Oxidative ring cleavage of cyclic acetals with hypervalent tert-butylperoxy-λ3-iodanes

Article abstract of DOI:10.1021/ol016202x

(matrix presented) Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.

Full text of DOI:10.1021/ol016202x

ORGANIC
LETTERS
2001
Vol. 3, No. 15
2387-2390
Oxidative Ring Cleavage of Cyclic
Acetals with Hypervalent
tert-Butylperoxy-λ3-iodanes
Takuya Sueda, Sonoko Fukuda, and Masahito Ochiai*
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi,
Tokushima 770-8505, Japan
mochiai@ph2.tokushima-u.ac.jp
Received May 30, 2001
ABSTRACT
Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate
in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.
The crystalline alkylperoxy-λ3-iodane 1-tert-butylperoxy-1,2-
benziodoxol-3(1H)-one (2), prepared from 1-hydroxy-1,2-
benziodoxol-3(1H)-one by Lewis acid catalyzed ligand
exchange with tert-butyl hydroperoxide, is stable in the solid
state but gradually decomposes in solution at room temper-
ature to generate tert-butylperoxy radical.1,2 The hypervalent
(tert-butylperoxy)iodane 2 oxidizes benzyl and allyl ethers
to esters at room temperature in the presence of alkali metal
carbonates via a radical process.1 A variety of sulfides and
4-alkylphenols are readily oxidized to sulfoxides and 4-(tert-
butylperoxy)-2,5-cyclohexadien-1-ones, respectively, in good
yields.3,4 The (tert-butylperoxy)iodane 2 also oxidizes sec-
ondary and tertiary amines to imines and tert-butylper-
oxyamino acetals, respectively.5 Oxidation of amides with
2 affords imides or tert-butylperoxyamide acetals, depending
on the reaction conditions.6 We report herein the oxidative
conversion of cyclic acetals 1 to hydroxy esters 3 with (tert-
butylperoxy)iodane 2 in the presence of tert-butyl hydro-
peroxide and potassium carbonate (Scheme 1). Substituent
effects for the oxidation of cyclic aryl acetals 1 and the effect
of the free-radical scavenger galvinoxyl were also examined.
1,3-Dioxolanes are among the most widely used protective
groups for carbonyl compounds and vicinal diols.7 Oxidation
of 2-aryl- and 2-alkyl-1,3-dioxolanes derived from aldehydes
provides a useful route for the synthesis of 2-hydroxyethyl
esters. Reagents used for direct oxidative cleavage of 1,3-
Scheme 1
(1) (a) Ochiai, M.; Ito, T.; Masaki, Y.; Shiro, M. J. Am. Chem. Soc.
1992, 114, 6269. (b) Ochiai, M.; Ito, T.; Takahashi, H.; Nakanishi, A.;
Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M. J. Am. Chem. Soc. 1996, 118,
7716.
(2) The (tert-butylperoxy)iodane 2 is commercially available and was
purchased from Tokyo Chemical Industry.
(3) Ochiai, M.; Nakanishi, A.; Ito, T. J. Org. Chem. 1997, 62, 4253.
(4) Ochiai, M.; Nakanishi, A.; Yamada, A. Tetrahedron Lett. 1997, 38,
3927.
(5) Ochiai, M.; Kajishima, D.; Sueda, T. Heterocycles 1997, 46, 71.
10.1021/ol016202x CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/29/2001

dioxolanes include ozone,8 molecular oxygen-Co(II),9 hy-
pochlorous acid,10 potassium permanganate,11 N-hydroxyph-
thalimide in electrochemical oxidation,12 and tert-butyl
hydroperoxide in the presence of Pd(II), Ru(III), or pyri-
dinium dichromate (PDC).13 2-Hydroxyethyl esters have
found use in selective Diels-Alder reactions, because the
functionality can be preferentially activated with Lewis acids
by forming a seven-membered chelated structure in the
presence of simple ester groups.14
than 60% (compare entries 1, 2, and 7 in Table 1). It has
been reported that alkali metal carbonates markedly acceler-
ate benzylic oxidation of benzyl ethers with the peroxyiodane
21b and that the yields of oxidation of 4-alkylphenols to
4-(tert-butylperoxy)-2,5-cyclohexadien-1-ones with 2 are
significantly improved when tert-butyl hydroperoxide is used
as an additive.4 When both of these additives are used in
the oxidation of 1a, the yield of benzoate 3a increased to
80-94% (Table 1, entries 9-11). No appreciable effects of
molecular dioxygen were observed in this oxidative cleavage;
thus, reactions carried out under argon and in air gave
comparable yields of 3a (Table 1, entries 3 and 4). The
oxidative ring cleavage requires a stoichiometric amount of
peroxyiodane 2, and without 2, only a trace of 3a was
detected (Table 1, entries 11-13).
Oxidations of 2-phenyl-1,3-dioxolane (1a; R ) Ph, n )
1) with (tert-butylperoxy)iodane 2 in benzene were examined
at room temperature under a variety of conditions (Table
1). The reaction with the peroxyiodane 2 (1 equiv) was slow,
The radical nature of this oxidation with 2 was substanti-
ated by complete inhibition of reaction with the added radical
scavenger galvinoxyl (Table 1, entries 5 and 14); in these
reactions, a large amount of 1a was recovered unchanged.
A typical experimental procedure is as follows (Table 1,
entry 11). To a stirred suspension of 2-phenyl-1,3-dioxolane
(1a, 0.2 mmol) and potassium carbonate (0.4 mmol) in
benzene (3 mL) was added a solution of tert-butyl hydrop-
eroxide (4.1 M solution in dichloroethane, 1 mmol) and
peroxyiodane 2 (0.2 mmol) at room temperature in air. After
24 h, the reaction mixture was quenched with 5% aqueous
potassium carbonate solution and extracted with diethyl ether
three times. The combined organic layers were washed with
water and brine, dried over Na2SO4, and concentrated in
vacuo. Purification of the crude product by preparative TLC
(silica gel, 7:3 hexane/ethyl acetate) gave â-hydroxyethyl
benzoate (3a, 94%). Very interestingly, in the crude product
formation of a large amount of the unstable tert-butylperoxy
ortho ester 4a (R ) Ph, n ) 1) was detected by 1H NMR, in
addition to the benzoate 3a. The ortho ester 4a, upon
exposure to silica gel, readily hydrolyzes to benzoate 3a in
high yield. The structure of 4a was confirmed by the
independent synthesis via acid-catalyzed exchange of ortho
ester 5 with tert-butyl hydroperoxide (Scheme 2).15 These
Table 1. Oxidative Ring Opening of Cyclic Acetal 1a with
Hypervalent (tert-Butylperoxy)iodane 2a
2
K2CO3
(equiv)
t-BuOOH
time
(h)
3a yieldb
entry
(equiv)
(equiv)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
1
2
2
2
2
1
1
1
1
1
0.5
24
24
11
8d
11d,e
11f
24
24
24
24
24
24
24
24d,e
24f
24c
63
79
73
0c
71
65
56
80
86
94
50
3c
2
4
4
4
4
5
0.5
1
3
5
5
5
5
5
2
2
2
2
2
2
2
2
1
1
0c
58
a The reaction was carried out at room temperature in benzene in the
air. b Isolated yields. c 1a (entry 1, 64%; entry 5, 81%; entry 13, 70%; entry
14, 79%) was recovered unchanged. d The reaction was carried under argon.
e Galvinoxyl (1-2 equiv) was used as an additive. f TEMPO (1 equiv) was
used as an additive.
and â-hydroxyethyl benzoate (3a; R ) Ph, n ) 1) was
obtained in a low yield (24%) after 24 h at room temperature.
The use of potassium carbonate or tert-butyl hydroperoxide
as an additive increased the yield of benzoate 3a to more
Scheme 2
(6) Ochiai, M.; Kajishima, D.; Sueda, T. Tetrahedron Lett. 1999, 40,
5541.
(7) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis; Wiley: New York, 1991.
(8) Deslongchamps, P.; Atlani, P.; Frehel, D.; Malaval, A.; Moreau, C.
Can. J. Chem. 1974, 52, 3651.
(9) (a) Ikeda, C. K.; Braun, R. A.; Sorenson, B. E. J. Org. Chem. 1964,
29, 286. (b) Rieche, A.; Schmitz, E.; Beyer, E. Chem. Ber. 1958, 91, 1935.
(10) Sugai, S.; Kodama, T.; Akaboshi, S.; Ikegami, S. Chem. Pharm.
Bull. 1984, 32, 99.
(11) Nai-ju, H.; Liang-heng, X. Synth. Commun. 1990, 20, 1563.
(12) Masui, M.; Kawaguchi, T.; Yoshida, S.; Ozaki, S. Chem. Pharm.
Bull. 1986, 34, 1837.
(13) (a) Hosokawa, T.; Imada, Y.; Murahashi, S. J. Chem. Soc., Chem.
Commun. 1983, 1245. (b) Murahashi, S.; Oda, Y.; Naota, T. Chem. Lett.
1992, 2237. (c) Chidambaram, N.; Bhat, S.; Chandrasekaran, S. J. Org.
Chem. 1992, 57, 5013. (d) Luzzio, F. A.; Bobb, R. A. Tetrahedron Lett.
1997, 38, 1733.
results clearly suggest that the primary product of oxidation
of 2-phenyl-1,3-dioxolane (1a) with (tert-butylperoxy)iodane
2 is the ortho ester 4a.
The results of oxidation of a variety of acetals with
peroxyiodane 2 in the presence of tert-butyl hydroperoxide
and potassium carbonate are summarized in Table 2.
Aromatic and aliphatic 1,3-dioxolanes undergo oxidative ring
cleavage, yielding â-hydroxyethyl esters in good yields. The
(14) Clapham, G.; Shipman, M. Tetrahedron Lett. 1999, 40, 5639.
(15) Rieche, A.; Schmitz, E.; Beyer, E. Chem. Ber. 1958, 91, 1942.
Org. Lett., Vol. 3, No. 15, 2001
2388

Scheme 4
Table 2. Oxidation of Acetals with (tert-Butylperoxy)iodane 2
and tert-Butyl Hydroperoxidea
time
(h)
yieldb
(%)
entry
acetal
R
n
3
1
2
3
4
5
6
7
8
9
1b
1c
1d
1e
1f
1g
1h
1i
p-MeC6H4
p-ClC6H4
m-ClC6H4
2-furyl
PhCHdCH
PhCH2
n-C9H19
c-C6H11
Ph
1
1
1
1
1
1
1
1
2
24
24
24
24
8
48
24
24
24
24
3b
3c
3d
3e
3f
3g
3h
3i
84
80
78
77c
65
54d
71d
62d
57d
19d,f
1j
6e
3j
7
10
assumed to involve the following key steps: (a) homolytic
cleavage of the hypervalent iodine(III)-peroxy bond in 2
to give tert-butylperoxy radical and [9-I-2] iodanyl radical
12,16,17 (b) hydrogen abstraction from acetals 1 by the tert-
butylperoxy radical to give the carbon-centered acetal radicals
13 and tert-butyl hydroperoxide, (c) coupling of 2-dioxolanyl
radicals 13 with tert-butylperoxy radical, regenerated from
tert-butyl hydroperoxide by the reaction with iodanyl radical
12,4 to give the tert-butylperoxy ortho esters 4, probably via
single electron transfer, (d) ring opening of ortho esters 4 to
â-hydroxyethyl esters 3 by silica gel catalyzed hydrolysis.
Formation of acetal radicals 13 via hydrogen abstraction in
1 by iodanyl radical 12 might compete with that by tert-
butylperoxy radical. Single electron transfer from 2-diox-
olanyl radicals 13 to peroxyiodane 2 might also produce the
ortho esters 4 with concomitant regeneration of the iodanyl
radical 12.18,19 The mechanism shown in Scheme 4 is in good
agreement with the intermediate formation of the tert-
butylperoxy ortho esters 4 and the product distribution
observed for oxidation of the unsymmetrical acetal 8. The
observation that attempted oxidation of 2-methyl-2-phenyl-
1,3-dioxolane, possessing no acetal hydrogens, led to recov-
ery of the acetal (91%) is also compatible with this
mechanism.
a The reaction was carried out using (tert-butylperoxy)iodane 2 (1 equiv)
and tert-butyl hydroperoxide (5 equiv) in the presence of K2CO3 (2 equiv)
at room temperature in benzene in the air. b Isolated yields. c 1H NMR yields.
d Acetals (entry 6, 12%; entry 7, 22%; entry 8, 10%; entry 9, 27%; entry
10, 47%) were recovered unchanged. e Benzaldehyde dimethylacetal (6) and
methyl benzoate (7). f 1-(tert-Butylperoxy)benzyl methyl ether (13%) was
obtained.
rate of oxidation of aromatic 1,3-dioxolanes appears to be
greater than that of aliphatic ones. Oxidation of acetal 1f,
derived from R,â-unsaturated aldehyde, affords the conju-
gated ester 3f in good yield. As reported in the oxidation
with ozone8 and N-hydroxyphthalimide,12 acyclic dialkoxy
acetals react much more slowly than cyclic ones; thus,
oxidation of benzaldehyde dimethylacetal (6) gave methyl
benzoate (7) in only 19% yield after 24 h and returned a
large amount of unreacted acetal (47%) (Table 2, entry 10).
The rates of oxidative cleavage seem to decrease in the order
five-membered 1a > six-membered ring acetal 1j > acyclic
acetal 6.
Oxidative cleavage of the unsymmetrical cyclic acetal
4-methyl-2-phenyl-1,3-dioxolane (8) with 2 favors formation
of secondary ester 9 over primary ester 10, although the
degree of regioselectivity is low. A mixture of isomeric
hydroxy esters 9 (54%) and 10 (39%) and keto ester 11 (2%)
was obtained in this reaction (Scheme 3). The keto ester 11
The slow step of this oxidation is probably acetal C-H
bond breaking in the cyclic acetals 1 yielding the carbon-
centered radicals 13. This is in good agreement with the
relatively large deuterium kinetic isotope effect kH/kD ) 8.5
measured for oxidation of protonated and deuterated 2-phen-
yl-1,3-dioxolanes 1a in benzene at 30 °C under argon. A
large isotope effect (kH/kD ) 13) has also been reported for
the radical oxidation of benzyl n-butyl ether with tert-
butylperoxyiodane 2, which most likely involves rate-limiting
benzylic hydrogen abstraction.1b
Scheme 3
(16) Hashimoto, J.; Segawa, K.; Itoh, H.; Sakuragi, H. Chem. Lett. 2000,
362.
is probably produced by further oxidation of secondary
alcohol 10 under the conditions; this was confirmed by a
separate experiment. A slight preference for formation of
the secondary ester 9 was observed in oxidative cleavage of
8 with tert-butyl hydroperoxide in the presence of PDC13c
and Pd(II).13a
(17) The first-order rate constant for decomposition of 2 in dichlo-
romethane at 30 °C is 2.62 × 10-5 s-1 1b
.
(18) Hypervalent [bis(acyloxy)iodo]benzenes act as good electron ac-
ceptors: (a) Kita, Y.; Tohma, H.; Hatanaka, K.; Takada, T.; Fujita, S.;
Mitoh, S.; Sakurai, H.; Oka, S. J. Am. Chem. Soc. 1994, 116, 3684. (b)
Kokkinidis, G.; Papadopoulou, M.; Varvoglis, A. Electrochim. Acta 1989,
34, 133.
(19) Homolytic cleavage of the iodine(III)-peroxy bond of the peroxy-
iodane 2 by nucleophilic attack of 13 may also produce the ortho esters 4
and the iodanyl radical 12.
As illustrated in Scheme 4, a mechanism for oxidative
cleavage of cyclic acetals 1 with peroxyiodane 2 might be
Org. Lett., Vol. 3, No. 15, 2001
2389

Relative rates of oxidation for a series of substituted 1,3-
dioxolanes 1a-d were measured by competitive reactions,
in which a mixture of a 10-fold excess of each of two
competing substrates was used. The electron-releasing p-Me
group increases the rate of oxidation (Table 3). A Hammett
peroxyiodane oxidation of 1a was not retarded by excess
amounts of 1,4-dimethoxybenzene, a single electron transfer
quencher with oxidation potential Eox ) 1.28 V (vs SCE in
MeCN).21
The decrease in the rate of oxidative cleavage in the order
of five-membered 1a > six-membered ring acetal 1j >
acyclic acetal 6 probably reflects differences in the rates of
acetal hydrogen abstractions. In fact, it has been reported
that the relative rates of hydrogen abstraction with tert-butoxy
radical at -60 °C in cyclopropane decreases in the order
1,3-dioxolane (1) > 4-methyl-1,3-dioxane (0.06) > dimethoxy-
methane (0.03).22 The stereoelectronic effect that a relatively
small dihedral angle (<30°) between the C-H bond and the
p-type lone pair orbital on the adjacent ethereal oxygen
results in high rates of the hydrogen abstraction might play
an important role in hydrogen atom abstraction from cyclic
and acyclic ethers.8,22
Table 3. Relative Reactivity of Acetals 1 with 2 in Benzene at
30 °C under Argon
substrate
R
krel
1a
1b
1c
1d
C6H5
1.0
p-MeC6H4
p-ClC6H4
m-ClC6H4
1.5
0.68
0.64
plot for the oxidation of 1,3-dioxolanes 1a-d, presented in
Table 3, showed a good linear correlation between the
relative rate factors and σ-constants of substituents in the
aromatic ring and gave the reaction constant F ) -0.69 (r
In conclusion, we have shown that the (tert-butylperoxy)-
iodane 2 is a useful reagent for oxidative cleavage of five-
membered cyclic acetals to the corresponding hydroxy esters
under mild conditions. It should be noted that the iodane 2
is very stable in the solid state and an environmentally
friendly oxidizing reagent containing no poisonous heavy
metals and that the o-iodobenzoic acid formed in the reaction
can be recycled by oxidation to the hypervalent iodane 2.
) 0.97). This F value appears to be comparable to F+
)
-0.30 for the radical oxidation of benzyl n-butyl ethers with
tert-butylperoxyiodane 2.1b
An alternative pathway involving single electron transfer
from the cyclic acetals 1 to the peroxyiodane 2 or tert-
butylperoxy radical, followed by loss of a proton generating
2-dioxolanyl radicals 13, dose not seem to operate.20 The
OL016202X
(21) Tanemura, K.; Dohya, H.; Imamura, M.; Suzuki, T.; Horaguchi, T.
Chem. Lett. 1994, 965.
(22) (a) Malatesta, V.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 609.
(b) Malatesta, V.; Scaiano, J. C. J. Org. Chem. 1982, 47, 1455. (c) Beckwith,
A. L. J.; Easton, C. J. J. Am. Chem. Soc. 1981, 103, 615. (d) Huyser, E. S.;
Garcia, Z. J. Org. Chem. 1962, 27, 2716.
(20) Ates, A.; Gautier, A.; Leroy, B.; Plancher, J.-M.; Quesnel, Y.;
Marko, I. E. Tetrahedron Lett. 1999, 40, 1799.
2390
Org. Lett., Vol. 3, No. 15, 2001