysed reaction has already been described.28 Since 13 was
obtained, in majority, with retention of configuration at C-1,
we hypothesised that it was the result of a Tsuji–Trost reaction
between 15b and the nucleophilic solvent EtOH. This product
Conclusion
We have shown that p-allylpalladium complexes could be
favourably generated in water by the palladium(0) water
Scheme 7 Rationalisation of the formation of syn-12a and syn-12b.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0
1 3 7 8

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soluble catalyst prepared in situ from palladium acetate and
TPPTS. These complexes were transmetalated with indium to
react with benzaldehyde. Best results were obtained with InBr
as the source of indium and trifluoroacetate as the leaving
group in the case of primary substrate whereas acetate leaving
group gave the best yields in the case of secondary substrates.
Furthermore, when using 10% of the catalyst, the aqueous layer
containing Pd(0)(TPPTS)n could be reused for two more cycles
of reaction without decrease of the yield or increase of the
reaction time. Studies of the stereochemical outcome of the
reaction showed that the indium species are formed with a
global inversion of configuration. When steric effects disfavour
the overall process, a complex mixture was obtained, coming
from the starting material isomerisation, a Tsuji–Trost reaction
with the nucleophilic solvent, and an hydrolysis of the ester.
adding benzaldehyde, allyltrifluoroacetate and InBr as described
above.
5-Phenyl-2-cyclohexenone22 (9). A solution of 5-phenyl-
cyclohexane-1,3-dione (5.00 g, 26.50 mmol) p-toluenesulfonic
acid monohydrate (68 mg, 0.35 mmol) and 2-methyl-1-propanol
(60 mL) in benzene (60 mL) was refluxed overnight into a Dean–
Stark apparatus. The resulting red solution was cooled to rt and
concentrated under reduced pressure to a volume of 40 mL
to which ethyl acetate (40 mL) was added. The solution was
washed three times with aq 10% NaOH (20 mL), and then
with brine (20 mL). The organic layer was dried (MgSO4) and
concentrated to give a yellow oil, which was solubilised in diethyl
ether (150 mL). LiAlH4 (780 mg, 20.50 mmol) was added to this
solution at 0 ◦C and the reacting mixture was stirred for 2 h
at rt and then poured into iced water and neutralized with aq.
10% HCl. The mixture was stirred at rt for 0.5 h and the organic
layer was separated. The aqueous layer was extracted twice with
ether (100 mL). The combined organic layers were washed with
sat. NaHCO3 (50 mL) and brine (50 mL), dried (MgSO4) and
concentrated. The residue was purified by flash chromatography
(petroleum ether–EtOAc from 7 : 1 to 6 : 1) to give compound 9
(4.10 g, 90%) as a colourless oil whose spectral properties were
in accordance with those previously reported.22
Experimental
All moisture-sensitive reactions were performed under a nitro-
gen atmosphere using oven-dried glassware. All solvents were
dried over standard drying agents and were freshly distilled
prior to use. Flash column chromatography was performed
on silica gel 60A C.C. (6–35 l). Reactions were monitored
by TLC on silica gel 60 F254 with detection by charring with
phosphomolybdic acid.
cis-5-Phenyl-2-cyclohexen-1-ol24 (10a). To a solution of 9
(500 mg, 2.91 mmol) and CeCl3·7 H2O (1.10 g, 2.91 mmol)
in methanol (30 mL) at 0 ◦C was added NaBH4 (120 mg,
2.91 mmol). The solution was stirred at 0 ◦C for 2.5 h, then
the solvent was removed under reduced pressure and the residue
was partitioned between water and EtOAc, the organic layer
was dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography (petroleum ether–EtOAc 7 : 1) to give
known24 10a (436 mg, 86%) as a white solid.
General procedure for the reactions between benzaldehyde and
primary allylic substrates 1 followed by HPLC analysis
A mixture of Pd(OAc)2 (11.2 mg, 0.05 mmol) and TPPTS
(142 mg, 0.25 mmol) in 5 mL of water was stirred for 30 min.
To 1 mL of this solution were added benzaldehyde (10.6 mg,
0.10 mmol), allylic substrate (0.20 mmol) and In (22.9 mg,
0.20 mmol) or InBr (38.9, 0.20 mmol). The resulting mixture was
stirred vigorously for the time indicated in the Tables. A solution
of anisole in CH3CN (1.2 mg mL−1, 2 mL) was added as well as
2 mL of MeOH. The mixture was centrifuged (15,000 tr min−1
for 5 min), 0.5 mL of the supernatant was diluted with 0.5 mL
of CH3CN and the solution was filtered through a 0.45 lm
syringe filter. A 20 lL aliquot of the solution was analysed
by HPLC (Hypersil C18, 125 × 4.6 mm, 5 lm; mobile phase:
CH3CN–H2O 65 : 35 at 1 mL min−1). The chromatograms were
integrated at 220 nm and the yields were deduced by comparison
with a standard curve obtained from dilutions of 2 (retention
time 9.2 min) and anisole (retention time 17.7 min).
cis-5-Phenyl-2-cyclohexen-1-yl acetate20 (11a). A solution of
10a (100 mg, 0.57 mmol), pyridine (2 mL) and acetic anhydride
(1 mL) was kept at rt overnight, then concentrated. The residue
was partitioned between CH2Cl2 and iced aq. 5% HCl. The
organic phase was washed with water, dried (MgSO4) and
concentrated to afford known20 11a (124 mg, 100%).
trans-5-Phenyl-2-cyclohexen-1-yl acetate21 (11b). To a solu-
tion of 10a (100 mg, 0.57 mmol), triphenylphosphine (228 mg,
0.86 mmol) and glacial acetic acid (42 lL, 0.75 mmol) in THF
(2 mL) was added dropwise DIAD (150 lL, 0.75 mmol) at
0 ◦C. After 5 min, the solution was concentrated and the residue
was purified by flash chromatography (petroleum ether–EtOAc
9 : 1) to give known21 11b (111 mg, 90%).
General procedure for the reactions between benzaldehyde and
primary allylic substrates 1 or secondary allylic substrate 6
followed by isolation of 2 or 7
Procedure for the reaction between benzaldehyde and 11a
The reaction mixture was prepared as indicated above in water
or water–EtOH (2 : 1) in the case of 6, generally on a 1 mmol
allylic substrate scale. After the time indicated in the Tables,
the reaction mixture was filtrated over a short pad of Celite,
extracted three times with ether (5 mL), the organic layer was
washed with aq. saturated NaHCO3 (10 mL) and brine (10 mL),
dried (MgSO4) and concentrated. The residue was purified by
flash chromatography (petroleum ether–EtOAc 7 : 1) to give 2
from 1 or 7 from 6.
A mixture of Pd(OAc)2 (22.4 mg, 0.10 mmol) and TPPTS
(284 mg, 0.50 mmol) in a 2 : 1 water–EtOH mixture (10 mL) was
stirred for 30 min. To this solution were added benzaldehyde
(106 mg, 1.00 mmol), 11a (432 mg, 2.00 mmol) and In (684 mg,
2.00 mmol). The resulting mixture was stirred vigorously at 50◦C
for 24 h. The reaction mixture was filtered over a short pad of
Celite, extracted three times with ether (10 mL), the organic
layer was washed with aq. saturated NaHCO3 (20 mL) and
brine (20 mL), dried (MgSO4) and concentrated. The residue
was purified by flash chromatography (petroleum ether–EtOAc
from 10 : 1 to 6 : 1) to give first syn-12a (145 mg, 55%).
General procedure for the recycling experiments
A mixture of Pd(OAc)2 (11.2 mg, 0.05 mmol or 22.4 mg,
0.10 mmol) and TPPTS (142 mg, 0.25 mmol or 284 mg,
0.50 mmol) in 5 mL of water–EtOH (2 : 1) was stirred for 30 min.
To this solution were added benzaldehyde (53 mg, 0.50 mmol),
allyltrifluoroacetate (154 mg, 1.00 mmol) and InBr (194 mg,
1.00 mmol). The resulting mixture was stirred vigorously for
the time indicated in Table 4 and filtered over a short pad of
Celite, extracted three times with ether (5 mL), the organic layer
was treated as described above. The aqueous phase was reused by
IR mmax cm−1, NaCl: 3404, 3061, 3026, 2915, 1601, 1493, 1431,
1020, 948, 910, 765, 699. EIMS 70 eV, m/z (%): 246 (11, M −
H2O), 172 (3), 158 (19), 155(19), 129 (6), 115 (8), 107 (100), 104
(31), 91 (18), 79 (17), 77 (11), 68 (3). dH (250 MHz, CDCl3) 1.84
(1 H, ddd, J6ax,6eq 17.5, J6ax,5 11.5, J6ax,1 6.0 Hz, H6 axial), 1.91 (1
ꢀ
H, d, J1 ,OH 2.5 Hz, OH), 2.10–2.25 (2 H, m, H6 equatorial, H4
axial), 2.36 (dddd, J4ax,4eq 18.0 Hz, J4eq,3 = J4eq,5 5.0, J4eq,2 1.5 Hz,
H4 equatorial), 2.50–2.62 (1 H, m, H1), 2.99 (1 H, dddd, J4ax,5
9.0, J4eq,5 5.0 Hz H-5), 4.68 (1 H, dd, J1,1 7.5 Hz, H1ꢀ), 5.34–5.42
ꢀ
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0
1 3 7 9

View Article Online
(m, 1 H, H2), 5.92 (1 H, dddd, J2,3 10.0, J3,4ax 2.5, J1,3 2.0 Hz,
H3), 7.18–7.41 (10 H, m, Ar). dC (100 MHz, CDCl3) 30.6 (C6),
32.7 (C4), 36.0 (C1), 42.0 (C5), 76.8 (C1ꢀ), 126.0–129.9 (C2, C3,
Ar); elemental analysis found C 86.46, H 7.66, C19H20O requires
C 86.32, H 7.63%.
7 S. Araki, T. Kamei, T. Hirashita, H. Yamamura and M. Kawai, Org.
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Ibuka, Tetrahedron Lett., 2001, 42, 1725.
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11 L. A. T. Cleghorn, I. R. Cooper, R. Grigg, W. S. MacLachlan; and
V. Sridharan, Tetrahedron Lett., 2003, 44, 7969–7973.
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2003, 5, 775–779.
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1981; (b) D. Sinou, Bull. Soc. Chim. Fr., 1987, 3, 480–486.
14 See for instance: (a) S. Jayasree, A. Seayad, B. R. Sarkar and
R. V. Chaudhari, J. Mol. Catal. A: Chem., 2002, 181, 221–235;
(b) M. Haumann, H. Koch, P. Hugo and R. Schoma¨cker, Appl.
Catal., A, 2002, 225, 239–249; (c) L. W. Francisco, D. A. Moreno
and J. D. Atwood, Organometallics, 2001, 20, 4237–4245; (d) C.
Dupuis, K. Adiey, L. Charruault, V. Michelet, M. Savignac and J. P.
Geneˆt, Tetrahedron Lett., 2001, 42, 6523–6526; (e) G. Verspui, G.
Papadogianakis and R. A. Sheldon, Catal. Today, 1998, 42, 449–458;
(f) C. Amatore, E. Blart, J. P. Geneˆt, A. Jutand, S. Lemaire-Audoire
and M. Savignac, J. Org. Chem., 1995, 60, 6829–6839; (g) E. Blart,
J. P. Geneˆt, M. Safi, M. Savignac and D. Sinou, Tetrahedron, 1994,
50, 505–514.
Eluted second was syn-12b contaminated by 5% of syn-12a
(8 mg, 3%).
dH (250 MHz, CDCl3) 1.70 (ddd, 1 H, J6ax,6eq = J6ax,5 = J6ax,1
=
12.0 Hz, H6 axial), 1.85–2.05 (m, 2 H, H4a and H6 equatorial),
2.12–2.40 (m, 2 H, H1 and H4b), 2.72–2.90 (m, 2 H, H5 and
ꢀ
OH), 4.72 (d, 1 H, J1,1 5.5 Hz), 5.55–5.65 (m, 1 H, H2), 5.90–
6.00 (m, 1 H, H3), 7.20–7.40 (m, 20 H, Ar). dC (100 MHz, CDCl3)
29.7 (C6), 32.3 (C4), 36.2 (C1), 45.0 (C5), 77.3 (C1ꢀ), 126.0–130.0
(C2, C3, Ar).
Procedure for the reaction between benzaldehyde and 11b
Benzaldehyde (106 mg, 1 mmol) was coupled with 11b (432 mg,
2 mmol) as described for 11a. The residue was purified by flash
chromatography (petroleum ether–EtOAc from 20 : 1 to 6 : 1)
to give first 1325 (40 mg, 10%) as an inseparable trans : cis 4.5
: 1 mixture, then syn-12a (13.4 mg, 5%), and a 1 : 1 mixture of
syn-12a and syn-12b (86.5 mg, 33%). Eluted last was 1024 (70 mg,
20%) as an inseparable trans : cis 4.5 : 1 mixture.
15 (a) W. K. Kohlpaintner, R. W. Fischer and B. Cornils, Appl. Catal.,
A, 2001, 221, 219–225; (b) B. Cornils, W. A. Herrmann and R. W.
Eckl, J. Mol. Catal. A: Chem., 1997, 116, 27–33; (c) B. Cornils and
E. G. Kuntz, J. Organomet. Chem., 1995, 502, 177–186.
16 I. P. Beletsaya, A. V. Cheprakov, in Organic Synthesis in Water, ed
P. A. Grieco, Blackie Academic & Professional London, 1998; ch. 5,
pp. 141–222.
Acknowledgements
This work was supported by the CNRS and the Ministe`re de
l’Education Nationale de l’Enseignement Supe´rieur et de la
Recherche.
17 J. Cossy, L. Tresnard and D. G. Pardo, Eur. J. Org. Chem., 1999,
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1 3 8 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 7 5 – 1 3 8 0