Cerium(IV) ammonium nitrate-mediated oxidative rearrangement of cyclobutanes and oxetanes

Article abstract of DOI:10.1016/S0040-4039(03)00978-X

A facile CAN-mediated oxidative rearrangement of alkoxyaryl cyclobutanes and oxetanes is described.

Full text of DOI:10.1016/S0040-4039(03)00978-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4585–4588
Cerium(IV) ammonium nitrate-mediated oxidative rearrangement
of cyclobutanes and oxetanes
Vijay Nair,* Roshini Rajan, Kishor Mohanan and V. Sheeba
Organic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum-695 019, India
Received 18 February 2003; revised 11 April 2003; accepted 16 April 2003
This paper is dedicated with best wishes to Professor Dr. H. M. R. Hoffmann
Abstract—A facile CAN-mediated oxidative rearrangement of alkoxyaryl cyclobutanes and oxetanes is described. © 2003 Elsevier
Science Ltd. All rights reserved.
As a consequence of the enormous growth in radical
methodology during the last two decades, there has
been considerable interest in the application of one
electron oxidants such as cerium(IV) ammonium nitrate
(CAN) in organic synthesis.1,2 In the course of our
investigations on carbonꢀcarbon bond forming reac-
Scheme 2. (i) hw, chloranil.
tions mediated by CAN, we discovered a facile
cyclodimerization of alkoxystyrenes leading to aryltet-
ralin derivatives (Scheme 1).3
We reasoned that if the formation of the long-bond
cyclobutane radical cation was involved, then the corre-
sponding reaction of alkoxyaryl cyclobutanes with
CAN should afford products similar to those obtained
in the CAN-mediated dimerization of alkoxystyrenes.
Thus, it was obligatory to investigate the reaction of
alkoxyaryl cyclobutanes with CAN and our results
validating the above assumption are discussed below.
Our studies were initiated with the reaction of cyclobu-
tane 9, prepared by the photochemical [2+2] cycloaddi-
tion of 4-benzyloxystyrene, with a methanolic solution
of CAN under an atmosphere of oxygen. The reaction
Scheme 1. (i) CAN, CH3OH, 0°C, 30 min.
furnished the keto-methoxybutane derivative 10 in 73%
yield (Scheme 3).6
In addition to the synthetic potential of the reaction,
vested in the close relationship of the aryltetralins to
The reaction under absolutely oxygen free conditions
naturally occurring bioactive lignans, we were intrigued
afforded the corresponding dimethoxybutane derivative
by the mechanistic implications of the cyclodimeriza-
11 (Table 1). Similar results were obtained with the
tion. By analogy with PET-mediated cyclodimerization
of alkoxystyrenes (Scheme 2),4 we invoked a mecha-
nism akin to that proposed by Bauld et al. essentially
involving the formation of a long-bond cyclobutane
radical cation.5
Scheme 3. (i) CAN (2.5 equiv.), dry CH3OH, oxygen, rt, 2 h,
* Corresponding author. Tel.: +91-471-490406; fax: +91-471-491712;
73%.
e-mail: gvn@csrrltrd.ren.nic.in
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00978-X

4586
V. Nair et al. / Tetrahedron Letters 44 (2003) 4585–4588
Table 1.
cyclobutane 12 obtained from the [2+2] photochemical
reaction of 4-methoxy styrene and the results are sum-
marized in Table 1.
Nucleophilic solvents like methanol can quench the
cationic site of the radical cation II to generate the
radical intermediate V. The radical center in V is inter-
cepted by oxygen to afford the keto-methoxy products.8
Alternatively, the radical intermediate V on further
oxidation by Ce(IV) generates the cationic intermediate
VI which is eventually quenched by methanol to afford
the dimethoxy products.
The reaction of cyclobutane 12 with a solution of CAN
in ethanol under an atmosphere of oxygen afforded the
products 15 and 16 in 35 and 30% yields, respectively
(Scheme 4).
The distonic radical cation II can also undergo 1,6-
cyclization to give a substituted hexatriene radical
cation III. The latter on losing a proton gives the
radical intermediate IV which is intercepted by oxygen
to give the tetralone 16, via the intermediacy of a
peroxy radical.8
As a logical extension to the CAN-mediated reactions
of aryl cyclobutanes, it was of interest to explore such
chemistry with oxetanes. In this context it may be
recalled that the oxidative protocol for the ring opening
of epoxides has received considerable attention. In par-
ticular, the study of CAN-mediated oxidative transfor-
mations of epoxides in the presence of different
nucleophiles has been pursued in detail.9 An intriguing
aspect of mechanistic importance evolves from the fact
that all these reactions are autocatalytic in nature
whereas the vast majority of CAN-mediated oxidations
require stoichiometric or super stoichiometric quantities
of the oxidant. A survey of the literature reveals that
even though the ring expansion as well as ring cleavage
reactions of oxetanes have been studied in detail,10 their
reactivity with CAN remains hitherto unexplored.
Scheme 4. (i) CAN (2.5 equiv.), CH3CH2OH, oxygen, rt, 1 h.
A tentative mechanistic rationale for the formation of
the above products is depicted in Scheme 5.
In a pilot experiment, when the oxetane 17 was treated
with a catalytic amount of CAN in methanol at room
temperature it underwent facile ring opening to afford
the product 18 in 90% yield (Scheme 6).11,12
Scheme 5.
Conceivably, the cyclobutane undergoes oxidative elec-
tron transfer in the presence of Ce(IV) to furnish the
radical cation7 I which will exist in equilibrium with II.
A tentative mechanistic rationale for the formation of
the product 18 is depicted in the following scheme
(Scheme 7).

V. Nair et al. / Tetrahedron Letters 44 (2003) 4585–4588
4587
Interestingly, the reaction of the oxetane 29 with a
catalytic amount of CAN in methanol at room temper-
ature afforded two products, the cyclohexenyl deriva-
tive 30 in 62% yield and the product 31 as a 3:1 mixture
of diastereoisomers in 35% yield (Scheme 8).
Scheme 6. (i) CAN (0.5 equiv.), CH3OH, rt.
Scheme 8. (i) CAN (0.5 equiv.), CH3OH, rt.
In conclusion, the reaction of cyclobutanes with CAN
affords products identical to those obtained by the
CAN-mediated dimerization of alkoxystyrenes. This
observation strongly supports our assumption of the
formation of a long-bond cyclobutane radical cation in
the CAN-mediated dimerization of alkoxy styrenes.
The regiospecific ring opening of oxetanes with cata-
lytic amounts of CAN leading to functionalized alco-
hols has also been achieved. It is anticipated that in
addition to the mechanistic implications, these reactions
will find use in organic synthesis.
Scheme 7.
The oxetane 17 is initially oxidized by Ce(IV) to the
radical cation VII which presumably exists in equi-
librium with its distonic version VIII. The alkoxy radi-
cal in VIII is reduced to the anion with the concomitant
re-oxidation of Ce(III) to Ce(IV), making the cycle
catalytic. The cationic center in VIII is quenched by
methanol affording the final product. The probability
of CAN functioning as a Lewis acid in these reactions
is minimal since in independent experiments using
Ce(III), which has comparable Lewis acidity, the oxe-
tane remained unchanged.
Acknowledgements
R.R., K.M. and V.S. thank the Council of Scientific
and Industrial Research, New Delhi, for research fel-
lowships. The authors also thank Ms. Saumini Mathew
for NMR data.
Similar results were obtained with a number of other
oxetanes and the results are shown in Table 2.
References
1. (a) Heiba, E. I.; Dessau, R. M. J. Am. Chem. Soc. 1971,
93, 524–527; (b) Baciocchi, E.; Civataresse, G.; Ruzzi-
coni, R. Tetrahedron Lett. 1987, 28, 5357–5360.
2. (a) Nair, V.; Mathew, J.; Prabhakaran, J. Chem. Soc.
Rev. 1997, 127–132; (b) Nair, V.; Mathew, J. J. Chem.
Soc., Perkin Trans. 1 1995, 187–188; (c) Nair, V.; Nair, L.
G.; George, T. G.; Augustine, A. Tetrahedron 2000, 56,
7607–7611; (d) Nair, V.; Balagopal, L.; Sheeba, V.; Pan-
icker, S. B.; Rath, N. P. Chem. Commun. 2001, 1682–
1683; (e) Nair, V.; Rajan, R.; Rath, N. P. Org. Lett. 2002,
4, 1575–1577.
Table 2.
3. (a) Nair, V.; Mathew, J.; Kanakamma, P. P.; Panicker, S.
B.; Sheeba, V.; Zeena, S.; Eigendorf, G. K. Tetrahedron
Lett. 1997, 38, 2191–2194; (b) Nair, V.; Sheeba, V.;
Panicker, S. B.; George, T. G.; Rajan, R.; Balagopal, L.;
Vairamani, M.; Prabhakar, S. Tetrahedron 2000, 56,
2461–2467.
4. Yamamoto, M.; Asanuma, T.; Nishijima, Y. J. Chem.
Soc., Chem. Commun. 1974, 53–54.
5. (a) Bauld, N. L. Tetrahedron 1989, 45, 5307–5363; (b)
Schepp, N. P.; Johnston, L. J. J. Am. Chem. Soc. 1996,
118, 2872–2881.
6. Typical experimental procedure and spectral data for com-
pound 10: A solution of CAN (329 mg, 0.60 mmol) in dry
methanol (10 mL), saturated with oxygen was added
dropwise to an oxygenated solution of the cyclobutane 9
(100 mg, 0.24 mmol) in dry methanol (5 mL). The

4588
V. Nair et al. / Tetrahedron Letters 44 (2003) 4585–4588
reaction mixture was stirred at ambient temperature for 2
42, 305–317; (b) Itoh, A.; Hirose, Y.; Kashiwagi, H.;
Masaki, Y. Heterocycles 1994, 38, 2165–2169; (c) Carless,
H. A. J.; Trivedi, H. S. J. Chem. Soc., Chem. Commun.
1979, 382–383; (d) Mudryk, B.; Cohen, T. J. Org. Chem.
1989, 54, 5657–5659; (e) Chini, M.; Crotti, P.; Favero, L.;
Macchia, F. Tetrahedron Lett. 1994, 35, 761–764; (f)
Fujiwara, T.; Tsuruta, Y.; Takeda, T. Tetrahedron Lett.
1995, 36, 8435–8438; (g) Sartillo-Piscil, F.; Quintero, L.;
Villegas, C.; Santacruz-Jua´rez, E.; Anaya de Parrodi, C.
Tetrahedron Lett. 2002, 43, 15–17; (h) Rama, K.; Pasha,
M. A. Tetrahedron Lett. 2000, 41, 1073–1074.
h. On complete consumption of the starting material the
reaction mixture was diluted with water (10 mL) and
extracted with dichloromethane (5×20 mL). The com-
bined organic extracts were washed with water, brine and
dried over anhydrous sodium sulfate. After the removal
of the solvent on a rotary evaporator, the residue was
subjected to column chromatography on silica gel using
90:10 hexane–ethyl acetate mixture to afford 10 as a
white crystalline solid (82 mg, 73%). Mp 161°C. IR (KBr)
wmax: 2928, 2881, 2827, 1681, 1593, 1512, 1458, 1249,
1169, 1013 cm−1
2.96 (t, 2H, J=7.1, CH
(m, 1H, CH), 5.05 (s, 2H, OCH
OCH2Ph), 6.95 (t, 4H, J=8.8, ArH), 7.19–7.40 (m, 12H,
ArH), 7.90 (d, 2H, J=8.7, ArH
). 13C NMR: l 32.66,
.
1H NMR: l 2.04–2.15 (m, 2H, CH2
2), 3.17 (s, 3H, OCH3), 4.13–4.17
2Ph), 5.11 (s, 2H,
6 ),
11. Typical experimental procedure and spectral data for com-
pound 18: A solution of CAN (274 mg, 0.50 mmol) in
methanol (10 mL) was added dropwise to a solution of
the oxetane 17 (230 mg, 1.10 mmol) in methanol (5 mL).
The reaction mixture was stirred at room temperature for
30 min. On complete consumption of the starting mate-
rial the reaction mixture was diluted with water (10 mL)
and extracted with dichloromethane (5×20 mL). The
combined organic extracts were washed with water, brine
and dried over anhydrous sodium sulfate. After the
removal of the solvent on a rotary evaporator, the
residue was subjected to column chromatography on
silica gel using 80:20 hexane–ethyl acetate solvent mixture
to afford pure 1813 as a colorless viscous liquid (240 mg,
90%). IR (film) wmax: 3341, 3059, 2946, 2893, 2827, 1598,
6
6
6
6
6
6
6
6
34.28, 56.48, 70.00, 70.07, 82.47, 114.50, 114.77, 127.42,
127.45, 127.82, 127.95, 128.22, 128.58, 128.69, 130.33,
130.40, 134.21, 136.23, 154.77, 158.38, 162.45, 198.26.
HRMS calcd for C31H30O4: 466.2144. Found: 466.2137.
7. Ledwith’s observation of the cyclobutane radical cation
in the reaction of the the cyclobutane from N-vinyl
carbazole with CAN is noteworthy in this context. See:
Beresford, P.; Lambert, M. C.; Ledwith, A. J. Chem. Soc.
(C) 1970, 2508–2510.
8. Nair, V.; Nair, L. G.; Mathew, J. Tetrahedron Lett. 1998,
39, 2801–2804.
1490, 1446, 1190, 1100, 1059, 1036 cm−1
2.50 (br s, 1H, OH), 2.58 (t, 2H, J=6.2, CH
3H, OCH3), 3.52 (t, 2H, J=6.1, CH2OH), 7.18–7.33 (m,
10H, ArH
). 13C NMR: l 37.24, 50.78, 59.28, 83.24,
126.96, 127.06, 128.13, 144.46.
.
1H NMR: l
6
6
2), 3.08 (s,
9. (a) Roy, S. C.; Adhikari, S. Ind. J. Chem. 1992, 31B, 459;
(b) Iranpoor, N.; Mohammadpour Baltork, I.; Zardaloo,
F. S. Tetrahedron 1991, 47, 9861–9866 and references
cited therein; (c) Iranpoor, N.; Kazemi, F.; Salehi, P.
Synth. Commun. 1997, 27, 1247–1248; (d) Iranpoor, N.;
Kazemi, F. Synth. Commun. 1999, 29, 561–566; (e) Iran-
poor, N.; Salehi, P. Tetrahedron 1995, 51, 909–912; (f)
Iranpoor, N.; Kazemi, F. Synthesis 1996, 821–822.
10. (a) Ito, K.; Yoshitake, M.; Katsuki, T. Heterocycles 1996,
6
6
6
12. For the prepapration of oxetanes, see: Okuma, K.;
Tanaka, Y.; Kaji, S.; Ohta, H. J. Org. Chem. 1983, 48,
5133–5134.
13. Virtanen, P. O. I.; Ruottinen, M.; Routsalainen, H.
Suom. Kemistil. B 1971, 44, 47–49.