Asymmetric oxidation of silyl enol ethers using chiral dioxiranes derived from α-fluoro cyclohexanones

Article abstract of DOI:10.1016/S0040-4039(03)01388-1

Asymmetric oxidation of silyl enolethers derived from tetralone, 2-methyl-tetralone, propiophenone and deoxybenzoin using chiral dioxiranes generated in situ from oxone and new chiral α-fluorinated cyclohexanones or fructose-derived ketone have been studied. It was observed that tetrasubstituted silyl enolethers are poor substrates, that substitution at C8 of the fluoro-ketones has a significant effect on the enantioselectivities obtained and that the fructose-derived-ketone provides higher enantioselectivities. The absolute configuration of the major hydroxy ketones obtained can be rationalized using a spiro model proposed for epoxidation of olefins.

Full text of DOI:10.1016/S0040-4039(03)01388-1

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TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6523–6526
Asymmetric oxidation of silyl enol ethers using chiral dioxiranes
derived from a-fluoro cyclohexanones
A. Solladie´-Cavallo,a,* P. Lupattelli,a,b L. Jierry,a P. Bovicelli,c,* F. Angeli,c R. Antoniolettic and
A. Kleina
aLaboratoire de Ste´re´ochimie Organome´tallique associe´ au CNRS, ECPM/Universite´ L. Pasteur, 25 rue Becquerel,
67087 Strasbourg, France
bDipartimento di Chimica, Universita` degli studi della Basilicata, via N. Sauro 85, 85100 Potenza, Italy
cCNR, Istituto di Chimica Biomolecolare, Sez. Roma c/o Dip. Chimica, Universita` ‘La Sapienza’, Ple A. Moro 5, Roma, Italy
Received 2 April 2003; revised 3 June 2003; accepted 3 June 2003
Abstract—Asymmetric oxidation of silyl enolethers derived from tetralone, 2-methyl-tetralone, propiophenone and deoxybenzoin
using chiral dioxiranes generated in situ from oxone and new chiral a-fluorinated cyclohexanones or fructose-derived ketone have
been studied. It was observed that tetrasubstituted silyl enolethers are poor substrates, that substitution at C8 of the
fluoro-ketones has a significant effect on the enantioselectivities obtained and that the fructose-derived-ketone provides higher
enantioselectivities. The absolute configuration of the major hydroxy ketones obtained can be rationalized using a spiro model
proposed for epoxidation of olefins.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
83% ee by oxidation of silyl enolether 3 with the
chiral dioxirane (0.3 equiv.) derived from ketone 5,
we envisaged to oxidize the silyl enolether of 2-
methyl-1-tetralone (4) with chiral dioxiranes derived
from a-fluoro cyclohexanones 6–9, which had already
proved to be efficient for epoxidation of trans
olefins.4,5
During work on the synthesis of unnatural amino
acids1 we became interested in the synthesis of enan-
tiopure or enantioenriched 2-hydroxy-2-methyl-1-tetra-
lone 1.2 Because 2-hydroxy-1-tetralone 2 had already
been obtained by Shi3 in reasonable yield (70%) and
Keywords: fluoro cyclohexanone; dioxiranes; asymmetric oxidation; a-hydroxyketone.
* Corresponding authors. Tel.: +33 3 90 24 27 72; fax: +33 3 90 24 27 06; e-mail: cavallo@chimie.u-strasbg.fr
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01388-1

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Moreover, some discrepancies having appeared between
Shi’s and Adam’s results3,6 concerning the necessary
amount of chiral ketone 5 and values of yields and ee%
during oxidation of the silyl enolether 11t, this enol has
been re-examined as well as enol 3.
oxidation of trimethylsilyl enol ethers 3 and 4 provided
directly the desired hydroxyketone 1.
The enantiomeric purities of the hydroxy-ketones were
determined by chiral chromatography10 and the abso-
lute configuration through correlation of the signs of
the optical rotation with known compounds.11–13
We therefore present here the use of ketones 7–9 for
oxidation of silyl enolethers 3t, 10t and 11t, the use of
ketones 6 for oxidation of silyl enolethers 3, 3t, 4, 4t
and 10t and the use of Shi’s ketone 5 for oxidation of
silyl enol ethers 3, 4 and 10t (for comparison with
literature’s results).
The results are gathered in Table 1.
All fluoro ketones gave good to quantitative overall
yields in the desired a-hydroxy ketones 1, 2, 12 and 13
(Scheme 1 and Table 1). No lactones coming from
Baeyer–Villiger oxidation have been detected and the
ketones can be recovered through chromatography
after reaction although sometimes in low yield because
of the small amounts used.
2. Results
The ketones have been synthesized from commercially
available (+)-dihydrocarvone;5 they were obtained as
1/1 diastereomeric mixture (creation of a new chiral
carbon C8) and used without separation because we
had already shown during asymmetric epoxidation of
olefins that the configuration at C8 has no effect on the
enantioselectivity.5
The t-butyl silyl enol ether 3t derived from 1-tetralone,
which is a trans silyl enol ether, led to a lower enan-
tioselectivity than 10t and 11t which are cis silyl enol-
ethers (40–52% ee instead of 56–68% and 54–74% ee)
(Table 1). When the less hindered SiMe3 group is used,
a lower enantioselectivity was obtained (Table 1) lines
1/5 (67/33 versus 75/25) and lines 7/8 (53/47 versus
58/42). This has already been observed by Adam et al.
in the case of the silyl enol ethers derived from
phenylethylketone6 (54% ee with SiMe3 versus 82% ee
with SiMe2tBu).
The silyl enol ethers have been prepared in quantitative
yields after modification of the literature work-up.7,8
Oxidation9 of t-butyldimethylsilyl enolethers 3t, 4t, 10t
and 11t provided the silyl-protected hydroxy-ketones
which were then hydrolyzed using HCl 5%/MeOH into
the desired hydroxy-ketones 1, 2, 12 and 13 while
Among the new ketones 6–9, ketone 9 provided the
highest levels of enantioselectivity upon oxidation of 3t,
10t and 11t (Table 1, lines 4, 13, 17).
Table 1. Oxidation of silyl enol ethers 3t, 3, 4t, 4, 10t and 11t using 0.3 equiv. of ketone9
Silyl enol ether
Ketone
Yield (%)a
er (%)b conf.
Absol. (%)
ee (%)
Product
3t
3t
3t
3t
3
3
4t
4
6
7
8
9
6
5
6
6
5
6
7
8
9
5
7
8
9
90
90
90
95
74
65
78
90
62
90
90
67
95
73
71
83
90
75/25
70/30
74/26
76/24
67/33
87/13
58/42d
53/47d
53/47d
81/19
78/22
80/20
84/16
91/09
77/23
85/15
87/13
S (−)
S (−)
S (−)
S (−)
S (−)
R (+)
S (−)
S (−)
S (−)
S (−)
S (−)
S (−)
S (−)
R (+)
S (+)
S (+)
S (+)
50
40
48
52
34
74c
16
6
2
2
2
2
2
2
1
1
4
6
1
10t
10t
10t
10t
10t
11t
11t
11t
62
56
60
68
82e
54
70
74
12
12
12
12
12
13f
13
13
a Overall yield of the two steps (Scheme 1).
b Determined by GC using a Chiralcel OD column (hexane/i-PrOH, 9/1; 0.5 mL/min).
c With the same ketone 5, 70% yield and 83% ee were announced by Shi, cf. Ref. 3.
d Determined by NMR using Eu(hfc)3.
e With ketone 5, 80% yield and 90% ee were announced by Shi3 but Adam6 obtained 92% yield and 82% ee by using 3 equiv. of ketone instead
of 0.3 equiv.
f Both enantiomers are commercially available.

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A. Solladie´-Ca6allo et al. / Tetrahedron Letters 44 (2003) 6523–6526
6525
Scheme 1.
Ketone 5 appeared to be the most efficient with 74 and
82% ee in the cases of silyl enol ethers 3 and 11t,
respectively, compared with 34% ee from silyl enol
ether 3 using ketone 6 and 68% ee from silyl enolether
11t using ketone 9. However, while ketone 5 provides
the R-(+) configuration, ketone 9 provides the S-(−). It
is also worth noting that, using ketone 5, we repro-
duced better Adam’s ee results (82% ee for oxidation of
10t and not 92% as announced by Shi, cf. note e at the
bottom of Table 1).
over, the low enantioselectivity obtained for compound
2 from tetrasubstituted substrate 4 (R=Me, Fig. 1a)
can also be explained by the model with approaches
E-exo-I and E-exo-II being equally difficult (E-exo-I
disfavored because of steric repulsions and E-exo-II
disfavored because of n.n repulsions). Similarly the
(S)-absolute configuration obtained for compounds 12
and 13 with ketones 6–9 and trisubstituted substrates
10t and 11t (Fig. 1b) can be rationalized by the fact
that the E-exo-II approach is favored because of
absence of n.p repulsions between F and the aryl group
(compared to approach E-exo-I).
As seen in Figure 1a, the (S)-absolute configuration
obtained for compound 1 with ketones 6–9 and sub-
strates 3 (R=H, Fig. 1a) can be rationalized using the
classical spiro model,13 the equatorial E-exo-I approach
being favored because of absence of n.n repulsions
between F and O over the E-exo-II approach. More-
Because 10t and 11t differ only by the R group (Me or
Ph), which remains in the exo position (Fig. 1b), it is
expected that they should lead to almost identical enan-
tioselectivities as observed.
Figure 1.

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A. Solladie´-Ca6allo et al. / Tetrahedron Letters 44 (2003) 6523–6526
References
The observation that the ‘size’ of the silyl-protecting
group influence the enantioselectivity (compare lines 5
and 1 in Table 1) is consistent with the model and the
ring-exo approaches (Fig. 1a). The OSiR3 substituent,
which changes ‘size’, is in the endo position, position
which, being close to the chiral auxiliary, determines
the enantioselectivity.
1. (a) Solladie´-Cavallo, A.; Schwarz, J.; Mouza, C. Tetra-
hedron Lett. 1998, 39, 3861; (b) Solladie´-Cavallo, A.;
Martin-Cabrejas, L.; Caravatti, G. Tetrahedron: Asymme-
try 2001, 12, 967.
2. Solladie´-Cavallo, A.; Sedy, O.; Salisova, M.; Biba, M.;
Welch, C. J.; Nafie´, L. Tetrahedron: Asymmetry 2001, 12,
2703.
3. Zhu, Y.; Tu, Y.; Yu, H.; Shi, Y. Tetrahedron Lett. 1998,
39, 7819.
3. Conclusion
4. Solladie´-Cavallo, A.; Boue´rat, L.; Jierry, L. Eur. J. Org.
Chem. 2001, 4557.
5. Solladie´-Cavallo, A.; Jierry, L.; Lupattelli, P.; Bovicelli, P.,
submitted for publication.
6. Adam, W.; Fell, R. T.; Saha-Mo¨ller, C. R.; Zhao, C.-G.
Tetrahedron: Asymmetry 1998, 9, 397.
As has already been observed for the epoxidation of
olefins,5,14 the C8-substitution on the isopropyl group
located at C5 has a significant influence on the enan-
tioselectivity of oxidations of silyl enol ethers (ketone
14 having no substituent at the iso-Pr group provides
34% ee with silyl enol ether 10t, while ketones 6–9
provide 60–68% ee) and it appears that an acetal group
on the isopropyl (ketone 9) provides higher enantiose-
lectivities for all silyl enol ethers (52, 68, and 74% ee for
3t, 10t and 11t, respectively).
7. Solladie´-Cavallo, A.; Jierry, L.; Boue´rat, L.; Taillasson, P.
Tetrahedron: Asymmetry 2001, 12, 883.
8. No addition of water. CH3CN was extracted with pentane
and the extraction monitored by TLC. Moreover, NEt3 and
TMSCl must be distilled and NaI dried; cf. also: Solladie´-
Cavallo, A.; Balaz, M.; Salisova, M.; Suteu, C.; Nafie´, L.;
Cao, X.; Freedmann, T. B. Tetrahedron: Asymmetry 2001,
12, 2605.
Ketone 5 is the most efficient in these cases and pro-
vides the other enantiomer.
9. To a stirred mixture of silyl enolether (1 mmol) and
a-fluoroketone (0.3 equiv.) were added successively (at 0°C)
Tetrasubstituted silyl enol ethers are poor substrates
and are oxidized with almost no enantioselectivity.
a
0.05 M Na2BO4 buffer solution (6 mL) and
dimethoxyethane/CH3CN 2:1 (18 mL) and then (within 1
h) 7 mL of aqueous solution of oxone (1.4 equiv.). During
the addition of oxone, the pH was regulated (8.5–9.0) by
addition of 1 M K2CO3 solution. The reaction mixture was
quenched by addition of CH2Cl2 and water. The organic
phase was recovered and the aqueous phase extracted with
CH2Cl2.
It is worth noting that the model (Fig. 1), involving a
spiro-approach proposed for epoxidation of olefins
holds in the case of oxidation of silyl enol ethers.
Sub-stoichiometric amounts (0.3 equiv.) of ketone have
been used in all cases and these ketones, which do not
undergo Baeyer–Villiger oxidation, can be recovered
and reused.
10. Honda, Y.; Ori, A.; Tsuchihashi, G. Bull. Chem. Soc. Jpn.
1987, 60, 1027.
11. Kenyon, J.; Patel, R. J. Chem. Soc. 1965, 435.
12. (a) Naemura, K.; Takanori, W.; Hirose, K.; Tobe, Y.
Tetrahedron: Asymmetry 1997, 8, 2585; (b) Jeffrey, A. M.;
Yeh, H. J. C.; Jerina, D. M.; Patel, T. R.; Davey, J. F.;
Gibson, D. T. Biochemistry 1975, 14, 575.
Acknowledgements
13. (a) Baumstark, A. L.; McCloskey, C. J. Tetrahedron Lett.
1987, 28, 3311; (b) Houk, K. N.; Liu, J.; DeMello, N. C.;
Condroski, K. R. J. Am. Chem. Soc. 1997, 119, 10147.
14. Yang, D.;Yip, Y.-C.;Chen, J.;Cheung, K.-K. J. Am. Chem.
Soc. 1998, 120, 7659.
We are grateful to the Ministe`re de l’Education et de la
Recherche-France for a Ph.D. grant (MNERT) to L.J.,
CNRS-France for a 3 months grant/position to P.L.
and CNR-Italy for financial support.