Communications
We further verified this effect by oxidizing methyl
levulinate in heptane with TBHP under the same re-
action conditions as those shown in Table 1. In
agreement with the product distribution changes
shown in Figure 1, a lower selectivity of 14% to di-
methyl succinate was obtained (Table S6, entry 5).
We observe that different oxidants also affect the
migratory preferences during BV oxidation. With Am-
berlyst-15 in methanol, aqueous H2O2 (black) gener-
ated higher methyl ester 9/acetate 10 ratios than
TBHP (blue), indicating the methyl migration is less
favorable with TBHP as oxidant. Hawthorne et al.
showed a higher differentiation of the migration
groups with peroxyacetic acid as oxidant when com-
pared to trifluoroperacetic acid for the BV oxidation
of cyclohexyl phenyl ketone.[14] It was hypothesized
that the impact of the migrating groups on the
energy barrier is larger for the less reactive inter-
mediate.[14] In our case, the different electronic and
steric effects between TBHP and H2O2 may be re-
sponsible for the different product selectivities ob-
served.
Figure 1. Product distribution for the oxidation of methyl ketones expressed as methyl
ester 9/acetate 10 molar ratios. Reaction conditions: substrate 61 mmolLÀ1, substrate/
peroxide molar ratio=1:2, substrate/acid molar ratio=1:1, 808C, 6 h. p-TsOH as catalyst,
50 wt% aqueous H2O2 as oxidant in methanol (red). Amberlyst-15 (A-15) as catalyst,
50 wt% aqueous H2O2 as oxidant in methanol (black). A-15 as catalyst, tert-butyl hydro-
peroxide (TBHP) in decane as oxidant in methanol (blue). A-15 as catalyst, TBHP in
decane as oxidant in heptane (yellow).
As a consequence, we observe that the molecular
structure of the ketones, i.e., carbon-chain length
and branching, also affects the migration preference.
In methanol with H2O2 as oxidant, a higher degree
of branching in the carbon backbone resulted in
droperoxide (TBHP) was used as oxidant in methanol (blue
bars in Figure 1, Table S5), methyl group migration continued
to dominate the product distribution under the reaction condi-
tions investigated. However, the branched ketones yielded
lower methyl ester 9/acetate 10 molar ratios when compared
to the H2O2 system. For instance, the 9d:10d molar ratio de-
creased from 10.5 to 0.9 when switching to TBHP. Moreover,
when the solvent was switched to heptane (yellow bars in
Figure 1, Table S6), all the methyl ester 9/acetate 10 molar
ratios became lower than 1.
higher methyl ester 9/acetate 10 molar ratios (Figure 1, red
and black bars). Although in methanol with TBHP as oxidant
the trend was reversed (Figure 1, blue bars), the ratios of
9a:10a (C5) were higher than those of 9b:10b (C6) under all
the reaction conditions investigated. To our knowledge, virtual-
ly no studies exist for the BV oxidation of asymmetric ketones
in alcohol solvents. Our data indicate that the migratory apti-
tude trend obtained in methanol is opposite to that in hep-
tane. Mora-Diez et al. showed that the polarity of solvents af-
fects the reaction mechanism.[15] Hence, the available studies
on BV oxidation provide limited guidance to understand the
effects of oxidants, catalysts, and the molecular structure on
the reaction selectivity in alcohol solvents. Future work in our
group is centering on obtaining a fundamental understanding
of these phenomena by way of coupled theoretical and experi-
mental investigations.
Lewis acids are known to catalyze BV oxidations.[9] Some
metal triflates have been shown to maintain their Lewis acid
activity in the presence of water, which allows their use with
aqueous solutions of H2O2.[16] Table 2 shows the activity of
metal triflates for the oxidation of methyl levulinate. Compared
to Brønsted acids, metal triflates generate lower levulinate con-
versions and yield a wider spectrum of product selectivities.
Among the metal triflates tested, Zn(OTf)2 showed the lowest
conversion (7%) with no significant succinate formation after
6 h (Table 2, entry 11). Increasing the reaction time to 24 h re-
sulted in a dimethyl succinate yield of 14%. The highest levuli-
nate conversions were obtained with Hf(OTf)4 (36%), Hg(OTf)2
(40%), and Sc(OTf)3 (38%), generating selectivities to succi-
nates exceeding 47% with the rest of the carbon ending up in
Evidently, the solvent choice seems to critically impact the
product selectivity. With Amberlyst-15 as catalyst and TBHP in
decane as oxidant, all methyl ester 9/acetate 10 molar ratios
were below 1 when heptane (yellow), instead of methanol
(blue), was used as solvent. The migration ratios obtained in
heptane are consistent with the general migratory aptitude for
BV oxidation.[9a,c] Selectivity shifts during the BV oxidation of al-
dehydes in different solvents were investigated by Lehtinen
et al.[13] Specifically, solvents capable of forming hydrogen
bonds, such as methanol and 1-propanol, were shown to favor
the migration of hydrogen over branched alkyl groups, while
the migration of branched alkyl groups was preferentially ob-
served in non-hydrogen-bonding solvents, such as toluene and
CH2Cl2. Indeed, when 1-propanol and 1-butanol were used as
solvents for the oxidation of 8a and 8b, respectively (Table S3,
entries 5–6), the product distributions obtained were similar to
those obtained in methanol (Table S3, entries 1–2). Considering
the highly oxygenated nature of our reactive species, alcohol
solvents are likely to interact strongly with the Criegee inter-
mediate, possibly altering the stability of the transition state.
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