Hypervalent (tert-butylperoxy)iodanes generate iodine-centered radicals at room temperature in solution: Oxidation and deprotection of benzyl and allyl ethers, and evidence for generation of α-oxy carbon radicals

Article abstract of DOI:10.1021/ja9610287

1-(tert-Butylperoxy)-1,2-benziodoxol-3(1H)-one (1a) oxidizes benzyl and allyl ethers to the esters at room temperature in benzene or cyclohexane in the presence of alkali metal carbonates. Since this reaction is compatible with other protecting groups such as MOM, THP, and TBDMS ethers, and acetoxy groups, and because esters are readily hydrolyzed under basic conditions, this new method provides a convenient and effective alternative to the usual reductive deprotection. Oxidation with 1a occurs readily with C-H bonds activated by both enthalpic effects (benzylic, allylic, and propargylic C-H bonds) and/or polar effects (α-oxy C-H bonds), generating α-oxy carbon-centered radicals, which can be detected by nitroxyl radical trapping. Measurement of the relative rates of oxidation for a series of ring-substituted benzyl n-butyl ethers 2d and 2p-s indicated that electron-releasing groups such as p-MeO and p-Me groups increase the rate of oxidation, and Hammett correlation of the relative rate factors with the σ⁺ constants of substituents afforded the reaction constant ρ⁺ = -0.30. The large value of the isotope effect obtained for the oxidation of benzyl n-butyl ether 2d (k(H)/k(D) = 12-14) indicates that the rate-determining step of the reactions probably involves a high degree of benzylic C-H bond breaking. The effects of molecular dioxygen were examined, and the mechanism involving the intermediacy of the tert-butylperoxy acetal 5 and/or the hydroperoxy acetal 32 is proposed. Particularly noteworthy is the finding that (tert-butylperoxy)iodane 1a can generate the tert-butylperoxy radical and the iodine-centered radical 33a, even at room temperature in solution, via homolytic bond cleavage of the hypervalent iodine(III)-peroxy bond.

Full text of DOI:10.1021/ja9610287

7716
J. Am. Chem. Soc. 1996, 118, 7716-7730
Hypervalent (tert-Butylperoxy)iodanes Generate
Iodine-Centered Radicals at Room Temperature in Solution:
Oxidation and Deprotection of Benzyl and Allyl Ethers, and
Evidence for Generation of R-Oxy Carbon Radicals
Masahito Ochiai,*,† Takao Ito,† Hideo Takahashi,† Akinobu Nakanishi,†
Mika Toyonari,† Takuya Sueda,† Satoru Goto,† and Motoo Shiro‡
Contribution from the Faculty of Pharmaceutical Sciences, UniVersity of Tokushima,
1-78 Shomachi, Tokushima 770, Japan, and Rigaku Corporation, 3-9-12 Matsubara,
Akishima, Tokyo 196, Japan
ReceiVed March 28, 1996X
Abstract: 1-(tert-Butylperoxy)-1,2-benziodoxol-3(1H)-one (1a) oxidizes benzyl and allyl ethers to the esters at room
temperature in benzene or cyclohexane in the presence of alkali metal carbonates. Since this reaction is compatible
with other protecting groups such as MOM, THP, and TBDMS ethers, and acetoxy groups, and because esters are
readily hydrolyzed under basic conditions, this new method provides a convenient and effective alternative to the
usual reductive deprotection. Oxidation with 1a occurs readily with C-H bonds activated by both enthalpic effects
(benzylic, allylic, and propargylic C-H bonds) and/or polar effects (R-oxy C-H bonds), generating R-oxy carbon-
centered radicals, which can be detected by nitroxyl radical trapping. Measurement of the relative rates of oxidation
for a series of ring-substituted benzyl n-butyl ethers 2d and 2p-s indicated that electron-releasing groups such as
p-MeO and p-Me groups increase the rate of oxidation, and Hammett correlation of the relative rate factors with the
σ+ constants of substituents afforded the reaction constant F+ ) -0.30. The large value of the isotope effect obtained
for the oxidation of benzyl n-butyl ether 2d (kH/kD ) 12-14) indicates that the rate-determining step of the reactions
probably involves a high degree of benzylic C-H bond breaking. The effects of molecular dioxygen were examined,
and the mechanism involving the intermediacy of the tert-butylperoxy acetal 5 and/or the hydroperoxy acetal 32 is
proposed. Particularly noteworthy is the finding that (tert-butylperoxy)iodane 1a can generate the tert-butylperoxy
radical and the iodine-centered radical 33a, even at room temperature in solution, via homolytic bond cleavage of
the hypervalent iodine(III)-peroxy bond.
Introduction
iodosylbenzene with 40% peracetic acid at 35 °C gave pen-
tavalent iodylbenzene via the transient formation of [bis-
(peracetoxy)iodo]benzene.2b,3
In spite of extensive studies on the chemistry of orga-
noiodanes, little is known about peroxyiodanes, probably
because of their high tendency to decompose.1 Bis(peracyloxy)-
iodanes of the type ArI(OOCOR)2 are believed to be an
intermediate in the oxidation of iodoarenes to pentavalent
arylperiodanes. In 1970, Plesnicar and Russell reported the first
synthesis of (peraroyloxy)iodanes.2 They obtained the sym-
metrically substituted [bis(perbenzoyloxy)iodo]benzenes as
labile amorphous solids, which under spontaneous ignition or
detonation upon manipulation in the solid state at room
temperature, by the reaction of iodosylbenzene with perbenzoic
acids. Derivatives of aliphatic peroxycarboxylic acids, being
less stable, could not be isolated, and thus, reaction of
Milas and Plesnicar reported the reaction of iodosylbenzene
with tert-butyl hydroperoxide in dichloromethane and proposed
the in situ generation of labile [bis(tert-butylperoxy)iodo]-
benzene, which decomposes homolytically even at -80 °C to
give tert-butylperoxy radical and iodobenzene.4 This ready
decomposition of the (alkylperoxy)iodane can be attributed to
the small dissociation energy of the apical hypervalent peroxy-
iodine(III) bond and is facilitated by conjugative overlap of the
breaking hypervalent bond with π-orbitals of the aromatic
nucleus. Recently, we reported the synthesis and characteriza-
tion of the first stable crystalline (alkylperoxy)iodane, 1-(tert-
butylperoxy)-1,2-benziodoxol-3(1H)-one (1a), in which fixation
of an apical peroxy ligand and an equatorial aromatic ligand
on iodine(III) by the formation of five-membered heterocycles
such as an iodoxolone leads to enhanced stability of the
(alkylperoxy)iodinanes:5 Lewis acid-catalyzed ligand exchange
of 1-hydroxy-1,2-benziodoxol-3(1H)-one with tert-butyl hydro-
peroxide in chloroform afforded the alkylperoxyiodane 1a in
† University of Tokushima.
‡ Rigaku Corp.
X Abstract published in AdVance ACS Abstracts, August 1, 1996.
(1) For reviews of organoiodanes, see: (a) Banks, D. F. Chem. ReV. 1966,
66, 243. (b) Koser, G. F. The Chemistry of Functional Groups, Supple-
mented D; Wiley: New York, 1983; Chapter 18. (c) Varvoglis, A. Synthesis
1984, 709. (d) Ochiai, M.; Nagao, Y. J. Synth. Org. Chem., Jpn. 1986, 44,
660. (e) Moriarty, R. M.; Prakash, O. Acc. Chem. Res. 1986, 19, 244. (f)
Merkushev, E. B. Russ. Chem. ReV. 1987, 56, 826. (g) Ochiai, M. ReVs.
Heteroatom Chem. 1989, 2, 92. (h) Moriarty, R. M.; Vaid, R. K. Synthesis
1990, 431. (i) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett. 1990,
365. (j) Stang, P. J. Angew. Chem., Int. Ed. Engl. 1992, 31, 274. (k)
Varvoglis, A. The Chemistry of Polycoordinated Iodine; VHC Publishers:
New York, 1992. (l) Koser, G. F. The Chemistry of Functional Groups,
Supplement D2; Wiley: New York, 1995; Chapter 21.
(3) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 43, 65.
(4) (a) Milas, N. A.; Plesnicar, B. J. Am. Chem. Soc. 1968, 90, 4450.
(b) Traylor, T. G.; Xu, F. J. Am. Chem. Soc. 1987, 109, 6201. (c) Traylor,
T. G.; Fann, W.-P.; Bandyopadhyay, D. J. Am. Chem. Soc. 1989, 110, 8009.
(5) Ochiai, M.; Ito, T.; Masaki, Y.; Shiro, M. J. Am. Chem. Soc. 1992,
114, 6269.
(2) (a) Plesnicar, B.; Russell, G. A. Angew. Chem., Int. Ed. Engl. 1970,
9, 797. (b) Plesnicar, B. J. Org. Chem. 1975, 40, 3267.
S0002-7863(96)01028-1 CCC: $12.00 © 1996 American Chemical Society

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7717
Table 1. Solvent Effects in the Oxidation of Benzyl n-Butyl Ether
2d with Peroxyiodane 1aa
high yield. This is stable in the solid state and can be safely
stored at room temperature for an indefinite period of time.6
entry
solvent
ꢀ
time (d)
yield of 3d (%)b
1
2
3
4
5
6
7
8
9
MeCN
MeOH
t-BuOH
CH2Cl2
AcOEt
C6H5Fc
Et2O
36.2
32.6
12.5
8.9
6.0
5.42
4
4
4.3
4
4
4
1
4
4.3
3.2
34 (36)
12 (88)
20 (67)
49 (4)
51 (14)
47 (14)
<1 (95)
70 (11)
83 (3)
4.2
C6H6
C6H6
2.27
2.27
2.27
c
We report here that the (alkylperoxy)iodane 1a oxidizes
benzyl and allyl ethers to the esters even at room temperature
in the presence of alkali metal carbonates, thus offering a new
method for the deprotection of benzyl and allyl ethers. The
oxidation of the activated C-H bonds with 1a generates R-oxy
carbon-centered radicals, which were detected by nitroxyl radical
trapping. The large value of the isotope effect obtained for the
oxidation of benzyl n-butyl ether 2d indicates that the rate-
determining step of the reactions probably involves a high degree
of benzylic C-H bond breaking. We also examined the effects
of molecular dioxygen on the reaction and propose a mechanism
involving the intermediacy of tert-butylperoxy acetals and/or
hydroperoxy acetals.
d
10
C6H6
11 (23)
a Unless otherwise noted, reactions were carried out using 2.2 equiv
of 1a at room temperature under nitrogen. b Yields were determined
by GC. Parentheses are recovered 2d. c 3 equiv of 1a was used. d BF3-
Et2O (0.1 equiv) was added.
days gave the methoxyiodane 410 in 50% yield. Use of diethyl
ether as a solvent also gave poor results (Table 1, entry 7).
Although all of the peroxyiodane 1a was consumed after 24 h,
3d was produced in less than 1% yield because of the oxidation
of the solvent diethyl ether with 1a under the conditions (for
the oxidation of dialkyl ethers, see below).
Results and Discussion
Optimization of Reaction Variables. The benzyl ether
function is one of the most common protecting groups for
alcohols, because of its ease of formation and stability to a
variety of reagents and to both acidic and basic conditions. It
is usually removed by catalytic hydrogenation or by alkali metal
reduction.7 If, however, the substrate contains additional
reducible functions, this procedure may not be applied8 and
oxidative debenzylation is an alternative to the usual reductive
methods.9
The oxidation of benzyl ethers to the corresponding esters
of benzoic acids with the peroxyiodane 1a takes place at room
temperature; however, the reaction was found to be very slow.
Oxidation of benzyl n-butyl ether 2d was carried out in MeCN
using 2.2 equiv of 1a under nitrogen atmosphere using a rubber
balloon. Even after 4 days at room temperature, 36% of 2d
was recovered unchanged and n-butyl benzoate 3d was obtained
in only 34% yield. As shown in Table 1, the benzylic oxidation
is very sensitive to the nature of the solvents used. When the
reaction was carried out in alcoholic solvents, such as methanol
and tert-butyl alcohol, poor results were obtained. Extensive
ligand exchange of the tert-butylperoxy group of 1a with an
alcohol would be responsible for low yields of the ester 3d: in
fact, treatment of 1a with methanol at room temperature for 2
As shown in Table 1, oxidation of 2d is very sensitive to
solvent polarity. Solvents of low dielectric constants seem to
give better results; in benzene (ꢀ ) 2.27), 70-83% yields of
n-butyl benzoate 3d were obtained (Table 1, entries 8 and 9).
Addition of BF3-Et2O decreased the yield of 3d. A good linear
correlation between Dimroth’s ET(30) values11 (MeCN, 46.0;
CH2Cl2, 41.1; AcOEt, 38.1; C6H6, 34.5) and the yields of 3d
[log (yields of 3d)] was obtained (n ) 4, r ) 0.98). Oxidation
of 2d with 1a in benzene resulted in a good yield of the ester
3d; however, the rate of the reaction was too slow to be useful
synthetically.
In the autoxidation of cumene, it has been shown that addition
of bases such as Na2CO3, NaHCO3, or Ca(OH)2 increases both
the rate of oxidation and the yields of the hydroperoxide product.
These bases are thought to remove benzoic acid formed in the
reaction as one of the byproducts.12,13 In this peroxyiodane
oxidation of benzyl ether 2d, the formation of o-iodobenzoic
acid, which is more acidic (pKa ) 2.85) than benzoic acid (pKa
) 4.19), from 1a would also be expected. Furthermore, as was
(6) Moss and Zhang also reported a synthesis of the peroxyiodane 1a
involving a ligand exchange of a labile (phosphoryloxy)iodane, prepared
in situ by the reaction of 1-chloro-1,2-benziodoxol-3(1H)-one with silver
diphenyl phosphate in DMSO, with tert-butyl hydroperoxide. See: Moss,
R. A.; Zhang, H. J. Am. Chem. Soc. 1994, 116, 4471.
(7) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis; Wiley: New York, 1991, Chapter 2.
(8) (a) Schmidt, W.; Steckhan, E. Angew. Chem., Int. Ed. Engl. 1978,
17, 673. (b) Schmidt, W.; Steckhan, E. Angew. Chem., Int. Ed. Engl. 1979,
18, 801. (c) Schmidt, W.; Steckhan, E. Angew. Chem., Int. Ed. Engl. 1979,
18, 802. (d) Baciocchi, E.; Piermattei, A.; Rol, C.; Ruzziconi, R.; Sebastiani,
G. V. Tetrahedron 1989, 45, 7409.
(9) (a) RuO4: Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless,
K. B. J. Org. Chem. 1981, 46, 3936. Schuda, P.; F.; Cichowicz, M. B.;
Heimann, M. R. Tetrahedron Lett. 1983, 24, 3829. (b) O3: Hirama, M.;
Shimizu, M. Synth. Commun. 1983, 13, 781. Angibeaud, P.; Defaye, J.;
Gadelle, A.; Utille, J.-P. Synthesis 1985, 1123. (c) CrO3: Bal, B. S.;
Kochhar, K. S.; Pinnick, H. W. J. Org. Chem. 1981, 46, 1492. (d) R4N+-
MnO4-: Schmidt, H.-J.; Schafer, H. J. Angew. Chem., Int. Ed. Engl. 1979,
18, 69. (e) DDQ: Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron
Lett. 1982, 23, 885. (f) Me2CO2: Marples, B. A.; Muxworthy, J. P.;
Baggaley, K. H. Synlett 1992, 646. (g) Electrochemical: Weinreb, S. M.;
Epling, G. A.; Comi, R.; Reitano, M. J. Org. Chem. 1975, 40, 1356.
(10) Baker, G. P.; Mann, F. G.; Sheppard, N.; Tetlow, A. J. J. Chem.
Soc. 1965, 3721.
(11) (a) Dimroth, K.; Reichardt, C.; Seipmann, T.; Bohlmann, F. Justus
Liebigs Ann. Chem. 1963, 661, 1. (b) Reichardt, C. Justus Liebigs Ann.
Chem. 1971, 752, 64. (c) Reichardt, C. SolVent Effects in Organic
Chemistry; Verlag Chemie: Weinheim, 1979.
(12) Benzoic acid formed has been shown to decompose the hydroper-
oxide product. See: Tunoda, Y.; Matumoto, Y. Kogyo Kagaku Zasshi 1959,
62, 1555.
(13) On the other hand, photoinitiated benzylic bromination with
bromotrichloromethane has been shown to be retarded by the addition of
K2CO3, which could scavenge the hydrogen bromide produced in the
reactions. For this bromination, both the trichloromethyl radical and the
bromine atom, generated from hydrogen bromide, have been suggested to
participate in benzylic hydrogen atom abstraction. See: (a) Tanner, D.
D.; Arhart, R. J.; Blackburn, E. V.; Das, N. C.; Wada, N. J. Am. Chem.
Soc. 1974, 96, 829. (b) Tanner, D. D.; Wada, N. J. Am. Chem. Soc. 1975,
97, 2190. (c) Krosley, K. W.; Gleicher, G. J. J. Org. Chem. 1990, 55,
4469.

7718 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
Figure 2. Time courses for the oxidation of 2d with 1 in the presence
of K2CO3 in benzene under nitrogen. Symbols are as follows: (b) 1a
(1 equiv)/K2CO3 (2 equiv)/25 °C, (O) 1a (2 equiv)/K2CO3 (4 equiv)/
25 °C, (×) 1a (3 equiv)/K2CO3 (6 equiv)/25 °C, (2) 1a (2 equiv)/K2-
CO3 (4 equiv)/50 °C, (0) 1b (2 equiv)/K2CO3 (4 equiv)/25 °C.
Figure 1. Time courses for oxidation of 2d with 1a (3 equiv) in the
presence and absence of alkali metal carbonates (6 equiv) at 25 °C in
benzene under nitrogen. Yields of 3d were determined by GC.
Symbols are as follows: (0) none, (9) Li2CO3, (4) Na2CO3, (b) K2-
CO3, (O) Rb2CO3, and (×) Cs2CO3.
zoic acid14 by the ligand exchange reaction with tert-butyl
hydroperoxide, was used instead of 1a, the oxidation rate was
slightly retarded (see Figure 2).
discussed above, addition of BF3-Et2O retards the oxidation.
Accordingly, we examined the reaction in the presence of alkali
metal carbonates as a base to remove acidic byproducts. Strong
bases such as sodium and potassium hydroxides cause hydrolysis
of the product esters and, therefore, are not suitable for this
purpose.
Substrate Generality. A. Oxidation of Benzyl Ethers.
Because alkyl benzoates are readily hydrolyzed to the corre-
sponding alcohols under basic conditions,7 oxidation of benzyl
ethers to the benzoate esters provides a method for the
deprotection of benzyl ether protecting groups. To illustrate
the utility of this reaction, we oxidized a wide range of benzyl
ethers 2. Table 2 shows the versatility of the peroxyiodane 1a
as an oxidizing reagent. Oxidation of benzyl ethers of methyl,
primary, secondary, and tertiary alcohols 2a-n occurred
smoothly under our standard conditions, and good to excellent
yields of the corresponding benzoate esters 3a-n were obtained.
In some cases, a small amount of deprotected alcohols and
benzoic acid was obtained, due to partial hydrolysis of the esters
during the reaction. In some reactions, formation of a small
amount of tert-butylperoxy acetals was observed; for instance,
in the reaction of 2d (Table 2, entry 4) the peroxyacetal 5 was
isolated in 3% yield in addition to 3d (76%).
We found that the use of alkali metal carbonates as an additive
markedly accelerated the benzylic oxidation, although these
bases are sparingly soluble in the solvent. The time courses of
the reaction of 2d with 1a (3 equiv) in the presence and absence
of various finely powdered alkali metal carbonates (6 equiv) in
benzene at room temperature under nitrogen are shown in Figure
1. The rate of formation of the ester 3d was increased
considerably using Li2CO3 as an additive; for instance, yields
of 3d at the reaction time of 50 h increased from 55% (without
Li2CO3) to 81% (with Li2CO3). Changing the metal cation of
the carbonate additive from Li to Na, K, Rb, and Cs accelerated
the rate of benzylic oxidation successively in the order of
ascending atomic number. Use of Cs2CO3 proved to be most
effective and afforded 93% yield of 3d in less than 10 h at room
temperature.
In contrast to the remarkable rate enhancement effected by
K2CO3, no such result was observed when KCl, KBr, or KBF4
was used as additives, clearly indicating that the counter cation
itself shows negligible effects on the rate of this oxidation. Based
on its powerful acceleration effect, its ease of handling, and its
low cost, K2CO3 was used primarly in this study, although in
some experiments Cs2CO3 was also used.
The isolation procedure of benzoate esters 3 is relatively
simple. After filtration of an excess K2CO3 and potassium
2-iodobenzoate produced during the reaction from 1a, silica gel
chromatography gave pure esters 3. Thus 1-menthyl benzoate
3j was obtained from benzyl ether 2j in 74% yield. Without
isolation of the benzoate esters, hydrolysis of the crude reaction
mixture gives the alcohols directly. After evaporation of the
solvent, the reaction mixture of 2j was treated with KOH in
aqueous methanol at room temperature, leading directly to
1-menthol in 82% yield.
The stoichiometry of the reaction and the effects of the
reaction temperature are shown in Figure 2. Oxidation with
an equimolar amount of 1a in the presence of K2CO3 afforded,
after 24 h at 25 °C, a 69% yield of the ester 3d. No
improvement in product yield resulted from prolonged treatment
(4 days at 25 °C), suggesting decomposition of 1a to some extent
under these conditions. Use of 2 equiv of 1a after 2 days led
to almost complete conversion of 2d to give 3d in 95% yield.
Slightly higher yield of 3d was obtained using 3 equiv of 1a.
When the reaction [1a (2 equiv)] was carried out at 50 °C and
compared to the reaction at 25 °C, some rate acceleration was
observed, especially at the beginning of the reaction; however,
after 8 h [3d (55%) and 2d (29%)], the reaction stopped and
no further oxidation was observed. We interpret these results
as indicating that the decomposition of 1a in benzene at 50 °C
is a relatively rapid process. Thus, 1a (2 equiv)/K2CO3 (4
equiv)/25 °C/PhH/N2 constituted our standard conditions. When
the p-nitroperoxyiodane 1b, prepared from 2-iodosyl-5-nitroben-
Oxidation of benzyl n-butyl ethers 2p-t with electron-
donating (MeO and Me) and electron-withdrawing groups (Cl
and Ph) on the aromatic ring afforded high yields of the
substituted benzoates 3p-t. Oxidation of cyclic benzyl ethers
(14) (a) Willgerodt, C.; Gartner, R. Chem. Ber. 1908, 41, 2813. (b)
Morrison, G. F.; Hooz, J. J. Org. Chem. 1970, 35, 1196.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7719
Table 2. Benzylic Oxidation of Benzyl Ethers 2 with the
Peroxyiodane 1aa
Table 3. Allylic Oxidation of Allyl Ethers with Peroxyiodane 1aa
a Unless otherwise noted, reactions were carried out using 2 equiv
of 1a and 2 equiv of Cs2CO3 at room temperature in cyclohexane under
an atmosphere. b Isolated yields. c Reactions were carried out under
nitrogen. d Instead of Cs2CO3, 4 equiv of K2CO3 was used. e 6g (90%)
was recovered. f 4 equiv of Cs2CO3 was used. g Instead of 1a, 2 equiv
of 1b was used.
opened up for selective oxidation of the benzyl ether protecting
group.
B. Oxidation of Allyl Ethers. Allyl ethers are also used to
protect alcohols, particularly in carbohydrate chemistry.15
Deprotection of allyl ethers is usually achieved by heavy metal-
catalyzed isomerization to the enol ethers with subsequent
hydrolysis,16 whereas the oxidative cleavage is very limited.17
Allylic methylene groups of allyl ethers could be oxidized to a
carbonyl group by the peroxyiodane 1a. Using an alkali metal
carbonate additive was again found to enhance the rate of
oxidation, and both K2CO3 and Cs2CO3 were used in the allylic
oxidation. As a solvent, cyclohexane afforded better yields of
R,â-unsaturated esters than benzene. Thus, 1a (2 equiv)/Cs2-
CO3 (2 equiv)/25 °C/cyclohexane/atmosphere was used as a
standard procedure for oxidation of allyl alkyl ethers; the results
are shown in Table 3.
a Unless otherwise noted, reactions were carried out using 2 equiv
of 1a and 4 equiv of K2CO3 in benzene at room temperature under
nitrogen using a rubber balloon. b Isolated yields. Parentheses are GC
yields. c 2o (61%) was recovered.
also took place; thus phthalan 2u afforded phthalide 3u (78%).
Regioselective oxidation of isochroman 2v at the benzylic
methylene group attached to the ring oxygen was observed, and
1-isochromanone 3v was obtained in an excellent yield. Benzyl
aryl ethers were not readily oxidized under our standard
conditions. The oxidation of phenyl ether 2o is very slow and
stops after stirring for 24 h (Table 2, entry 15), which makes
possible selective oxidation of the alkyl ether 2h in the presence
of the phenyl ether 2o. MOM, THP, and TBDMS ethers were
found to be stable under standard conditions; thus the benzoates
3w-y were obtained in good yields. The acetate protecting
group (entry 26) was also unaffected. An efficient route is thus
Oxidation of allyl ethers 6 of primary, secondary, and tertiary
alcohols under standard conditions afforded the R,â-unsaturated
esters 7 in 40-60% yields. As observed in the case of benzyl
phenyl ether 2o, allylic oxidation of the allyl aryl ether 6g is
(15) (a) Gigg, R. Am. Chem. Soc. Symp Ser. 1977, 39, 253. (b) Gigg,
R.; Conant, R. Carbohydrate Res. 1982, 100, C5.
(16) (a) Boss, R.; Scheffold, R. Angew. Chem., Int. Ed. Engl. 1976, 15,
558. (b) Corey, E. J.; Suggs, J. W. J. Org. Chem. 1973, 38, 3224. (c)
Gigg, R. J. Chem. Soc., Perkin Trans. 1 1980, 738. (d) Ito, H.; Taguchi,
T.; Hanzawa, Y. J. Org. Chem. 1993, 58, 774.
(17) Kariyone, K.; Yazawa, H. Tetrahedron Lett. 1970, 2885.

7720 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
Table 4. Oxidation of Hydrocarbons with the Peroxyiodane 1aa
entry
hydrocarbon
time (h)
product
1-indanone
5-methoxyindanone
6-methoxyindanone
R-tetralone
benzophenone
anthraquinone
anthraquinone
xanthone
9-fluoroenone (19a)
PhC(O)(CH2)4CH3 (19b)
yield (%)b
1
2
indan
36
18
(75)
50
16
(66)
(98)
89
5-methoxyindan
3
4
5
6
7
8
9
tetrahydronaphthalene
diphenylmethane
9,10-dihydroanthracene
anthrone
xanthene
fluorene (18a)
36c
36
24d
30
84
92
24
96e
82
87
Ph(CH2)5CH3 (18b)
(25)f
a Unless otherwise noted, reactions were carried out using 3 equiv of 1a and 6 equiv of Cs2CO3 at room temperature in benzene under nitrogen.
b Isolated yields. Parentheses are GC yields. c 1a (2 equiv) and Rb2CO3 (4 equiv). d 1a (4 equiv) and K2CO3 (8 equiv). e 1a (2 equiv) and K2CO3
(4 equiv). f Hexylbenzene (18b, 75%) was recovered unchanged.
very slow and, even after prolonged treatment, only 10% of
the ester 7g was obtained. Oxidation of the methallyl 8, prenyl
10, and cinnamyl ethers 12 occurred smoothly and produced
the conjugated esters 9, 11, and 13, respectively, in moderate
to good yields. Without isolation of the unsaturated esters,
hydrolysis of the crude oxidation mixture directly gives the
parent alcohols. For instance, when, after evaporation of the
solvent, the reaction mixture of 6a was treated with NaOH in
aqueous methanol at room temperature, 1-decanol was isolated
in 74% yield. Similarly, deprotection of allyl ethers 6e and
10a afforded menthol (68%) and 1-decanol (80%), respectively.
Furthermore, propargylic oxidation of ether 14 with 1a afforded
the conjugated alkynyl ester 15 in moderate yields.
This oxidation of arenes yielding ketones was sometimes
accompanied by the formation of some tert-butyl peroxides,
particularly in the reaction with fluorene (18a). Exposure of
18a to 1a (1.3 equiv) in dichloromethane for 10 days gave
9-fluorenone (19a) in 84% yield; however, when the reaction
was quenched after 1 day, 9-(tert-butylperoxy)fluorene 20 was
obtained in 15% yield, along with 9-fluorenone (19a, 9%) and
fluorene (18a, 60%). The peroxide 20, on treatment with 1a
in dichloromethane, afforded 9-fluorenone (19a), indicating that
the peroxide 20 would be a potential intermediate leading to
the formation of 19a. Similar observations on the formation
of the peroxide 20 in chromium-catalyzed benzylic oxidation
using tert-butyl hydroperoxide have been reported by Muzart.19
The attempted allylic oxidation of simple alkenes gave poor
results, and 1-eicosene [1a (2 equiv)/K2CO3 (4 equiv)/4 days]
was recovered unchanged (95%). 3â-Acetoxy-5-androsten-17-
one (21a), however, was readily oxidized at the C-7 allylic
position and gave rise to the conjugated enone 22a19 in 81%
yield. Cholesteryl acetate (21b) afforded the enone 22b (62%).
In the reaction of the benzyl ether 21c, both the benzylic and
allylic oxidations were observed and the keto ester 22c was
obtained in 55% yield.
No chemoselectivity was observed in the attempted intramo-
lecular competitions between benzylic and allylic oxidations of
ethers. Thus ether 16a with both allyloxy and benzyloxy groups
in the molecule afforded a 1:1:2 mixture of the R,â-unsaturated
ester 16b, the benzoate 16c, and the diester 16d in 64% yield.
Oxidation of 17a with 4 equiv of 1a gave the diester 17b in
52% yield.
C. Oxidation of Arenes at the Benzylic Position. The
peroxyiodane 1a can be used to oxidize arenes at the benzylic
position.18 Oxidation of arenes was carried out in benzene in
the presence of K2CO3 at room temperature. Indan was
converted to 1-indanone, tetrahydronaphthalene to R-tetralone,
diphenylmethane to benzophenone, 9,10-dihydroanthracene to
anthraquinone, anthrone to anthraquinone, xanthene to xanthone,
and fluorene (18a) to 9-fluorenone (19a). The yields are
summarized in Table 4. The oxidation of 5-methoxyindan
resulted in a higher yield of 5-methoxyindanone (50%) than
6-methoxyindanone (16%), thereby indicating that the methoxy
group activates side chains in the para position to a greater
extent than those in a meta position.
Radical Trapping. Isolation of the peroxides 5 and 20 in
the benzylic oxidations suggests the involvement of radical
species. Addition of an equivalent amount of p-methoxyphenol
(which has been shown to be a good radical inhibitor20) in the
reaction of 2d with 1a completely inhibits the benzylic oxidation
(Table 5, entry 5).21 The use of a less than stoichiometric
amount of p-methoxyphenol relative to 1a partly inhibits the
oxidation. A similar type of inhibition was observed using
R-tocopherol as an additive.22 Effective inhibition of the
oxidation was also observed on addition of galvinoxyl, which
is an efficient scavenger for both oxygen- and carbon-centered
(18) (a) Zhao, D.; Lee, D. G. Synthesis 1994, 915. (b) Pearson, A. J.;
Han, G. R. J. Org. Chem. 1985, 50, 2791. (c) Murahashi, S.; Oda, Y.;
Naota, T.; Kuwabara, T. Tetrahedron Lett. 1993, 34, 1299. (d) Barton, D.
H. R.; Wang, T.-L. Tetrahedron Lett. 1994, 35, 5149.
(19) Muzart, J. Tetrahedron Lett. 1986, 27, 3139.
(20) Li, P.; Alper, H. J. Mol. Catal. 1992, 72, 143.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7721
Table 5. Oxidation of Benzyl n-Butyl Ether 2d with Peroxyiodane 1aa
product yield (%)b,c
entry
2d (equiv)
1a (equiv)
K2CO3 (equiv)
additive (equiv)
conditionsd
time (h)
3d
5
2d
e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
1
1
1
2
2
2
0
2
2
4
4
4
0
4
4
4
4
2
2
2
30 °C, N2
48
48
72
72
48
48
48
48
72
72
48
48
48
70
67
30
14
0
3
14
24
21
54
100
90
5
5
2
25
38
43
95
5
30 °C, O2
30 °C, Are
30 °C, Are
30 °C, N2
30 °C, N2
2
49
11
-
-
2
p-methoxyphenol (1)
R-tocopherol (1)
3
e
30 °C, N2
90
90
62
23
46
53
5
95
596
638
24
30 °C, O2
30 °C, Are
30 °C, Are
30 °C, N2
30 °C, N2
30 °C, N2
30 °C, N2
30 °C, N2
30 °C, O2
30 °C, Ar
1
28
32
-
-
-
-
-
-
72
p-methoxyphenol (1)
R-tocopherol
galvinoxyl (2)
1
nitrobenzene (2)
48
25
25
25
410
410
450
-
-
-
a Reactions were carried out in benzene. b GC yields. Parentheses are NMR yields; “-” denotes that yields were not determined. c Yields of
entries 1-14 and 15-17 are based on benzyl n-butyl ether 2d and the peroxyiodane 1a, respectively. d N2: under dinitrogen rubber balloon. O2:
under dioxygen rubber balloon. Ar: in a degassed argon sealed tube. e Iodane was recovered as 1-chloro-1,2-benziodoxol-3(1H)-one, and the
yields based on 1a are: 30% (entry 1), 4% (entry 3), 30% (entry 4), 25% (entry 7), 29% (entry 9), 40% (entry 10).
radicals (Table 5, entry 13).23,24 On the other hand, no inhibition
was observed in the presence of nitrobenzene, often used as a
radical inhibitor.25
useful for studies of fast radical reactions.27 The reaction of
benzyl n-butyl ether 2d with 1a in the presence of 2,2,6,6-
tetramethylpiperidine-N-oxyl (TEMPO) under an argon atmo-
sphere resulted in a competition between a TEMPO trap of the
free radicals generated and the normal oxidation to the ester;
thus the TEMPO adduct 28 was obtained in 28% yield along
with the ester 3d (55%). In the reaction of isochroman 2v, the
TEMPO adduct 29 was obtained as a major product in 44%
yield. Furthermore, the TEMPO adduct 30 was obtained in
good yield from the allylic oxidation of the ether 6a. These
results clearly indicate the intermediacy of benzylic and allylic
radicals in the oxidation with 1a.
To establish the generation of radicals at benzylic positions,
appropriate radical probe substrates 23 and 26, which are based
upon the familiar 5-exo-trig cyclizations of the parent and
substituted 5-hexenyl radicals, were synthesized.26,27 Reaction
of 23 with 1a, however, proceeded without detectable cyclization
and afforded the ester 24 (56%) along with a small amount of
the peroxyacetal 25 (2%).28 Attempted cyclization of the more
efficient radical probe 2629 gave the epoxy ester 27 without the
formation of cyclization products. The selective formation of
the epoxy ester 27 may be due to the more rapid oxidation of
the trisubstituted double bond with two phenyl groups compared
to the benzylic oxidation. Reductive removal of benzyl ether
protecting groups by catalytic hydrogenation is not compatible
with the presence of olefins. That the terminal monosubstituted
double bond remains unchanged in the reaction of 23 is
indicative of the possibility that chemoselective deprotection
of a benzyl group may occur in the presence of isolated
monosubstituted double bonds.
The formation of both the TEMPO adducts and esters or
lactones in these reactions implies that the rate constant for the
reaction of benzyl radicals with 1a, which leads to the formation
of normal oxidation products (see below), would be of the same
order of magnitude as the rate constant for the reaction of benzyl
Rate constants for alkyl radical coupling with nitroxyl radicals
are very large and relatively insensitive to the carbon radical
stability. Therefore, the nitroxyl radical coupling method is most
(21) It is not at all clear whether or not the added p-methoxyphenol traps
radicals generated in the reaction. We found that oxidation of phenols with
the peroxyiodane 1a takes place, and the results will be reported elsewhere.
(22) For peroxy radical-trapping with R-tocopherol, see: (a) Barclay,
L. R. C.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 6478. (b) Jackson,
R. A.; Hosseini, K. M. J. Chem. Soc., Chem. Commun. 1992, 967.
(23) Bartlett, P. D.; Funahashi, T. J. Am. Chem. Soc. 1962, 84, 2596.
(24) Furthermore, added galvinoxyl completely inhibits the oxidation of
the allyl ether 6a.
(28) For 5-exo cyclizations of 1-phenyl-5-hexenyl radicals, see: (a)
Walling, C.; Cioffari, A. J. Am. Chem. Soc. 1972, 94, 6064. (b) Pines, H.;
Sih, N. C.; Rosenfield, D. B. J. Org. Chem. 1966, 31, 2255.
(29) The first order cyclization rate constants at 25 °C for the 5-hexenyl
and 6,6-diphenyl-5-hexenyl radicals are 2.3 × 105 s-1 and 5 × 107 s-1
,
respectively. See: (a) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J.
Am. Chem. Soc. 1981, 103, 7739. (b) Ha, C.; Horner, J. H.; Newcomb,
M.; Varick, T. R.; Arnold, B. R.; Lusztyk, J. J. Org. Chem. 1993, 58, 1194.
(c) Newcomb, M.; Horner, J. H.; Shahin, H. Tetrahedron Lett. 1993, 34,
5523.
(25) Stavber, S.; Planinsek, Z.; Zupan, M. J. Org. Chem. 1992, 57, 5334.
(26) Motherwell, W. B. Crich, D. Free Radical Chain Reactions in
Organic Synthesis; Academic Press: New York, 1992.
(27) Newcomb, M. Tetrahedron 1993, 49, 1151.

7722 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
Table 6. Relative Reactivity of Benzyl Ethers 2 and Related
Compounds with 1a at 30 °C
(k2s/k2d-d ) 10.2) under argon at 30 °C in benzene and compared
2
with the relative rate k2s/k2d ) 0.84 in Table 6. A very large
deuterium kinetic isotope effect kH/kD ) 12 was obtained. This
large isotope effect was further confirmed by the competition
of p-chloro ether 2r vs 2d-d2, which resulted in the value kH/kD
) 14. The average isotope effect of 13 is very large. Similarly,
very large isotope effects have been reported for the radical
abstraction of hydrogen from tetralin (kH/kD; 16) and cumene
(kH/kD; 20) by tert-butylperoxy radicals,36 for the generation of
benzylic radical from 10-methyl-9,10-dihydroacridine (kH/kD;
21) by aminoxyl radicals,37 and for formation of the allylic
hydroperoxide from linoleic acid by soybean lipoxygenase.38
This large value of isotope effect obtained for oxidation of
benzyl butyl ether 2d indicates that the rate-determining step
of the reactions probably involves a high degree of benzylic
C-H bond breaking.
substrate
krel
substrate
krel
2p (p-MeO)
2q (p-Me)
2d (H)
2r (p-Cl)
2s (m-Cl)
1.93 ( 0.16
1.15 ( 0.05
1.0
0.96 ( 0.03
0.84 ( 0.02
18b Ph(CH2)5CH3
(n-Bu)2O
0.12
0.05
radicals with TEMPO (k ≈ 108 M-1 s-1).30 These results
strongly suggest that the attempted 5-exo-cyclization of the
benzyl radical derived from 23 could not have competed with
the reaction with 1a leading to the formation of the ester 24,
since the reaction was carried out at a concentration of 0.1 M
for 1a.29 Furthermore, compared to 5-hexenyl radical, a
substantially reduced rate constant for cyclization of 2-oxa-5-
hexenyl radical (k ) 5 × 104 s-1 at 25 °C) has been reported,31,32
which probably shows the cyclization of the benzyl radical
derived from 26 also could not compete with the reaction with
1a. This reduced rate constant has been attributed to an
increased activation energy required to adopt a conformation
for cyclization in which resonance between the radical center
and the oxygen atom is lost.
Substituent Effect. To gain further insight into the mech-
anism of the oxidation of benzyl ethers by the peroxyiodane
1a, the relative rates of oxidation for a series of ring-substituted
benzyl butyl ethers 2d and 2p-s were measured under argon
at 30 °C in benzene by competitive reactions, in which a mixture
of each 25-fold excess of two competing substrates was used.
Table 2 shows that benzoate esters 3d and 3p-s were formed
in high yields, regardless of the substitution of the phenyl ring.
Electron-releasing groups such as p-MeO and p-Me groups
increase the rate of oxidation; the effect of substituents on the
rate of oxidation is shown in Table 6. Hammett correlation
plot for the oxidation of these benzyl butyl ethers presented in
Table 6 showed a better correlation of relative rate factors with
the σ+ rather than the σ constants of substituents in the aromatic
ring and afforded the reaction constant F+ ) -0.30 (r ) 0.97).33
This F+ value appears to be comparable to F+ ) -0.65 for
benzylic hydrogen abstractions from dibenzyl ethers by ben-
zoyloxy radical.34
Effects of Molecular Dioxygen and Characterization of
Reaction Intermediates. Effects of molecular dioxygen in the
reaction of 2d with 1a were examined, and the results are
summarized in Table 5. No differences in the yields and product
profiles were observed between the reactions carried out under
dinitrogen rubber balloon and dioxygen rubber balloon. How-
ever, when the reaction was carried out in a degassed argon
sealed tube, the yield of the ester 3d decreased to a great extent,
and a large amount of the peroxyacetal 5 was produced (Table
5, entries 1-3, and 7-9). Atmospheric dioxygen has been
shown to penetrate into a rubber balloon,39 which, in turn, leads
to the same results in the product profiles and the yields of the
reactions under dinitrogen rubber balloon and under dioxygen
rubber balloon. Very interestingly, in the presence of a 25-
fold excess of 2d relative to 1a, the prolonged reactions (410
h) under dinitrogen as well as dioxygen balloons afforded more
than stoichiometric amounts of 3d (ca. 600%), while the reaction
in the absence of dioxygen (a degassed argon tube experiment)
gave 24% of 3d and 72% of 5 even after 450 h (Table 5, entries
15-17). These results clearly show that the presence of oxygen
will be required for facile oxidation of 2d to the ester 3d by
the peroxyiodane 1a. As shown in Table 5, in the reaction under
an argon atmosphere, adding K2CO3 enhanced the rate of
benzylic oxidation.
It is significant that a large amount of the peroxyacetal 5,
whose structure was unambiguously established by the synthesis
from di-n-butyl acetal 31 via ruthenium(III)-catalyzed acetal
exchange reaction,40 was isolated in the reactions under an argon
atmosphere. As discussed above, the tert-butyl peroxide 20
appears to be an intermediate for the oxidation of fluorene (18a)
to 9-fluorenone (19a) with 1a. Furthermore, tert-butylperoxy
acetals have been shown to undergo base-catalyzed decomposi-
tion to esters in high yields,41 and, therefore, we regard it as
important to investigate the possibility of decomposition of the
peroxy acetal 5 to the ester 3d under the conditions. As shown
in Table 7, the peroxyacetal 5 was stable in benzene toward
o-iodobenzoic acid, which is produced during the benzylic
oxidation of 2d with 1a, whereas formation of the ester 3d,
albeit in low yields, resulted from the reaction with either K2-
A reasonable rate of oxidation of methylene groups to
carbonyl groups requires the presence of both the phenyl and
alkoxy groups (see Table 6). When oxygen of 2d was replaced
by a methylene group, the rate of oxidation decreased to one-
tenth. Similarly, dibutyl ether is 20 times less reactive than
2d. These relative reactivities appear to correlate well with their
respective C-H bond dissociation energies:35 H-CH(OMe)-
Ph (77 kcal mol-1), H-CH(CH3)Ph (85.4 kcal mol-1), and
H-CH(CH3)OEt (91.7 kcal mol-1).
Deuterium Isotope Effect. To obtain the deuterium isotope
effect, the relative rate constant for the competitive oxidation
of m-chloro ether 2s vs n-BuOCD2Ph (2d-d2) was measured
(30) (a) Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U. J. Am. Chem.
Soc. 1992, 114, 4983. (b) Bowry, V. W.; Ingold, K. U. J. Am. Chem. Soc.
1992, 114, 4992.
(31) Beckwith, A. L. J.; Glover, S. A. Aust. J. Chem. 1987, 40, 157.
(32) On the other hand, the cyclization rate constants of 1-methoxy-5-
hexenyl radicals have been shown to be nearly equal to those for related
alkyl radicals lacking the methoxy group. See: (a) Johnson, C. C.; Horner,
J. H.; Tronche, C.; Newcomb, M. J. Am. Chem. Soc. 1995, 117, 1684. (b)
Newcomb, M.; Filipkowski, M. A.; Johnson, C. C. Tetrahedron Lett. 1995,
36, 3643.
(33) Brown, H. C.; Okamoto, Y. J. Am. Chem. Soc. 1958, 80, 4979.
(34) (a) Huang, R. L.; Lee, H. H.; Ong, S. H. J. Chem. Soc. 1962, 3336.
(b) Russell, G. A.; Williamson, R. C. J. Am. Chem. Soc. 1964, 86, 2357.
(35) (a) Lide, D. R., Ed. CRC Handbook of Chemistry and Physics, 73rd
ed.; CRC Press: Boca Raton, FL, 1992; pp 9-138. (b) Baciocchi, E. Acta
Chem. Scand. 1990, 44, 645.
(36) (a) Howard, J. A.; Ingold, K. U.; Symonds, M. Can. J. Chem. 1968,
46, 1017. (b) Russell, G. A. J. Am. Chem. Soc. 1957, 79, 3871.
(37) Fukuzumi, S.; Tokuda, Y.; Chiba, Y.; Greci, L.; Carloni, P.;
Damiani, E. J. Chem. Soc., Chem. Commun. 1993, 1575.
(38) Glickman, M. H.; Wiseman, J. S.; Klinman, J. P. J. Am. Chem.
Soc. 1994, 116, 793.
(39) Sasai, H. Farumashia 1992, 28, 581.
(40) (a) Murahashi, S.; Oda, Y.; Naota, T. Chem. Lett. 1992, 2237. (b)
Rieche, A.; Schmitz, E.; Beyer, E. Chem. Ber. 1958, 91, 1942.
(41) (a) Mukaiyama, T.; Kato, J.; Miyoshi, N.; Iwasawa, N. Chem. Lett.
1985, 1255. (b) Mukaiyama, T.; Miyoshi, N.; Kato, J.; Ohshima, M. Chem.
Lett. 1986, 1385. (c) Ganem, B.; Heggs, R. P.; Biloski, A. J.; Schwartz,
D. R. Tetrahedron Lett. 1980, 21, 685.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7723
Table 7. Reaction of t-Butylperoxy-5 and Hydroperoxyacetals 32
Scheme 1
5 or 32 PhH, 30 °C, 3 day8 3d
N2
product yield (%)a
entry
acetal
additive (equiv)
none
o-iodobenzoic acid (1)
K2CO3 (6)
1a (1)
1a (1), K2CO3 (2)
none
o-iodobenzoic acid (1)
K2CO3 (6)
1a (1)
3d
acetal
1
2
3
4
5
6
7
8
9
5
5
5
5
5
32
32
32
32
3
1
7
21
20
0
1
44
66
97
80
93
74
80
100
79
27
5
a Yields of entries 1-5 and 6-9 were determined by GC and NMR,
respectively.
acetal 32 with concomitant regeneration of benzyl radical 34,
and (g) decomposition of the hydroperoxy acetal 32 to produce
the ester 3d.
CO3 or 1a. Combining K2CO3 and 1a was not found to improve
the yield of 3d.
The radical nature of the oxidation was substantiated by the
inhibition of the reaction with added radical scavengers. Rates
for decomposition of 1a were measured spectrophotometrically
in dichloromethane at 30 °C. The first-order rate constant kobsd
) 2.62 × 10-5 s-1 was obtained, and the half-life of 1a was
about 7.4 h. The major pathway of the decomposition of PhI-
(OOtBu)2 at -80 °C has been reported to be the homolytic
cleavage of the hypervalent I-O bonds.4a,45 Furthermore, the
unimolecular free radical decomposition of [bis(perbenzoyloxy)-
iodo]benzenes has been studied kinetically.2 Therefore, it seems
reasonable to assume that the initial step of the benzylic
oxidation would involve the homolytic bond cleavage of the
weak iodine(III)-peroxy bond of 1a, which generates the [9-I-
2] iodanyl radical 33a and tert-butylperoxy radical.
It has been well established that autoxidation of benzyl ethers
produces R-hydroperoxybenzyl ethers via the reaction of
generated benzyl radicals with dioxygen, and dehydration of
the resulting hydroperoxyacetals gives rise to esters.34,42 The
reactions of benzyl radicals with dioxygen are exothermic to
the extent of about 13 kcal/mol, and activation energies for the
reaction have been estimated to be zero.43 Therefore, although
we have no explicit evidence for the intervention of 32, it seems
most likely that the reaction of 2d with 1a under standard
conditions, that is, in the presence of oxygen, would produce
the hydroperoxy acetal 32 as an intermediate via the reaction
of generated benzyl radical with dioxygen. As shown in Table
7, treatment of 32, prepared by ruthenium(III)-catalyzed acetal
exchange of 31 with hydrogen peroxide, with K2CO3 and 1a
afforded the ester 3d in 44% and 66% yields, respectively. These
reactivity differences between the peroxy acetal 5 and the
hydroperoxy acetal 32 toward K2CO3 might be attributed to the
higher leaving group ability of the HO group compared to that
of the tert-BuO group.44
Reaction Mechanism. As illustrated in Scheme 1, a reaction
mechanism for the benzylic oxidation of 2d with 1a might be
assumed to involve the following key steps: (a) bond cleavage
of the hypervalent iodine(III)-peroxy bond of 1a generating
tert-butylperoxy radical and iodanyl (iodinanyl) radical 33a, (b)
benzylic hydrogen abstraction of 2d with iodanyl radical 33a
or benzoyloxy radical 33b generating benzylic radical 34, (c)
nucleophilic attack of the benzylic radical 34 to iodine(III)-
peroxy bond of 1a yielding the tert-butylperoxy acetal 5 with
concomitant regeneration of iodanyl radical 33a, and (d)
decomposition of the tert-butylperoxy acetal 5 to produce the
ester 3d. In the presence of dioxygen, the following alternative
pathway would also compete: (e) reactions of benzyl radical
34 with dioxygen generating peroxy radical 35, (f) hydrogen
abstraction with the peroxy radical 35 yielding the hydroperoxy
Generation of the iodine-centered radicals from hypervalent
iodanes has been shown to be an energetically favorable process,
since it involves breaking weak bonds to iodine(III).46 The
intermediacy of electrophilic iodanyl radicals as a highly
selective hydrogen-abstracting species has been established in
the photoinitiated for thermally initiated chlorination with
(dichloroiodo)benzene,47,48 [chloro(tert-butoxy)iodo]benzene,49
and the Martin’s cyclic chloroiodane 36.46 For instance, under
photochemical conditions, 36 generates the cyclic alkoxyiodanyl
radical 37. Thermolysis and photolysis of (diacyloxyiodo)-
(45) The unimolecular free-radical decomposition of [bis(perbenzoyloxy)-
iodo]benzenes in chloroform has been reported to involve the homolytic
cleavage of the O-O bonds.2b
(46) Amey, R. L.; Martin, J. C. J. Am. Chem. Soc. 1979, 101, 3060.
(47) (a) Russell, G. A. J. Am. Chem. Soc. 1958, 80, 4987. (b) Banks,
D. F.; Huyser, E. S.; Kleinburg, J. J. Org. Chem. 1964, 29, 3692. (c) Tanner,
D. D.; Bostelen, P. B. J. Org. Chem. 1967, 32, 1517. (d) Tanner, D. D.;
Gidley, G. C. J. Org. Chem. 1968, 33, 38. (e) Arase, A.; Hoshi, M.; Masuda,
Y. Chem. Lett. 1979, 961.
(48) Breslow and his co-workers developed the template-directed
chlorination of steroids via generation of iodanyl radicals. See: (a) Breslow,
R.; Corcoran, R.; Dale, J. A.; Liu, S.; Kalicky, P. J. Am. Chem. Soc. 1974,
96, 1973. (b) Breslow, R.; Corcoran, R. J.; Snider, B. B. J. Am. Chem.
Soc. 1974, 96, 6791. (c) Breslow, R.; Snider, B. B.; Corcoran, R. J. J. Am.
Chem. Soc. 1974, 96, 6794. (d) White, P.; Breslow, R. J. Am. Chem. Soc.
1990, 112, 6842.
(42) (a) Sharp, D. B.; Patrick, T. M. J. Org. Chem. 1961, 26, 1389. (b)
Rieche, A.; Schmitz, E. Chem. Ber. 1957, 90, 1084. (c) Rieche, A.; Seyfarth,
H. E.; Brand, F. Liebigs Ann. Chem. 1969, 725, 93. (d) Schenck, G. O.;
Becker, H.-D.; Schulte-Elte, K.-H.; Krauch, C. H. Chem. Ber. 1963, 96,
509. (e) Milas, N. A.; Peeler, R. L.; Mageli, O. L. J. Am. Chem. Soc.
1954, 76, 2322. (f) Schreiber, S.; Hulin, B.; Liew, W. Tetrahedron 1986,
42, 2945.
(43) Howard, J. A. Free Radicals; Wiley: New York, 1973; Vol. 2,
Chapter 12.
(44) Curci, R.; DiFuria, F. Tetrahedron Lett. 1974, 4085.
(49) Tanner, D. D.; Gidley, G. C. Can. J. Chem. 1968, 46, 3537.

7724 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
benzenes also generate [9-I-2] iodanyl radicals.50 The genera-
tion of the iodanyl radical 33a has been proposed in the iodine-
accelerated facile rearrangement of bis(o-iodobenzoyl) peroxide
38 to the cyclic iodane 39 in chloroform at 25 °C.51
the estimated rate constant k ≈ 108 M-1 s-1. In the presence
of dioxygen, this ligand-transfer process would compete with
the reaction of 34 with dioxygen, producing the peroxy radical
35, which is one of the steps in autoxidation, since the rate
constants for dioxygen trapping of benzyl radicals have been
estimated to be greater than 108 M-1 s-1 43
.
The benzylic oxidation by 1a must involve hydrogen abstrac-
tion by the iodanyl radical 33a or benzoyloxy radical 33b;
however, the radical 33a or 33b could not be the sole radical
that abstracts benzylic hydrogens, since a large amount of the
ester 3d (ca. 600%) was formed in the presence of dioxygen
(Table 5, entries 15 and 16). Therefore, it seems reasonable to
assume that hydrogen abstraction by the peroxy radical 35
generating 34 and the hydroperoxy acetal 32, which was
observed in autoxidation, plays an important role in this
oxidation under standard conditions.58
The iodanyl radical 33a or the benzoyloxy radical 33b could
selectively abstract benzylic R-hydrogens of 2d, generating the
benzyl radical 34.52,53 It is very difficult to determine whether
benzylic hydrogen abstraction by 33a occurs at the iodine or at
the oxygen attached to iodine.46 The former process leads to a
hydridoiodane 41, which might rearrange to o-iodobenzoic acid,
while the latter process gives the acid directly.54 Both Huyser47b
and Tanner47c have suggested that in chlorination of hydrocar-
bons the iodanyl radicals such as PhI˙Cl and PhI˙OtBu abstract
hydrogens of hydrocarbons at the iodine. On the other hand,
molecular mechanics calculations on template-directed steroid
chlorinations, as reported by Breslow,48 have led to the
suggestion that hydrogen abstraction occurs at a chlorine
attached to the iodine. The large value of isotope effect (kH/kD
) 13) observed for oxidation of benzyl n-butyl ether 2d shows
the high sensitivity of the radical 33a or 33b to the bond strength
of the breaking C-H, and the relative rates of oxidation of
substituted benzyl ethers 2d and 2p-s shown in Table 6, where
electron-releasing groups such as p-MeO and p-Me increase the
rate of oxidation, indicate the electrophilic nature of 33a or 33b.
The better Hammett correlation of the oxidation rates of the
benzyl ethers with σ+ implies that there is some separation of
charge in the transition state such as 40 for hydrogen abstrac-
tion.55
Li and Alper have reported that Co(II)-catalyzed oxidation
of benzyl ethyl ether (2b) with atmospheric oxygen at 80 °C
produces a mixture of the ester 3b (47%) and benzoic acid
(50%) via formation of the benzyl radical 42. They attribute
the formation of benzoic acid to the facile fragmentation of the
radical 42 to ethyl radical and benzaldehyde which is oxidized
to benzoic acid.20 Here, oxidation of 2b with 1a at room
temperature gave the ester 3b selectively, in high yield, and
neither benzaldehyde nor benzoic acid was detected (Table 2,
entry 2). This result is probably due to the rapid reaction of
the benzyl radical 42 with 1a as well as with dioxygen, and the
low reaction temperature. On the other hand, this type of
fragmentation of benzyl radicals becomes important when it
leads to the generation of very stable radicals. For instance, in
the oxidation of benzyl R-methylbenzyl ether 43 with 1a,
significant amounts of fragmentation products, acetophenone
(79%) and benzaldehyde (67%), in addition to the normal
oxidation product R-methylbenzyl benzoate 44 (20%) were
obtained.
The benzyl radical 34 is then oxidized through a ligand-
transfer process57 by the peroxyiodane 1a, which produces the
tert-butylperoxy acetal 5 and regenerates the iodanyl radical 33a.
As discussed above, the TEMPO trapping experiments under
argon show that this ligand-transfer process is very rapid, with
An alternative pathway to the formation of the benzyl radicals
involves electron transfer which generates benzyl ether cation
radicals and the follow-up proton transfer. In fact, oxidation
of the benzyl ether protecting group by a stable cation radical
derived from tris(p-bromophenyl)amine or by electrochemical
methods has been shown to involve generation of the benzyl
(50) (a) Fontana, F.; Minisci, F.; Yan, Y. M.; Zhao, L. Tetrahedron Lett.
1993, 34, 2517. (b) Wang, T. T.; Leffler, J. E. J. Org. Chem. 1971, 36,
1531. (c) Cribb, C. J.; Gill, G. B.; El-Jamali, H. A. R. J. Chem. Soc.,
Perkin Trans. 2 1977, 860. (d) Minisci, F.; Vismara, E.; Fontana, F.;
Barbosa, M. C. N. Tetrahedron Lett. 1989, 30, 4659. (e) Togo, H.; Aoki,
M.; Yokoyama, M. Chem. Lett. 1991, 1691. (f) Togo, H.; Aoki, M.;
Yokoyama, M. Tetrahedron Lett. 1991, 32, 6559. (g) Togo, H.; Aoki, M.;
Yokoyama, M. Tetrahedron 1993, 49, 8241.
(51) (a) Leffler, J. E.; Faulkner, R. D.; Petropoulos, C. C. J. Am. Chem.
Soc. 1958, 80, 5435. (b) Honsberg, W.; Leffler, J. E. J. Org. Chem. 1961,
26, 733. (c) Bentrude, W. G.; Martin, J. C. J. Am. Chem. Soc. 1962, 84,
1561. (d) Tuleen, D. L.; Bentrude, W. G.; Martin, J. C. J. Am. Chem. Soc.
1963, 85, 1938.
(54) Benzylic hydrogen abstractions of benzyl ethers by benzoyloxy
radical have been studied in detail.34a See also: (a) Cass, W. E. J. Am.
Chem. Soc. 1947, 69, 500. (b) Cass, W. E. J. Am. Chem. Soc. 1950, 72,
4915.
(55) Polar transition states for hydrogen abstraction by ROO•,34,56
halogen,34b and iodanyl radicals46 have been generally accepted.
(56) (a) Hendry, D. G.; Russell, G. A. J. Am. Chem. Soc. 1964, 86, 2368.
(b) Russell, G. A. J. Am. Chem. Soc. 1957, 79, 3871. (c) Rust, F. F.;
Youngman, E. A. J. Org. Chem. 1962, 27, 3778.
(52) tert-Butylperoxy radical may also abstract benzylic hydrogens of
2d.
(53) Benzoyloxy radicals have been shown to be easily decarboxylated
with a rate constant 2.4 × 104 s-1 at 80 °C;50c however, since no formation
of iodobenzene was detected in the reactions, the iodanyl radical 33 does
not seem to undergo decarboxylation under our standard conditions. This
finding may be due to a neighboring group effect of the o-iodine, which
stabilizes carboxy radicals by resonance.51
(57) Minisci, F.; Fontana, F.; Araneo, S.; Recupero, F.; Banfi, S.; Quici,
S. J. Am. Chem. Soc. 1995, 117, 226.
(58) The rate constant for hydrogen abstraction by alkylperoxy radicals
has been measured for benzylic ethers, and typically has a value of 6 M-1
s-1 43
.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7725
ether cation radical via electron transfer.8,59 The subsequent
proton transfer from the cation radical will generate benzyl
radicals and be considerably accelerated in the presence of a
base such as Na2CO3, AcOK, and 2,6-dimethylpyridine.
The addition of alkali metal carbons markedly accelerates
the benzyl ether oxidation with 1a, which suggests an electron
transfer-proton transfer mechanism involving the intermediacy
of benzyl ether cation radicals. It should be noted, however,
that deprotonation of the benzyl methyl ether radical cation in
MeCN is exergonic by -15 kcal mol-1 and occurs very
rapidly.35b,60 Furthermore, the very large deuterium isotope
effect (kH/kD ) 12-14) observed in the reaction of 2d indicates
that the rate-determining step is not an electron-transfer process,
a conclusion further supported by the findings that no good
correlation was obtained between the relative rates of oxidation
of substituted benzyl ethers 2d and 2p-s (Table 6) and their
ionization potentials calculated by the PM3 molecular orbital
method.61 Additional evidence against the single electron
transfer mechanism is the observation that peroxyiodane oxida-
tion of 2d62 was not retarded in the presence of 1,4-dimethoxy-
benzene, a single electron transfer quencher with the oxidation
potential Eox ) 1.28 V (vs SCE in MeCN).63
The peroxyiodane oxidation of 2d is sensitive to the nature
of solvents. The solvent effects presented in Table 1 indicate
that changes in solvent polarity have a great influence on product
yields, which increase with decreasing solvent polarity. We
obtained a good linear correlation between the yields of 3d and
Dimroth’s ET(30) values.11 This solvent effect can be attributed
to the polar character of the cyclic iodanyl radical 33a as well
as to the alkylperoxy radicals in their ground state. The
alkylperoxy radicals have been shown to be π-radicals with large
dipole moments.64,65 These hydrogen abstracting radicals would
be more efficiently solvated in polar solvents, which lead to
deactivation of these radicals. The reactivity of these radicals
is probably reduced by hydrogen bonding with protic solvents.56
activated by both enthalpic effects (benzylic, allylic, and
propargylic C-H bonds) and/or polar effects (R-oxy C-H
bonds), generating R-oxy carbon-centered radicals. Finally,
(tert-butylperoxy)iodane 1a, very stable in the solid state, can
generate a tert-butylperoxy radical and the iodanyl radical via
homolytic bond cleavage of the hypervalent iodine(III)-peroxy
bond eVen at room temperature in solution with a first-order
rate constant kobsd ) 2.62 × 10-5 s-1 (in CH2Cl2).
Experimental Section
General Information. IR spectra were recorded on Jasco IRA-1
and Perkin Elmer 1720 FT-IR spectrometers. 1H and 13C NMR were
recorded in CDCl3 on JEOL JMN-GX 270 and 400 spectrometers.
Chemical shifts were reported in parts per million (ppm) downfield
from internal Me4Si. Mass spectra (MS) were obtained on a JEOL
JMS-DX300 spectrometer. Melting points were determined with a
Yanaco micro melting points apparatus and are uncorrected.
Unless otherwise noted, reactions were performed under nitrogen
atmosphere using a rubber balloon. Benzene and cyclohexane were
dried over CaH2 and distilled. BF3-Et2O was distilled from CaH2 under
nitrogen. Analytical gas chromatography (GC) was carried out on a
Shimadzu GC-14A gas chromatograph with a column of 20% Silicone
GE SF-96 on Chromosorb W (AW-DMCS). Preparative thin-layer
chromatography (TLC) was carried out on precoated plates of silica
gel (Merck, silica gel F-254). Kieselgel 60 (Merck, 230-400 mesh)
was used for flash chromatography.
Substrates. Benzyl methyl ether (2a), phthalan (2u), isochroman
(2v), indan, 5-methoxyindan, tetrahydronaphthalene, and 1-phenylhex-
ane (18b) were purchased from Tokyo Kasei Kogyo Co. and distilled
prior to use. Diphenylmethane, 9,10-dihydroanthracene, anthrone,
xanthene, and fluorene (18a) are commercially available. Other benzyl
ethers were prepared by the reaction of sodium alkoxides with benzyl
bromide in the presence of tetrabutylammonium iodide.66 Benzyl ethers
1
prepared by this way and their H NMR are as follows: benzyl ethyl
ether (2b),67 δ 7.35-7.28 (m, 5H), 4.50 (s, 2 H), 3.53 (q, J ) 6.4 Hz,
2 H), 1.24 (t, J ) 6.4 Hz, 3 H); benzyl 2-propyl ether (2c),68 δ 7.34-
7.28 (m, 5 H), 4.50 (s, 2 H), 3.67 (sept, J ) 6.1 Hz, 1 H), 1.21 (d, J
) 6.1 Hz, 6 H); benzyl n-butyl ether (2d),9d δ 7.33 (m, 5 H), 4.50 (s,
2 H), 3.47 (t, J ) 6.5 Hz, 2 H), 1.67-1.31 (m, 4 H), 0.92 (t, J ) 7.3
Hz, 3 H); benzyl 2-butyl ether (2e),69 δ 7.33 (m, 5 H), 4.56 (d, J )
11.7 Hz, 1 H), 4.46 (d, J ) 11.7 Hz, 1 H), 3.44 (sext, J ) 6.1 Hz, 1
H), 1.81-1.43 (m, 2 H), 1.18 (d, J ) 6.1 Hz, 3 H), 0.93 (t, J ) 6.4
Hz, 3 H); benzyl tert-butyl ether (2f),9a,70 δ 7.40-7.20 (m, 5 H), 4.45
(s, 2 H), 1.29 (s, 9 H); benzyl cyclopentyl ether (2g),9b δ 7.31 (m, 5
H), 4.47 (s, 2 H), 4.06-3.88 (m, 1 H), 1.80-1.39 (m, 8 H); benzyl
cyclohexyl ether (2h),9a,70 δ 7.30 (m, 5 H), 4.53 (s, 2 H), 3.43-3.24
(m, 1 H), 2.00-1.17 (m, 10 H); benzyl 1-methylcyclohexyl ether (2i),
δ 7.40-7.21 (m, 5 H), 4.41 (s, 2 H), 1.90-1.20 (m, 10 H), 1.22 (s, 3
H); benzyl menthyl ether (2j),9c δ 7.33 (m, 5 H), 4.66 (d, J ) 11.5 Hz,
1 H), 4.39 (d, J ) 11.5 Hz, 1 H), 3.17 (dt, J ) 4.2, 10.5 Hz, 1 H),
2.43-2.12 (m, 2 H), 1.80-0.90 (m, 7 H), 0.93 (d, J ) 7.3 Hz, 3 H),
0.90 (d, J ) 7.3 Hz, 3 H), 0.70 (d, J ) 6.8 Hz, 3 H); benzyl cis-4-
tert-butylcyclohexyl ether (2k), δ 7.40-7.18 (m, 5 H), 4.50 (s, 2 H),
3.68-3.56 (m, 1 H), 2.08-1.92 (m, 2 H), 1.60-1.20 (m, 7 H), 0.86
(s, 9 H); benzyl trans-4-tert-butylcyclohexyl ether (21), δ 7.40-7.17
(m, 5 H), 4.55 (s, 2 H), 3.25 (tt, J ) 11.0, 4.4 Hz, 1 H), 2.20-2.04 (m,
2 H), 1.87-1.72 (m, 2 H), 1.40-0.90 (m, 5 H), 0.84 (s, 9 H); benzyl
cis-2-methylcyclohexyl ether (2m), δ 7.46-7.18 (m, 5 H), 4.58 (d, J
) 12.2 Hz, 1 H), 4.43 (d, J ) 12.2 Hz, 1 H), 3.44 (dt, J ) 6.1, 3.0 Hz,
1 H), 1.97-1.12 (m, 9 H), 0.97 (d, J ) 7.1 Hz, 3 H); benzyl trans-
2-methylcyclohexyl ether (2n), δ 7.46-7.18 (m, 5 H), 4.64 (d, J )
11.7 Hz, 1 H), 4.43 (d, J ) 11.7 Hz, 1 H), 2.90 (dt, J ) 4.5, 9.5 Hz,
1 H), 2.30-2.00 (m, 1 H), 1.89-1.09 (m, 8 H), 1.02 (d, J ) 6.4 Hz,
Conclusion
Compared to other oxidizing reagents such as CrO3,
PhCH2N+Et3‚MnO4-, and RuO4, used for deprotection of benzyl
and allyl ethers, the (tert-butylperoxy)iodane 1a is more useful
for three reasons: it does not contain poisonous heavy metals,
the o-iodobenzoic acid formed can be recycled by oxidation to
the hypervalent iodane, and the oxidation proceeds under mild
conditions, making the reaction compatible with other protecting
groups such as MOM, THP, and TBDMS ethers, and acetoxy
groups. Oxidation with 1a occurs readily with C-H bonds
(59) Photoelectron spectroscopy shows that the oxidation potential of
aromatic π electrons of benzyl ethers is lower than that of the nonbonding
electrons on oxygen. Therefore, the charge density of benzyl ether cation
radicals has been assumed to be located in the π system rather than localized
on the potentially oxidizable oxygen atom. See: (a) Mayeda, E. A.; Miller,
L. L.; Wolf, J. F. J. Am. Chem. Soc. 1972, 94, 6812. (b) Pincock, J. A.;
Pincock, A. L.; Fox, M. A. Tetrahedron 1985, 41, 4107.
(60) However, large deuterium kinetic isotope effects for reactions of
para-substituted N,N-dimethylaniline cation radicals with pyridine, which
involve a rate-determining proton transfer step, have been reported; kH/kD;
22 (p-MeO) and 12 (p-Cl). See: Parker, V. D.; Tilset, M. J. Am. Chem.
Soc. 1991, 113, 8778.
(61) Ionization potential calculated by MOPAC7: 2d, 9.42 eV; 2p, 8.90
eV; 2q, 9.17 eV; 2r, 9.18 eV; 2s, 9.30 eV. See: Steward, J. J. P. J. Comput.
Chem. 1989, 10, 221.
(62) The oxidation potential of 2d has been estimated to be greater than
1.65 V.9g
(66) Czernecki, S.; Georgoulis, C.; Provelenghiou, C. Tetrahedron Lett.
1976, 3535.
(67) Grandi, R.; Marchesini, A.; Pagnoni, U. M.; Trave, R. J. Org. Chem.
1976, 41, 1755.
(68) Hatakeyama, S.; Mori, H.; Kitano, K.; Yamada, H.; Nishizawa, M.
Tetrahedron Lett. 1994, 35, 4367.
(69) Dimitridis, E.; Massy-Westropp, R. A. Aust. J. Chem. 1984, 37,
619.
(63) Tanemura, K.; Dohya, H.; Imamura, M.; Suzuki, T.; Horaguchi, T.
Chem. Lett. 1994, 965.
(64) (a) Boyd, S. L.; Boyd, R. J.; Barclay, L. R. C. J. Am. Chem. Soc.
1990, 112, 5724. (b) Howard, J. A. Can. J. Chem. 1979, 57, 253.
(65) Using the technique of time-resolved microwave dielectric absorp-
tion, the dipole moment of benzylperoxy radical has been reported to be
2.4 ( 0.2 D. See: Fessenden, R. W.; Hitachi, A.; Nagarajan, V. J. Phys.
Chem. 1984, 88, 107.
(70) Liotta, L. J.; Ganem, B. Tetrahedron Lett. 1989, 30, 4759.

7726 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
3 H); benzyl phenyl ether (2o),9a,70 δ 7.47-7.19 (m, 7 H), 7.00-6.88
(3 H), 5.04 (s, 2 H); n-butyl p-methoxybenzyl ether (2p),71 δ 7.25 (dt,
J ) 8.5, 2.2 Hz, 2 H), 6.86 (dt, J ) 8.5, 2.2 Hz, 2 H), 4.42 (s, 2 H),
3.79 (s, 3 H), 3.44 (t, J ) 6.5 Hz, 2 H), 1.64-1.30 (m, 4 H), 0.91 (t,
J ) 7.2 Hz, 3 H); n-butyl p-methylbenzyl ether (2q),72 δ 7.22 (d, J )
8.1 Hz, 2 H), 7.13 (d, J ) 8.1 Hz, 2 H), 4.46 (s, 2 H), 3.45 (t, J ) 6.6
Hz, 2 H), 2.33 (s, 3 H), 1.66-1.25 (m, 4 H), 0.91 (t, J ) 7.1 Hz, 3 H);
n-butyl p-chlorobenzyl ether (2r),71 δ 7.28 (m, 4 H), 4.45 (s, 2 H),
3.46 (t, J ) 6.5 Hz, 2 H), 1.63-1.37 (m, 4 H), 0.92 (t, J ) 7.2 Hz, 3
H); n-butyl m-clorobenzyl ether (2s),71 δ 7.33 (br s, 1 H), 7.25 (m, 3
H), 4.46 (s, 2 H), 3.47 (t, J ) 6.3 Hz, 2 H), 1.67-1.22 (m, 4 H), 0.92
(t, J ) 7.6 Hz, 3 H); n-butyl p-phenylbenzyl ether (2t), δ 7.66-7.50
(m, 4 H), 7.50-7.26 (m, 5 H), 4.52 (s, 2 H), 3.49 (t, J ) 6.5 Hz, 2 H),
1.69-1.31 (m, 4 H), 0.92 (t, J ) 7.1 Hz, 3 H); benzyl 3â-cholesteryl
ether (21c), δ 7.44-7.20 (m, 5 H), 5.33 (m, 1 H), 4.56 (s, 2 H), 3.38-
3.14 (m, 1 H), 2.51-2.16 (m, 2 H), 2.12-1.72 (m, 5 H), 1.72-0.76
(m, 21 H), 1.01 (s, 3 H), 0.91 (d, J ) 6.6 Hz, 3 H), 0.86 (d, J ) 6.6
Hz, 6 H), 0.68 (s, 3 H); benzyl 3-butenyl ether (23),73 δ 7.73 (m, 5 H),
5.84 (ddt, J ) 17.1, 10.0, 6.5 Hz, 1 H), 5.12 (br d, J ) 17.1 Hz, 1 H),
5.08 (br d, J ) 10.0 Hz, 1 H), 4.53 (s, 2 H), 3.53 (t, J ) 6.8 Hz, 2 H),
2.38 (br q, J ) 6.6 Hz, 2 H); benzyl R-methylbenzyl ether (43), δ 7.33
(m, 10 H), 4.50 (q, J ) 6.5 Hz, 1 H), 4.45 (d, J ) 11.7 Hz, 1 H), 4.29
(d, J ) 11.7 Hz, 1 H), 1.48 (d, J ) 6.5 Hz, 3 H).
5-Acetoxy-1-(benzyloxy)-3-methylpentane (2z): To a solution of
1-(benzyloxy)-5-hydroxy-3-methylpentane (462 mg, 2.21 mmol) in
pyridine (21 mL) was added acetic anhydride (2.4 g, 24 mmol) under
nitrogen at 0 °C, and the solution was stirred for 0.5 h. After
evaporation in vacuo, flash chromatography yielded 2z (375 mg,
64%): colorless oil; IR (CHCl3) 2929, 1740, 1455, 1367, 1240, 1101,
738, 699 cm-1; 1H NMR δ 7.32 (m, 5 H), 4.49 (s, 2 H), 4.10 (dt, J )
6.6, 1.3 Hz, 2 H), 3.51 (t, J ) 6.5 Hz, 2 H), 2.03 (s, 3 H), 1.84-1.32
(m, 5 H), 0.92 (d, J ) 6.4 Hz, 3 H); MS m/z (rel intensity) 250 (8,
M+), 190 (16), 133 (16), 107 (97), 92 (55), 61 (100), 43 (93); HRMS,
calcd for C15H22O3 (M+) 250.1569, found 250.1569.
Benzyl 4,4-Diphenyl-3-butenyl Ether (26): A mixture of sodium
4-hydroxybutanoate (126 mg, 1.00 mmol) and sodium hydride (24 mg,
1.0 mmol, 60% dispersion in oil) in N,N-dimethylformamide (10 mL)
was stirred under nitrogen at room temperature for 1 h. Benzyl bromide
(429 mg, 2.50 mmol) was added, and the mixture was stirred for 25 h.
The mixture was poured into water and extracted with diethyl ether.
The organic phase was washed with brine and dried over anhydrous
Na2SO4 and concentrated. Chromatography of the crude mixture
yielded benzyl 4-(benzyloxy)butanoate (61 mg, 21%): IR (film) 3032,
1
2860, 1735, 1455, 1166, 1106, 738, 698 cm-1; H NMR δ 7.34 (s, 5
H), 7.31 (s, 5 H), 5.10 (s, 2 H), 4.47 (s, 2 H), 3.50 (t, J ) 6.3 Hz, 2 H),
2.49 (t, J ) 7.2 Hz, 2 H), 1.96 (br quint, J ) 6.7 Hz, 2 H). To a
solution of benzyl 4-(benzyloxy)butanoate (90 mg, 0.32 mmol) in
tetrahydrofuran (10 mL) was added dropwise a tetrahydrofuran solution
of phenylmagnesium bromide (2 M solution, 0.47 mL, 0.96 mmol)
under nitrogen at room temperature, and the mixture was heated at
reflux for 16 h. The mixture was quenched with water, acidified with
5% aqueous HCl, and extracted with dichloromethane. The organic
phase was washed with brine, dried over anhydrous Na2SO4, and
concentrated. Chromatography of the crude mixture yielded 4-(ben-
zyloxy)-1,1-diphenylbutanol (57 mg, 55%): pale yellow oil; IR (film)
1-(Benzyloxy)-5-(methoxymethoxy)-3-methylpentane (2w): 1-(Ben-
zyloxy)-5-hydroxy-3-methylpentane was prepared by reaction of the
sodium alkoxide of 1,5-dihydroxy-3-methylpentane with benzyl bromide
in the presence of tetrabutylammonium iodide in 73% yield.66 To a
stirred suspension of sodium hydride (96 mg, 2.4 mmol) in tetrahy-
drofuran (5 mL) were added dropwise 1-(benzyloxy)-5-hydroxy-3-
methylpentane (500 mg, 2.4 mmol) and chloromethyl methyl ether (231
mg, 2.87 mmol) under nitrogen at room temperature, and stirring was
continued for 21 h. The mixture was poured over ice and extracted
with diethyl ether, and the organic phase was washed with brine. The
solution was dried over anhydrous Na2SO4 and concentrated. Flash
chromatography of the crude product mixture yielded 2w (313 mg,
49%): colorless oil; IR (CHCl3) 2928, 1455, 1366, 1109, 1040, 737,
1
3423, 3029, 2862, 1494, 1449, 1363, 1102, 747, 699 cm-1; H NMR
δ 7.45-7.19 (m, 15 H), 4.47 (s, 2 H), 3.50 (t, J ) 6.0 Hz, 2 H), 3.39
(s, 1 H), 2.42 (t, J ) 7.2 Hz, 2 H), 1.65 (m, 2 H). A mixture of
4-(benzyloxy)-1,1-diphenylbutanol (7.9 mg, 0.024 mmol) and p-
toluenesulfonic acid (1.0 mg) in benzene (1 mL) was heated at reflux
for 1 min. The mixture was poured into water and extracted with
dichloromethane. The organic phase was washed with brine, dried with
anhydrous Na2SO4, and concentrated. Preparative TLC of the crude
product mixture yielded (26) (5.5 mg, 74%):74 pale yellow oil; IR (film)
1
698 cm-1; H NMR δ 7.33 (m, 5 H), 4.61 (s, 2 H), 4.50 (s, 2 H),
3.62-3.44 (4 H), 3.35 (s, 3 H), 1.88-1.28 (m, 5 H), 0.92 (d, J ) 6.4
Hz, 3 H); MS m/z (rel intensity) 253 (1, M+ + 1), 131 (5), 110 (30),
94 (100), 81 (59), 66 (100), 51 (45); HRMS, calcd for C15H25O3 (M+
+ 1) 253.1804, found 253.1844.
1
3028, 2856, 1495, 1445, 1362, 1099, 1029, 770, 698 cm-1; H NMR
1-(Benzyloxy)-3-methyl-5-(tetrahydropyranoxy)pentane (2x): To
a solution of 1-(benzyloxy)-5-hydroxy-3-methylpentane (300 mg, 1.40
mmol) and 3,4-dihydro-2H-pyran (639 mg, 7.17 mmol) in dichlo-
romethane (15 mL) was added p-toluenesulfonic acid (3.0 g, 16.8 mmol)
under nitrogen at room temperature, and the mixture was stirred for
27 h. The mixture was poured over ice and extracted with diethyl
ether, and the organic phase was washed with brine. The solution was
dried over anhydrous Na2SO4 and concentrated. Flash chromatography
of the crude product mixture yielded 2x (264 mg, 62%): colorless oil;
1H NMR δ 7.32 (m, 5 H), 4.57 (m, 1 H), 4.50 (s, 2 H), 4.00-3.68 (m,
2 H), 3.60-3.28 (m, 4 H), 1.96-1.28 (m, 11 H), 0.92 (d, J ) 6.4 Hz,
3 H); MS m/z (rel intensity) 207 (11, M+ - C5H9O), 191 (9), 185 (7),
105 (100), 101 (72), 83 (67), 67 (34), 55 (73); HRMS, calcd for
C13H19O2 (M+ - C5H9O) 207.1385, found 207.1372.
δ 7.37-7.16 (m, 15 H), 6.14 (t, J ) 7.0 Hz, 1 H), 4.50 (s, 2 H), 3.56
(t, J ) 7.0 Hz, 2 H), 2.45 (q, J ) 7.0 Hz, 2 H).
Allyl and propargyl ethers were prepared by the reaction of sodium
alkoxides with 2-propenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl,
trans-cinnamyl, propargyl, and 2-butynyl bromides in the presence of
tetrabutylammonium iodide.66 Allyl and propargyl ethers prepared by
1
this way and their H NMR are as follows: allyl n-decyl ether (6a),75
δ 5.92 (ddt, J ) 17.1, 10.5, 5.5 Hz, 1 H), 5.26 (br d, J ) 17.1 Hz, 1
H), 5.16 (br d, J ) 10.5 Hz, 1 H), 3.96 (br d, J ) 5.5 Hz, 2 H), 3.42
(t, J ) 6.6 Hz, 2 H), 1.70-1.50 (m, 2 H), 1.42-1.16 (14 H), 0.88 (t,
J ) 6.4 Hz, 3 H); allyl 2-phenylethyl ether (6b),76 δ 7.41-7.13 (m, 1
H), 5.91 (ddt, J ) 17.1, 10.3, 5.6 Hz, 1 H), 5.25 (br d, J ) 17.1 Hz,
1 H), 5.16 (br d, J ) 10.3 Hz, 1 H), 3.99 (d, J ) 5.6 Hz, 2 H), 3.65
(t, J ) 7.2 Hz, 2 H), 2.91 (t, J ) 7.2 Hz, 2 H); allyl 4-decyl ether (6c),
δ 5.93 (ddt, J ) 17.3, 10.5, 5.6 Hz, 1 H), 5.25 (dq, J ) 17.3, 1.5 Hz,
1 H), 5.13 (br d, J ) 10.5 Hz, 1 H), 3.97 (dt, J ) 5.6, 1.5 Hz, 2 H),
3.28 (quint, J ) 6.1 Hz, 1 H), 1.60-1.16 (14 H), 0.91 (t, J ) 6.8 Hz,
1-(Benzyloxy)-5-(tert-butyldimethylsiloxy)-3-methylpentane (2y):
To a solution of 1-(benzyloxy)-5-hydroxy-3-methylpentane (500 mg,
2.4 mmol) and imidazole (570 mg, 8.4 mmol) in N,N-dimethylforma-
mide (2 mL) was added tert-butyldimethylchlorosilane (432 mg, 2.87
mmol) under nitrogen at room temperature, and the mixture was stirred
for 5 h. The mixture was poured over ice and extracted with diethyl
ether, and the organic phase was washed with brine. The solution was
dried over anhydrous Na2SO4 and concentrated. Flash chromatography
of the crude product mixture yielded 2y (756 mg, 98%): colorless oil;
3 H), 0.88 (t, J ) 6.5 Hz, 3 H); allyl 3â-cholestanyl ether (6d),77
δ
5.92 (ddt, J ) 17.3, 10.3, 5.6 Hz, 1 H), 5.26 (br d, J ) 17.3 Hz, 1 H),
5.14 (br d, J ) 10.3 Hz, 1 H), 4.01 (d, J ) 5.6 Hz, 2 H), 3.40-3.10
(m, 1 H), 2.08-0.70 (m, 31 H), 0.90 (d, J ) 6.8 Hz, 3 H), 0.86 (d, J
) 6.6 Hz, 6 H), 0.80 (s, 3 H), 0.65 (s, 3 H); allyl menthyl ether (6e),75
δ 5.93 (ddt, J ) 17.1, 10.0, 5.6 Hz, 1 H), 5.26 (br d, J ) 17.1 Hz, 1
H), 5.13 (br d, J ) 10.0 Hz, 1 H), 4.12 (dd, J ) 12.5, 5.6 Hz, 1 H),
3.88 (dd, J ) 12.5, 5.6 Hz, 1 H), 3.08 (dt, J ) 4.2, 10.5 Hz, 1 H),
IR (CHCl3) 2929, 2857, 1463, 1255, 1098, 836, 776, 734, 697 cm-1
;
1H NMR δ 7.33 (m, 5 H), 4.50 (s, 2 H), 3.66 (dt, J ) 1.2, 6.8 Hz, 2
H), 3.53 (t, J ) 6.8 Hz, 2 H), 1.84-1.24 (m, 5 H), 0.91 (d, J ) 6.4
Hz, 3 H), 0.90 (s, 9 H), 0.05 (s, 6 H); MS m/z (rel intensity) 265 (3,
M+ - C4H9), 173 (56), 143 (25), 92 (100), 75 (54); HRMS, calcd for
C15H25O2Si (M+ - C4H9) 265.1624, found 265.1585.
(74) Brownbridge, P.; Warren, S. J. Chem. Soc., Chem. Commun. 1975,
820.
(75) Corey, E. J.; Suggs, J. W. J. Org. Chem. 1973, 38, 3224.
(76) Espanet, B.; Dunach, E.; Perichon, J. Tetrahedron Lett. 1992, 33,
(71) Xavier, N.; Arulraj, S. J. Tetrahedron 1985, 41, 2875.
(72) Alphonse, I.; Arulraj, S. J. Indian J. Chem., Sect. B 1985, 24B, 199.
(73) Sakurai, H.; Sakata, Y.; Hosomi, A. Chem. Lett. 1983, 409.
2885.
(77) Akiyama, T.; Hirofuji, H.; Ozaki, S. Bull. Chem. Soc. Jpn. 1992,
65, 1932.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7727
2.42-1.91 (m, 2 H), 1.78-1.48 (m, 2 H), 1.48-1.10 (m, 2 H), 1.10-
0.90 (m, 3 H), 0.92 (d, J ) 6.4 Hz, 3 H), 0.89 (d, J ) 6.8 Hz, 3 H),
0.77 (d, J ) 6.8 Hz, 3 H); 1-adamantyl allyl ether (6f),78 δ 5.93 (ddt,
J ) 17.4, 10.3, 5.0 Hz, 1 H), 5.26 (br d, J ) 17.4 Hz, 1 H), 5.12 (br
d, J ) 10.3 Hz, 1 H), 3.99 (br d, J ) 5.0 Hz, 2 H), 2.15 (m, 3 H),
1.82-1.51 (m, 12 H); allyl 4-tert-butylphenyl ether (6g),79 δ 7.29 (d,
J ) 8.7 Hz, 2 H), 6.85 (d, J ) 8.7 Hz, 2 H), 6.06 (ddt, J ) 17.3, 10.5,
5.1 Hz, 1 H), 5.40 (br d, J ) 17.3 Hz, 1 H), 5.27 (br d, J ) 10.5 Hz,
1 H), 4.51 (br d, J ) 5.1 Hz, 1 H), 1.29 (s, 9 H); n-decyl 2-methyl-
2-propenyl ether (8), δ 4.95 (s, 1 H), 4.88 (s, 1 H), 3.86 (s, 2 H), 3.39
(t, J ) 6.4 Hz, 2 H), 1.74 (s, 3 H), 1.70-1.46 (m, 2 H), 1.46-1.10 (14
H), 0.88 (t, J ) 6.4 Hz, 3 H); n-decyl 3-methyl-2-butenyl ether (10a),
δ 5.36 (br t, J ) 6.8 Hz, 1 H), 3.94 (d, J ) 6.8 Hz, 2 H), 3.40 (t, J )
6.6 Hz, 2 H), 1.74 (s, 3 H), 1.67 (s, 3 H), 1.69-1.45 (m, 2 H), 1.45-
1.13 (14 H), 0.88 (t, J ) 6.4 Hz, 3 H); 3-methyl-2-butenyl-2-phenylethyl
ether (10b), δ 7.44-7.13 (m, 5 H), 5.35 (br t, J ) 6.8 Hz, 1 H), 3.98
(d, J ) 6.8 Hz, 2 H), 3.63 (t, J ) 7.3 Hz, 2 H), 2.90 (t, J ) 7.3 Hz,
2 H), 1.74 (s, 3 H), 1.66 (s, 3 H), menthyl 3-methyl-2-butenyl ether
(10c), δ 5.35 (br t, J ) 6.8 Hz, 1 H), 4.10 (dd, J ) 10.8, 6.8 Hz, 1 H),
3.84 (dd, J ) 10.8, 6.8 Hz, 1 H), 3.04 (dt, J ) 4.2, 10.5 Hz, 1 H),
2.32-2.00 (m, 2 H), 1.74 (s, 3 H), 1.67 (s, 3 H), 1.48-0.9 (m, 7 H),
0.92 (d, J ) 6.6 Hz, 3 H), 0.90 (d, J ) 7.1 Hz, 3 H), 0.77 (d, J ) 6.8
Hz, 3 H); n-decyl trans-cinnamyl ether (12), δ 7.41-7.17 (m, 5 H),
6.60 (br d, J ) 15.9 Hz, 1 H), 6.29 (dt, J ) 15.9, 5.9 Hz, 1 H), 4.12
(dd, J ) 5.9, 1.2 Hz, 2 H), 3.47 (t, J ) 6.6 Hz, 2 H), 1.71-1.48 (m,
2 H), 1.48-1.12 (14 H), 0.88 (t, J ) 6.3 Hz, 3 H); n-decyl propargyl
ether (14a),80 δ 4.13 (d, J ) 2.3 Hz, 2 H), 3.51 (t, J ) 6.3 Hz, 2 H),
2.41 (t, J ) 2.3 Hz, 1 H), 1.72-1.46 (m, 2 H), 1.46-1.10 (14 H), 0.88
(t, J ) 6.4 Hz, 3 H); n-decyl 2-pentynyl ether (14b), δ 4.10 (t, J ) 2.0
Hz, 2 H), 3.47 (t, J ) 6.7 Hz, 2 H), 2.23 (tq, J ) 2.0, 7.5 Hz, 2 H),
1.70-1.10 (m, 16 H), 1.14 (t, J ) 7.5 Hz, 3 H), 0.88 (t, J ) 6.2 Hz,
3 H); n-decyl 3-(trimethylsilyl)-2-propynyl ether (14c), δ 4.12 (s, 2
H), 3.48 (t, J ) 6.6 Hz, 2 H), 1.71-1.44 (m, 2 H), 1.44-1.10 (m, 14
H), 0.87 (t, J ) 6.6 Hz, 3 H), 0.16 (s, 9 H); 1-(allyloxy)-5-(benzyloxy)-
3-methylpentane (16a), δ 7.58-7.12 (m, 5 H), 5.91 (ddt, J ) 17.0,
10.3, 5.6 Hz, 1 H), 5.26 (br d, J ) 17.0 Hz, 1 H), 5.16 (br d, J ) 10.3,
1 H), 4.49 (s, 2 H), 3.95 (br d, J ) 5.6, 2 H), 3.51 (t, J ) 6.8 Hz, 2 H),
3.46 (t, J ) 6.3 Hz, 2 H), 1.94-1.16 (m, 5 H), 0.91 (d, J ) 6.4 Hz, 3
H); 5-(benzyloxy)-3-methyl-1-(3-methyl-2-butenyloxy)pentane (17a),
δ 7.56-7.16 (m, 5 H), 5.35 (br t, J ) 6.8 Hz, 1 H), 4.49 (s, 2 H), 3.93
(d, J ) 6.8, 2 H), 3.51 (t, J ) 6.6 Hz, 2 H), 3.44 (t, J ) 6.6 Hz, 2 H),
2.04-1.20 (m, 5 H), 1.74 (s, 3 H), 1.67 (s, 3 H), 0.91 (d, J ) 6.1 Hz,
3 H).
added dropwise BF3-Et2O (2.22 mL, 18.0 mmol) at room temperature
under nitrogen, and the mixture was stirred for 3.5 h. The reaction
mixture was quenched with water, and the resulting precipitate was
removed by filtration. The mixture was extracted with dichloromethane.
The extract was washed with 1% aqueous Na2CO3 and water, dried
over Na2SO4, and concentrated in vacuo to give the peroxyiodane 1b.
Recrystallization from methanol-dichloromethane gave colorless needles
(2.79 g, 41%): mp 131-133 °C dec; IR (CHCl3) 2970, 1695, 1675,
1
1610, 1575, 1535, 1375, 1350, 1260, 1150 cm-1; H NMR δ 9.03 (d,
J ) 2.4 Hz, 1 H), 8.72 (dd, J ) 8.8, 2.4 Hz, 1 H), 8.36 (d, J ) 8.8 Hz,
1 H), 1.35 (s, 9 H); 13C NMR δ 165.5, 150.9, 132.0, 129.1, 127.0,
126.2, 84.0, 26.0; MS m/z (rel intensity) 293 (100), 276 (21), 92 (38),
75 (46), 57 (89), 43 (91). Anal. Calcd for C11H12INO6: C, 34.66; H,
3.17; N, 3.68. Found: C, 34.30; H, 3.14; N, 3.33.
Solvent Effects for Oxidation of Benzyl n-Butyl Ether (2d) to
n-Butyl Benzoate (3d). To a stirred mixture of the peroxyiodane 1a
(148 mg, 0.44 mmol) in an appropriate solvent (4 mL) was added benzyl
n-butyl ether (2d) (33 mg, 0.20 mmol) under nitrogen using a rubber
balloon at room temperature, and the mixture was stirred for the periods
shown in Table 1. The yield of the benzoate 3d was determined by
gas chromatography using n-tridecane as an internal standard and is
shown in Table 1. The authentic sample of 3d was prepared by the
reaction of 1-butanol with benzoyl chloride. 3d:9d colorless oil; IR
(film) 2961, 2874, 1719, 1452, 1315, 1277, 1177, 1112, 1071, 1028,
1
711 cm-1; H NMR δ 8.04 (br d, J ) 8.3 Hz, 2 H), 7.64-7.38 (m, 3
H), 4.33 (t, J ) 6.5 Hz, 2 H), 1.83-1.40 (m, 4 H), 0.98 (t, J ) 7.3 Hz,
3 H); MS m/z (rel intensity) 178 (3, M+), 167 (37), 149 (100), 123
(57), 105 (79), 77 (41), 71 (25), 57 (40).
Reaction of the Peroxyiodane 1a with Methanol. A solution of
the peroxyiodane 1a (34 mg, 0.1 mmol) in methanol (1 mL) was stirred
at room temperature for 2 days under nitrogen. After evaporation of
the solvent, the residue was dissolved in dichloromethane. The
insoluble precipitate was filtered off and washed with dichloromethane.
Concentration in vacuo gave 1-methoxy-1,2-benziodoxol-3(1H)-one
(4)81 (13.9 mg, 50%) as colorless plates: mp 168-170 °C (recrystallized
from methanol); IR (KBr) 3083, 1640, 1566, 1442, 1292, 966, 831,
744 cm-1; 1H NMR δ 8.29 (dd, J ) 7.6, 1.7 Hz, 1 H), 7.91 (ddd, J )
8.3, 7.6, 1.7 Hz, 1 H), 7.77 (br d, J ) 8.3 Hz, 1 H), 7.71 (br dd, J )
8.3, 7.6 Hz, 1 H), 4.28 (s, 3 H); MZ m/z (rel intensity) 278 (M+), 248
(100), 231 (68), 203 (56), 76 (76), 50 (42).
Time Courses for Oxidation of the Ether 2d to n-Butyl Benzoate
(3d). To a stirred mixture of the peroxyiodane 1a and an appropriate
alkali metal carbonate in benzene (5 mL) was added benzyl n-butyl
ether (2d) (33 mg, 0.20 mmol) under nitrogen using a rubber balloon.
The mixture was stirred under the conditions described in Figures 1
and 2. As an internal standard, n-tridecane was added, and the time
course for the reaction was determined by gas chromatography.
General Procedure for Benzylic Oxidation of Benzyl Ethers 2
with the Peroxyiodane 1a. To a stirred mixture of the peroxyiodane
1a (135 mg, 0.40 mmol) and potassium carbonate (111 mg, 0.80 mmol)
in benzene (5 mL) was added a benzyl ether 2 (0.20 mmol) under
nitrogen using a rubber balloon at room temperature, and the mixture
was stirred for the periods shown in Table 2. The resulting precipitate,
which contains potassium salt of o-iodobenzoic acid and potassium
carbonate, was filtered off and washed with dichloromethane several
times. Concentration in vacuo gave an oil, which was purified by
preparative TLC. The yields of pure products are given in Table 2. In
some experiments, yields were determined by gas chromatography.
n-Butyl r-(tert-Butylperoxy)benzyl Ether (5): Colorless oil; IR
Synthesis of 1-(tert-Butylperoxy)-1,2-benziodoxol-3(1H)-one (1a).
To a stirred suspension of commercially available and finely powdered
1-hydroxy-1,2-benziodoxol-3(1H)-one (5.53 g, 21.0 mmol) and tert-
butyl hydroperoxide (3.90 mL of 80% solution in di-tert-butyl peroxide,
31.4 mmol) in 60 mL of chloroform was added dropwise BF3-Et2O
(2.58 mL, 21.0 mmol) at 0 °C under nitrogen, and the mixture was
stirred for 3 h. The reaction mixture was quenched with water and the
resulting precipitate was removed by filtration. The mixture was
extracted with dichloromethane. The extract was washed with water,
dried over Na2SO4, and concentrated in vacuo to give the peroxyiodane
1a. Recrystallization from hexane-dichloromethane gave colorless
plates (6.33 g, 90%): mp 128.5-129 °C dec; IR (CHCl3) 3030, 3010,
1680, 1600, 1580, 1445, 1370, 1290, 1250, 1190, 1135, 1030, 835 cm-1
;
1H NMR δ 8.26 (dd, J ) 7.7, 1.5 Hz, 1 H), 8.12 (dd, J ) 8.2, 1.0 Hz,
1 H), 7.93 (ddd, J ) 8.2, 7.7, 1.5 Hz, 1 H), 7.71 (dt, J ) 1.0, 7.7 Hz,
1 H), 1.33 (s, 9 H); 13C NMR δ 167.9, 135.2, 132.3, 130.9, 129.7,
127.5, 120.1, 83.1, 25.9; MS m/z (rel intensity) 330 (83), 248 (100),
231 (64), 203 (57), 76 (91). Anal. Calcd for C11H13IO4: C, 39.31; H,
3.90. Found: C, 39.35; H, 3.96.
1
(film) 2961, 2934, 1364, 1198, 1100, 1003, 754, 698 cm-1; H NMR
δ 7.61 (br d, J ) 7.6 Hz, 2 H), 7.19-7.07 (m, 3 H), 5.91 (s, 1 H), 4.09
(dt, J ) 9.5, 6.7 Hz, 1 H), 3.64 (dt, J ) 9.5, 6.1 Hz, 1 H), 1.60 (m, 2
H), 1.41 (m, 2 H), 1.21 (s, 9 H), 0.86 (t, J ) 7.3 Hz, 3 H); 13C NMR
δ 136.9, 128.7, 128.1, 126.9, 106.0, 80.7, 69.3, 32.0, 26.5, 19.3, 13.8;
MS m/z (rel intensity) 251 (M+ - 1), 179 (41), 163 (100), 108 (100);
HRMS, calcd for C11H15O3 (M+ - Bu) 195.1020, found 195.0979. Anal.
Calcd for C15H24O3: C, 71.39; H, 9.59. Found: C, 71.31; H, 9.82.
Oxidative Deprotection of Benzyl Menthyl Ether (2j). To a stirred
mixture of the peroxyiodane 1a (202 mg, 0.60 mmol) and potassium
carbonate (166 mg, 1.20 mmol) in benzene (5 mL) was added the benzyl
ether 2j (74 mg, 0.30 mmol) under nitrogen using a rubber balloon at
room temperature, and the mixture was stirred for 36 h. After
Synthesis of 1-(tert-Butylperoxy)-5-nitro-1,2-benziodoxol-3(1H)-
one (1b). To a stirred suspension of powdered 1-hydroxy-5-nitro-1,2-
benziodoxol-3(1H)-one (5.56 g, 18.0 mmol), prepared from 2-iodo-
benzoic acid by the reaction with concentrated sulfuric acid and fuming
nitric acid,14 and tert-butyl hydroperoxide (3.38 mL of 80% solution
in di-tert-butyl peroxide, 27.0 mmol) in 100 mL of chloroform was
(78) Kropp, P. J.; Fryxell, G. E.; Tubergen, M. W. J. Am. Chem. Soc.
1991, 113, 7300.
(79) Gasanzade, G. R.; Musaeva, B. I. Zh. Org. Khim. 1976, 12, 1449.
(80) Glazunova, E. M.; Khafizov, K.; Rakitin, I. I.; Ramazanov, V. Z.;
Potapova, I. M.; Korenskaya, L. L. Zh. Org. Khim. 1980, 16, 924.
(81) Siebelt, H.; Handrich, M. Anorg. Allg. Chem. 1976, 426, 178.

7728 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
evaporation of the solvent in vacuo and addition of a solution of KOH
(500 mg, 9.0 mmol) in methanol (5.4 mL) and water (1.3 mL), the
mixture was stirred for 17 h at room temperature under nitrogen. The
mixture was poured into an aqueous solution of Na2S2O3 and extracted
with dichloromethane, and the organic phase was washed with brine.
The solution was dried over anhydrous Na2SO4 and concentrated. Flash
chromatography of the crude product yielded 1-menthol (39 mg, 82%)
as colorless needles: mp 41-42 °C.
General Procedure for Allylic Oxidation of Allyl Ethers with
the Peroxyiodane 1a. To a stirred mixture of the peroxyiodane 1a
(135 mg, 0.40 mmol) and cesium carbonate (130 mg, 0.40 mmol) in
cyclohexane (5 mL) was added an allyl ether (0.20 mmol) under an
atmosphere at room temperature, and the mixture was stirred for the
periods shown in Table 3. The resulting precipitate, which contains
cesium salt of o-iodobenzoic acid and cesium carbonate, was filtered
off and washed with dichloromethane several times. Concentration in
vacuo gave an oil, which was purified by preparative TLC. The yields
of pure products are given in Table 3.
Oxidative Deprotection of Allyl n-Decyl Ether (6a). To a stirred
mixture of the peroxyiodane 1a (202 mg, 0.60 mmol) and potassium
carbonate (166 mg, 1.20 mmol) in cyclohexane (5 mL) was added the
allyl ether 6a (60 mg, 0.30 mmol) under an atmosphere at room
temperature, and the mixture was stirred for 3 days. After evaporation
of the solvent in vacuo and addition of a solution of NaOH (360 mg,
9.0 mmol) in methanol (6 mL) and water (1.5 mL), the mixture was
stirred for 6 h at room temperature under nitrogen. The mixture was
poured into an aqueous solution of Na2S2O3 and extracted with
dichloromethane, and the organic phase was washed with brine. The
solution was dried over anhydrous Na2SO4 and concentrated. Flash
chromatography (10% ethyl acetate in n-hexane) of the crude product
yielded 1-decanol (35.4 mg, 74%).
Oxidative Deprotection of Allyl Menthyl Ether (6e). The allyl
ether 6e (20 mg, 0.10 mmol) was treated with the peroxyiodane 1a
(67 mg, 0.20 mmol) and cesium carbonate (130 mg, 0.40 mmol) in
cyclohexane (5 mL) under an atmosphere at room temperature for 68
h. After evaporation of the solvent in vacuo, the mixture was further
treated with a solution of KOH (168 mg, 3.0 mmol) in methanol (1.5
mL) and water (0.4 mL) at room temperature for 18 h under nitrogen.
Flash chromatography (2% ethyl acetate in n-hexane) of the crude
product yielded 1-menthol (10.7 mg, 68%).
Oxidative Deprotection of n-Decyl 3-Methyl-2-butenyl Ether
(10a). The allyl ether 10a (67 mg, 0.30 mmol) was treated with the
peroxyiodane 1a (202 mg, 0.60 mmol) and potassium carbonate (166
mg, 1.20 mmol) in cyclohexane (4 mL) under an atmosphere at room
temperature for 3 days. After evaporation of the solvent in vacuo, the
mixture was further treated with a solution of NaOH (360 mg, 9.0
mmol) in methanol (6 mL) and water (1.5 mL) at room temperature
for 3 h under nitrogen. Flash chromatography (10% ethyl acetate in
n-hexane) of the crude product yielded 1-decanol (37.4 mg, 80%).
Oxidation of n-Decyl Propargyl Ether (14a) with the Peroxy-
iodane 1a. To a stirred mixture of the peroxyiodane 1a (135 mg, 0.40
mmol) and potassium carbonate (55 mg, 0.40 mmol) in cyclohexane
(5 mL) was added the propargyl ether 14a (45 mg, 0.20 mmol) under
an atmosphere at room temperature, and the mixture was stirred for 62
h. The resulting precipitate, which contains potassium salt of o-
iodobenzoic acid and potassium carbonate, was filtered off and washed
with dichloromethane several times. Concentration in vacuo gave an
oil, which was purified by preparative TLC (n-hexane-ethyl acetate-
dichloromethane 95:5:0.5) to give the alkynyl ester 15a (21.5 mg, 51%):
82 colorless oil; IR (film) 2927, 2121, 1718, 1467, 1234, 757 cm-1; 1H
NMR δ 4.19 (t, J ) 6.6 Hz, 2 H), 2.87 (s, 3 H), 1.89 (s, 1 H), 1.80-
1.52 (m, 2 H), 1.48-1.16 (14 H), 0.88 (t, J ) 6.6 Hz, 3 H); MS m/z
(rel intensity) 195 (1), 97 (27), 83 (53), 69 (61), 57 (100).
Oxidation of n-Decyl 2-Pentynyl Ether (14b) with the Peroxy-
iodane 1a. The propargyl ether 14b (34 mg, 0.15 mmol) was treated
with the peroxyiodane 1a (101 mg, 0.30 mmol) and potassium carbonate
(83 mg, 0.60 mmol) in cyclohexane (5 mL) under an atmosphere at
room temperature for 72 h. Preparative TLC (n-hexane-ethyl acetate-
dichloromethane 95:5:0.5) gave the alkynyl ester 15b (21.8 mg, 61%):
colorless oil; IR (film) 2920, 2850, 2240, 1708, 1457, 1310, 1250, 1081,
1055, 757 cm-1; 1H NMR δ 4.15 (t, J ) 6.7 Hz, 2 H), 2.35 (q, J ) 7.6
Hz, 2 H), 1.76-1.52 (m, 2 H), 1.48-1.08 (m, 14 H), 1.21 (t, J ) 7.6
Hz, 3 H), 0.88 (t, J ) 6.9 Hz, 3 H); MS m/z (rel intensity) 238 (3,
M+), 140 (19), 111 (11), 99 (100), 81 (81), 69 (28), 57 (34), 43 (28);
HRMS, calcd for C15H26O2 (M+) 238.1933, found 238.1906.
Oxidation of n-Decyl 3-(Trimethylsilyl)-2-propynyl Ether (14c)
with the Peroxyiodane 1a. The propargyl ether 14c (27 mg, 0.10
mmol) was treated with the peroxyiodane 1a (67 mg, 0.20 mmol) and
potassium carbonate (28 mg, 0.20 mmol) in cyclohexane (3 mL) under
an atmosphere at room temperature for 60 h. Preparative TLC (n-
hexane-ethyl acetate-dichloromethane 95:5:0.5) gave the alkynyl ester
15c (21.9 mg, 65%): colorless oil; IR (film) 2910, 2850, 2170, 1710,
1
1460, 1345, 1250, 1220, 1100, 990, 845, 760 cm-1; H NMR δ 4.16
(t, J ) 6.5 Hz, 2H), 1.84-1.50 (m, 2 H), 1.50-1.10 (m, 14 H), 0.88
(t, J ) 6.4 Hz, 3 H), 0.25 (s, 9 H); MS m/z (rel intensity) 283 (4, M+
+ 1), 267 (25), 209 (26), 143 (100), 125 (49), 97 (27), 83 (33), 75
(36), 43 (26); HRMS, calcd for C16H30O2Si (M+) 282.2015, found
282.1990.
Oxidation of 1-(Allyloxy)-5-(benzyloxy)-3-methylpentane (16a).
The ether 16a (23 mg, 0.10 mmol) was treated with the peroxyiodane
1a (67 mg, 0.20 mmol) and cesium carbonate (65 mg, 0.20 mmol) in
cyclohexane (5 mL) under an atmosphere at room temperature for 4
days. Preparative TLC (n-hexane-ethyl acetate-dichloromethane 90:
10:0.5) gave 5-(benzyloxy)-3-methylpentyl acrylate (16b) (3.7 mg,
15%), 3-methyl-5-(2-propenyloxy)pentyl benzoate (16c) (4 mg, 16%),
and 5-(benzoyloxy)-3-methylpentyl acrylate (16d) (8.5 mg, 33%).
16b: colorless oil; IR (film) 2928, 1724, 1455, 1408, 1275, 1192, 1070,
1
812, 714 cm-1; H NMR δ 7.37-7.26 (m, 5 H), 6.39 (dd, J ) 17.3,
1.7 Hz, 1 H), 6.11 (dd, J ) 17.3, 10.3 Hz, 1 H), 5.80 (dd, J ) 10.3,
1.7 Hz, 1 H), 4.50 (s, 2 H), 4.20 (t, J ) 7.1 Hz, 2 H), 3.51 (t, J ) 6.7
Hz, 2 H), 1.84-1.38 (m, 5 H), 0.94 (d, J ) 6.4 Hz, 3 H); MS m/z (rel
intensity) 262 (M+), 190 (14), 162 (16), 107 (81), 91 (100), 83 (36),
77 (19), 55 (80); HRMS, calcd for C16H22O3 (M+) 262.1569, found
262.1561. 16c: colorless oil; IR (film) 2928, 1722, 1454, 1275, 1111,
1
1028, 714 cm-1; H NMR δ 8.04 (br d, J ) 8.1 Hz, 2 H), 7.56 (br t,
J ) 8.1, 1 H), 7.43 (br t, J ) 8.1 Hz, 2 H), 5.90 (ddt, J ) 17.5, 10.0,
5.6 Hz, 1 H), 5.26 (br d, J ) 17.5 Hz, 1 H), 5.16 (br d, J ) 10.0 Hz,
1 H), 4.37 (t, J ) 6.6 Hz, 2 H), 3.96 (d, J ) 5.6 Hz, 2 H), 3.50 (t, J
) 5.9 Hz, 2 H), 1.96-1.35 (m, 5 H), 1.00 (d, J ) 5.9 Hz, 3 H); MS
m/z (rel intensity) 262 (M+), 205 (3), 149 (13), 105 (87), 91 (100), 83
(29), 77 (31), 55 (31), 41 (29); HRMS, calcd for C16H22O3 (M+)
262.1569, found 262.1570. 16d: colorless oil; IR (film) 2961, 1723,
1603, 1453, 1409, 1315, 1276, 1192, 1113, 1070, 1027, 985, 811, 713
cm-1; 1H NMR δ 8.03 (br d, J ) 7.8 Hz, 2 H), 7.56 (br t, J ) 7.0 Hz,
1 H), 7.43 (br t, J ) 7.8 Hz, 2 H), 6.38 (dd, J ) 17.3, 1.2 Hz, 1 H),
6.09 (dd, J ) 17.3, 10.3 Hz, 1 H), 5.79 (dd, J ) 10.3, 1.2 Hz, 1 H),
4.38 (t, J ) 6.3 Hz, 2 H), 4.24 (t, J ) 5.8 Hz, 2 H), 1.96-1.50 (m, 5
H), 1.03 (d, J ) 6.1 Hz, 3 H); MS m/z (rel intensity) 277 (M+ + 1),
204 (3), 123 (7), 105 (100), 82 (64), 77 (29), 67 (27), 55 (26); HRMS,
calcd for C16H20O4 (M+) 276.1362, found 276.1368.
Oxidation of 5-(Benzyloxy)-3-methyl-1-(3-methyl-2-butenyloxy)-
pentane (17a). The ether 17a (28 mg, 0.10 mmol) was treated with
the peroxyiodane 1a (135 mg, 0.40 mmol) and cesium carbonate (130
mg, 0.40 mmol) in cyclohexane (5 mL) under an atmosphere at room
temperature for 74 h. Preparative TLC (n-hexane-ethyl acetate-
dichloromethane 90:10:0.5) gave 5-(benzoyloxy)-3-methylpentyl 3-methyl-
2-butenoate (17b) (15.5 mg, 52%): colorless oil; IR (film) 2950, 1715,
1650, 1600, 1450, 1380, 1315, 1275, 1230, 1150, 1110, 1075, 850,
715 cm-1; 1H NMR δ 8.03 (br d, J ) 7.1 Hz, 2 H), 7.56 (br t, J ) 7.1
Hz, 1 H), 7.43 (br t, J ) 7.1 Hz, 2 H), 5.65 (br s, 1 H), 4.38 (t, J ) 6.5
Hz, 2 H), 4.16 (dt, J ) 1.7, 6.6 Hz, 2 H), 2.15 (d, J ) 1.0 Hz, 3 H),
1.96-1.30 (m, 5 H), 1.87 (d, J ) 1.2 Hz, 3 H), 1.02 (d, J ) 6.4 Hz,
3 H); MS m/z (rel intensity) 304 (15, M+), 105 (100), 83 (65), 77 (29),
55 (28); HRMS, calcd for C18H24O4 (M+) 304.1675, found 304.1682.
General Procedure for Oxidation of Arenes with the Peroxy-
iodane 1a. To a stirred mixture of the peroxyiodane 1a (202 mg, 0.60
mmol) and cesium carbonate (391 mg, 1.20 mmol) in benzene (5 mL)
was added an arene (0.20 mmol) under nitrogen at room temperature,
and the mixture was stirred for the periods shown in Table 4. In some
experiments, rubidium carbonate or potassium carbonate was used. The
resulting precipitate was filtered off and washed with dichloromethane
several times. Concentration in vacuo and preparative TLC gave pure
products. The yields of pure products are given in Table 4. In some
experiments, yields were determined by gas chromatography.
(82) Baldwin, J. E.; Adlington, R. M.; Ramcharitar, S. H. Tetrahedron
1992, 48, 3413.

(tert-Butylperoxy)iodane-Generated Iodine-Centered Radicals
J. Am. Chem. Soc., Vol. 118, No. 33, 1996 7729
Oxidation of Fluorene (18a) without Base. Fluorene (18a) (33
mg, 0.20 mmol) was treated with the peroxyiodane 1a (88 mg, 0.26
mmol) in dichloromethane (2 mL) at room temperature for 10 days
under nitrogen. Preparative TLC gave 9-fluorenone (19a) (30 mg,
84%).
NMR δ 8.04 (br d, J ) 7.7 Hz, 2 H), 7.60-7.26 (m, 3 H), 5.88 (ddt,
J ) 17.1, 10.3, 6.6 Hz, 1 H), 5.18 (br d, J ) 17.1 Hz, 1 H), 5.11 (br
d, J ) 10.3 Hz, 1 H), 4.38 (t, J ) 6.8 Hz, 2 H), 2.53 (tq, J ) 1.5, 6.8
Hz, 2 H); MS m/z (rel intensity) 176 (M+), 105 (100), 77 (43), 54
(51); HRMS, calcd for C11H12O2 (M+) 176.0837, found 176.0823. 25:
colorless oil; IR (film) 2979, 2928, 1642, 1455, 1364, 1197, 1100, 772,
When the reaction was quenched after 24 h at room temperature,
preparative TLC gave 9-fluorenone (19a) (3 mg, 9%) and 9-(tert-
butylperoxy)fluorene (20) (8 mg, 15%), in addition to the recovered
18a (20 mg, 60%). 20: colorless prisms; mp 100-101 °C;19 IR (film)
1
698 cm-1; H NMR δ 7.48 (m, 2 H), 7.36 (m, 3 H), 5.87 (ddt, J )
17.1, 10.0, 6.6 Hz, 1 H), 5.85 (s, 1 H), 5.10 (m, 1 H), 5.03 (m, 1 H),
4.02 (dt, J ) 9.7, 6.8 Hz, 1 H), 3.73 (dt, J ) 9.7, 6.8 Hz, 1 H), 2.44
(tq, J ) 1.2, 6.8 Hz, 2 H), 1.28 (s, 9 H); MS m/z (rel intensity) 161
(23), 131 (29), 105 (100), 91 (35), 77 (56), 55 (88); HRMS, calcd for
C11H13O3 (M+ - t-Bu) 193.0864, found 193.0861.
1
2981, 1451, 1363, 1195, 767, 743 cm-1; H NMR δ 7.73 (br d, J )
7.4, 2 H), 7.63 (br d, J ) 7.4 Hz, 2 H), 7.38 (dt, J ) 7.4, 1.2 Hz, 2 H),
7.28 (dt, J ) 7.4, 1.2 Hz, 2 H), 5.95 (s, 1 H), 1.35 (s, 1 H); MS m/z
(rel intensity) 254 (4, M+), 181 (21), 165 (100), 152 (25), 83 (17);
HRMS, calcd for C17H18O2 (M+) 254.1307, found 254.1298. Anal.
Calcd for C17H18O2: C, 80.28; H, 7.13. Found: C, 79.79; H, 6.99.
Oxidation of 3â-Acetoxy-5-androsten-17-one (21a).83 The olefin
21a (33 mg, 0.10 mmol) was treated with the peroxyiodane 1a (67
mg, 0.20 mmol) and potassium carbonate (55 mg, 0.40 mmol) in
benzene (5 mL) under an atmosphere at room temperature for 80 h.
Preparative TLC (40% ethyl acetate in n-hexane) gave 3â-acetoxy-5-
androstene-7,17-dione (22a) (27.7 mg, 81%):84 colorless prisms; mp
165-166 °C (recrystallized from dichloromethane-methanol); IR
Reaction of Benzyl 4,4-Diphenyl-3-butenyl Ether (26) with the
Peroxyiodane 1a. According to the general procedure, 4,4-diphenyl-
3-butenyl ether 26 (29 mg, 0.091 mmol) was treated with 1a (61 mg,
0.18 mmol) and potassium carbonate (50 mg, 0.36 mmol) at room
temperature for 6 days. The crude product was purified by preparative
TLC to give the epoxy ester (27) (15 mg, 46%): colorless oil; IR (film)
1723, 1602, 1451, 1275, 1111, 764, 703 cm-1; 1H NMR δ 8.04 (dd, J
) 7.1, 4.6 Hz, 2 H), 7.56 (t, J ) 6.4 Hz, 1 H), 7.45-7.25 (m, 12 H),
4.47 (dd, J ) 7.1, 6.1 Hz, 2 H), 3.63 (dd, J ) 7.1, 4.7 Hz, 2 H), 2.01
(ddt, J ) 14.9, 4.7, 7.1 Hz, 1 H), 1.70 (ddt, J ) 14.9, 7.1, 6.1 Hz, 1
H); 13C NMR δ 166.5, 140.6, 137.2, 133.0, 130.1, 129.6, 128.4, 128.3,
128.3, 128.0, 127.9, 127.8, 127.1, 66.2, 63.4, 62.1, 29.3; MS m/z (rel
intensity) 344 (M+), 239 (13), 222 (14), 194 (37), 165 (100), 149 (26),
105 (90), 83 (35), 77 (47), 57 (31); HRMS, calcd for C23H20O3 (M+)
344.1413, found 344.1396. The structure of 27 was unambiguously
determined by two-dimensional (2D) NMR techniques, i.e., 1H,1H-
correlated spectroscopy (COSY) and 13C,1H-correlated spectroscopy via
long-range coupling spectroscopy (COLOC).
1
(CHCl3) 2940, 2850, 1730, 1665, 1370, 1225 cm-1; H NMR δ 5.76
(s, 1 H), 4.85-4.67 (m, 1 H), 2.94-1.12 (m, 17 H), 2.06 (s, 3 H), 1.24
(s, 3 H), 0.90 (s, 3 H); MS m/z (rel intensity) 344 (4, M+), 284 (100),
256 (21), 187 (15), 161 (21), 134 (15); HRMS, calcd for C21H28O4
(M+) 344.1988, found 344.1989.
Oxidation of Cholesteryl Acetate (21b). The olefin 21b (86 mg,
0.20 mmol) was treated with the peroxyiodane 1a (135 mg, 0.40 mmol)
and potassium carbonate (111 mg, 0.80 mmol) in benzene (4 mL) under
nitrogen at room temperature for 3 days. Preparative TLC (20% ethyl
acetate in n-hexane) gave 3â-acetoxy-5-cholesten-7-one (22b) (54.5
mg, 62%):85 colorless needles; mp 165-166 °C (recrystallized from
dichloromethane-methanol); IR (KBr) 2948, 1734, 1673, 1633, 1242,
1038 cm-1; 1H NMR δ 5.71 (s, 1 H), 4.84-4.64 (m, 1 H), 2.70-0.90
(26 H), 2.05 (s, 3 H), 1.21 (s, 3 H), 0.92 (d, J ) 6.4 Hz, 3 H), 0.87 (d,
J ) 6.6 Hz, 6 H), 0.68 (s, 3 H). Anal. Calcd for C29H46O3: C, 78.68;
H, 10.47. Found: C, 78.30; H, 10.75.
Oxidation of Benzyl Cholesteryl Ether (21c). According to the
general procedure, the benzyl ether 21c (95 mg, 0.20 mmol) was treated
with 1a (148 mg, 0.40 mmol) and potassium carbonate (111 mg, 0.80
mmol) at room temperature for 4 days. The crude product was purified
by preparative TLC to give the keto ester 22c (55 mg, 55%):86 colorless
needles; mp 161-162 °C (recrystallized from dichloromethane-
methanol); IR (KBr) 2951, 1718, 1674, 1635, 1451, 1273, 1115, 713
cm-1; 1H NMR δ 8.04 (d, J ) 8.0 Hz, 2 H), 7.57 (t, J ) 8.0 Hz, 1 H),
7.44 (t, J ) 8.0 Hz, 2 H), 5.75 (s, 1 H), 5.08-4.85 (m, 1 H), 2.80-
0.90 (26 H), 1.26 (s, 3 H), 0.93 (d, J ) 6.6 Hz, 3 H), 0.87 (d, J ) 6.6
Hz, 6 H), 0.69 (s, 3 H); MS m/z (rel intensity) 504 (1, M+), 382 (100),
269 (17), 174 (88), 161 (24), 119 (45), 105 (71) 51 (75); HRMS, calcd
for C34H48O3 (M+) 504.3602, found 504.3602.
Oxidation of Benzyl Ether 2d in the Presence of TEMPO. To a
benzene (5 mL) solution of the peroxyiodane 1a (135 mg, 0.40 mmol)
in a glass ampule were added the benzyl ether 2d (33 mg, 0.20 mmol),
potassium carbonate (110 mg, 0.80 mmol), and 2,2,6,6-tetramethylpi-
peridine-N-oxyl (31 mg, 0.20 mmol). The reaction mixture was freeze-
pump-thaw degassed (three cycles, 0.2 Torr) and flame sealed under
argon. The mixture was stirred for 3 days at room temperature, and
the resulting precipitate was filtered off and washed with dichlo-
romethane several times. Concentration in vacuo gave an oil, which
was purified by preparative TLC to give n-butyl benzoate (3d) (18.8
mg, 55%) and the TEMPO adduct 28 (18 mg, 28%). 28: colorless
oil; IR (film) 2900, 2850, 1430, 1355, 1340, 1110, 1060, 1000, 960,
1
940, 680 cm-1; H NMR δ 7.60-7.24 (m, 5 H), 5.72 (s, 1 H), 3.54-
3.30 (m, 2 H), 1.80-0.90 (m, 10 H), 1.35 (s, 3 H), 1.17 (s, 3 H), 1.12
(s, 3 H), 1.00 (s, 3 H), 0.84 (t, J ) 7.2 Hz, 3 H); FABMS m/z (rel
intensity) 320 (3, M+ - 1), 163 (100), 140 (72), 107 (100), 79 (8), 57
(10); HRFABMS, calcd for C20H33NO2 (M+) 319.2511, found 319.2466.
Oxidation of Isochroman (2v) in the Presence of TEMPO. To a
benzene (5 mL) solution of the peroxyiodane 1a (202 mg, 0.60 mmol)
in a glass ampule were added isochroman (2v) (40 mg, 0.30 mmol),
potassium carbonate (166 mg, 1.20 mmol), and TEMPO (47 mg, 0.30
mmol). The reaction mixture was degassed by freeze-pump-thaw
(three cycles, 0.2 Torr) and sealed by flame under argon. The mixture
was stirred for 2 days at room temperature, and the resulting precipitate
was filtered off and washed with dichloromethane several times.
Concentration in vacuo gave an oil, which was purified by preparative
TLC to give 1-isochromanone (3v) (13 mg, 29%) and the TEMPO
adduct 29 (38.2 mg, 44%). 29: colorless plate; mp 89-91 °C
(recrystallized from dichloromethane-methanol); IR (CHCl3) 2930,
1600, 1453, 1365, 1315, 1130, 1090, 975, 955, 916 cm-1; 1H NMR δ
7.75-7.55 (m, 1 H), 7.38-7.00 (m, 3 H), 6.00 (s, 1 H), 4.02 (dt, J )
3.2, 10.7 Hz, 1 H), 3.87 (ddd, J ) 10.7, 5.4, 3.2 Hz, 1 H), 2.93 (ddd,
J ) 16.1, 10.7, 5.4 Hz, 1 H), 2.67 (dt, J ) 16.1, 3.2 Hz, 1 H), 1.78-
0.87 (m, 6 H), 1.42 (s, 3 H), 1.30 (s, 6 H), 1.10 (s, 3 H); FABMS m/z
(rel intensity) 290 (10, M+ + 1), 140 (30), 133 (100); HRFABMS,
calcd for C18H28O2N (M+ + 1) 290.2120, found 290.2146.
Oxidation of 2d in the Presence of Radical Inhibitor (Entries 5,
6, and 11-14 in Table 5). To a mixture of the peroxyiodane 1a, a
radical inhibitor, and potassium carbonate in benzene (5 mL) was added
the benzyl ether 2d (33 mg, 0.20 mmol) under nitrogen using a rubber
balloon at 30 °C, and the mixture was stirred for the periods shown in
Table 5. The yield of the benzoate 3d and the recovered 2d was
determined by gas chromatography using n-tridecane as an internal
standard and is shown in Table 5.
Reaction of Benzyl 3-Butenyl Ether (23) with the Peroxyiodane
1a. According to the general procedure, benzyl 3-butenyl ether (23)
(33 mg, 0.20 mmol) was treated with 1a (148 mg, 0.40 mmol) and
potassium carbonate (111 mg, 0.80 mmol) at room temperature for 4
days. The crude product was purified by preparative TLC to give
3-butenyl benzoate (24) (20 mg, 58%) and the tert-butylperoxy acetal
25 (1.0 mg, 2%). 24: colorless oil; IR (film) 2958, 1723, 1643, 1603,
1
1452, 1382, 1315, 1276, 1177, 1113, 1027, 919, 773, 7125 cm-1; H
Oxidation of n-Decyl Allyl Ether (6a) in the Presence of TEMPO.
To a cyclohexane (5 mL) solution of the peroxyiodane 1a (202 mg,
0.60 mmol) in a glass ampule were added n-decyl allyl ether (6a) (60
mg, 0.30 mmol), potassium carbonate (166 mg, 1.20 mmol), and
TEMPO (47 mg, 0.30 mmol). The reaction mixture was degassed by
freeze-pump-thaw (three cycles, 0.2 Torr) and sealed by flame under
argon. The mixture was stirred for 3 days at room temperature, and
(83) Weidmam, B.; Maycock, C. D.; Seeback, D. HelV. Chim. Acta 1981,
64, 1552.
(84) Tecon, P.; Hirano, Y.; Djerassi, C. Org. Mass Spectrom. 1982, 17,
277.
(85) Shafiallah, S.; Kuhn, B. Z. J. Indian. Chem. Soc. 1981, 58, 919.
(86) Cook, J. W.; Paige, M. F. C. J. Chem. Soc. 1944, 336.

7730 J. Am. Chem. Soc., Vol. 118, No. 33, 1996
Ochiai et al.
the resulting precipitate was filtered off and washed with dichlo-
romethane several times. Concentration in vacuo gave an oil, which
was purified by preparative TLC to give n-decyl acrylate (7a) (8.1 mg,
13%) and the TEMPO adduct 30 (58.3 mg, 55%). 30: colorless oil;
with diethyl ether, and the organic layer was washed with water and
brine, dried over Na2SO4, and filtered. Evaporation of the filtrate
followed by column chromatography on silica gel (n-hexane-diethyl
ether-dichloromethane 400:5:0.5) gave the peroxy acetal 5 (2.02 g,
40%) as a colorless oil.
IR (film) 2920, 2850, 1460, 1375, 1360, 1130, 1060, 970, 710 cm-1
;
1H NMR δ 5.82 (ddd, J ) 17.6, 10.5, 5.6 Hz, 1 H), 5.31 (br d, J )
17.6 Hz, 1 H), 5.24 (br d, J ) 10.5 Hz, 1 H), 5.04 (d, J ) 5.6 Hz, 1
H), 3.54 (dt, J ) 9.3, 7.1 Hz, 1 H), 3.44 (dt, J ) 9.3, 6.6 Hz, 1 H),
2.10-0.96 (m, 34 H), 0.88 (t, J ) 6.8 Hz, 3 H); FABMS m/z (rel
intensity) 354 (20, M+ + 1), 197 (31), 140 (100), 85 (17), 55 (20);
HRFABMS, calcd for C22H44O2N (M+ + 1) 354.3372, found 354.3381.
General Procedure for the Competition Experiments. To a stirred
mixture of the peroxyiodane 1a (34 mg, 0.10 mmol) and potassium
carbonate (28 mg, 0.20 mmol) in benzene (3 mL) was added a solution
of benzyl n-butyl ether (2d) (411 mg, 2.5 mmol) and a substituted
benzyl n-butyl ether (2.5 mmol) in benzene (2 mL) under argon. The
reaction was allowed to proceed at 30 ( 0.2 °C for 12 h and, after
addition of an appropriate internal standard, analyzed directly without
workup for the two esters by GC. Each reaction mixture was analyzed
four to six times and averaged. The reaction was repeated two times,
and the results are reported in Table 6. Relative reactivity of
1-phenylhexane (18b) and di-n-butyl ether was determined in a similar
manner.
Preparation of Benzyl-r,r-d2 n-Butyl Ether (2d-d2). To a stirred
suspension of sodium hydride (500 mg, 12.5 mmol, 60% dispersion in
oil), washed with hexane three times, in N,N-dimethylformamide (20
mL) was added benzyl-R,R-d2 alcohol (550 mg, 5.0 mmol, 99.8%
isotopic purity) dropwise at room temperature under nitrogen, and the
mixture was stirred for 1 h. n-Butyl bromide (1.71 g, 12.5 mmol) was
added and stirring was continued for 24 h. The mixture was poured
over ice and extracted with diethyl ether, and the organic phase was
washed with water and brine. The solution was dried over anhydrous
Na2SO4 and concentrated. Flash chromatography of the crude product
mixture yielded 2d-d2 (709 mg, 85%): colorless oil; IR (film) 3028,
2959, 2872, 2072, 1496, 1446, 1380, 1227, 1115, 1026, 717 cm-1; 1H
NMR δ 7.33 (m, 5 H), 3.46 (t, J ) 6.4 Hz, 2 H), 1.69-1.25 (m, 4 H),
0.91 (t, J ) 7.2 Hz, 3 H); MS m/z (rel intensity) 166 (2, M+), 94 (61),
93 (100); HRMS, calcd for C11H14D2O (M+) 166.1326, found 166.1322.
Deuterium Kinetic Isotope Effect. A. Competition between
Benzyl-r,r-d2 n-Butyl Ether (2d-d2) and n-Butyl p-Chlorobenzyl
Ether (2r). To a stirred mixture of the peroxyiodane 1a (17 mg, 0.05
mmol) and potassium carbonate (14 mg, 0.10 mmol) in benzene (2
mL) was added a solution of benzyl-R,R-d2 ether 2d-d2 (208 mg, 1.25
mmol) and p-chlorobenzyl ether 2r (248 mg, 1.25 mmol) in benzene
(1 mL) under argon, and the mixture was stirred at 30 ( 0.2 °C for 12
h. After addition of n-tridecane as an internal standard, the ratio 3r/
3d measured by GC was 13.4. The ratio was compared with the relative
rate k2r/k2d ) 0.96 in Table 6. The deuterium kinetic isotope effect
kH/kD ) 14.0 was obtained.
Synthesis of n-Butyl r-(Hydroperoxy)benzyl Ether (32). To a
mixture of benzaldehyde di-n-butyl acetate (473 mg, 2.0 mmol) and
RuCl3‚nH2O (15.7 mg, 0.06 mmol) in benzene (3 mL) was added a
solution of hydrogen peroxide88 (6.9 mL of a 0.87 M solution in diethyl
ether, 6 mmol) in benzene (3 mL) dropwise at room temperature over
a period of 0.5 h under argon, and the mixture was stirred for an
additional 1.5 h. The mixture was diluted with diethyl ether, and the
organic layer was washed with water and brine, dried over Na2SO4,
and filtered. Evaporation of the filtrate followed by column chroma-
tography on silica gel (3% ethyl acetate in n-hexane) gave the
hydroperoxy acetal 32 (62 mg, 16%): colorless oil; IR (film) 3382,
2960, 2874, 1455, 1309, 1202, 1098, 839, 754, 699 cm-1; 1H NMR δ
8.49 (s, 1 H), 7.56-7.29 (m, 5 H), 5.80 (s, 1 H), 3.90 (dt, J ) 9.5, 6.5
Hz, 1 H), 3.64 (dt, J ) 9.5, 6.5 Hz, 1 H), 1.82-1.32 (m, 4 H), 0.94 (t,
J ) 7.3 Hz, 3 H); MS m/z (rel intensity) 163 (48, M+ - OOH), 123
(47), 107 (100), 105 (96), 77 (64), 56 (33); HRMS, calcd for C11H15O
(M+ - OOH) 163.1123, found 163.1126.
Reaction of the tert-Butylperoxy Acetal 5 and the Hydroperoxy
Acetal 32. To a solution of the peroxy acetal 5 (50 mg, 0.2 mmol) or
the hydroperoxy acetal 32 (39 mg, 0.2 mmol) in benzene (5 mL) was
added an additive shown in Table 7 under nitrogen using a rubber
balloon at 30 °C, and the mixture was stirred for 3 days. After cooling
to 0 °C, the yields of the benzoate 3d and the recovered acetal were
determined by GC using n-tridecane and n-octane as internal standards,
1
or by H NMR analyses. The results are shown in Table 7.
Oxidation of Benzyl r-Methylbenzyl Ether (43). The ether 43
(318 mg, 1.5 mmol) was treated with the peroxyiodane 1a (20 mg,
0.06 mmol) and potassium carbonate (17 mg, 0.12 mmol) in benzene
(4 mL) under argon at 30 °C for 12 h. Analytical GC showed the
formation of R-methylbenzyl benzoate (44) (20%), acetophenone (79%),
and benzaldehyde (67%). These yields are based on the peroxyiodane
1a. A pure sample of 44 and acetophenone was obtained by preparative
TLC. 44: colorless oil; IR (film) 2982, 1718, 1602, 1452, 1271, 1110,
1068, 712 cm-1; 1H NMR δ 8.09 (d, J ) 7.1 Hz, 2 H), 7.6-7.2 (m, 8
H), 6.14 (q, J ) 6.6 Hz, 1 H), 1.67 (d, J ) 6.6 Hz, 3 H); MS m/z (rel
intensity) 226 (8, M+), 122 (16), 105 (100), 77 (67), 51 (42); HRMS,
calcd for C15H14O2 (M+) 226.0993, found 226.0988. The authentic
sample of 44 was prepared by the reaction of 1-phenylethanol with
benzoyl chloride.
Rates of Decomposition of the Peroxyiodane 1a. Rates of
decomposition of 1a were measured by monitoring the decrease in
absorbance at 275 nm at 30 ( 0.1 °C on a Shimadzu UV-160A
spectrophotometer. A stock solution of 1a was prepared by dissolving
in acetonitrile (0.06 M). To 3.0 mL of dichloromethane in a quartz
cuvette inserted in a cell compartment of the spectrophotometer and
equilibrated at 30 °C was added 10 µL of the stock solution of 1a
from a microsyringe. The absorbance change was fed to a computer
NEC PC-9801FA through an interface and processed by a pseudo-
first-order kinetics program. The reaction followed pseudo-first-order
kinetics for 4 half-lives, and the pseudo-first-order rate constant kobsd
) 2.62 × 10-5 s-1 was obtained.
B. Competition between Benzyl-r,r-d2 n-Benzyl Ether (2d-d2)
and n-Butyl m-Chlorobenzyl Ether (2s). To a stirred mixture of the
peroxyiodane 1a (17 mg, 0.05 mmol) and potassium carbonate (14 mg,
0.10 mmol) in benzene (2 mL) was added a solution of benzyl-R,R-d2
ether 2d-d2 (208 mg, 1.25 mmol) and m-chlorobenzyl ether 2s (248
mg, 1.25 mmol) in benzene (1 mL) under argon, and the mixture was
stirred at 30 ( 0.2 °C for 12 h. After addition of n-tridecane as an
internal standard, the ratio 3s/3d measured by GC was 10.2. The ratio
was compared with the relative rate k2s/k2d ) 0.84 in Table 6. The
deuterium kinetic isotope effect kH/kD ) 12.2 was obtained.
Synthesis of n-Butyl r-(tert-Butylperoxy)benzyl Ether (5) from
Benzaldehyde.40 To a mixture of benzaldehyde di-n-butyl acetal87 (4.73
g, 20.0 mmol) and RuCl3‚nH2O (157 mg, 0.60 mmol) in benzene (10
mL) was added a solution of tert-butyl hydroperoxide (7.5 mL of 80%
solution in di-tert-butyl peroxide, 60 mmol) in benzene (20 mL)
dropwise at room temperature over a period of 1 h under argon, and
the mixture was stirred for an additional 6 h. The mixture was diluted
Supporting Information Available: Spectroscopic data for
compounds 3a-c, 3e-z, 7a-g, 9, 11a-c, and 13 (7 pages).
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JA9610287
(88) Saito, I.; Nagata, R.; Yuba, K.; Matuura, T. Tetrahedron Lett. 1983,
24, 1737.
(87) Stewart, A. T.; Hauser, C. R. J. Am. Chem. Soc. 1955, 77, 1098.