Regio- and diastereoselection in the oxaziridinium salt oxidation of acyclic allylic acetates

Article abstract of DOI:10.1016/S0040-4039(01)00536-6

Oxaziridinium salt 1 is a versatile oxygen transfer agent towards olefins. An important threo selectivity is observed with acyclic allylic acetates due to 1,3-allylic strain (A^1,3). The π-facial selectivity in the epoxide formation is interpretated as a consequence of an interaction between the residual positive charge on nitrogen and the neighbouring acetate in the transition state. Such an interaction is not strong enough to balance the lowered nucleophilicity of the 2,3 double bond in the geraniol acetate 3a.

Full text of DOI:10.1016/S0040-4039(01)00536-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3745–3748
Regio- and diastereoselection in the oxaziridinium salt oxidation
of acyclic allylic acetates
David Poisson, Gilles Cure, Guy Solladie´ and Gilles Hanquet*
Laboratoire de Ste´re´ochimie associe´ au CNRS, ECPM, Universite´ Louis Pasteur, 25 rue Becquerel, 67087 Strasbourg, France
Received 16 January 2001; revised 23 March 2001; accepted 29 March 2001
Abstract—Oxaziridinium salt 1 is a versatile oxygen transfer agent towards olefins. An important threo selectivity is observed with
acyclic allylic acetates due to 1,3-allylic strain (A1,3). The p-facial selectivity in the epoxide formation is interpretated as a
consequence of an interaction between the residual positive charge on nitrogen and the neighbouring acetate in the transition
state. Such an interaction is not strong enough to balance the lowered nucleophilicity of the 2,3 double bond in the geraniol
acetate 3a. © 2001 Elsevier Science Ltd. All rights reserved.
Oxaziridinium salts have been known since 19761 as
oxygen atom transfer agents towards nucleophiles.
Since 1987, several oxaziridinium salts have been
described2 and used for epoxidation in stoichiometric
amounts3 or in catalytic processes.4 The oxaziridinium
salt 1 derived from tetrahydroisoquinoline and its chiral
analogue 2 have been extensively studied for oxygen
transfer to olefins,5 N-nucleophiles,6 and S-
nucleophiles.7
of hydrogen bonds with the allylic alcohols. In order to
explain this selectivity, we postulated a transition state
based on an interaction between the residual positive
charge on nitrogen and the neighbouring acetate.
Stereoselective hydroxyl directed epoxidations of chiral
allylic alcohols have been reported with a variety of
oxidizing agents10 as a result of a p-facial selectivity in
epoxide formation from chiral allylic alcohols due to
dominant 1,3-allylic strain (A1,3) (threo-selectivity), with
respect to the 1,2-allylic strain (A1,2
selectivity).
)
(erythro-
These studies afforded valuable information on the
transition state geometry for oxygen transfer processes
from metal (peroxy and peroxo) complexes and non-
metallic (peracids and dioxirane) oxidants.11
Despite the description of numerous examples of
oxaziridinium salt oxidations, little is known to date
about the mechanism of the oxygen transfer. Recently
Houk8 proposed a flexible spiro transition state in
stereoselective epoxidations.3c,4,9
In order to get more information about the hypothesis
proposed for cyclic allylic acetates, we decided to use
the acyclic stereochemical probe 6d (R=H) described
by Adam10–12 for dioxirane epoxidation and to study
the epoxidation of acetates 6a–e with the oxaziridinium
salt 1. We completed this work by studying the regio-
selectivity obtained in the epoxidation of geranyl ace-
tate 3, as well as the comparative epoxidation of the
allylic acetate 7 versus the homoallylic acetates 8.11
A few years ago,5 we observed an important syn-direct-
ing effect of the acetate group in the epoxidation of
cyclic allylic substrates by the oxaziridinium salt 1
(de>95% with 2-cyclohexene-1-acetate and 3-methyl-2-
cyclohexene-1-acetate). Such interactions were not
observed with the corresponding alcohols (de=6/4), the
strong electrophilic character of the oxygen atom in the
oxaziridinium salt is not compatible with the formation
Diastereoselectivity
The stabilization effect due to acetate assistance5 should
direct the epoxidation of chiral acyclic allylic acetates
with the oxaziridinium salt 1 as already demonstrated
for the allylic alcohol epoxidation by various oxidizing
* Corresponding author. Fax: 33 3 90 24 27 42; e-mail: hanquet@
chimie.u-strasbg.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00536-6

3746
D. Poisson et al. / Tetrahedron Letters 42 (2001) 3745–3748
Table 1. Diastereoselectivities in the epoxidation of allylic acetates 6 and their corresponding trifluoroacetates 11 by the
oxaziridinium salt 1
Entry
Substrate
R
R1
R2
R3
Epoxides threo/erythroa,b
1
2
3
4
6a
6b
6c
6d
Ac
Ac
Ac
Ac
H
H
Me
Me
Me
Me
H
H
Me
H
50/50
90/10
65/35
95/5
H
Me
60/40 in acetone-d6
65/35 in CD3NO2
93/7
5
6e13
Ac
Me
Me
Me
73/27 in acetone-d6
60/40
58/42
65/35
68/32
6
7
8
9
11bc
11c
COCF3
COCF3
COCF3
COCF3
H
Me
H
H
Me
H
Me
Me
Me
Me
Me
11d
11ec
Me
a Reactions are monitored by 1H NMR analysis until complete conversion (>95%). Oxaziridinium salt is quantitatively deoxygenated into its
corresponding iminium salt. Structures of epoxy-acetates and trifluoroacetates were confirmed by chemical correlation to the known
epoxy-alcohols.10a
b dr Determined by 1H NMR.
c Trifluoroacetates bearing a methyl group at the R2 position are very sensitive and were prepared in low yields using imidazole trifluoroacetate
in dichloromethane.
agents.10 We have compared the diastereoselectivity of
the epoxidation of acetates 6a–e with that of the corre-
sponding trifluoroacetates 11a–e in apolar or polar
solvents. The results are listed in Table 1.
gives the threo epoxide, all trifluoroacetate derivatives
11b–e, which possess a less basic carbonyl, and there-
fore a lower stabilisation effect in the transition state,
yield the corresponding epoxides with a low threo-selec-
tivity.
The large difference in the stereoselectivities for the
oxaziridinium salt epoxidation of the allylic acetates
(entries 1–5) compared with their corresponding tri-
fluoroacetates (entries 6–9) is consistent with our previ-
ous hypothesis.5 Of more interest is the diastereoselec-
tivity observed with the acetates 6a–e. Clearly, the
diastereoselectivity in the epoxide formation depends
on the substitution pattern of the allylic acetates 6. For
substrates without allylic strain (entry 1) no diastereose-
lectivity is observed, whereas for substrates bearing a
methyl group at the R1 or R3 position (entries 2 to 5),
a threo selectivity is observed in the oxaziridinium salt
epoxidation. This diastereoselectivity increased from
1,2-allylic strain (entry 3) to 1,3-allylic strain (entries 2,
4 and 5). In the case of 6d,12a which possesses both 1,2
and 1,3-allylic strain, threo-selectivity is shown demon-
strating the domination of 1,3-allylic strain versus 1,2-
allylic strain, without any ambiguity. Clearly, the
diastereoselective epoxidations of the chiral allylic
acetates (Table 1) provide evidence for an interaction of
the acetate group with the cationic transition state.
Further support for this proposed association is also
gained from the oxaziridinium salt 1 promoted epoxi-
dation of 6d in acetone or nitromethane and of the
trifluoroacetates 11b–e (entries 6–9). While the acetate
function in 6b,d,e directs oxaziridinium salt attack and
These results can be explained by the transition state
depicted in Fig. 1 in which the p-facial selectivity is
controlled by the acetate in a geometry with minimiza-
tion of 1,3-allylic strain (A1,3).
Regioselectivity
Geranyl-acetate is an allylic acetate with two trialkyl
substituted double bonds. The next experiments
involved a comparison of the p reactivity of the 2,3 and
6,7 double bonds to provide more evidence about ace-
tate assistance. The results are reported in Table 2.
A1,3 minimal
+δ
Me
A1,2
H
H Me
Me
Me
O
O
+δ
N
+δ
O
-δ
Figure 1.

D. Poisson et al. / Tetrahedron Letters 42 (2001) 3745–3748
Table 2. Epoxidation of geranyl-acetate 3a–c by the oxaziridinium salt 1
3747
Entry
Substrate
Equivalents of 1
Conditionsa
Conversion%b
Products
1
2
3
4
3a
3a
3b
3c
0.4
1
0.4
0.4
CD2Cl2, 5 min
CH2Cl2, 30 min
CD2Cl2, 5 min
CD2Cl2, 5 min
40
97
40
32
5a and traces of 4a
5a only, 92% isolated
5b only
5c only
a Time required to observe a negative KI (potassium iodide) test.
b Determined by 1H NMR analysis on the crude product mixture.
2. (a) Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron
Lett. 1987, 28, 6061–6064; (b) Hanquet, G.; Lusinchi, X.;
Milliet, P. Tetrahedron 1993, 49, 423–438; (c) Armstrong,
A.; Ahmed, G.; Garnett, I.; Goacolou, K. Synlett 1997,
1075–1076.
3. (a) Bohe´, L.; Hanquet, G.; Lusinchi, M.; Lusinchi, X.
Tetrahedron Lett. 1993, 34, 7271–7274; (b) Chiaroni, A.;
Hanquet, G.; Lusinchi, M.; Riche, C. Acta Crystallogr.,
Sect. C 1995, 51, 2047–2050; (c) Bohe´, L.; Lusinchi, M.;
Lusinchi, X. Tetrahedron 1999, 55, 141–154.
Scheme 1. Competitive epoxidation of a mixture of allylic
acetate 7 and homoallylic acetate 8 with the oxaziridinium
salt 1.
4. (a) Hanquet, G.; Lusinchi, X.; Milliet, P. C.R. Acad. Sci.
Paris 1991, 313, 625–628; (b) Aggarwal, V. K.; Wang, H.
F. J. Chem. Soc., Chem. Commun. 1996, 191–192; (c)
Page, P. C. B.; Rassias, G. A.; Bethell, D.; Schilling, M.
B. J. Org. Chem. 1998, 63, 2774–2777; (d) Minakata, S.;
Takemiya, A.; Nakamura, K.; Ryu, I.; Komatsu, M.
Synlett 2000, 1810–1812.
5. Hanquet, G.; Lusinchi, X. Tetrahedron 1997, 53, 13727–
13738.
6. Hanquet, G.; Lusinchi, X. Tetrahedron 1994, 50, 12185–
12200.
7. (a) Hanquet, G.; Lusinchi, X. Tetrahedron Lett. 1993, 34,
5299–5302; (b) Bohe´, L.; Lusinchi, M.; Lusinchi, X.
Tetrahedron 1999, 55, 155–166.
8. Houk, K. N.; Washington, I. J. Am. Chem. Soc. 2000,
122, 2948–2949.
9. Armstrong, A.; Draffan, A. G. Tetrahedron Lett. 1999,
40, 4453–4456.
10. (a) Adam, W.; Smerz, A. K. J. Org. Chem. 1996, 61,
3506–3510; (b) Hoveyda, A. H.; Evans, D. A.; Fu, G. C.
Chem. Rev. 1993, 93, 1307–1370.
Finally, we tested the reactivities of allylic versus
homoallylic acetates 8 and 9 in a competitive experi-
ment (Scheme 1).
The results listed in Table 2 (entries 1 and 2) showed
that the terminal 6,7 double bond in geranyl acetate is
exclusively epoxidized. No di-epoxidation was
observed. The nucleophilicity of the 2,3 double bond is
therefore strongly lowered by the electron-withdrawing
effect of the acetate group. The presence of a more
basic carbonyl group such as a carbonate (entry 4) does
not induce any change in the regioselectivity. For prob-
ably the same reason, the epoxidation of a homoallylic
acetate occurs predominantly in the presence of the
corresponding allylic acetate (Scheme 1).
Conclusion
The p-facial selectivity observed in the epoxidation of
various allylic acyclic acetates by the oxaziridinium salt
1, provides convincing experimental evidence in favor
of the assistance of the acetate group in stabilising the
positively charged transition state. These results sup-
port our previous results showing such effects in
diastereoselective oxaziridinium salt epoxidation of
cyclic allylic acetates.5
11. Adam, W.; Mitchell, C. M.; Saha-Mo¨ller, C. R. J. Org.
Chem. 1999, 64, 3699–3707.
12. (a) Adam, W.; Nestler, B. Tetrahedron Lett. 1993, 34,
611–614; (b) Adam, W.; Smerz, A. K.; Paredes, R.;
Veloza, A. Eur. J. Org. Chem. 1998, 349–354.
13. Preparative epoxidation of 3,4-dimethylpent-3-en-2-ace-
tate 6e by oxaziridinium salt 1
100 mg (0.6 mmol) of acetate 6e was dissolved in 5 mL of
dichloromethane. Freshly recrystallized oxaziridinium
salt 1 (150 mg, 1 equiv.) was added in one portion to the
solution. Stirring was maintained until total disappear-
ance of active oxygen (KI test). The crude solution was
concentrated under vacuum, the resulting solid was
stirred with diethyl ether (10 mL) and after filtration, the
etheral solution was concentrated to give 86 mg (78%
References
1. (a) Picot, A.; Milliet, P.; Lusinchi, X. Tetrahedron Lett.
1976, 17, 1573–1576; (b) Picot, A.; Lusinchi, X. Tetra-
hedron Lett. 1976, 17, 1577–1580; (c) Picot, A.; Milliet,
P.; Lusinchi, X. Tetrahedron 1981, 37, 4201–4208.

3748
D. Poisson et al. / Tetrahedron Letters 42 (2001) 3745–3748
yield) of pure epoxide in a diastereoisomeric mixture
17.4 (Me); 20.9 (Me); 21.6 (Me); 21.7 (Me); 62.0 (C); 65.5
(C); 73.9 (CH); 170.8 (CꢀO).
(threo/erythro: 92/8). The diastereoisomers are easily sep-
arated by silica gel chromatography using hexane/ether
gradient.
1H NMR (400 MHz, CDCl3) erythro epoxide: 1.3 (s, 3H);
1.32 (d, 3H, J=6.5 Hz); 1.34 (s, 3H); 1.38 (s, 3H); 2.06 (s,
3H); 4.81 (q, 1H, J=6.5 Hz).
1H NMR (400 MHz, CDCl3) threo epoxide: 1.25 (d, 3H,
J=6.5 Hz); 1.33 (s, 3H); 1.36 (s, 3H); 1.39 (s, 3H); 2.09
(s, 3H); 4.86 (q, 1H, J=6.5 Hz).
13C NMR (100 MHz, CDCl3) erythro epoxide: 13.2 (Me);
16.0 (Me); 20.8 (Me); 21.5 (Me); 21.8 (Me); 64.2 (C); 64.6
(C); 71.2 (CH); 170.4 (CꢀO).
13C NMR (100 MHz, CDCl3) threo epoxide: 13.1 (Me);
.