Angewandte
Chemie
this method for a large number of compounds. In some cases,
the yields of isolated products were significantly lower than
those obtained from gas-chromatographic analysis of the
reaction mixture; this might be due to the loss of volatile
products during purification by column chromatography.
When diaryl ethers were employed as the substrates, only
(Table 1, entries 2, 5, 20, and 23), whereas the b-O-4 linkage
of a series of lignin model compounds was smoothly cleaved
to give phenols in high yields (Table 2) and acetophenone
derivatives in low yields (Table S4). In fact, the acetophenone
product could be further converted into organic products
under the reaction conditions (see Scheme S1), which might
explain why a high yield of acetophenone could not be
obtained. Some unknown organic products were also
observed, but our attempts to identify these products were
not successful. In line with previous work related to the
cleavage of lignin-related b-O-4 linkages,[16a] a small amount
of 2-phenoxyacetophenone, which is an intermediate of the
dehydrogenation of the benzylic alcohol moiety of the
substrate, was also detected (Scheme S2); this intermediate
could then undergo cleavage of the ether bond to yield
acetophenone and phenol (Scheme S3). However, we are not
sure whether the primary mechanistic pathway involves the
formation of 2-phenoxyacetophenone followed by hydro-
À
aryl C O bonds were cleaved, and hydrogenation of the aryl
rings hardly occurred (Table 1, entries 1–7). This complete
À
selectivity for the cleavage of the C O bonds over the
hydrogenation of aryl p-bonds is in clear contrast to the
hydrogenation of aryl ethers with heterogeneous catalysts,[18]
which typically leads to a mixture of arenes, cycloalkanes,
phenols, and cycloalkanols. Furthermore, we found that aryl
hydroxy groups were tolerated (Table 1, entries 13 and 16),
whereas aryl carbon–fluorine and carbon–chlorine bonds
were cleaved under our reaction conditions (Table 1, entries 9
and 11). The desired products were not observed when diaryl
ether substrates that bear carboxyl, nitryl, or ester groups
were employed (data not shown).
genative cleavage of the ether bond,[16a] because the C O
À
The substrate that bears an electron-withdrawing fluorine
substituent was less reactive than substrates bearing electron-
donating alkyl or methoxy moieties. For example, the
reductive cleavage of 4-fluorodiphenyl ether required a high
temperature (1808C) to ensure the reaction to proceed
smoothly (Table 1, entries 8 and 9). The bond-cleavage
reaction did not occur with diaryl ethers bearing two fluorine
substituents. Steric hindrance had a crucial effect on the
reaction, and the cleavage of 2,6-dimethyldiphenyl ether
cleavage reaction possibly occurs under experimental con-
ditions where the hydroxy group in the substrate was replaced
by a methoxy group to block the formation of 2-phenoxy-
acetophenone as an intermediate. Although the cleavage of
the ether bond also occurred in the absence of hydrogen gas,
the desired product was obtained in a lower yield (Table 2,
entry 2), which prompted us to perform the cleavage reac-
tions under hydrogen atmosphere. As shown in Table 2,
several functional groups, including methoxy, fluoro, bromo,
nitryl, and amido groups, were tolerated (Table 2, entries 5–
9), whereas the presence of aryl hydroxy groups significantly
hindered the reaction (Table 2, entry 10).
The [Fe(acac)3] catalyst precursor was further used to
address another challenge in organic synthesis; in this case,
a methoxy group was employed as a removable directing
group to synthesize rare regioisomeric products that are
difficult to obtain from the direct functionalization of
substituted benzene derivatives.[7,17] As shown in Scheme 1,
À
hardly occurred at the sterically more-hindered C O bond
(Table 1, entry 7).
À
In the presence of both aryl and alkyl C O bonds,
À
reductive cleavage selectively occurred at the aryl C O
À
bonds, and only trace amounts of the products of alkyl C O
bond cleavage were observed (Table 1, entries 4, 10, 14–21).
Phenyl methyl ether without any further substituents showed
poor reactivity (Table 1, entry 14), whereas the cleavage of
naphthalene derivatives always resulted in high product yields
(Table 1, entries 19 and 21). However, in contrast to the
results of previously reported reactions using nickel catalyst
systems,[7,14] the introduction of methoxy or phenyl groups
onto the aryl rings increased the reactivity of the aryl methyl
ether (Table 1, entries 15–18). Our results therefore suggest
that the iron-based catalyst developed in this work has
additional unique features over the reported nickel-based
catalysts.[7,14]
Having identified a catalyst for the reductive cleavage of
simple aryl ethers, we tested the ability of this system to
catalyze the cleavage of the b-O-4 linkage of lignin model
compounds, which is the most abundant linkage in lignin.[6b,16]
A dimeric lignin model compound that contained a b-O-4
linkage was smoothly converted into the desired products
with high selectivity and without saturation of the aromatic
rings (Table 1, entry 25). The reductive cleavage selectively
Scheme 1. Synthesis of the regioisomeric products that are unattain-
able from conventional toluene functionalization (for the reaction
conditions, see the Supporting Information, Scheme S4).
the meta-substituted products are often unattainable from
a reaction of toluene, because the methyl group is an ortho/
para-directing substituent. However, when applying our
strategy, the meta-substituted products prevail, and two
meta-substituted toluene derivatives were obtained from 3-
methylanisole in moderate yield (Scheme 1). Although our
method has obvious limitations, the previously unattainable
regioisomeric products can be synthesized from the function-
alization of substituted benzenes with this strategy.[7–9,17]
À
occurred at the alkyl C O bond. Considering that the use of
LiAlH4 would severely limit the application of this trans-
formation to real-world biomass processing, we chose to
replace LiAlH4 with hydrogen gas as the hydrogen source.
The experimental results suggest that aryl ethers were almost
inactive under the conditions using H2 as the reductant
Angew. Chem. Int. Ed. 2013, 52, 12674 –12678
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