The stereoselective thermal rearrangement of chiral lophine peroxides

Article abstract of DOI:10.1016/j.tetlet.2007.01.146

The thermal reaction of chiral 2-phenyl-4-(p-X-phenyl)-5-(p-Y-phenyl)-4-tert-butyldimethylsilylperoxy-4H-isoimidazoles (5b: X = CF₃, Y = OMe; 5c: X = CF₃, Y = F) was carried out in DMSO. The chiral 2-phenyl-5-(p-X-phenyl)-5-(p-Y-phen

Full text of DOI:10.1016/j.tetlet.2007.01.146

Tetrahedron Letters 48 (2007) 3109–3113
The stereoselective thermal rearrangement of chiral
lophine peroxides
Masaru Kimura,a,* Gonghao Lu,a Hiroshi Iga,a Mitsuru Tsunenaga,a
Zhiqiang Zhangb and Zhizhi Hub
aDepartment of Chemistry, Faculty of Science, Okayama University, Okayama 700-8530, Japan
bDepartment of Applied Chemistry, University of Science and Technology Liaoning, Anshan 114044, PR China
Received 19 January 2007; accepted 26 January 2007
Available online 30 January 2007
Abstract—The thermal reaction of chiral 2-phenyl-4-(p-X-phenyl)-5-(p-Y-phenyl)-4-tert-butyldimethylsilylperoxy-4H-isoimidazoles
(5b: X = CF3, Y = OMe; 5c: X = CF3, Y = F) was carried out in DMSO. The chiral 2-phenyl-5-(p-X-phenyl)-5-(p-Y-phenyl)-5H-
imidazol-4-ones (4b: X = CF3, Y = OMe; 4c: X = CF3, Y = F) were quantitatively obtained in 50–60% enantiomer excess (ee). The
mechanism for the reaction was proved to be stereoselective 1,5-phenyl migration. Although the sigmatropic 1,5-phenyl migration
should be thermally allowed according to the Woodward–Hoffmann rule, the migration actually includes a stepwise process.
Ó 2007 Published by Elsevier Ltd.
Since 4-hydroperoxy-2,4,5-triphenyl-4H-imidazole (1a)
was identified as the intermediate of the chemilumines-
cence (CL) of lophine (2a) by Sonnenberg et al.,1 White
et al.,2 and Kimura et al.,3 the CL reaction of lophine-
peroxides has been gradually revealed. Recently, we
reported that lophineperoxide (1a) underwent three
different but simultaneous reactions upon treatment
with base to provide the corresponding amidine (3a)
accompanied with chemiluminescence, imidazole (2a)
with singlet oxygen, and a trace of imidazolone (4a)2b
as illustrated in Scheme 1. The peroxides, after protec-
tion as silyl peroxide, 2,4,5-tirphenyl-4-tert-butyldimeth-
ylsilyl-peroxy-4H-iso-imidazole (5a), underwent an
exclusive 1,5-phenyl migration in DMSO to give solely
imidazolone (4a) in excellent yield (Scheme 2).
Ph
Ph
Ph
N
O2 or 1O2
N
N
OOH
Ph
Ph
N
H
Ph
1a
Ph
2a
N
O
Ph
O
NH
Ph
+
+
hv
3a
base
1O2
2a
or heat
O
N
We became aware of two reports which suggested impor-
tant meanings of this type rearrangement. It had been
demonstrated that tetrahydrobenzimidazoles rearrange,
on treatment with base, an alkyl halide and the singlet
oxygen, to provide 4-imidazolonespirocyclopentane.4
Further, Lovely et al.5 reported that tetrahydrobenzimi-
dazoles, on treatment with dimethyldioxiane (DMDO),
Ph
N
H
4a
Scheme 1.
rearranged to provide 5-imidazolones exclusively with
good to excellent levels of diastereoselectivity. This kind
of stereochemistry is a key for the synthesis of natural
compounds including imidazolone moieties.4–6 Further,
the sigmatropic migration of an aryl group is known
Keywords: 1,5-Sigmatropic migration; Lophine peroxide; Imidazolone;
Imidazol-4-ol; Rearrangement; Stereoselectivity.
*
Corresponding author. Tel./fax: +81 86 251 7839; e-mail: kimuram@
cc.okayama-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.01.146

3110
M. Kimura et al. / Tetrahedron Letters 48 (2007) 3109–3113
O
N
Ph
Si
O
N
X
Y
heat
X
N
H
*
O
DMSO
*
Ph
N
4
Y
X
5
base
DMSO
X
N
N
Ph
Ph
O
O
Y
4
+
+
N
H
NH
trace
Y
2
3
a: X = H,
Y = H
b: X = CF3, Y = OCH3
c: X = CF3, Y = F
main
Scheme 2.
for 1,2,3,4,5-pentaphenylcyclopentadienol,7 which is a p
analogue of 5, but its stereochemistry has not been
tested.
recorded, and the calculation of CD spectra were carried
out based on the GAUSSIAN 03w software package,10 as
show in Figure 1. A geometry optimization was per-
formed using the B3LYP functional with 6-31G* basis
sets. The absolute configurations of 5-I and 5-II were
assigned as S-5 and R-5, respectively, as illustrated in
Figure 1. The absolute configurations of products 4-I
(HPLC: the first fraction) and 4-II (HPLC: the second
fraction) were also assigned to R-4 and S-4, respectively,
as illustrated in Figure 2.
We thought that two chiral peroxides 5b and c (Scheme
2) could straightforwardly contribute to elucidate the
stereochemistry of the migration. When the chiral per-
oxides (5b and c) were subjected to the thermal reaction,
the corresponding imidazolones 4b and c were exclu-
sively obtained in 50–60 ee % in DMSO.
The Assignment of the absolute configuration by compari-
son between the CD spectra and the calculated CD spec-
tra. Chiral peroxides 5-I (HPLC: the first fraction) and
5-II (HPLC: the second fraction) were prepared in five
steps as shown in Scheme 3.3,8,9 In order to determine
the absolute configuration, the CD spectra were
Thermal rearrangement of chiral lophine peroxides. The
chiral peroxides R- and S-5b and R- and S-5b (about
0.001 mmol) were dissolved in DMSO (1 ml), and
refluxed for 10 min. The reaction mixture was subjected
to HPLC analysis using a chiral column. The results are
summarized in Tables 1 and 2. Figure 3 shows the
H
O
N
X
X
Y
benzaldehyde
AcONH4
O2, hv
O
O
N
methylene blue
1
Ph
Ph
+
AcOH
reflux
N
O
H
N
CH2Cl2 / MeOH
O
O
X
-78 °C
Y
Y
2
Yield = 75% (1a)
59% (1b)
2'
Yield = 93% (2a)
95% (2b and 2'b, molar ratio = 4 : 1)
72% (2c and 2'c, molar ratio = 14 : 1)
65% (1c)
X
Y
N
Imidazole
TBDMSCl
5-I
Ph
recrystal
Chiral HPLC
+
N
O
Si
5
5
Pyridine
0 °C
O
2-propanol
5-II
5'
Yield = 64% (5a)
Yield = 67% (5b)
38% (5c)
87% (5b and 5'b, molar ratio = 4 : 1)
a: X = H, Y = H
b: X = CF3, Y = OCH3
c: X = CF3, Y = F
77% (5c and 5'c, molar ratio = 14 : 1)
Scheme 3.

M. Kimura et al. / Tetrahedron Letters 48 (2007) 3109–3113
3111
15
15
10
5
CD for 5c-I
CD for 5c-II
15
CD for
5b-II
15
10
5
CD for 5b-I
10
10
5
5
0
0
0
0
-5 250 275 300 325 350 375 400
250 275 300 325 350 375 400
-5
250 275 300 325 350 375 400
250 275 300 325 350 375 400
-5
-5
-10
-10
-15
-10
-15
-10
-15
-15
Wavelength / nm
Wavelength / nm
Wavelength / nm
Wavelength / nm
Calculated CD for S-5b
100
50
0
Calculated CD for R-5b
Calculated CD for S-5c
Calculated CD for R-5c
60
40
20
100
50
100
50
0
-20
-40
-60
-80
-100
0
300
325
350
375
400
0
300
325
350
375
400
300
325
350
375
400
300
325
350
375
400
-50
-50
-100
-50
-1 00
Wavelength / nm
Wavelength / nm
Wavelength / nm
Wavelength / nm
-100
Figure 1. The CD spectra (above) of 5b,c recorded in EtOH and the calculated CD spectra (below) of 5b,c using the TDDFT-B3LYP method.
Rotational strengths (R) are given in cgs (10À40 erg esu cm/G).
10
5
10
5
10
5
CD for 4b-I
CD for 4c-II
CD for 4b-II
CD for 4c-I
10
5
0
0
0
0
250
275
300
325
350
250
275
300
325
350
250
275
300
325
350
250
275
300
325
350
-5
-10
-5
-5
-10
-5
-10
-10
Wavelength / nm
Wavelength / nm
Calculated CD for S-4b
Wavelength / nm
Wavelength / nm
100
Calculated CD for R-4b
100
50
0
Calculated CD for R-4c
Calculated CD for S-4c
100
50
60
30
0
50
0
0
250
275
300
325
350
250
275
300
325
350
250
275
300
325
350
250 275 300 325 350
-30
-50
-100
-50
-50
-100
-100
-60
Wavelength / nm
Wavelength / nm
Wavelength / nm
Wavelength / nm
Figure 2. The CD spectra (above) of 4b,c recorded in EtOH and the calculated CD spectra (below) of 4b,c using the TDDFT-B3LYP method.
Rotational strengths (R) are given in cgs (10À40 erg esu cm/G).
Table 1. The ee % for the rearrangement of S-5 (reaction time = 10 min)
O
O
N
Si
O
N
N
X
Ph
Ph
X
N
H
Y
O
heat
N
H
+
Ph
*
DMSO
N
Y
Y
S-4
X
S-5
R-4
Minor
Main
b: X = CF3, Y = OCH3
c:
X = CF3, Y = F
Temperature (°C)
Yielda,b (%)
R-4b
S-4b
ee (%)
R-4c
S-4c
ee (%)
100
130
160
180
200
75.5
75
75
74.5
74.5
24.5
25
25
25.5
25.5
51
50
50
49
49
80
79.5
79
78
75.5
20
20.5
21
26
24.5
60
59
58
52
51
a Yields calculated on the basis of HPLC integral quantity.
b The conversion was estimated to be 100% because of no other peak appearing in the 1H NMR spectra.
relation between the ee % and reaction temperature for
chiral imidazolones 4b and c as products. In DMSO, the
ee % slowly decreased as the temperature increased. It is
noteworthy that the ee % was found to be rather low
compared to the expected results of thermally allowed
1,5-sigmatropic rearrangement. To find a reason, we

3112
M. Kimura et al. / Tetrahedron Letters 48 (2007) 3109–3113
Table 2. The ee % for the rearrangement of R-5 (reaction time = 10 min)
X
O
N
O
N
Ph
Ph
X
N
H
Y
heat
Si
N
H
O
*
N
N
+
O
Ph
DMSO
Y
R-4
S-4
Y
X
R-5
Minor
Main
b:
X = CF3, Y = OCH3
c: X = CF3, Y = F
Temperature (°C)
Yielda,b (%)
R-4b
S-4b
ee (%)
R-4c
S-4c
ee (%)
100
130
160
180
200
25
25
25
26.5
27
75
75
75
73.5
73
50
50
50
47
46
20.5
21
21.5
22.5
23
79.5
79
78.5
77.5
75
59
58
57
55
52
a Yields calculated on the basis of HPLC integral quantity.
b The conversion was estimated to be 100% because of no other peak appearing in the 1H NMR spectra.
65
60
55
50
45
40
O
N
base
Ph
+
R-4
S-4
X
N
H
DMSO
100 oC
R-4b
S-4b
R-4c
S-4c
< 2%
Y
R-4
O
N
75
100
125
150
175
200
225
base
Ph
R-4
+
S-4
º
Y
Temp. / C
N
H
DMSO
100 oC
Figure 3. Relation between the ee % of 4b,c and the reaction
temperature in DMSO (reaction time = 10 min).
< 2%
S-4
X
b: X = CF3, Y = OCH3
c: X = CF3, Y = F
took the isomerization of R- and S-4 into account. Opti-
cally pure chiral compounds 4 were dissolved in DMSO,
and an excess of base (tetrabutyl ammonium fluoride in
THF, or KOH/methanol) was added. The solution was
heated for 10 min at 100 °C (Scheme 4). The HPLC
analysis showed the conversions of the isomerization
were less than 2%. It was much less than the decreases
of ee % in the thermal rearrangement reactions of 5.
Scheme 4.
NMR spectroscopy. The 1H NMR spectra of these
byproducts were identified by comparison with those
of authentic samples. Silanol 7 was further isolated by
sublimation of the reaction mixture, and the IR, 1H
NMR and 13C NMR were identical with those of the
product prepared from the hydrolysis of tert-butyldi-
methylsilyl chloride. In DMSO, the thermal reaction
of peroxides (5) solely provided imidazolones (4) in
excellent yield. The mechanism for the reaction was
proved to be substantially stereoselective 1,5-phenyl
migration by use of chiral peroxides 5. It is noteworthy
that although the sigmatropic 1,5-phenyl migration
should be thermally allowed according to the Wood-
ward–Hoffmann rule, the migration actually includes a
stepwise process.
We can draw a mechanism for the stereoselective 1,5-
phenyl migration of the chiral peroxides (4b and c) as
shown in Scheme 5. It is reasonable to imagine the for-
mation of alcohol anion 6À as an intermediate. Fortu-
nately, alcohol 6a was available from hydroperoxide
1a. Smooth rearrangement to 4a, on the treatment of
base, was confirmed even at the room temperature, as
shown in Scheme 6.
Further the byproducts tert-butyldimethylsilanol (7) and
dimethyl sulfone (DMSO2, 8) were confirmed by 1H

M. Kimura et al. / Tetrahedron Letters 48 (2007) 3109–3113
3113
O
O
S
O
O
N
N
X
N
N
N
X
i)
Ph
O
H+
Ph
Ph
X
X
N
N
N
H
O
Si
Ph
Heat
X
O
N
6-
Ph
DMSO
Y
N
ii)
+
Y
Y
Y
R-4
O
X
Si
S
O
O
N
N
O
O
N
Y
N
Ph
Ph
S-5
Ph
H+
Y
N
Y
N
H
H2O
O
Y
Si OH
S
+
X
O
8
X
S-4
b: X = CF3, Y = OCH3
c: X = CF3, Y = F
7
Scheme 5.
Cazaubon, C. F.; Breliere, J.-C.; Le Fur, G.; Nisato, D.
J. Med. Chem. 1993, 36, 3371–3380.
5. Lovely, C. J.; Du, H. W.; He, Y.; Dias, R. H. V. Org. Lett.
2004, 6, 737–738.
Ph
Ph
N
N
N
r.t.
OOH
Ph
Ph
OH
Ph
Ph
DMSO
N
6. (a) Reichard, G. A.; Stengone, C.; Paliwal, S.; Mergels-
berg, I.; Majmundar, S.; Wang, C.; Tiberi, R.; McPhail, A.
T.; Piwinski, J. J.; Shih, N. Y. Org. Lett. 2003, 5, 4249–
4251; (b) Lee, S. H.; Yoshida, K.; Matsushita, H.;
Clapham, B.; Koch, G.; Zimmermann, J.; Janda, K. D.
J. Org. Chem. 2004, 69, 8829–8835; (c) Anthony, P.;
Adam, D.; Luc, V. H. J. Org. Chem. 2006, 71, 5303–5311.
7. (a) Allen, C. F. H.; VanAllan, J. A. J. Am. Chem. Soc.
1943, 65, 1384–1389; (b) Breslow, R.; Chang, H. W. J. Am.
Chem. Soc. 1961, 83, 3727–3728; (c) Youssef, A. F.;
Ogliaruso, M. J. Org. Chem. 1972, 37, 2601–2604.
8. (a) Davidson, D.; Weiss, M.; Jelling, M. J. Org. Chem.
1937, 2, 319–327; (b) Coraor, G. R.; Cescon, L. A.;
Dessauer, R.; Silversmith, E. F.; Urban, E. J. J. Org.
Chem. 1971, 36, 2262–2267; (c) Corey, E. J.; Ven-
kateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190–6191;
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Org. Chem. 1985, 50, 1994–1996.
Y = 69%
6a
1a
TBAF/THF
DMSO
Y = 78%
i) r.t./DMSO
O
N
N
Ph
Ph
ii) TBAF/THF
DMSO
H Ph
4a
Y = 81%
TBAF = (CH3CH2CH2CH2)4NF
Scheme 6.
Acknowledgements
9. Experimental data (synthesis, reactions, spectral data for
new compounds) are available from the author.
We thank Professor M. Kojima for CD measurement
and the staff of the SC-NMR Laboratory of Okayama
University for measuring NMR spectra. This work
was supported by the Ministry of Education, Science,
Sports, and Culture of the Japanese Government
(17029042).
10. Frisch, M. J.; Trucks; G. W.; 9. Schlegel, H. B.; Scuseria,
G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J.
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