First enantioselective allylic etherification with phenols catalyzed by chiral ruthenium bisoxazoline complexes

Article abstract of DOI:10.1039/b406039c

Regio- and enantioselective substitution of cinnamyl chloride by phenols has been achieved with up to 82% enantiomeric excess, using a ruthenium catalyst prepared from [Cp*(CH₃CN)₃Ru] [PF₆] and a chiral bisoxazoline ligand.

Full text of DOI:10.1039/b406039c

First enantioselective allylic etherification with phenols catalyzed by
chiral ruthenium bisoxazoline complexes
Mbaye D. Mbaye, Jean-Luc Renaud,* Bernard Demerseman and Christian Bruneau*
Institut de Chimie, UMR 6509, Organométalliques et Catalyse, Université de Rennes 1, Campus de
Beaulieu-35042, Rennes, Cedex, [France]. E-mail: christian.bruneau@univ-rennes1.fr;
jean-luc.renaud@univ-rennes1.fr; Fax: 33(0)223236939; Tel: 33(0)223236283
Received (in Cambridge, UK) 22nd April 2004, Accepted 1st June 2004
First published as an Advance Article on the web 2nd July 2004
Regio- and enantioselective substitution of cinnamyl chloride by
phenols has been achieved with up to 82% enantiomeric excess,
using
a
ruthenium
catalyst
prepared
from
[Cp*(CH3CN)3Ru][PF6] and a chiral bisoxazoline ligand.
Allylic aryl ethers are suitable precursors for the Claisen rearrange-
ment and useful intermediates for access to biologically active
natural compounds.1 They have been prepared via palladium-
catalyzed allylation of phenols2,3 and the stereospecificity of the
allylic etherification has been demonstrated with catalyst pre-
cursors based on palladium,4 rhodium,5 and ruthenium.6 Enantiose-
lective allylations of phenols have been successfully performed
with palladium catalysts containing chiral bis-diphenylphosphino-
benzamide ligands7,8 and has provided elegant routes to the
synthesis of optically active natural compounds.8 Recently, an
iridium catalyst containing a chiral monophosphoramidite ligand
has revealed a high efficiency for the enantioselective etherification
of phenoxides with allylic carbonates.9 Ruthenium catalysts are
also known to promote the regioselective formation of chiral
branched compounds via allylic substitution from unsymmetrical
carbonates,10 but apart from the C–C bond formation from
1,3-diphenyl-2-propenyl ethyl carbonate and sodiomalonate deriv-
atives in the presence of planar-chiral cyclopentadienylruthenium
catalysts,11 no example of enantioselective substitution of achiral
allylic derivatives has been reported.
Fig. 1
line ligand in acetone led to poor regioselectivities, and the
branched ether 2 was merely obtained as a racemate. Enantiose-
lectivity of the allylic etherification was reached when the reactions
were carried out at 0 °C (Table 1).† Decreasing the temperature
below 0 °C does not improve the regio- or the enantioselectivity.
Table 1 Influence of the nature of the bisoxazoline ligand on the
etherification of cinnamyl chloride with phenola
Selectivity
Ligand
Conversion (%)b (2/3)b
e.e.(%)c,d
4
5
6
7
8
82
70
76
38
70
9/1
2/1
7.5/1
5/1
8/1
27 (R)
77 (R)
7.5 (S)
0
We wish to report that new catalytic systems based on chiral
dinitrogen chelating ligands and a pentamethylcyclopentadienylru-
thenium moiety provide the first examples of ruthenium-catalyzed
regio- and enantioselective etherification of allylic chlorides with
phenols.
10 (S)
a conditions : 0.75 mmol of phenol, 0.75 mmol of K2CO3, 0.5 mmol of
cinnamyl chloride 1, 0.015 mmol of [Cp*Ru(CH3CN)3][PF6] and ligand (3
mol%) in 4 mL of acetone, 0 °C, 40 h. b Determined by 1H NMR
spectroscopy. c Determined by HPLC. d Absolute configuration of the
products were established by correlation with previous data.9
We have previously reported that ruthenium complexes contain-
ing chelating dinitrogen ligands such as bis-imines12 or 2,2A-
bipyridines13 are useful catalysts for the regioselective nucleophilic
substitution of unsymmetrical allylic carbonates. Of peculiar
interest, the study of [Cp*(bipy)(CH3CN)Ru][PF6]-catalyzed reac-
Among the chiral bisoxazolines, it appeared that the enantiose-
lectivity was enhanced by the presence of a phenyl group at the
C(4)-position of the oxazoline rings (Table 1, Fig. 1). Thus, ligands
4 and 5 provided moderate to good enantioselectivities (27 and
77%, respectively), whereas low enantioselectivities were obtained
from ligands 6–8, with Me, iPr or tBu groups as substituents at the
C(4)-position. Furthermore, the additional presence of a phenyl
group at the C(5)-position in 5 (as compared to 4) resulted in a
markedly enhanced enantioselectivity (77 e.e. with 5 vs. 27% e.e.
with 4).
3
tions emphasized the key role of [Cp*(h -allyl)(bipy)Ru(IV)]2+
intermediates, still bearing a dinitrogen chelating bipyridine ligand,
in the catalytic process.13 More recently, we have also shown that
the reaction of cinnamyl chloride 1 with phenols and potassium
carbonate in the presence of [Cp*(CH3CN)3Ru][PF6] as catalyst,
regioselectively afforded the allyl aryl ethers 2–3 in a branched :
linear ratio higher than 40 : 1 (Scheme 1).14
Both regioselectivity and enantioselectivity of the O-allylation of
phenol by cinnamyl chloride in the presence of ligand 5 were found
to be dependent on the nature of the solvent (Table 2). Coordinating
solvents (acetone, acetonitrile, THF) led to good enantiomeric
excesses (63–80%) but with moderate regioselectivities (2–2.5/1).
Dichloromethane provided a significantly increased regioselectiv-
ity (6.5/1) but a lower enantioselectivity (53%). Finally, good
regioselectivities (4/1) and satisfactory enantioselectivities
(70–75%) were reached when THF–CH2Cl2 (1 : 1) or acetone–
CH2Cl2 (1 : 1) mixtures were used as solvent.
The scope of the allylic substitution of cinnamyl chloride 1 by
para-substituted phenols catalyzed by ruthenium complexes in the
presence of K2CO3 was studied in acetone at 0 °C in the presence
of the bisoxazoline 5 (Table 3). Very good conversions and
enantioselectivities were obtained, which showed that the catalyst
Scheme 1
These results provided impetus to study the enantioselective
reaction in the presence of chiral dinitrogen ligands. Our first
attempts with enantiomerically pure bis-imines were unsuccessful.
The use of bisoxazolines (See Fig. 1) which are efficient chiral
ligands in many asymmetric catalytic reactions, was then investi-
gated.15
At room temperature, the reaction of 0.5 mmol of cinnamyl
chloride with 0.75 mmol of phenol in the presence of 0.015 mmol
(3 mol%) of [Cp*Ru(CH3CN)3][PF6] and 0.015 mmol of bisoxazo-
1870
C h e m . C o m m u n . , 2 0 0 4 , 1 8 7 0 – 1 8 7 1
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 4

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Table 2 Solvent effects in allylic etherification of phenola
The authors wish to thank the European Union COST Pro-
gramme D24/0005/02 for support.
Conversion
(%)b
Selectivity
(2/3)b
Solvent
e.e.(%)c
Notes and references
† After stirring 0.015 mmol (3 mol%) of [Cp*Ru(CH3CN)3]PF6 and 0.015
mol (3 mol%) of bisoxazoline ligand in acetone at room temperature for one
hour, 0.75 mmol of potassium carbonate and 0.5 mmol of cinnamyl chloride
were added and the mixture was cooled to 0 °C. After 15 min., 0.75 mmol
of phenol was added and the mixture was stirred at 0 °C for 40 hours, then
Acetone
Acetonitrile
THF
CH2Cl2
Acetone/CH2Cl2
THF/CH2Cl2
70
88
88
70
96
90
2/1
77
63
80
53
70
75
2.2/1
2.5/1
6.5/1
4/1
1
4/1
filtered on silica and concentrated. The resulting oil was analyzed by H
NMR spectroscopy and the enantiomeric excess was determined by
HPLC.
a conditions : 0.75 mmol of phenol, 0.75 mmol of K2CO3, 0.5 mmol of
cinnamyl chloride, 0.015 mmol of [Cp*Ru(CH3CN)3][PF6] and 5 (3 mol%)
1
in 4 mL of solvent, 0 °C, 40 h. b Determined by H NMR spectroscopy.
1 B. M. Trost and M. L. Crawley, Chem. Rev., 2003, 103, 2921.
2 (a) B. M. Trost and C. Lee, in Catalytic Asymmetric Synthesis, I. Ojima,
Ed., Wiley, 2000, pp. 593–649; (b) A. Pfaltz and M. Lautens in
Comprehensive. Asymmetric Catalysis, E. N. Jacobsen, A. Pfaltz, H.
Yamamoto, Eds.; Springer: Berlin, 1999, p. 833.
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c Determined by HPLC.
tolerated the presence of methoxy and chloro substituents at the
phenyl ring. Moreover, changing the electronic properties of the
substituted phenol has little influence on the enantioselectivity. On
the other hand, cinnamyl carbonate was found to be much less
reactive than 1.
Table 3 Allylic etherification of substituted phenolsa
Conversion
(%)b
Selectivity
(2/3)b
ArOH
e.e.(%)c,d
4-MeO–C6H4
4-Cl–C6H4
4-H–C6H4
75
96
70
2.2/1
1.6/1
2/1
81 (R)
82 (R)
77 (R)
a Conditions : 0.75 mmol of ArOH, 0.75 mmol of K2CO3, 0.5 mmol of
cinnamyl chloride 1, 0.015 mmol of [Cp*Ru(CH3CN)3][PF6] and 5 (3
mol%) in 4 mL of acetone, 0 °C, 40 h. b as determined by 1H NMR
spectroscopy. c Determined by HPLC. d Absolute configuration of the
products were established by correlation with previous data.9
9 F. Lopez, T. Ohmura and J. F. Hartwig, J. Am. Chem. Soc., 2003, 125,
3426.
In conclusion, we developed the first enantioselective allylic
etherification with phenols catalyzed by a system based on the
association of a (pentamethylcyclopentadienyl)ruthenium pre-
cursor and a chiral bisoxazoline. This catalytic system favoured the
formation of branched allyl aryl ethers starting from cinnamyl
chloride and provided good enantioselectivities with highly
substituted chiral bisoxazoline ligands. The scope of the method
when starting from other types of nucleophiles and other allylic
substrates, as well as the elucidation of the structure of the
ruthenium catalyst are now under investigation.
10 T. Kondo, H. Ono, N. Satabe, T. Mitsudo and Y. Watanabe,
Organometallics, 1995, 14, 1945.
11 Y. Matsushima, K. Onitsuka, T. Kondo, T. Mitsudo and S. Takahashi,
J. Am. Chem. Soc., 2001, 123, 10405.
12 J.-L. Renaud, C. Bruneau and B. Demerseman, Synlett, 2003, 408.
13 M. D. MBaye, B. Demerseman, J.-L. Renaud, L. Toupet and C.
Bruneau, Angew. Chem. Int. Ed., 2003, 42, 5066.
14 M. D. MBaye, B. Demerseman, J.-L. Renaud, L. Toupet and C.
Bruneau, Adv. Synth. Catal., 2004, 346, in press.
15 A. K. Ghosh, P. Mathivanan and J. Cappiello, Tetrahedron: Asymmetry,
1998, 9, 1.
C h e m . C o m m u n . , 2 0 0 4 , 1 8 7 0 – 1 8 7 1
1871