Palladium-tetraphosphine catalysed allylic substitution in water

Article abstract of DOI:10.1016/S0040-4039(01)00174-5

The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl (C₃H₅)]₂ system catalyses allylic amination in water with very high substrate/catalyst ratio in good yields. A turnover number of 980 000 can be obtained for the addition of dipropylamine to allyl acetate in the presence of this catalyst.

Full text of DOI:10.1016/S0040-4039(01)00174-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2313–2315
Palladium-tetraphosphine catalysed allylic substitution in water
Marie Feuerstein, Dorothe´e Laurenti, Henri Doucet* and Maurice Santelli*
Laboratoire de Synthe`se Organique associe´ au CNRS, Faculte´ des Sciences de Saint Je´roˆme,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 17 December 2000; accepted 25 January 2001
Abstract—The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C3H5)]2 system catalyses allylic amination
in water with very high substrate/catalyst ratio in good yields. A turnover number of 980 000 can be obtained for the addition
of dipropylamine to allyl acetate in the presence of this catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
Palladium allylic substitution is probably the most
widely employed palladium methodology in organic
synthesis.1 The use of water as solvent for organic
synthesis is very attractive for environmental, economi-
cal and safety reasons. A few years ago, Genet et al.
and Sinou et al. reported an efficient method for per-
forming the allylic substitution2,3 in water. They
employed palladium complexes associated with sul-
fonated phosphine ligands4 in a two-phase aqueous–
organic medium. Recently, Kobayashi et al. and Sinou
et al. reported that palladium-catalysed alkylation also
occurred in water in the presence of non-water-soluble
ligands, but the addition of surfactants such as
cetyltrimethylammonium bromide was required.5,6
However, these procedures suffer from high catalyst
loading and some of them from high temperatures and
long reaction times. Moreover, few results have been
obtained so far for allylic amination in water.
The nature of the phosphine ligand on complexes has a
tremendous influence on the stability of the catalysts
and on the rate of catalysed reactions. In order to find
more stable and more efficient palladium catalysts, we
have decided to study the influence of the new tetra-
podal
phosphine
ligand,
cis,cis,cis-1,2,3,4-tetra-
kis(diphenylphosphinomethyl)cyclopentane or Tedicyp
1 (Fig. 1),7 in which the four diphenylphosphinoalkyl
groups are stereospecifically bound to the same face of
the cyclopentane ring, in several catalysed reactions.
We have reported recently that the complex formed by
association of 1 with [PdCl(C3H5)]2 is an extremely
efficient catalyst for allylic amination.8 For example, a
Figure 1.
Scheme 1.
Keywords: tetraphosphine; palladium; water; allylic amination; allylamine; allylacetate.
* Corresponding authors. Fax: 04 91 98 38 65; e-mail: henri.doucet@lso.u-3mrs.fr; m.santelli@lso.u-3mrs.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00174-5

2314
M. Feuerstein et al. / Tetrahedron Letters 42 (2001) 2313–2315
Table 1. Palladium catalysed allylic alkylation of secondary amines 6–11 in water10
Allyl acetate
Nucleophile
Product (major isomer)
Ratio a/b
Ratio substrate/catalyst
Yield (%)
2
2
2
2
3
3
3
3
4
4
4
4
4
5
6
7
8
9
10
8
9
11
6
10
8
11
9
15
16
17
18
–
–
–
1 000 000
1000
98a,d,f
97b
100 000
100 000
10 000
10 000
10 000
10 000
1000
1000
1000
1000
1000
80c,d
96b,d
100a,e
100a,d
62b
–
19a
20a
21a
22a
23a
24a
25a
26a
27a
28
99/1
100/0
85/15
84/16
99/1
98/2
100/0
95/5
98/2
–
97b
85a
85a,e
97b
95a
91b
6
100
45b
Conditions: catalyst: [Pd(C3H5)Cl]2/1 1/2,9 H2O, 25°C, 20 h.
a Allyl acetate: 1 equiv., amine: 2 equiv.
b Allyl acetate: 2 equiv., amine: 1 equiv., K2CO3: 1 equiv.
c Water saturated with NaCl.
d 55°C.
e 40 h.
f 240 h.
Scheme 2.
TON (turnover number) of 680 000 for the addition of
dipropylamine 6 to allyl acetate 2 had been obtained
when the reaction was conducted in THF. In this paper
we wish to describe the results obtained in water for the
catalysed allylic amination using 1 as a ligand. We
could expect that if a small amount of this complex is
soluble in the reaction mixture when water is used as
the solvent, and if this catalyst is water-stable, some
addition product should be observed.
much slower reaction rate in water than in THF: 4 and
99% yields were observed, respectively. However, if this
reaction was conducted in brine instead of water the
conversion rose to 80%. With primary amines, we
obtained mixtures of monoalkylation and dialkylation
products (Scheme 2, Table 2). Benzylamine 12 led to
the dialkylation product 29b in 96% conversion and
95% selectivity in the presence of 0.001% catalyst. The
alkylation rate of phenylethylamine 13 and cyclohexyl-
amine 14 is slower but a high selectivity in favour of the
dialkylation products 30b and 31b was observed.
First, we tried with the substrates which were the most
reactive when the reaction was performed in THF:
addition of dipropylamine 6 to allyl acetate 2. Surpris-
ingly, we observed that the reaction rate was in fact
slightly higher in water than in THF. The complex
formed by association of Tedicyp and [PdCl(C3H5)]2
seemed to be very water-stable. A conversion of 98%
(Scheme 1, Table 1) was observed when a substrate/cat-
alyst ratio of 1 000 000 was used. In THF the conver-
sion was 68% in the same conditions. Moreover, this
reaction was carried out in the absence of surfactants.
In the presence of cetyltrimethylammonium bromide a
slower reaction rate and a lower conversion was
obtained. A similar tendency was observed for the
alkylation of morpholine 9 by allyl acetate 2. In the
presence of 0.001% catalyst, the conversion was 96% in
water and 57% in THF. On the other hand, an amine
with long alkyl groups such as dioctylamine 8 led to a
Next we tried to evaluate the scope and limitations of
Tedicyp–palladium complex for this reaction, so we
investigated the allylation of amines with substituted
allyl acetates. We noted good regio- and stereoselectiv-
ity for the amination of cinnamyl acetate 3 in favour of
the linear E isomer. When we used cinnamyl acetate 3
in the presence of 0.1% catalyst, high yields and high
selectivity were obtained for the alkylation of dioctyl-
amine 8 and diallylamine 10. The regioselectivity of the
addition of cyclic amines 9 and 11 was slightly lower;
15% and 16 of the branched products 21b and 22b were
obtained. High selectivity was also observed for the
addition of 6, 8, 9 and 10 to (E)-hex-2-en-1-yl acetate 4,
however, 5% of the branched isomer was obtained with
pyrrolidine 11. A similar selectivity was observed in
THF. Much lower TON was observed in the course of

M. Feuerstein et al. / Tetrahedron Letters 42 (2001) 2313–2315
2315
Table 2. Palladium catalysed allylic alkylation of primary amines 12–14 in water
Allyl acetate
Nucleophile
Product (major isomer)
Ratio a/b
Ratio substrate/catalyst
Yield (%)
2
2
2
3
3
4
12
13
14
12
14
14
29b
30b
31b
32a
33a
34a
5/95
3/97
100 000
1000
1000
1000
1000
96b,c
96b
1/99
100b
96a
99/1d
99/1d
7/93
87a
1000
94b
a,b
Conditions: catalyst: [Pd(C3H5)Cl]2/1 1/2,9 H2O, 25°C, 20 h. For
see Table 1.
c 55°C.
d For compounds 32 and 33, 4% of the branched isomer of the mono addition product was also observed.
the amination of hindered 3-acetoxy-1,3-diphenyl-1-
propene 5.
Springer: Berlin, 1999, p. 833; (d) Malleron, J.-L.; Fiaud,
J.-C.; Legros, J.-Y.; Handbook of Palladium Catalyzed
Organic Reaction; Academic Press: London, 1997.
2. For a review on allylic amination: Johannsen, M.; Jor-
gensen, K. Chem. Rev. 1998, 98, 1689.
3. For a review on palladium catalysed reactions in aqueous
medium: Genet, J.-P.; Savignac, M. J. Organomet. Chem.
1999, 576, 305.
4. (a) Genet, J.-P.; Blart, E.; Savignac, M. Synlett 1992, 715;
(b) Safi, M.; Sinou, D. Tetrahedron Lett. 1991, 32, 2025;
(c) Blart, E.; Genet, J.-P.; Safi, M.; Savignac, M.; Sinou,
D. Tetrahedron 1994, 50, 505; (d) Lemaire-Audoire, S.;
Blart, E.; Savignac, M.; Pourcelot, G.; Genet, J.-P.;
Bernard, J.-M. Tetrahedron Lett. 1994, 35, 8783.
5. Rabeyrin, C.; Nguefack, C.; Sinou, D. Tetrahedron Lett.
2000, 41, 7461.
In conclusion, the Tedicyp–palladium complex
obtained by addition of Tedicyp to [Pd(C3H5)Cl]2 pro-
vides a convenient catalyst for the allylic amination
reaction in water. This catalyst seems to be very water-
stable. This stability probably comes from the presence
of the four diphenylphosphinoalkyl groups stereospe-
cifically bound to the same face of the cyclopentane
ring. All four phosphines probably cannot bind at the
same time to the same palladium centre, but the pres-
ence of these four phosphines on the ligand close to the
metal centre along with steric factors seems to increase
the coordination of the ligand to the palladium com-
plex. In the presence of this catalyst the allylic substitu-
tion reaction can be performed in water with as little as
0.0001% catalyst. This procedure represents an environ-
mentally friendly method for the preparation of allylic
compounds. Further applications of this ligand will be
reported in due course.
6. Kobayashi, S.; Lam, W.; Manabe, K. Tetrahedron Lett.
2000, 41, 6115.
7. Laurenti, D.; Feuerstein, M.; Pe`pe, G.; Doucet, H.; San-
telli, M. J. Org. Chem. 2001, 66, 000.
8. Feuerstein, M.; Laurenti, D.; Doucet, H.; Santelli, M.
Chem. Commun. 2001, 43–44.
9. The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-
cyclopentane/[PdCl(C3H5)]2 complex was prepared by
stirring under argon the tetraphosphine 18 (14 mg, 16.2×
10−3 mmol) with [PdCl(C3H5)]2 (3 mg, 8.1×10−3 mmol) in
THF (10 mL) for 10 minutes at room temperature fol-
lowed by evaporation of the solvent. 31P NMR (162
MHz, CDCl3) l 25 (w=80 Hz), 19.4 (w=110 Hz); 31P
NMR (162 MHz, H2O–pyrrolidine) l 14 (w=600 Hz).
10. As a typical experiment the reaction of (E)-hex-2-en-1-yl
acetate 4 (0.33 g, 2.3 mmol) and dioctylamine 8 (1.4 mL,
4.6 mmol) at 50°C for 20 h in distilled water (2 mL) in
the presence of the Tedicyp–palladium complex (2.3×10−3
mmol) under argon affords the corresponding addition
product 25a after addition of an NaOH solution, extrac-
tion with ether, drying over MgSO4, evaporation and
filtration on silica gel (ether/pentane: 1/9) in 97% (0.718
g) isolated yield.
Acknowledgements
We thank the CNRS for providing financial support.
M.F. and D.L. are grateful to the MEN for a grant.
References
1. For reviews on palladium catalysed allylic substitution
reactions: (a) Hayashi, T. In Catalytic Asymmetric Syn-
thesis, Ojima, I., Eds.; VCH: New York, 1993, p. 325; (b)
Tsuji, J. Palladium Reagent and Catalysis, Innovation in
Organic Synthesis; Wiley: New York, 1995; (c) Pfaltz, A.;
Lautens, M. Comprehensive Asymmetric Catalysis II,
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.;
.