Diastereoselective and regioselective epoxidations of allylic alcohols by the in situ-generated dioxirane of 2,2,2-trifluoroacetophenone

Article abstract of DOI:10.1016/S0040-4020(99)01081-9

The diastereoselective epoxidations of cyclohex-2-en-1-ols and the regioselective epoxidations of geraniol and their acetates using the in situ- generated dioxirane from 2,2,2-trifluoroacetophenone are reported along with comparable epoxidations with Oxone. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01081-9

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 989–992
Diastereoselective and Regioselective Epoxidations of Allylic
Alcohols by the in situ-generated Dioxirane of
2
,2,2-Trifluoroacetophenone
*
Estella L. Grocock, Brian A. Marples and Richard C. Toon
Department of Chemistry, Loughborough University, Leicestershire LE11 3TU, UK
Received 16 June 1999; revised 24 November 1999; accepted 9 December 1999
Abstract—The diastereoselective epoxidations of cyclohex-2-en-1-ols and the regioselective epoxidations of geraniol and their acetates
᭨
using the in situ-generated dioxirane from 2,2,2-trifluoroacetophenone are reported along with comparable epoxidations with Oxone .
᭧
2000 Elsevier Science Ltd. All rights reserved.
Epoxidation of allylic alcohols with isolated dimethyl-
dioxirane (DMDO) has been extensively studied and
shown to depend markedly on solvent, substrate and
molecular hydrogen bonding in cyclohexenols (1) and (2)
and 1-methylgeraniol (7), although in all of these reactions
low conversions were observed.
1
–6
temperature. Intramolecular hydrogen bonding between
the OH group and DMDO in a spiro transition state is shown
to be important in determining regio- and diastereo-
selectivity. Reactions of allylic alcohols with in situ-
generated dioxiranes are relatively few and are complicated
1
0,11
We recently reported
the use of 2,2,2-trifluoroaceto-
᭨
phenone (TFAP)/Oxone as a useful reagent for epoxidation
of alkenes. In order to explore further the scope of this reagent
᭨
and of Oxone itself, we have examined their reactions with
᭨
6–9
by concomitant reaction with Oxone directly. Although
isophorol (3), 3-phenylcyclohex-2-en-1-ol (4), geraniol (8)
and their respective acetates (5), (6) and (9). The results of
the epoxidation reactions are shown in Tables 1 and 2.
such direct reactions are dependent on the pH of the reaction
7
medium, little detailed preparative or mechanistic evalua-
6
,8,9
tion has been reported. Recent work
suggests that
diastereoselectivity and regioselectivity in the direct
Oxone -mediated epoxidations are determined by intra-
Cyclohexene epoxidations: The greater conversions for the
partial reactions of 3-phenylcyclohex-2-en-1-ol (4) versus
᭨
Figure 1.
Keywords: diastereoselection; regioselection; epoxidation; dioxiranes.
*
Corresponding author. Tel.:ϩ01509-222554; fax: ϩ01509-223925; e-mail: b.a.marples@lboro.ac.uk
0
040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01081-9

9
90
E. L. Grocock et al. / Tetrahedron 56 (2000) 989–992
Table 1. Epoxidation of cyclohexenols
᭨a
᭨a
Oxidant: TFAP/Oxone
Oxidant: Oxone
Entry
Substrate
Time (h)
Temp
% Conversion
cis: trans epoxides
% Conversion
cis: trans epoxides
1
1
1
6
7
8
19
1
2
3
4
5
6
7
4
4
4
6
6
3
5
24
RT
0ЊC
0ЊC
RT
0ЊC
RT
RT
100
91
82
14:86
80
38
25
10
0
74:26
69:31
71:29
21:79
–
4.5
1.5
24
1.5
24
21:79
22:78
19:81
25:75
100
50
b
3
100
100
53:47
100
10
97:3
50:50
18
24
43:57
a
1
Conversions and ratios determined by analysis of H NMR spectra of the crude mixtures.
b
Somewhat variable but consistently Ͻ that for alcohol.
its acetate (6) (Table 1, entries 3 and 5) presumably arises
reactions (Table 1, entries 4 and 7) in contrast to the parent
alcohols (3) and (4) where intramolecular hydrogen bonding
facilitates the cis-selectivity for the direct reaction (see
above).
from the lower nucleophilicity of the double bond which is
due to the greater electron withdrawing properties of OAc
versus OH. The high trans-selectivity for (4) and the much
lower selectivity for (3) confirms the controlling importance
of steric effects rather than intramolecular hydrogen bond-
The presence of the bulky phenyl group in the dioxirane
generated from TFAP seems to have a minor effect on dia-
stereoselectivity since with isophorol (3) this [53:47,
cis:trans] is not markedly different from that observed
[62:38] with isolated DMDO in acetone: methanol (1:9) in
which the effects of intramolecular hydrogen bonding are
8
ing for in situ dioxirane epoxidations. The trans-selectivity
might be expected to be greater than that observed were it
not for the background cis-selective and intramolecular
᭨
hydrogen bond-mediated direct reactions with Oxone
(Table 1, entries 1 and 6). However, this looks to be only
3
significant for (3) and may be a reflection of the greater rate
of the catalysed reaction for (4) versus (3), the latter being
subject to much more steric hindrance to approach on the
trans-face (Fig. 1).
minimised. Furthermore, the high trans-selectivity for the
reactions of (4) [86:14] and (6) [81:19] in TFAP-mediated
reactions are similar to that observed [82:18] for the reaction
of DMDO in the same solvent with 3-methylcyclohex-2-en-
4
1
-ol (2). In situ reactions for (2) with a variety of ketones
᭨
In general the direct Oxone reactions with (3) and (4) are
excluding acetone and cyclohexanone gave trans-selectivities
Ͼ74% and that closest to the TFAP value with (4) was with
relatively slow and the reactions with the acetates (5) and
8
(
6) even slower. Both of the acetates show similar trans-
1,3-dichloropropanone. Interestingly, 1,1,1-trifluoropropa-
᭨
8
selectivity in the TFAP-mediated and direct Oxone
none (TFP) gave trans-selectivities in the range 86–95%
Table 2. Epoxidation of geraniol and geranyl acetate
᭨a
᭨a
Oxidant: TFAP/Oxone
Oxidant: Oxone
Entry
Substrate
Time (h)
Temp
% Conversion
% 6,7-epoxide
% bis-epoxide
% Conversion
% 6,7-epoxide
% bis-epoxide
1
2
3
4
5
8
8
8
9
9
1
2
24
2
0ЊC
0ЊC
RT
0ЊC
RT
89
100
100
76
46
Trace
0
76
41
43
Ͼ97
Ͼ99
–
84
93
100
15
40
34
0
15
98
45
59
Ͼ99
–
24
100
59
100
2
a
1
Conversions and ratios determined by H NMR spectra of the crude mixtures.

E. L. Grocock et al. / Tetrahedron 56 (2000) 989–992
991
Scheme 1.
᭨
for (2) and other 1-substituted 3-methylcyclohex-2-enes.
The results with TFAP are probably best explained through
the spiro transition states depicted in Scheme 1 in which the
tions with Oxone alone were performed in the same
manner but TFAP was omitted. After the stated time (see
Tables 1 and 2) water (100 ml) was added and the solution
was extracted with DCM (3×20 ml), the combined extracts
then being dried over magnesium sulfate and evaporated to
dryness. (In the case of volatile compounds the solutions
were evaporated to just dryness at room temperature.)
3
phenyl group is remote from the ring substituent (R ), and it
can be concluded that TFAP is a reasonable and more easily
recoverable alternative to TFP for in situ dioxirane-
1
0,11
mediated epoxidations.
Polar effects appear to make
1
only minor contributions to diastereoselectivity (compare
Ref. [8]).
Product ratios were determined from H NMR spectra of
the crude products.
7
Geraniol and geranyl acetate epoxidations: Shi reported
that background epoxidation of geraniol (8) by Oxone
The allylic alcohols and their acetates are all literature
compounds as are all of the isolated epoxides (see Table 1
᭨
1
2
3
reduced the enantioselectivity in using the catalyst (12).
Our results (Table 2) confirm that Oxone readily oxidises
both double bonds of geraniol (8) and suggest that the 6,7-
double bond oxidises first. We have used considerably more
Oxone than Shi in accordance with our previously
published procedure with TFAP and did not detect the
,3-epoxide (13). As expected from observations with
geranyl TBS ether (10), the acetate (9) was much less reac-
tive with Oxone than geraniol (Table 2, entries 1, 2 and 4)
and text) except the trans-epoxide (14, R ˆR ˆH, R ˆPh)
᭨
and the epoxides from (6). Simple acetylation of cis-epoxide
1
2
3
(15, R ˆR ˆH, R ˆPh) with acetic anhydride in pyridine
1
2
3
gave the acetate, an oil, (15, R ˆAc, R ˆH, R ˆPh), n
max
᭨
Ϫ1
(neat) 1733 (CyO) cm , d (250 MHz; CDCl ) 7.35 (5H,
H 3
1
0
m, Ph), 5.23 (1H, dt, Jˆ6.5 and 2.5 Hz, 1-CH), 3.27 (1H, d,
2
Jˆ2.5 Hz, 2-CH) 2.13 (3H, s, Me), d (62.9 MHz; CDCl )
c
3
170.8 (CO), 140.9 (Ar-C), 128.3 (Ar-CH), 127.6 (Ar-CH),
125.3 (Ar-CH), 69.9 (1-CH), 62.8 (3-C), 61.6 (2-CH), 27.7
᭨
ϩ
but it can be used to selectively oxidise the 6,7-double to
(CH ), 24.9 (CH ), 21.1 (Me), 19.1 (CH ). Found: M
2
2
2
᭨
ϩ
give (16, RˆAc) (Table 2, entry 5) as can TFAP/Oxone
232.1079, C H O requires M 232.1099.
14 16 3
(
Table 2, entry 4). Similar selectivity has been observed in
the reactions of (9) with mCPBA, RuTMP(O) and UHP-
In a slightly modified procedure, oxidation of (4) (500 mg,
2.87 mmol) was carried out at room temperature and
excluding light in a rapidly stirred reaction mixture contain-
ing 2,2,2-trifluoroacetophenone (0.805 ml, 5.74 mmol),
2
1
3–15
maleic anhydride.
The use of TFAP allows complete
oxidation of geraniol (8) to the bis-epoxide (17, RˆH) at
᭨
0
ЊC in 2 h (Table 2, entry 2) and Oxone alone may be used
Ϫ4
to effect the same transformation under somewhat more
vigorous conditions (Table 2, entry 3). The greater nucleo-
philicity of the 6,7-double bond seems to be the controlling
feature in all of these reactions, in common with those
observed in the reactions of geraniol (8) and its methyl
EDTA (20 ml of a 4×10 M solution) in acetonitrile
᭨
(30 ml), Oxone (8.81 g, 14.3 mmol) and sodium bicarbo-
nate (3.69 g, 44.4 mmol). After ca. 18 h, water (100 ml) was
added and the solution was extracted with DCM (3×30 ml);
the combined extracts were dried over sodium sulfate and
evaporated to dryness. Careful chromatography of the
reaction mixture, using diethyl ether: hexane mixtures as
1
,5
ether (11) with DMDO in acetone: methanol (1:9).
᭨
1
2
3
The work reported here demonstrates that TFAP/Oxone
eluent, afforded the trans-epoxide (14, R ˆR ˆH, R ˆPh)
᭨
and Oxone itself are useful for epoxidation of allylic
alcohols and complements recent reports on similar
systems and on the use of Oxone as a useful general
(23%), mp 75–76ЊC (white crystalline solid, from diethyl
Ϫ1
ether: hexane), nmax (CDCl film) 3406 (OH) cm , d
3
H
6
–9
᭨
(250 MHz; CDCl ) 7.3 (5H, m, Ph), 4.1 (1H, dt,
3
1
2,20
oxidant in its own right.
Jˆ8.8 Hz, 5.6 Hz, 1-CH), 3.07 (1H, s, 2-CH), 2.2 (3H, m,
CH ), 1.77 (1H, d, Jˆ5.2 Hz, OH), 1.4 (3H, m, CH ), d
2
2
c
(
62.9 MHz; CDCl ) 141.1 (Ar-C), 128.3 (Ar-CH), 127.5
3
Experimental
(Ar-CH), 125.4 (Ar-CH), 66.8 (1-CH), 65.5 (2-CH), 61.4
ϩ
(
3-C), 30.2 (CH ), 28.4 (CH ), 15.8 (CH ). Found: M
2 2 2
ϩ
᭨
A mixture of Oxone (0.85 g, 1.38 mmol) and sodium
190.0993, C12H O requires M 190.0994.
14 2
bicarbonate (0.39 g, 4.5 mmol) was added to a mixture of
the alcohol or its acetate (0.27 mmol), 2,2,2-trifluoroaceto-
1
2
3
Acetylation of (14, R ˆR ˆH, R ˆPh) in the usual way
phenone (0.185 ml, 1.32 mmol) and EDTA (5 ml of a
afforded a quantitative yield of the trans-epoxide, an oil,
Ϫ4
1
2
3
4
×10 M solution) in acetonitrile (7.5 ml). The solution
(14, R ˆAc, R ˆH, R ˆPh), nmax (CDCl
film) 1738
3
Ϫ1
was stirred rapidly overnight excluding light and at room
temperature except where indicated otherwise. The reac-
(CyO) cm , d (400 MHz; CDCl ) 7.3 (5H, m, Ph), 5.1
H 3
(1H, dd, Jˆ8.8 Hz, 6.4 Hz, 1-CH), 3.04 (1H, br s, 2-CH),

9
92
E. L. Grocock et al. / Tetrahedron 56 (2000) 989–992
.3 (1H, m, CH ), 2.2 (1H, m, CH ), 2.06 (3H, s, Me), 2.0
7. Wang, Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 3099–3104.
2 2
2
(
1H, m, CH ), 1.6 (1H, m, CH ), 1.5 (1H, m, CH ), 1.3 (1H,
8. Yang, D.; Jiao, G.-S.; Yip, Y.-C.; Wong, M.-K. J. Org. Chem.
2
2
2
m, CH ), d (100 MHz; CDCl ) 170.1 (CO), 140.7 (Ar-C),
1999, 64, 1635–1639.
2
c
3
1
28.3 (Ar-CH), 127.6 (Ar-CH), 125.3 (Ar-CH), 68.7
9. Kurihara, M.; Ito, S.; Tsutsumi, N.; Miyata, N. Tetrahedron
Lett. 1994, 35, 1577–1580.
10. Boehlow, T. R.; Buxton, P. C.; Grocock, E. L.; Marples, B. A.;
Waddington, V. L. Tetrahedron Lett. 1998, 39, 1839–1842.
(
2
1-CH), 62.9 (2-CH), 60.9 (3-C), 28.0 (CH ), 26.4 (CH ),
1.1 (Me), 15.7 (CH ). Found: M 233.1177, C H O
2
2
ϩ
2
14 16
3
ϩ
requires M 233.1178.
1
5
1
2
1
1. Harburn, J. J.; Loftus, G. C.; Marples, B. A. Tetrahedron 1998,
4, 11907–11924.
2. Van Horn, J. D.; Burrow, C. J. Tetrahedron Lett. 1999, 40,
069–2070 and references cited therein.
3. Dodd, D. S.; Oehlschlager, A. C.; Georgopapadakou, N. H.;
Acknowledgements
We thank Loughborough University for financial support of
E. L. G. and R. C. T.
Polak, A. -M.; Hartman, P. G. J. Org. Chem. 1992, 57, 7226–7234.
1
3
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4. Ohtake, H.; Higuchi, T.; Hirobe, M. Tetrahedron Lett. 1992,
3, 2521–2524.
5. Astudillo, L.; Galindo, A.; Gonzalez, A. G.; Mansilla, H.
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