Tetrahydrofuranylation of alcohols catalyzed by alkylperoxy- λ3-iodane and carbon tetrachloride

Article abstract of DOI:10.1016/j.tetlet.2004.03.049

Reaction of primary and secondary alcohols with tetrahydrofuran and a catalytic amount of 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of carbon tetrachloride at 50°C provides an efficient method for protecting the hydroxy group as 2-tetrahydrofuranyl ethers.

Full text of DOI:10.1016/j.tetlet.2004.03.049

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3557–3559
Tetrahydrofuranylation of alcohols catalyzed by alkylperoxy-k3-
iodane and carbon tetrachloride
Masahito Ochiai* and Takuya Sueda
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan
Received 17 February 2004; revised 5 March 2004; accepted 10 March 2004
Abstract—Reaction of primary and secondary alcohols with tetrahydrofuran and a catalytic amount of 1-tert-butylperoxy-1,2-
benziodoxol-3(1H)-one in the presence of carbon tetrachloride at 50 °C provides an efficient method for protecting the hydroxy
group as 2-tetrahydrofuranyl ethers.
Ó 2004 Elsevier Ltd. All rights reserved.
Commercially available crystalline 1-tert-butylperoxy-
1,2-benziodoxol-3(1H)-one 1, which is stable in the solid
state but gradually decomposes in solution at ambient
temperature to generate tert-butylperoxy radical and
[9-I-2] iodanyl radical 2 through homolytic cleavage of
the hypervalent iodine(III)-peroxy bond (Eq. 1),1 serves
as a versatile oxidizing agent.2 Oxidation of benzyl and
allyl ethers with the tert-butylperoxy-k3-iodane 1 in the
presence of alkali metal carbonates affords the corre-
sponding esters via the intermediacy of benzylic and
allylic radicals.1 Cyclic acetals generate a-oxy carbon-
centered radicals and undergo oxidative ring cleavage
to give hydroxy esters through the formation of tert-
butylperoxy ortho-esters.3 Sulfides, secondary and
tertiary amines, and amides are readily oxidized to
sulfoxides, imines, tert-butylperoxyamino acetals, and
imides (or tert-butylperoxyamide acetals), respectively.4
4-Substituted phenols are readily transformed to 4-(tert-
butylperoxy)-2,5-cyclohexadien-1-ones in good yields.5
We report herein a new method for protection of alco-
hols as 2-tetrahydrofuranyl ethers by using the tert-but-
ylperoxy-k3-iodane 1 in THF. Addition of carbon
tetrachloride not only suppressed a competing side
reaction but also decreased the amounts of the k3-
iodane 1 required in the reaction.
When a THF solution of the peroxy-k3-iodane 1 was
heated at 50 °C for 10 h under argon, acid-labile 2-tetra-
hydrofuranyl o-iodobenzoate 3 was produced in a 45%
yield along with the formation of a large amount of
o-iodobenzoic acid 5 (55%). These product profiles
indicate that the reaction involves not only reduction of
the trivalent iodine in 1 to iodide but also oxidation of
the solvent THF. It seems reasonable to assume that the
reaction of o-iodobenzoic acid 5 generated in situ with
THF-derived cationic species (See below, Eq. 3) is
responsible for the formation of 2-tetrahydrofuranyl
o-iodobenzoate 3. With these considerations in mind,
we envisioned that, if the decomposition of the peroxy-
k3-iodane 1 in THF is carried out in the presence of
an alcohol, tetrahydrofuranylation of the hydroxy
group would take place in preference to that of
less nucleophilic o-iodobenzoic acid 5 yielding the ester
3.6
O
I
O
O
Ph
O
O
3
4
t-BuOO
O
I
I
O
In fact, exposure of 2-phenylethanol to a stoichiometric
amount of the peroxy-k3-iodane 1 in THF at 50 °C for
10 h resulted in the formation of 2-tetrahydrofuranyl
ether 4 in 41% yield; the reaction, however, competes
with the esterification that produces the labile ester 3
(16%, Table 1, entry 1). Use of 2 equiv of 1 increased the
yield of 4 up to 73%. As shown in Table 1, good yields of
THF ethers were obtained in the reactions with primary
+
O
t-BuOO
O
ð1Þ
2
1
Keywords: Protection; Hypervalent; Iodine; Iodane; Alcohol; Radical.
* Corresponding author. Tel.: +81-88-633-7281; fax: +81-88-633-9504;
e-mail: mochiai@ph.tokushima-u.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.049

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M. Ochiai, T. Sueda / Tetrahedron Letters 45 (2004) 3557–3559
Table 1. Tetrahydrofuranylation of alcohols with peroxy-k3-iodane 1a
7
ROH
+
ð4Þ
O
Entry
Alcohol
Product [yield (%)]
OR
THF etherb
3c
Our attention is focused on developing the method that
not only affords high yields of THF ethers but also
requires only a catalytic amount of the peroxy-k3-iodane
1, which in turn makes it possible to suppress the
competing side reaction that is, the ester formation by
decreasing the amounts of o-iodobenzoic acid 5 gener-
ated in situ. Recently, Mioskowski and co-workers
reported an efficient method for tetrahydrofuranylation
of alcohols using a stoichiometric amount of carbon
tetrachloride and CrCl2, in which CrCl2 undergoes sin-
gle electron reduction of both carbon tetrachloride and
trichloromethyl radical generated in situ.9 We found
that the use of carbon tetrachloride as an additive meets
the above requirements (Table 2).
1
2
3
4
5
6
7
8
PhCH2CH2OHd
PhCH2CH2OH
n-C8H17OH
41
73
63
52
54
30
30
––
16
17
27
29
18
55
60
51
EtOCH2CH2OH
BrCH2CH2OH
c-C6H11OH
PhCH2CHMeOH
PhCH2CMe2OH
a Unless otherwise noted, tetrahydrofuranylation of an alcohol [0.1 M]
was carried using peroxy-k3-iodane 1 (2 equiv) at 50 °C for 10 h in
THF under argon.
b GC yields.
1H NMR yields based on iodane 1.
d Iodane 1 (1 equiv) was used.
c
Use of 3–4 equiv of carbon tetrachloride in the presence
of the peroxy-k3-iodane 1 (1 equiv) and potassium car-
bonate (1 equiv) afforded excellent yields of 2-tetra-
hydrofuranylated alcohol 4 (Table 2, entries 4 and 5). A
comparable yield (93%) of 4 was obtained with the use
of a catalytic amount of 1 (0.3 equiv) (Table 2, entry 6).
The presence of molecular dioxygen completely inhibits
the reaction, and instead a large amounts of c-butyro-
lactone was produced under oxygen (Table 2, entry 9).
Use of radical scavenger galvinoxyl as an additive also
inhibits the reaction (Table 2, entry 7). These results
indicate radical nature of the reaction. Carbon tetra-
bromide is also useful for protection of the alcohol and
afforded the ether 4 in 70% yield, but with formation of
a large amount of by-product, 2-(4-bromobutoxy)tetra-
hydrofuran. In marked contrast, carbon tetraiodide
gave a complex mixture of products.
alcohols but not with secondary and tertiary alcohols.
The protection of alcohols always competes with for-
mation of the ester 3.
The tetrahydrofuranylation of alcohols with the peroxy-
k3-iodane 1 in THF probably involves the following
sequences: (a) a-hydrogen atom abstraction of THF
with tert-butylperoxy radical and/or the iodanyl radical
2 to give a-tetrahydrofuranyl radical 6 (Eq. 2),7 (b) a
single-electron transfer from a-THF radical 6 to the
peroxy-k3-iodane 1 (or tert-butylperoxy radical and the
iodanyl radical 2), generating the oxonium ion 7 (Eq.
3).8 Finally, nucleophilic attack of an alcohol on 7
produces the desired THF ethers, whereas the ester 3 is
produced by the reaction of 7 with o-iodobenzoic acid 5.
+
t-BuOO
THF
ð2Þ
ð3Þ
As shown in Table 3, the tetrahydrofuranylation using a
catalytic amount of the peroxy-k3-iodane 1 and excess
carbon tetrachloride proceeds smoothly for a variety of
primary and secondary alcohols, but not for tertiary
alcohols and phenol. Thus, selective protection of a
primary alcohol, 2-phenylethanol, was successfully car-
O
6
+
O
1
6
+
7
Table 2. Tetrahydrofuranylation of 2-phenylethanol with peroxy-k3-iodane 1 in the presence of CX4
a
Entry
1 (equiv)
K2CO3 (equiv)
CX4 (equiv)
Product [yield (%)]b
4
1
1
––
1
1
1
1
1
1
1
1
1
1
CCl4 (1)
CCl4 (1)
CCl4 (2)
CCl4 (3)
CCl4 (4)
CCl4 (4)
CCl4 (4)c
CCl4 (4)
CCl4 (1)d
CBr4 (3)
CI4 (3)
30
55
84
93
89
93
0
2
1
3
1
4
1
5
1
6
0.3
0.3
0.1
1
7
8
30
0e
70f
9
10
11
1
1
1
a Unless otherwise noted, tetrahydrofuranylation of 2-phenylethanol [0.1 M] was carried at 50 °C for 10 h in THF under argon.
b GC yields.
c Galvinoxyl (0.3 equiv) was used.
d Under oxygen.
e c-Butyrolactone (190%, based on the iodane 1) was obtained and 2-phenylethanol (84%) was recovered unchanged.
f 2-(4-Bromobutoxy)tetrahydrofuran (109%, based on the iodane 1) was obtained.

M. Ochiai, T. Sueda / Tetrahedron Letters 45 (2004) 3557–3559
3559
Table 3. Tetrahydrofuranylation of alcohols with peroxy-k3-iodane 1
in the presence of CCl4
hydrogen atom from THF to regenerate a-THF radical
6 with liberation of chloroform, which constitutes a
radical chain reaction. Potassium carbonate traps the
hydrogen chloride liberated during the transfer of the
tetrahydrofuranyl group in 8 to alcohols. Hydrogen
chloride probably promotes the decomposition of the
peroxy-k3-iodane 11b as well as the products THF ethers
(compare Table 2, entries 1 and 2). The observed large
deuterium isotope effect (kH=kD ¼ 4:7) in the protection
of 1-octanol in THF-d8 is compatible with the proposed
mechanism.
a
Entry
Alcohol
THF ether [yield (%)]b
1
n-C8H17OH
93
94
94
87
77
98
63e
30e;f
0
2
EtOCH2CH2OH
BrCH2CH2OHc
NCCH2CH2OH
PhCH2OH
3
4
5
6
c-C6H11OHd
7
PhCH2CHMeOHc
2-Cyclohexenol
PhCH2CMe2OHd
PhOHd
8
9
10
11
5e
2-Tetrahydrofuranyl ethers have been used as useful
protecting groups for alcohols, because they are
removed under weakly acidic conditions.11 We have
developed an efficient method for protecting hydroxy
groups as 2-tetrahydrofuranyl ethers using the tert-
butylperoxy-k3-iodane 1 in THF in the presence of
carbon tetrachloride.
PhCH2CH2OHd;g
43h
a Unless otherwise noted, tetrahydrofuranylation of an alcohol [0.1 M]
was carried using peroxy-k3-iodane 1 (0.3 equiv), K2 CO3 (1 equiv),
and CCl4 (4 equiv) at 50 °C for 10 h in THF under argon.
b GC yields.
c K2CO3 (5 equiv) was used.
d Peroxy-k3-iodane 1 (1 equiv) was used.
e Isolated yields.
f Cyclohexenone (17%) was obtained.
g Instead of THF, tetrahydropyran was used.
h THP ether.
References and notes
1. (a) Ochiai, M.; Ito, T.; Takahashi, H.; Nakanishi, A.;
Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M. J. Am.
Chem. Soc. 1996, 118, 7716; (b) Ochiai, M.; Ito, T.;
Masaki, Y.; Shiro, M. J. Am. Chem. Soc. 1992, 114, 6269.
2. For reviews, see: (a) Ochiai, M. In Topics in Current
Chemistry; Wirth, T., Ed.; Springer: Berlin, 2003; Vol. 224,
p 5; (b) Ochiai, M. TCI Mail 1999 (104), 2; (c) Zhdankin,
V. V. Rev. Heteroat. Chem. 1997, 17, 133; (d) Zhdankin,
V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523; (e) Muraki,
T.; Togo, H.; Yokoyama, M. Rev. Heteroat. Chem. 1997,
17, 213.
3. Sueda, T.; Fukuda, S.; Ochiai, M. Org. Lett. 2001, 3, 2387.
4. (a) Ochiai, M.; Nakanishi, A.; Ito, T. J. Org. Chem. 1997,
62, 4253; (b) Ochiai, M.; Kajishima, D.; Sueda, T.
Heterocycles 1997, 46, 71; (c) Ochiai, M.; Kajishima, D.;
Sueda, T. Tetrahedron Lett. 1999, 40, 5541.
CCl4
O
Cl
8
CCl3
O
6
CHCl3
THF
5. Ochiai, M.; Nakanishi, A.; Yamada, A. Tetrahedron Lett.
1997, 38, 3927.
Scheme 1.
6. Solvent nucleophilicity (N0OTS values): MeOH (0.19),
EtOH (0.55), AcOH ()2.06). See: Kevill, D. N.; Anderson,
S. W. J. Org. Chem. 1991, 56, 1845.
ried out in 87% yield in the presence of a tertiary alco-
hol, 1-phenyl-2-methyl-2-propanol (95% recovered).
Ethoxy, bromo, and cyano groups are compatible with
our conditions: however, competitive oxidation to a
carbonyl compound was observed in the protection of
an allylic alcohol (Table 3, entry 8). Instead of THF, use
of tetrahydropyran resulted in a modest yield of tetra-
hydropyranyl ether (Table 3, entry 11).
7. Malatesta, V.; Scaiano, J. C. J. Org. Chem. 1982, 47, 1455.
8. Reduction potentials (Ered V vs SCE): ROOÅ (0.53), RCO2Å
(1.72) and PhI(OAc)2 ()0.24). See: (a) Merenyi, G.; Lind,
J.; Engman, L. J. Chem. Soc., Perkin Trans. 2 1994, 2551;
(b) Kokkinidis, G.; Papadopoulou, M.; Varvoglis, A.
Electrochim. Acta 1989, 34, 133.
9. (a) Baati, R.; Valleix, A.; Mioskowski, C.; Barma, D. K.;
Falck, J. R. Org. Lett. 2000, 2, 485; (b) Barks, J. M.;
Gilbert, B. C.; Parsons, A. F.; Upeandran, B. Tetrahedron
Lett. 2000, 41, 6249; (c) Jung, J. C.; Choi, H. C.; Kim, Y.
H. Tetrahedron Lett. 1993, 34, 3581.
10. Kruse, C. G.; Jonkers, F. L.; Dert, V.; Gen, A. Recl. Trav.
Chim. Pays-Bas 1979, 98, 371.
11. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis; Wiley: New York, 1991.
The carbon tetrachloride-mediated protection of alco-
hols presumably involves the intervention of 2-chloro-
tetrahydrofuran 8 as a reactive intermediate, being
generated by chlorine atom abstraction from CCl4 with
a-THF radical 6 (Scheme 1).9 2-Chlorotetrahydrofuran
8 undergoes a facile transfer of the tetrahydrofuranyl
group to alcohols.10 Trichloromethyl radical abstracts a