5
400
I. Carrera et al. / Tetrahedron Letters 50 (2009) 5399–5402
Table 1
Table 3
a
Solvent effect in oxidative cleavage of 1
Periodate:acyloin ratio for cleavage of 1 under microwave irradation
pb
e
c
1:2 ratiod
Entry
Periodate equivalents
Conversion at 60 min, 50 °C
Entry
Solvent
1
2
3
4
5
Ethyl acetate
Tetrahydrofuran
Dichloromethane
Toluene
4.3
4.2
3.4
2.3
—
6.0
7.4
9.1
2.4
85:15
87:13
80:20
12:88
0:100
1
2
3
1.5
3.0
4.5
50:50
21:79
16:84
No solvent
—
a
Reactions were carried out with 0.11 mmol of 1 in 1.5 mL of solvent and 3 equiv
/SiO , at ambient temperature for 24 h.
of NaIO
4
2
the conversion was complete (100%) and the product was isolated
with an excellent yield of 90%.
Having these conditions at hand, the optimum NaIO
4
/substrate
ratio was determined (Table 3). Given the non-significant differ-
ence in conversion achieved with 3.0 and 4.5 equiv, the use of a
b
19
Solvent eluotropic strenght parameter for silica gel, according to Halpaap.
Dielectric constant at 20 °C.
c
d
All ratios were determined by 1H NMR of the crude reaction mixture.
3
:1 ratio was chosen as the optimum.
As can be seen from Table 1, the solvent has a profound effect
Once optimal conditions for the oxidative cleavage of a-hydro-
on the reaction conversion. The data show that the eluotropic
strength of the solvent is more related than its polarity to the con-
version. This seems to indicate that higher conversions are ob-
tained when the substrate is more retained to the surface of the
silica, in agreement with the fact that best results were found using
no solvent (entry 5), where complete conversion was achieved
upon 24 h.
Given the long reaction time needed for full conversion, the
possibility of accelerating the reaction by microwave irradiation
on a monomode microwave reactor (CEM corporation, model Dis-
cover) was considered (representative results are shown in Table
xy ketone 1 were defined (3 equiv of sodium metaperiodate, sol-
vent-free, 50 °C, 200 W) , an array of representative acyloins, diols,
and sulfides was subjected to them. As can be seen from Table 4,
most
a-hydroxyketones gave the expected products in good to
excellent isolated yields. For entries 2 and 3, the yields were calcu-
lated based on the carboxylic acids since the resulting aldehydes
were volatile. The mild conditions of this method allowed perform-
ing the oxidation on sensitive compounds such as acyloin 9, which
rapidly afforded the labile formylacid 10 in good isolated yield (entry
5). Conversely, this mildness could also explain the lack of reactivity
of compound 11, which was recovered unchanged even after 4 h of
irradiation (entry 6). As expected, diols were more reactive than acy-
loins, giving the dicarbonyl compounds in a fast and clean reaction
(entry 7). In the conditions tested, sulfides were reluctant to react,
affording less than 10% of oxidized products after 4 h of irradiation
(entry 8). This observation could lead to a selective method for cleav-
age of acyloins and/or vic-diols in the presence of sulfur-containing
2).
This was indeed the case, although the effects were dependent
on the solvent used. For ethyl acetate and dichloromethane (en-
tries 1 and 3), 10 min of irradiation at 80 °C was enough to pro-
duce
a conversion similar to that of the non-irradiated
experiment run for 24 h at ambient temperature. Unfortunately,
irradiation at higher temperature (110 °C) or for longer periods
2
0,21
compounds.
Further studies in this direction are under way. Fi-
(
up to 20 min, data not shown) did not result in improvement
of the yield. Irradiation of the tetrahydrofuran suspension (entry
) for 10 min afforded a higher conversion than that at ambient
nally, the reaction was performed in a 1 mmol scale (the maximum
capacity of the microwave reactor used), obtaining the same clean
conversions and isolated yields, although in a consistently 20–25%
longer reaction time.
2
temperature. However, similar to the previous results, upon fur-
ther irradiation the conversion did not improve significantly
(
hand, toluene (entry 4) showed a good initial conversion in the
first 10 min at 80 °C, but further irradiation at this temperature
resulted in decomposition, which also occurred after 10 min at
1
8
In summary, the facile oxidative cleavage of acyloins with
wet silica-supported sodium metaperiodate under microwave
irradiation has the advantages of manipulative convenience,
excellent yield, and wide application. This protocol is attractive
for vicinal diols, alpha-hydroxyketones that are not soluble in
polar media, and for aldehydes and acids that are water soluble
(where the product recovery from an aqueous solvent is diffi-
cult). It is worth mentioning the mildness of the method which
allows its use with sensitive compounds, and probably produces
selective oxidative cleavage in the presence of sulfur
functionalities.
reaching a maximum near 70%, data not shown). On the other
10 °C. Likewise, irradiation of the sample without solvent at
0 °C resulted in decomposition.
The results are in agreement with an acceleration of the reac-
tion induced by microwave irradiation, despite the different sol-
vent-dependent outcomes. Considering that solvent-free
a
approach was desirable, we searched for a temperature where no
decomposition of the sample in the solid support occurred. After
some experimentation, it was found that at 50 °C the reaction pro-
ceeded smoothly (entry 5), giving no decomposition products
through a very clean reaction. Moreover, upon 2 h of irradiation,
In a typical procedure, silica gel-supported sodium metaperiodate is prepared
according to the procedure described by Shing:16 NaIO
dissolved in 5 mL of hot water (70 °C) in a 25 mL round-bottomed flask. To the hot
(2.57 g, 12.0 mmol) was
Table 2
4
Oxidative cleavage of 1 under microwave irradiationa
solution silica gel (230–400 mesh, 10 g) was added with vigorous swirling and
Entry
Solvent
1:2 ratio
0 °C/10 min
1:2 ratio
110 °C/10 min
1:2 ratio
50 °C/1 h
shaking. The resultant silica gel coated with NaIO
free-flowing, with a concentration of approximately 15% in NaIO
kept in a bottle for 1 month with negligible loss of activity. The oxidative cleavage is
carried out in the following manner. The -hydroxyketone (0.11 mmol) is dissolved in
a round-bottomed flask and silica-supported sodium metaperiodate (3.0 equiv in
NaIO ) is added. Solvent is evaporated and the free-flowing silica is placed in a proper
4
was in a powder form and was
8
4
. The reagent can be
1
2
3
4
5
EtOAc
THF
85:15
70:30
72:28
44:56
80:20
40:60
66:34
Decompose
Decompose
No reaction
No reaction
84:16
80:20
21:79
a
2
CH Cl
2
Toluene
No solvent
4
Decompose
microwave test tube (sure sealed 10 mL test tubes with magnetic stirring). After the
indicated time of irradiation at 200 W, 50 °C, in a monomode microwave reactor from
CEM corporation, model Discover, ethyl acetate is added and the silica is filtered off.
Solvent is evaporated and the reaction crude is purified by column chromatography if
needed.
a
All reactions were carried out with 0.11 mmol of 1 in 1.5 mL of solvent and
/SiO and irradiated at 200 W, at the temperature and time spec-
ified in the table.
3
equiv of NaIO
4
2
Carrera, Ignacio
