Wu et al.
FULL PAPER
General procedure for the oxidative reaction
a
Table 1 The optimization of reaction conditions
Caution! tert-Butyl hydroperoxide is an exception-
ally dangerous chemical that is highly reactive, flam-
mable and toxic. It is corrosive to skin and mucous
membranes and causes respiratory distress when inhaled.
It may cause explosion in the presence of Cu salt.
A solution of diarylmethanes or secondary alcohols
b
Entry
Cu source/%
TBHP (equiv.)
T/℃ Yield /%
(
1 mmol), and 70% TBHP (6 equiv.) in the presence of
1
2
3
4
5
6
7
8
9
no
6
80
80
80
80
80
80
80
80
80
60
25
80
27
84
Cu(OAc) •H O as a catalyst was stirred at 80 ℃ for 8
2
2
CuCl/10
6
h. The reaction mixture was quenched with the saturated
solution of sodium thiosulfate (5 mL) and extracted with
dichloromethane (3×10 mL). The combined dichloro-
CuI/10
6
88
CuSO •5H O/10
6
91
4
2
4
methane extracts were dried over anhydrous MgSO ,
Cu(OAc) •H O/10
6
95
2
2
filtrated, and then the solvent was removed under re-
duced pressure. The residue was purified by flash col-
umn chromatography on silica gel with PE or PE/EtOAc
as the eluent to obtain the desired products.
Cu(OAc)
•H
2
O/5
6
94
2
Cu(OAc) •H O/1
6
75
2
2
Cu(OAc) •H O/5
3
76
2
2
Cu(OAc) •H O/5
1.5
3
27
2
2
Results and Discussion
10
Cu(OAc) •H O/5
67
2
2
Initially, the oxidation of 9H-fluorene was selected
as a model reaction in the presence of 70% aqueous
TBHP to optimize the reaction conditions (Table 1).
Only TBHP (6 equiv.) showed lower catalytic activity in
water at 80 ℃, and only a 27% yield was obtained (Ta-
ble 1, Entry 1). The comparison of different copper
1
1
Cu(OAc) •H O/5
3
trace
trace
O, 8 h,
2
2
c
12
Cu(OAc) •H O/5
6
2
2
a
Reaction conditions: 0.5 mmol 9H-fluorene, 2 mL H
0% TBHP aqueous. Isolated yield. H O as oxidation.
2 2
2
b
c
7
sources indicates that 10 mol% Cu(OAc)
perior to other sources, including CuCl, CuI, and
CuSO •5H O (Table 1, Entries 2-5). When the amount
of Cu(OAc) •H O was decreased from 10 mol% to 5
mol%, the reaction still afforded a 94% yield of the
product (2a) (Table 1, entry 6). However, a significantly
2 2
•H O was su-
tempted under standard reaction conditions, affording
the desired product 2l, 9H-xanthen-9-one, with the yield
of 88%. The substrates anthracene and 1-(tert-butyl)-3-
ethylbenzene were also oxidized to the desired carbonyl
compounds 2m and 2n with yields of 68% and 77%,
respectively. Furthermore, the oxidations of the 1-ethyl-
4-methylbenzene and 1-ethylnaphthalene were also
performed under these conditions and gave the desired
products 2o and 2p in 46% and 69% yields, respective-
ly.
4
2
2
2
lower yield was obtained with 1 mol% Cu(OAc)
2 2
•H O
(
Table 1, Entry 7). Meanwhile, the amount of TBHP
was found to be a crucial parameter as the product yield
decreased from 94% to 27% when the TBHP loading
was decreased from 6.0 equivalents to 1.5 equivalents
To explore the generality of this protocol, a variety
of secondary alcohols were subjected to these reaction
conditions. The results are summarized in Scheme 2.
The substituted 9H-fluoren-9-ols were successfully oxi-
dized in the presence of 70% TBHP (6 equiv.) under 5%
Cu(OAc) •H O to afford the desired products 2a, 2b, 2d,
(
Table 1, Entries 8 and 9). Simarily, the yield of the
product was reduced when the reaction was carried out
at 60 ℃ or at room temperature (Table 1, Entries 10
and 11). In addition, when H
only trace product was obtained. Finally, the combina-
tion of Cu(OAc) •H O (5 mol%), 70% TBHP (6 equiv.)
2 2
O as oxidant was used,
2
2
2
2
and 2g with 81%-95% yields. Similarly, the oxidation
of the 9H-xanthen-9-ol and 9,10-dihydroanthracen-9-ol
was also performed under these conditions and gave the
desired products 2l and 4a in 98% and 81% yields, re-
spectively. Subsequently, a series of diphenylmethanol
derivatives were investigated. The substituted diphe-
nylmethanols bearing an electron-withdrawing group or
an electron-donating group were all well-tolerated and
were transformed to the corresponding products 2i, 2j
and 4b-4i in good yields. To further investigate the
range of substrates that could be used in this process,
1-phenylethanol derivatives were investigated. The re-
sults showed that 1-phenylethanol and 1-(4-methoxy-
phenyl) ethanol produced the corresponding ketones 4j
and 4k with 72% and 85% yields, respecttively. The
at 80 ℃ for 8 h in water (2 mL) was found to be the
most suitable reaction conditions.
Using the optimized reaction conditions, we sur-
veyed the scope of diarylmethane substrates for this
oxidation reaction in water. As shown in Scheme 1, the
substrates 2-NO
9
2
2
, 2-COMe, and 2-Br substituted
H-fluorenes were oxidized to the desired products
b-2d with yields of 78%-98%. Similarly, using
di-substituted 9H-fluorenes as substrates resulted in the
formation of the products 2e-2h in 67%-92% yields.
Additionally, the oxidative reactions involving substi-
tuted diphenylmethanes produced the corresponding
products 2i-2k in excellent yields ranging from 88% to
9
8%. The oxidations of 9H-xanthene were also at-
2
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Chin. J. Chem. 2017, XX, 1—5