C. M. Binder et al. / Tetrahedron Letters 49 (2008) 2764–2767
2765
and CH3CN solvents worked well for this reaction and
all subsequent reactions were performed using either
THF/H2O or CH3CN/H2O.
2 - 5 equiv NaIO4
THF or CH3CN/H2O (2:1)
O
R1
O
R1
R2
R2
24 - 48 h, 25 oC
R1 = H, CH3
R2 = aromatic
alkyl
up to 91% yield
Six aliphatic epoxides, including terminal epoxides, were
screened in the cleavage reaction (Table 1).13 Facile conver-
sion of cyclohexene oxide, limonene oxide, and 3-carene
oxide was achieved in moderate to high yields with just
2 equiv of sodium periodate (entries 4–6). The lower yield
of adipaldehyde is likely due to the high volatility of the
product. Less reactive substrates, such as epoxyoctane
and 1,2-epoxy-9-decene (entries 1 and 3), required at least
4 equiv of periodate to facilitate the full consumption of
starting material. The reaction carried out in the THF/
H2O solvent system gave impure aldehyde, contaminated
with a significant amount of unidentified by-products.
However, aqueous acetonitrile eliminated this by-product
and gave essentially analytically pure aldehyde product
(entry 1). It is possible that the lipophilic tails of these
epoxides are forming micelles, preventing the polar epoxide
heads from reacting with aqueous periodate. The reactions
of 1,2-epoxy-9-decene and limonene oxide (entries 3 and 5)
demonstrate the chemoselectivity of this reaction, which is
complementary to conventional ozonolysis.
Periodate cleavage is known to prefer cis-diols as sub-
strates, whereas acid-induced epoxide opening is known
to create a trans-diol intermediate.14 While this may not
be of consequence to linear epoxides, it is somewhat unex-
pected to observe such facile conversion of the cyclic exam-
ples. This leads us to believe that isomerization of the diol
may be occurring under the acidic reaction conditions.15 It
is also worth noting that in the case of epoxydodecane, a
significant amount of unreacted starting material was
recovered (Table 1, entry 2). This implies that epoxide
opening is the rate-limiting step of the reaction. The trisub-
stituted epoxides generally gave products in higher yield
compared to monosubstituted epoxides, reflecting the ease
of epoxide hydrolysis in the former.
Scheme 2. General scheme for epoxide C–C bond cleavage with sodium
periodate.
the one-pot cleavage of the C–C bonds of several epoxides
in the absence of catalyst is explored (Scheme 2).
During the course of our work, Ochiai demonstrated the
novel use of iodosylbenzene for the one-pot oxidative
cleavage of olefins.10 In some cases, a considerable amount
of epoxide was detected and implicated as a reaction inter-
mediate. A few aromatic epoxides were then tested in the
reaction with iodosylbenzene to yield substituted benzalde-
hydes.10 Similar findings were reported in a recent paper by
Liu, in which a Mn-porphyrin catalyst was used in combi-
nation with NaIO4 to facilitate the oxidative cleavage of
olefins.11 Although no epoxide was detected, the reaction
was thought to proceed through an epoxide intermediate,
with the epoxidation being the rate limiting step. The
authors were able to cleave the C–C bond of cyclohexene
oxide and styrene oxide using their method; however,
terminal alkenes and 1,1-disubstituted alkenes, such as
1-octene and b-pinene, respectively, were not good sub-
strates for this reaction.11 The corresponding epoxides were
not tested in the Mn-porphyrin mediated C–C cleaving
reaction. While the cleavage of styrene oxide can be envi-
sioned to proceed through the acyclic diol, it was puzzling
how a trans-diol from cyclohexene oxide could be cleaved
by sodium periodate. These reports prompted us to
disclose our results, where epoxides are converted to the
corresponding carbonyl compounds using aqueous sodium
periodate without the need for the use of transition metal
or acid catalyst.
Initial studies were performed with (+)-b-pinene oxide 1
with the goal of forming nopinone 2 (Scheme 3). Unfortu-
nately, a significant amount of rearrangement product 3
was observed and nopinone 2 could only be obtained in
up to 32% yield.12 This occurred using a variety of solvents
and solvent mixtures including water, methanol, and THF.
A similar ring rearrangement occurred in the reaction with
a-pinene oxide as well. We then turned our interest toward
simpler aliphatic and aromatic epoxides. Water was chosen
as one of the co-solvents in order to partially dissolve the
periodate and to provide a slightly acidic environment to
promote epoxide opening. We also found that both THF
Initial attempts to perform this reaction on styrene
oxide in THF/H2O resulted in a mixture of benzaldehyde
and phenacetaldehyde. The production of the latter is
due to a rearrangement that occurs before ring opening.16
Carrying out the reaction in CH3CN/H2O exclusively pro-
vided benzaldehyde in 84% isolated yield (entry 7). It
should be pointed out that the reaction of styrene with iod-
osylbenzene gave phenacetaldehyde in 85% yield along
with 5% benzaldehyde, whereas styrene oxide gave only
benzaldehyde in 89% yield, which is comparable to the
results realized in our reaction.10
Extension to halogenated aromatic epoxides gave fair to
moderate yields for p-fluoro, p-chloro, and o-bromo-sty-
rene oxide (Table 1, entries 8–10). We believe these lower
yields may be due to the incomplete hydrolysis of the epox-
ide. The recovery of starting material in the o-bromo deriv-
ative leads us to believe that the epoxide-opening is the
rate-limiting step. Disubstituted aromatic epoxides such
as the TBS-protected cinnamyl epoxide and trans-stilbene
oxide (entries 11 and 12) gave comparable results.
HO
O
O
2 equiv NaIO4
+
solvent,
OH
24 h, 25 oC
1
2
3
Scheme 3. Attempted cleavage of (+)-b-pinene oxide.