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L. Diab et al. / Tetrahedron Letters 49 (2008) 5186–5189
Table 2
Palladium-catalyzed methoxycarbonylation of styrene using enantiomerically pure chiral ligands
Entry
Catalyst
T (°C)
Time (h)
Conversion (%)
Yield (%)
b/l
ee (%)
14
15a
16
17
18
19
20
Pd(OAc)2/(S)-1
Pd(OAc)2/(R)-1
Pd(OAc)2/(S)-1
Pd(OAc)2/(S)-2
Pd(OAc)2/(S)-2
Pd(OAc)2/(S)-3
Pd(OAc)2/5
50
50
25
50
30
55
50
24
24
48
24
50
24
48
83
60
20
50
89
95
14
80
58
19
42
87
88
8
98/2
99/1
99/1
99/1
98/2
97/3
84/16
10
13
17
7.5
13
2
13
Conditions: substrate = styrene; substrate/catalyst = 50; L/Pd = 1; acid (CH3SO3H)/catalyst = 7.5; acid/substrate = 0.015; 20 bar CO in MeOH.
a
Substrate/catalyst = 50; L/Pd = 2.
lectivity was recorded giving predominantly the branched ester
(88%) although with lower activity and chemoselectivity (entry
11). These results are another example of unusual regioselectivity
in favour of branched ester using a bidentate ligand as already
reported only to the best of our knowledge by van Leeuwen
et al.6 and Tanaka et al.7 Using ligand 4 or dppe, which have the
same length of the bridge between the two phosphorus atoms,
different chemoselectivities are observed (entries 11 and 12,
respectively). Therefore, such results cannot be attributed only to
the size of the chelate ring on the complex,5a but probably to the
electronic effect on phosphorus atoms.6,7
Coming back to the results observed with the P,S ferrocenyl li-
gands 1–3, we could envisage that these ligands, if they are biden-
tate ligands in this catalytic reaction, primarily affect the catalytic
outcome through the electronic effect of the sulfur atom, since the
use of dppp which has the same length of the carbon chain be-
tween the coordinating atoms than ligands 1–3 leads to completely
different regioselectivities (entries 11 and 12 vs entry 13).
Stereoelectronic effects of the ligands on the methoxycarbony-
lation reaction are still to be understood and further investigations
ought to be conducted.
Because of these excellent results in terms of regioselectivity,
we decided to explore the asymmetrical version of this reaction
by using ligands 1–3 and 5 which can be easily obtained in enan-
tiomerically pure forms. Due to the importance of enantiomerically
pure esters or derivatives, the development of enantioselective alk-
oxycarbonylation reactions are of great interest. However, if good
regioselectivities or enantioselectivities6,7,14,16 have already been
reported, to the best of our knowledge, no catalytic systems pos-
sess both types of selectivities. The results are listed in Table 2.17
Enantiomerically pure ferrocenyl ligands 1 have been tried in
the same conditions as described above (50 °C, 20 bar CO, 24 h)
(Table 2, entry 14): the catalytic systems produced esters in good
yields (80%) with excellent chemoselectivity (96%), regioselectivity
(98%) but low enantiomeric excess (10%) as usually observed for
highly regioselective systems.6,7,14,16 The enantiomeric excess can
be improved up to 13% using an excess of ligand (L/Pd = 2, Table
2, entry 15) or 17% decreasing the temperature down to 25 °C
(Table 2, entry 16). With other ferrocenyl ligands 2 and 3, good
yields, excellent chemoselectivities and regioselectivities can also
be obtained (Table 2, entries 17 and 18). However, enantioselectiv-
ities are lower than using 1.
isomer are observed even in presence of the bidentate biphosp-
holes 4 and 5. However, enantiomeric excesses are moderate (up
to 17%).
Taking advantage of the high modularity of ferrocenyl P,S li-
gands and of biphospholes, we will try to improve enantioselectiv-
ities in this reaction by modulating the stereoelectronic properties
of the ligands in both families.
Acknowledgements
The Ministère de l’Education Nationale, de la Recherche et de la
Technologie is gratefully acknowledged for a research grant to L.D.
We thank the Institut National Polytechnique de Toulouse (ENSI-
ACET) and the CNRS for financial support.
References and notes
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2718–2719; (b) van Leeuwen, P. W. N. M.; Zuideveld, M. A.; Swennenhuis, B. H.
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With phosphole-based ligand 5,18 good regioselectivity (84%)
and significant enantioselectivity (ee = 13%) are observed but the
catalytic activities and the chemoselectivities remain at a low level
(Table 2, entry 20).
In this study, we have shown that palladium complexes of fer-
rocene- and biphosphole-based ligands can catalyze the methoxy-
carbonylation of styrene in rather mild conditions (T = 50 °C,
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Malacea, R.; Routaboul, L.; Manoury, E.; Daran, J.-C.; Poli, R. J. Organomet. Chem.
2008, 693, 1469–1477; (c) Diab, L.; Daran, J.-C.; Gouygou, M.; Manoury, E.;
Urrutigoïty, M. Acta Crystallogr., Sect. C 2008, 64, m43–m45.
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Organometallics 2000, 19, 3736–3739; (b) Tissot, O.; Gouygou, M.; Dallemer, F.;
Daran, J.-C.; Balavoine, G. G. A. Angew. Chem., Int. Ed. 2001, 40, 1076–1078; (c)
Mourgues, S.; Serra, D.; Lamy, F.; Vincendeau, S.; Daran, J.-C.; Manoury, E.;
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PCO = 20 bar, 15 mol % of promoting acid per substrate molecule).
Indeed, esters can be obtained in good yields (up to 92%). In addi-
tion, high regioselectivities (up to 99%) in favour of the branched