New development in the enantioselective ring opening of meso-epoxides by various chloride ion silicon sources catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base

Article abstract of DOI:10.1016/S0957-4166(00)00432-8

New developments in the enantioselective ring opening of meso-epoxides catalyzed by a chiral Lewis base have been achieved using various chloride ion silicon sources. Thus, the use of TMSCl led to enantioselectivities varying from 6 to 98% ee depending on

Full text of DOI:10.1016/S0957-4166(00)00432-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4441–4445
New development in the enantioselective ring opening
of meso-epoxides by various chloride ion silicon sources
catalyzed by an o-methoxyaryldiazaphosphonamide
Lewis base
S e´ bastien Reymond, Jean Michel Brunel* and G e´ rard Buono
Ecole Nationale Sup e´ rieure de Synth e` ses, de Proc e´ d e´ s et d’Ing e´ nierie Chimiques d’Aix Marseille, UMR CNRS 6516,
Facult e´ de St J e´ r oˆ me, Av. Escadrille Normandie Niemen, 13397 Marseille, Cedex 20, France
Received 11 October 2000; accepted 27 October 2000
Abstract
New developments in the enantioselective ring opening of meso-epoxides catalyzed by a chiral Lewis
base have been achieved using various chloride ion silicon sources. Thus, the use of TMSCl led to
enantioselectivities varying from 6 to 98% ee depending on the nature of the considered epoxide. © 2000
Elsevier Science Ltd. All rights reserved.
1
. Introduction
Since it establishes two contiguous stereogenic centers, the desymmetrization of meso-epoxides
appears to be a method of choice for producing valuable intermediates for the stereocontrolled
1
preparation of non-racemic chiral organic compounds. In this area, numerous asymmetric
methodologies have been developed using halide ions as nucleophiles leading to the synthesis of
2
enantiomerically enriched halohydrins. Recently, we have reported the synthesis of various
o-methoxyaryldiazaphosphonamide Lewis bases and their successful use in the asymmetrization
3
of meso-epoxides with silicon tetrachloride. Moreover, a beneficial secondary ligand interaction
effect has been demonstrated as well as the passage via a hexacoordinate stabilized silicon
4
intermediate. In the context of our studies, we report here the enantioselective ring opening of
meso-epoxides catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base using various
halide ion silicon sources.
*
Corresponding author. E-mail: brunel@spi-chim.u-3mrs.fr
0
957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00432-8

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S. Reymond et al. / Tetrahedron: Asymmetry 11 (2000) 4441–4445
2
. Results and discussion
Numerous silicon chloride compounds are now easily available and may constitute an
interesting alternative versus the use of silicon tetrachloride because of their lower reactivity and
their easier handling. On the basis of such considerations, we have investigated the use of such
reagents in the enantioselective ring opening of cyclooctene oxide in dichloromethane catalyzed
by 10 mol% of Lewis base 1. The results are summarized in Table 1.
Table 1
5
Enantioselective catalyzed ring opening of cyclooctene oxide using various chloride ion silicon sources
a
c
d
Entry
R R R SiCl
T (°C)
Time (h)
Yield (%)
E.e. (%)
1
2
3
1
2
3
4
5
6
7
8
9
MeSiCl3
PhSiCl3
−78
−78
4
4
73
61
80
\98
\98
34
48
20
86
60
64
56
e
C H SiCl
0
0
0
0
0
48
48
48
48
48
48
48
4
6
11
3
n-BuSiCl3
80
75
79
85
Ph SiCl2
2
MePhSiCl2
Me SiCl2
2
e
n-BuMe SiCl
0
0
83
2
PhMe SiCl
70
49
21
50
2
1
1
1
1
0
1
2
3
tert-BuMe SiCl
−78
−78
−78
0
60
\98
62
2
C H SiMe Cl
4
4
48
6
13
2
tert-BuPh SiCl
TMSCl
2
b
e
57
\98
a
b
c
Reactions performed on 1.2 mmol scale at −78°C using 1.5 equiv. of chloride ion silicon source.
Reaction performed using freshly distilled TMSCl.
Isolated yield after flash chromatography.
d
Ee determined by GC analysis using a Lipodex E column, the major enantiomer possessing (1R,2R) absolute
configuration.
e
No reaction occurred at −78°C.
Thus, whatever the nature of the source of chloride used, the formation of the expected
chlorohydrin was observed in isolated yields varying from 21 to 83%. Furthermore, the
enantiomeric excesses observed are highly chloride source dependent. Thus, enantiomeric
excesses (ee) up to 98% for (1R,2R)-2-chlorocyclooctan-1-ol were obtained only using MeSiCl3,
PhSiCl , C H SiMe Cl and Me SiCl (TMSCl) sources (Table 1, entries 1, 2, 11 and 13), whereas
3
6
13
2
3
low enantioselectivities have been measured in all the other cases. Nevertheless, the result
obtained using TMSCl as the chloride source appeared to be the most interesting in terms of
enantioselectivity due to its easy handling with respect to Me SiCl or PhSiCl .
3
3
3

S. Reymond et al. / Tetrahedron: Asymmetry 11 (2000) 4441–4445
4443
In this case, the experimental conditions have been optimized varying the nature of the
solvent, the temperature and the reaction time (Table 2).
Table 2
Enantioselective catalyzed ring opening of cyclooctene oxide using TMSCl as chloride ion silicon source
a
b
c
Entry
Solvent
T (°C)
Time (h)
Yield (%)
Ee (%)
1
2
3
4
5
6
CH Cl2
25
0
0
0
0
48
48
96
48
48
48
60
57
86
76
66
90
40
\98
70
34
56
70
2
CH Cl2
2
CH Cl2
2
d
CH Cl2
2
THF
CH CN
0
3
a
Reactions performed on 1.2 mmol scale at −78°C using 1.5 equiv. of freshly distilled TMSCl.
Isolated yield after flash chromatography.
Ee determined by GC analysis using a Lipodex E column, the major enantiomer possessing (1R,2R) absolute
b
c
configuration.
d
Reaction performed using 10 mol% of catalyst and 10 mol% of HMPA.
It clearly appears that CH CN is the best solvent in terms of chemical yield (Table 2, entry
3
2
, 90%), whereas only an enantioselectivity up to 70% ee has been encountered. On the other
hand, THF led to poor yield and low enantioselectivity (Table 2, entry 5, 66 and 56%,
respectively). The best enantiomeric excess up to 98% was obtained using CH Cl at 0°C, but in
2
2
this case the chlorohydrin has been isolated in only 57% yield (Table 2, entry 2).
Under these best experimental conditions in terms of enantioselectivity, a range of meso-epox-
ides have been subjected to the enantioselective ring opening reaction using TMSCl as the
chloride silicon source (Table 3).
In all cases, the expected chlorohydrins have been obtained in good yields varying from 60 to
8
5%. Nevertheless, poor enantiomeric excesses have been observed varying from 0 to 80%
depending on the nature of the epoxide. Thus, cis-stilbene oxide afforded the (2S,3S)-2-chloro-
,2-diphenylethan-1-ol in 60% yield and 80% ee. As an extension of this reaction, we have used
1
trimethylsilylbromide or trimethylsilyliodide in the enantioselective ring opening of meso-epox-
ides, but whatever the experimental conditions no significant enantioselectivity (up to 10% ee7)
has been detected whereas a total conversion into bromo- and iodohydrins has been achieved.
3
. Conclusion
In conclusion, new developments in the enantioselective ring opening of meso-epoxides
catalyzed by a chiral Lewis base have been achieved using various chloride ion silicon sources.
Further studies dealing with mechanistic features are under current investigations.

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S. Reymond et al. / Tetrahedron: Asymmetry 11 (2000) 4441–4445
Table 3
Catalytic asymmetric ring opening of various meso-epoxides using TMSCl as chloride silicon source
a
b
Entry
Epoxide
Yield (%)
85
Ee (%)
c
1
40
c
2
70
12
d
3
4
80
79
22
d
6
e
5
6
60
78
80
e
0
a
Reactions performed on 1.2 mmol scale at −78°C using freshly distilled TMSCl (1.5 equiv.).
Isolated yield after flash chromatography.
b
c
Ee determined by GC analysis using a Lipodex E column.
d
e
31
Ee determined by P NMR analysis using a chiral organophosphorus derivatizing agent (Ref. 6).
Ee determined by HPLC analysis on a Daicel Chiralcel OD-H column.
Acknowledgements
We thank CNRS for its financial support. S. Reymond acknowledges MENRT for a doctoral
fellowship.

S. Reymond et al. / Tetrahedron: Asymmetry 11 (2000) 4441–4445
4445
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. General procedure for the preparation of chiral chlorohydrins: To a stirred solution of catalyst 1 (0.1 equiv.) in
CH Cl or THF (6 mL) at −78°C under argon is added the desired chloride ion source (1 equiv.). After 5 min,
2
2
epoxide (1 equiv.) is added. After the addition is completed, the mixture was stirred at −78°C for 4 to 48 hours
depending on the nature of the chloride ion source) and then quenched by pouring into cold (−78°C), rapidly
stirring sat. NaHCO or 1/1 sat. KF/sat. KH PO (15 mL) and allowed to warm to rt. The resulting mixture was
(
3
2
4
extracted with CH Cl (2×15 mL) and the combined organic extracts were washed with water (10 mL), dried over
2
2
MgSO , filtered, and evaporated under reduced pressure. The residue is purified by silica gel chromatography.
4
6. Reymond, S.; Brunel, J. M.; Buono, G. Tetrahedron: Asymmetry 2000, 11, 1273.
7. The same reaction performed using trimethylsilylazide in the enantioselective ring opening of cyclohexene oxide at
room temperature for 2 days catalyzed by 1 led to the synthesis of the racemic azido alcohol in only 30% yield.
.