Biphasic copper-catalyzed C–H bond activation of arylalkanes to ketones with tert-butyl hydroperoxide in water at room temperature

Article abstract of DOI:10.1016/j.tet.2016.05.066

A facile C–H bond activation of arylalkanes to their corresponding ketones catalyzed by copper salts using tert-butyl hydroperoxide as an oxidant in water at room temperature is described. Easy product separation, simple reaction procedures (without using base or phase transfer catalysis), and catalyst recycling make the catalytic system attractive. It is also active beyond activated benzylic methylene positions and could tolerate factionalized arylalkanes with diverse groups.

Full text of DOI:10.1016/j.tet.2016.05.066

Accepted Manuscript
Biphasic copper-catalyzed C–H bond activation of arylalkanes to ketones with tert-
butyl hydroperoxide in water at room temperature
Munkir Hossain, Shin-Guang Shyu
PII:
S0040-4020(16)30483-5
10.1016/j.tet.2016.05.066
TET 27793
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 April 2016
Revised Date: 23 May 2016
Accepted Date: 26 May 2016
Please cite this article as: Hossain M, Shyu S-G, Biphasic copper-catalyzed C–H bond activation of
arylalkanes to ketones with tert-butyl hydroperoxide in water at room temperature, Tetrahedron (2016),
doi: 10.1016/j.tet.2016.05.066.
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Biphasic copper-catalyzed C−H bond activation of arylalkanes to ketones with tert-butyl
hydroperoxide in water at room temperature
Md. Munkir Hossain and Shin-Guang Shyu*
Institute of Chemistry, Academia Sinica, Taipei 155, Taiwan, ROC

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Biphasic copper-catalyzed C−H bond activation of arylalkanes to ketones with
tert-butyl hydroperoxide in water at room temperature
Munkir Hossain, Shin-Guang Shyu*
Institute of Chemistry, Academia Sinica, Taipei 155, Taiwan, ROC
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A facile C−H bond activation of arylalkanes to their corresponding ketones catalyzed by copper
salts using tert-butyl hydroperoxide as an oxidant in water at room temperature is described.
Easy product separation, simple reaction procedures (without using base or phase transfer
catalysis), and catalyst recycling make the catalytic system attractive. It is also active beyond
activated benzylic methylene positions and could tolerate factionalized arylalkanes with diverse
groups.
Available online
Keywords:
C−H bond activation
Arylalkanes
2016 Elsevier Ltd. All rights reserved
.
tert-Butyl hydroperoxide (TBHP)
Room temperature
Water
1. Introduction
Aromatic compounds are integral parts of various natural
products and key intermediates for the synthesis of drugs,
perfumes, insecticides, and photo initiators.1 Traditionally, their
synthesis through acylation of aromatic compounds catalyzed by
acids requires harsh reaction conditions, and stoichiometric
amounts of oxidants, resulting in the formation of toxic and
corrosive wastes.2 Oxidation of methylene groups of
alkylaromatics to benzylic ketones using stoichiometric
quantities of KMnO4 as an oxidant produces a large volume of
wastes, and product separation is also difficult.3 The Industrial
production of benzylic ketones using oxygen and a cobalt
catalyst in acetic acid is often limited due to the corrosive nature
of the solvent and the homogeneous feature of the catalyst.4
Several methods using homogeneous,5 heterogeneous,6 and
metal-free7 catalysts are reported for the synthesis of ketones by
benzylic C−H bond activation of alkylaromatics. Despite the
importance of such a process, green as well as economic
protocols are still scarce.
Thus, instead of a catalyst/oxidant combination, solvent is also an
important factor from the environmental perspective of such a
process.8 Among the solvents, water, a green solvent, is not only
non-toxic, non-flammable, and abundantly available, but also
exhibits different reactivity in comparison to organic solvents.9
Reactions in water can enhance the reaction rate and the
selectivity owing to its hydrophobic effect.9c In addition, aqueous
biphasic systems offer easy separation of the product (dissolved
in the organic phase) and the catalyst (resides in the water
phase).9a Thus, the development of a catalytic system operating in
water is highly desirable.
Regarding the catalyst, the use of copper salts or complexes as
the catalyst has gained much prominence recently because of
their viability, reduced handling hazard, good functional group
tolerance, and scalability in synthetic procedures.5a,e,f On the
other hand, in consideration of the oxidant, cheap and readily
available 70% aqueous tert-butyl hydroperoxide (TBHP) is used
frequently as a promising alternate to H2O2 in combination with
various metal catalysts.10 Moreover, TBHP has fewer handling
risks than does H2O2 in water,10g,h and its reduction to a volatile
and non-toxic10d,g,11 alcohol by-product simplifies purification.
Thus, the catalytic combination of Cu/TBHP/H2O can provide
economic, environmental, and separation benefits.
In this context, a process with inexpensive catalyst and benign
oxidant are considered to be environmentally friendly. However,
a process with a reasonable catalyst/oxidant combination can be
overshadowed by a single parameter, i.e., solvent, as it is the
main contributor to the organic wastes.
Recently, we reported the oxidative cleavage of alkene double
bonds to their corresponding carbonyl compounds with oxygen
Corresponding author. Tel.: +886 2 2789 8592; fax: +886 2 2783
123; e-mail: sgshyu@chem.sinica.edu.tw
catalyzed by
a
water soluble copper complex [Cu(µ-
Cl)Cl(phen)]212 (which was synthesized in high yield using a

2
Tetrahedron
ACCEPTED MANUSCRIPT
simple method)13 and copper salts with neocuproine (2,9-
dimethyl-1, 10-phenanthroline) with TBHP in water (denoted as
catalytic system A).14 In continuation of our explorations in
developing a simple and sustainable catalytic process for the
oxidation of organic substrates, herein we report a facile and
selective C−H bond activation of arylalkanes to their
corresponding carbonyl compounds catalyzed by Cu(II)/Cu(I)
salts using TBHP as an oxidant in water at room temperature
without using any phase transfer catalyst or base. The catalyst is
recyclable and retains its high activity up to several cycles.
These observations support the individual inertness of CuCl2 and
neocuproine toward the reaction. In the presence of other
bidentate ligands (entries 2-4), the yields are comparable to that
of only TBHP (entry 7) suggesting that these ligands are inert
toward the reaction. Thus, both copper and neocuproine are
needed for the catalytic reactions (entry 1). The cause behind
reactivity and product selectivity enhancements by neocuproine
as compared to other ligands (entries 2-4) is not clear. Reactivity
enhancement due to the inductive effect of a methyl substituent
should be minor as the ligand 4,7-dimethyl-1,10-phenanthroline
(DMP) with a similar methyl substituent shows a lower reactivity
(entry 4). The structures of the ligands are shown in Chart 1.
2. Results and discussion
To optimize the reaction conditions, the reactions of fluorene
with different ligands, copper salts, and oxidants were carried out
under identical conditions. The results are summarized in Table 1.
Among different bidentate bipyridine ligands (Table 1, entries
1-4), neocuproine completes the oxidation reaction in an hour in
the presence of CuCl2·2H2O and water with high yield (Table 1,
entry 1). Reactions in the absence of CuCl2 (entry 5) and/or
ligand (entry 6) affording comparable product yields with that of
only TBHP (entry 7) suggest that TBHP is responsible for the
conversion. In addition, no reaction was observed when TBHP
was removed from the CuCl2/neocuproine/TBHP catalytic
system (entry 8) or when CuCl2 was used in the absence of
neocuproine and TBHP (entry 9).
Chart 1
Both Cu(I) and Cu(II) salts (entries 1 and 11-17) are effective
in catalyzing the reaction. However, the counterions have
significant impact on the reactivity toward activation.5a Thus,
Cu(NO3)2 (entry 15) and CuSO4 (entry 16) are less reactive than
other copper salts (entries 1, 11-14, 17). Reactions with Cu
halides afforded similar product yields irrespective of their
oxidation states and counterions (entries 1 and 11-14), indicating
that they may have similar active species and follow a similar
reaction path in the reactions. The active species should be Cu(II)
and Cu(I) moieties formed in situ in the redox reaction in the
catalytic cycle. The typical green color of Cu(II) observed in the
reaction mixture further supports the above hypothesis (Fig. 1).
Among different oxidants, H2O2 is not active (entry 18),
whereas organic peroxides, 2-hydroperoxy-tetrahydrofuran
(THFHP) is less active as compared to tert-butyl hydroperoxide
(TBHP) and cumene hydroperoxide (CHP) (entries 1, 19 and 20).
Hence, the order of reactivity is TBHP ~ CHP > THFHP > H2O2.
Formation and stabilisation of the usual free radical intermediates
(generated during oxidation) may be facilitated according to the
positive inductive effect of alkyl substituent of organic peroxides,
and accordingly they then interact with the substrates for their
conversion.14 TBHP is miscible in both water and organic phase
in the reaction mixture and thus favors close interaction with the
organic reagent and results in smooth oxidation. Water soluble
H2O2 cannot provide such miscibility and interaction toward
hydrophobic arylalkanes, and therefore oxidation reaction is
limited.
Table 1 Optimization of the reaction conditions for the oxidation of
fluorene in different copper salts, oxidants, and ligands.a
Entry Ligands
Oxidants
Copper
Conv./GC
Select.
Salts
CuCl2
CuCl2
CuCl2
CuCl2
no
CuCl2
no
CuCl2
CuCl2
CuCl2
CuCl
CuBr2
CuBr
CuI
Cu(NO3)2
CuSO4
Cu(OAc)2
CuCl2
CuCl2
CuCl2
Yield (%)
100/98
12/3
13/4
14/4
14/6
15/5
18/7
−
(%)
98
25
31
29
43
33
39
−
1
2
3
4
5
6
7
8
neob
phen
bipyc
DMPd
neo
no
no
nuo
no
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
no
9
no
−
−
10
11f
12
13
14
15
16
17
18
19
20
neoe
neo
neo
neo
neo
neo
neo
neo
neo
neo
neo
TBHPe
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
H2O2
100/89
100/99
100/98
100/99
100/98
66/54
18/13
97/95
−
89
99
98
99
98
82
72
98
−
THFHg
CHPh
7/2
91/85
29
94
To evaluate the role of water as a solvent, we used TBHP in
decane and solid CuCl2·2H2O without adding water (entry 10).
The reactions are smooth both in aqueous TBHP (organic solvent
free) and TBHP in decane. Yields and selectivity in the former
case is better than those in the latter case (entries 1 and 10). This
indicates that reactions in water may proceed in the organic phase,
and water not only forms a biphasic system but also influences
the product selectivity of the reaction to some extent.9c It is also
advantageous to use the biphasic system because water is
unavoidable in product separation and reused of the aqueous
aReaction conditions: fluorene (0.2 mmol), copper salts (0.01 mmol),
ligands (0.01 mmol), oxidants (1.4 mmol) 70% aq. TBHP, H2O (0.7 mL).
bneocuproine.
cbipyridine.
d4,7-dimethyl-1,10-phenanthroline.
e5M-6M decane solution, solid CuCl2·2H2O.
ffluorene (0.4 mmol), neocuproine (0.02 mmol), TBHP (2.8 mmol),
CuCl (0.02 mmol).
gTHF-hydroperoxide.
hcumene hydroperoxide.

3
phase, containing the catalyst (Fig. 1). The catalytic system was
then applied to various arylalkanes in water. The results are
summarized in Table 2.
It is noted that monoarylalkane (Table 2, entry 1) is less
reactive than diarylalkane (entry 2). When aryl substituents are
part of a tricyclic substrate, oxidation is even faster (entries 3-5).
Bicyclic arylalkanes (entries 6 and 7) are more reactive than
acyclic arylalkanes (entries 1 and 2) indicating that the aromatic
substituent plays a pivotal role in affecting the reactivity.
cumbersome task of separation) by drying the ethyl acetate
ACCEPTED MANUSCRIPT
extract or filtering the solid without chromatographic workup
(entry 4). Thus, the yields are also better or comparable to the
literature values.5e On the other hand, substrates with more than
one methylene group are involved in over-oxidation (entries 5-9),
and in a few cases afforded more than one product (entries 5, 7,
and 9). However, as a whole, the products are obtained in good to
moderate in yields and more or less comparable to the literature
values.5e
To evaluate the tolerance of this catalytic system toward the
functionalized arylalkanes with diverse groups and to elaborate
activity of this process toward methylene groups beyond the
activated benzylic position were also carried out. The results are
summarized in the Table 3. Arylalkanes bearing a methyl,
methoxy, and chloride, carboxylic acid and amide groups are
tolerated and yielded methylene oxidative product ketones with
high to moderate yields (Table 3, entries 1-5). Moreover,
substrates with electron withdrawing groups (entries 3-5) are less
reactive than those with electron donating group (entries 1 and 2).
Table 2 Oxidation of arylalkanes into ketonesa
Entry
Arylalkanes
Products
Time Conv. GC Yieldsb
(h) (%)
/Select. (%)
1
2
17
98
97 (91)/99
7
>99
93 (89)/94
Table 3. Oxidation of functionalized arylalkanes and substrates
containing different type of methylene groups.a
3
4
1
1
100
100
99 (95)/99
99 (95)/99
81 (76)/81
10 (−) /10
Entry
Substrates
Products
Time Conv. GC Yieldb
(h) (%)
Select. (%)
51 (46)/52
1
2
15
7
99
O
100
96 (92)/96
5
6
7
8
9
1
1
1
1
1
100
100
100
100
100
O
MeO
MeO
3
4
5
6
7
19
30
95
95
89 (85)/94
Cl
O
− (81)/85
56 (51)/56
29 (25)/29
40
40
15
30
87
54 (49)/62
31 (25)/94
65 (58)/65
21 (15) /21
trace
33
33 (29)/33
78 (72)/78
24 (21)/24
41 (37)/41
100
100
O
O
8
9
20
86
37(31)/43
aReaction conditions: as it is like Table 1 for arylalkanes.
bGC yield using internal standard 1,4-di-tert-butylbezene and isolated
yields in parenthesis.
aReaction conditions: arylalkanes (0.2 mmol), CuCl2·2H2O (0.01 mmol),
neocuproine (0.01 mmol), H2O (0.7 mL), tert-butyl hydroperoxide (1.4
mmol).
On the other hand, methylene group adjacent to a heterocyclic
ring in 2-ethylpyridine and 2-ethylthiophene, which are usually
regarded as difficult substrates in oxidation involving transition
metals due to their strong coordinating ability, were also
converted into the corresponding carbonyl compounds with
moderate yields (entries 6 and 7).5f Oxidation of cyclooctene
afforded cyclooctene oxide instead of methylene oxidative
product (entry 8). This indicates the allylic methylene group is
bGC yield using internal standard 1,4-di-tert-butylbezene and isolated
yields in parenthesis.
Furthermore, substrates with a single methylene group were
converted selectively to their corresponding carbonyl compounds
without any side products (entries 1-4). Hence, in these cases
(entries 2-4), we obtained pure product (avoiding the

4
Tetrahedron
ACCEPTED MANUSCRIPT
less active than the allylic double bond. Oxidation of
Equilibrium between catalytically active monomer and inactive
cyclooctane gave cyclooctanone, indicating that the aliphatic
methylene group is also active toward this catalytic system.
To check the sustainability of the catalyst, we observed that the
Cu(II) catalyst retained its activity through the end of the
reaction because further conversion of arylalkanes to the
corresponding ketone occurred when additional arylalkanes (e.g.,
fluorene) and TBHP were added to the aqueous layer containing
the dissolved catalyst after the product separation. The product 9-
fluorenone was transferred to the organic layer, leaving soluble
copper catalyst in water when ethyl acetate was added into the
reaction mixture under stirring (Fig. 1). Leaching of the ligand
neocuproine into organic phase during product separation was
not observed based on the NMR spectra (see the supporting
information Fig S10-11) of the isolated product (through drying
the ethyl extract without chromatographic workup). It is mostly
coordinated to the dissolved copper complex in the aqueous
phase.
dimer of copper complexes with bidentate bipyridyl ligands in
neutral solution is reported (Scheme 2).18 At room temperature,
the equilibrium favors the active monomeric form in the case of
neocuproine due to its steric effect of methyl substituent.18a,b
Thus, efficient oxidation for using neocuproine is observed.
H
N
N
N
OH2
OH
N
O
Cu
Cu
Cu
O
H
N
N
active monomer
inactive dimer
N
phenanthroline and neocuproine
N
Scheme 2. Monomeric and dimeric forms of copper complexes
with bidentate bipyridyl ligands.
Based on the literature19 and the above results, a plausible
reaction pathway is proposed in Scheme 3. The in situ generated
alkoxyl radical tBuO• abstracts one of the hydrogen atoms from
fluorene to produce fluorene radical A which is then reacted with
oxygen (atmospheric or generated by decomposition of peroxyl
ROO• radical) to form fluorene peroxide derivative B.19c,d Finally,
oxidative decomposition of B afforded the desired product
fluorenone.
H
Fig. 1. (a) Reaction mixture in water, (b) organic phase
containing products and the aqueous phase including copper
catalyst after addition ethyl acetate.
.
.
tBuO
The ethyl acetate layer was decanted for the product and the
aqueous layer containing the catalyst is used for further oxidation.
The reaction was repeated 7 times similarly with similar activity
using the same catalyst dissolved in the aqueous layer each time
(Fig. S1). The aqueous phase containing the catalyst was charged
only with fresh substrate and TBHP each time with continued
stirring as usual for the oxidation. It is also noted that the utility
of TBHP is smooth for a gram scale conversion when water is a
reaction medium.10g, h
A
fluorene
O
tBuOH
O2
O
O
H
H
H2O
B
fluorenone
In general, in peroxide activation reactions, several reactive
oxidizing species (i.e., oxygen-centered radicals) are generated.15
For the case of metal ion catalyzed hydroperoxy reactions; the
most important function of the catalyst is the decomposition of
the relatively stable hydroperoxides into radicals.16 Addition of
the radical scavenger 2,6-di-tert-butyl-4-methylphenol in our
system inhibited the cleavage reaction, indicating the presence of
a free radical pathway.16 According to the literature, copper ions
can react with TBHP and generate alkoxyl (RO•) and peroxyl
(ROO•) radicals from overall conversion of two molecules TBHP
Scheme 3. Proposed pathways for oxidation of arylalkanes to
ketones by TBHP.
3. Conclusions
We report a catalytic system which operates in water featuring
sustainability criteria such as stability, activity, easy product
separation (drying the ethyl extract or filtration of the solid
product in few cases without chromatographic workup), simple
operation, and recycling of the catalyst (the catalyst can be
recycled up to seven times without any loss of activity).
Moreover, diversity in group tolerance toward functionalized
arylalkanes and in activation of C−H bonds beyond activated
benzylic methylene positions are noteworthy. In addition, a
smooth gram scale preparation indicates the capability of the
catalytic system toward large scale preparation in the future.
(Scheme 1)5a,17
.
Scheme 1. Proposed decomposition path of TBHP by copper salt

5
Further use of the system to other oxidative reactions is under
exploration.
mg (89%). 1H NMR (300 MHz, CDCl ) δ ppm 7.79 (d, J = 7.8,
3
ACCEPTED MANUSCRIPT
4H), 7.59-7.54 (m, 2H), 7.48-7.43 (m, 4H), 13C NMR (300 MHz,
4. Experimental section
CDCl3) δ ppm 196.6, 137.5, 132.3, 130.0, 128.2.
4.2.5. 9-Fluorenone:5h,q,r,7b,d Drying of ethyl acetate extract under
4.1. General
vacuum gave pure 9-fluorenone as a yellow solid; yield: 34.2 mg
1
(95%). H NMR (300 MHz, CDCl3) δ ppm 7.60 (d, J = 7.8, 2H),
All chemicals were obtained from commercial sources and used
without further purification. 2-hydroperoxytetrahydrofuran was
synthesized according to literature.20 Gas chromatographic
analyses were performed on an Agilent 6890 instrument with a
FID detector and an Aglient 30 m x 0.53 mm x 3.0 µm HP-1
capillary column. Product isolation was carried out by TLC
(Merck, TLC silica gel 60 F254 25 Aluminum sheets 20x20 cm).
NMR spectra were recorded in CDCl3 on a Bruker AV 300 MHz,
at room temperature.
7.46-7.40 (m, 4H), 7.26-7.21 (m, 2H); 13C NMR (300 MHz,
CDCl3) δ ppm 193.8, 144.4, 134.1, 129.0, 124.2, 120.2.
4.2.6. Anthracene-9,10-dione:5q,r,7d TLC (hexane/ethyl acetate =
95:5) gave anthracene-9,10-dione as a light brown solid; yield:
31.6 mg (76%). 1H NMR (300 MHz, CDCl3)
δ ppm 8.31−8.28 (dd, J = 5.5, 3.1, 4H), 7.80-7.77 (dd, J = 5.4,
3.3, 4H), 13C NMR (300 MHz, CDCl3) δ ppm 183.1, 134.1,
133.6, 127.2.
4.2. Typical procedure for arylalkanes oxidation
4.2.7. 9-Xanthenone:5h,q,r,7d Filtration gave pure 9-xanthenone as a
colorless solid; yield: 37.1 mg (95%). 1H NMR (300 MHz,
CDCl3) δ ppm 8.29 (d, J = 7.8, 2H), 7.66 (t, J = 7.8, 2H), 7.42 (d,
J = 8.4, 2H) 7.32 (t, J = 7.5, 2H); 13C NMR (300 MHz, CDCl3)
δ ppm 177.1, 156.1, 134.7, 126.6, 123.8, 121.8, 117.9.
A stock solution of CuCl2·2H2O in water (0.0171 g/mL) was
prepared (by dissolving 0.171 g in 10 mL H2O). To a Teflon
screw cap glass tube, catalyst A (100 µL of a stock solution, 0.01
mmol of CuCl2, 2.1 mg, 0.01 mmol of neocuproine) was added.
Then 0.7 mL of H2O, 0.2 mmol of arylalkanes, and 70% aq. tert-
butyl hydroperoxide (200 µL, 1.4 mmol) were added in each
case. The mixture was stirred vigorously at room temperature till
to its reaction time specified in the Table 2 and Table 3. The
reaction mixture was then diluted with ethyl acetate and the
products dissolved in ethyl acetate layer were analyzed by GC
using internal standard 1,4-di-tert-butylbenzene (19.4 mg, 0.1
mol). For product separation, the aqueous phase was extracted
with ethyl acetate (3x10 mL). The combined extracts were dried
over anhydrous MgSO4 and filtered. The filtrate was
concentrated and product isolation was carried out by TLC. The
pure products of benzophenone, 9-fluorenone (Table 2, entries 2
and 3) and 4-methoxyacetophenone (Table 3 entry 2) were
obtained from drying their ethyl acetate extract without
chromatographic workup. Filtration of the reaction mixture
afforded pure 9-xanthenone (Table 2, entry 4).
4.2.8. Indan-1-one:5h,q,r,7d TLC (hexane/ethyl acetate = 95:5) gave
1
indan-1-one as a colorless solid; yield: 13.5 mg (51%). H NMR
(300 MHz, CDCl3) δ ppm 7.71 (d, J = 7.8, 1H), 7.59-7.51 (m,
1H), 7.43 (d, J = 7.8, 1H), 7.34-7.28 (m, 1H) 3.09 (t, J = 5.8,
2H), 2.66-2.62 (m, 2H); 13C NMR (300 MHz, CDCl3) δ ppm
206.9, 155.1, 137.0, 134.5, 127.2, 126.6, 123.6, 36.1, 25.7.
4.2.9. 1-Tetralone:5h,q,7d TLC (hexane/ethyl acetate = 95:5)) gave
1
1-tetralone as a colorless liquid; yield: 14.6 mg (25%). H NMR
(300 MHz, CDCl3) δ ppm 7.99 (d, J = 7.8, 1H), 7.45-7.40 (m,
1H), 7.32-7.20 (m, 2H), 2.92 (t, J = 6.0, 2H), 2.61 (t, J = 6.6,
2H), 2.14-2.05 (m, 2H); 13C NMR (300 MHz, CDCl3) δ ppm
198.2, 144.4, 133.3, 132.6, 128.7, 127.1, 126.5, 39.1, 29.6, 23.2.
4.2.10. Naphthalene-1,4-dione:5h TLC (hexane/ethyl acetate =
95:5) gave naphthalene-1,4-dione as a light yellow solid; yield:
19.4 mg (29%). 1H NMR (300 MHz, CDCl3) δ ppm 8.07-
8.04 (dd, J = 5.7, 3.3, 2H), 7.73 (dd, J = 5.7, 3.6, 2H), 6.95 (s,
2H); 13C NMR (300 MHz, CDCl3) δ ppm 185.0, 138.7, 133.9
131.9, 126.4.
4.2.1. Acetophenone:5q,r,7b TLC (hexane/ethyl acetate = 95:5)
gave acetophenone as a colorless liquid; yield: 22.0 mg (91%).
1H NMR (300 MHz, CDCl3) δ ppm 7.69 (d, J = 7.5, 2H), 7.28 (t,
J = 7.2, 1H), 7.17 (t, J = 7.8, 2H), 2.29 (s, 3H); 13C NMR (300
MHz, CDCl3) δ ppm 197.5, 136.7, 132.6, 128.1, 127.8, 26.0.
4.2.11. Isochroman-1-one:7d TLC (hexane/ethyl acetate = 95:5)
gave isochroman-1-one as a colorless solid; yield: 21.4 mg
(72%). H NMR (300 MHz, CDCl3) δ ppm 7.92 (d, J = 7.8, 1H),
7.43-7.38 (m, 1H), 7.24 (t, J = 7.5, 1H), 7.14 (d, J = 7.5, 1H),
4.38 (t, J = 6.0, 2H), 2.92 (t, J = 6.0, 2H); 13C NMR (300 MHz,
CDCl3) δ ppm 164.7, 139.2, 133.3, 129.8, 127.2, 127.0, 124.9,
67.0, 27.4.
4.2.2. 4-Methoxyacetophenone:5h,q,r Drying of ethyl acetate
extract under vacuum gave pure 4-metoxyacetophenone as a
colorless solid; yield: 27.1 mg (92%). 1H NMR (300 MHz,
CDCl3) δ ppm 7.90 (d, J = 8.7, 2H), 6.89 (d, J = 9.0, 2H), 3.83 (s,
3H), 2.52 (s, 3H); 13C NMR (300 MHz, CDCl3) δ ppm 196.7,
163.4, 130.5, 113.6, 55.4, 26.3.
1
4.2.12. Phthalide:7d TLC (hexane/ethyl acetate = 95:5) gave
phthalide as a colorless solid; yield: 11.2 mg (21%). H NMR
(300 MHz, CDCl3) δ ppm 7.85 (d, J = 0.9, 1H), 7.66-7.61 (m,
1H), 7.47 (t, J = 7.5, 2H), 5.27 (s, 2H); 13C NMR (300 MHz,
CDCl3) δ ppm 171.0, 146,5, 133.9, 128.9, 125.5, 122.1, 69.6.
4.2.3. 4-Chloroacetophenone:5r TLC (hexane/ethyl acetate =
1
95:5) gave 4-chloroacetophenone as a colorless liquid; yield:
1
26.3 mg (85%). H NMR (300 MHz, CDCl3) δ ppm 7.79 (d, J =
8.7, 2H), 7.32 (d, J = 9.9, 2H), 2.50 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ ppm 196.3, 139.1, 135.2, 129.4, 128.5, 26.1.
4.2.13. Phthalic anhydride:5v TLC (hexane/ethyl acetate = 95:5)
gave phthalic anhydride as a colorless solid; yield: 21.8 mg
4.2.4. Benzophenone:5h,q,7b,d Drying of ethyl acetate extract under
vacuum gave pure benzophenone as a colorless solid; yield: 31.5

6
Tetrahedron
1
(37%). H NMR (300 MHz, CDCl ) δ ppm 8.02-7.99 (dd, J =
temperature for 1h. It was then diluted with ethyl acetate and the
products dissolved in ethyl acetate layer were analyzed by GC
using internal standard 1,4-di-tert- butylbezene (19.4 mg, 0.1
mol). For a control reaction without water, a solution of 70% aq.
TBHP (240 uL, 1.4 mmol) in decane solution and fluorene (33.9
mg, 0.2 mmol) were added to a solid mixture of CuCl2 2H2O (1.7
mg, 0.01 mmol) and neocuproine (2.1 mg, 0.01 mmol). Then the
reaction was continued as above for 1h and the products
identified by GC diluting with ethyl acetate.
ACCEPTED MANUSCRIPT
3
5.4, 3.3, 2H), 7.92-7.89 (dd, J = 5.5, 3.0, 2H); 13C NMR (300
MHz, CDCl3) δ ppm 162.7, 136.1, 131.3, 125.7.
4.2.14. 4-Methylaectophenone:7d TLC (hexane/ethyl acetate =
(95:5) gave acetophenone as a colorless liquid; yield: 12.0 mg
(46%). 1H NMR (300 MHz, CDCl3) δ ppm 7.76 (d, J = 8.4, 2H),
7.15 (d, J = 8.1, 2H), 2.47 (s, 3H), 2.31 (s, 3H); 13C NMR (300
MHz, CDCl3) δ ppm 197.6, 143.7, 134.6, 129.1, 128.3, 26.4,
21.5.
Acknowledgments
4.2.15. 2-Acetylthiophenee:5u TLC (hexane/ethyl acetate = 95:5)
gave acetophenone as a colorless liquid; yield: 14.7 mg (58%).
1H NMR (300 MHz, CDCl3) δ ppm 7.51−7.49 (m, 1H), 7.45-743
(m, 1H), 6.93-6.9 (m, 1H), 2.34 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ ppm 190.3, 144.2, 133.5, 132.4, 127.9, 26.5.
We are grateful to the National Science Council, Republic of
China and Academia Sinica for financial support of this work.
Supplementary data
4.2.16. 2-Acetylpyridine:5t TCL (hexane/ethyl acetate/
dichloromethane = 55:5:40) gave acetophenone as a colorless
liquid; yield: 12.0 mg (25%). 1H NMR (300 MHz, CDCl3)
δ ppm 8.46 (d, J = 4.5, 1H), 7.82-790 (m, 1H), 7.65-7.59 (m,
1H), 7.29-725 (m, 1H), 2.50 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ ppm 199.6, 153.3, 148.8, 136.6, 126.9, 121.3, 25.5.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/.......
References and notes
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2.
3.
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mg (81%). 1H NMR (300 MHz, DMSO-d6) δ ppm 13.30 (s, 1H),
8.04 (s, 4H), 2.62 (s, 3H); 13C NMR (300 MHz, DMSO-d6) δ
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1
(15%). H NMR (300 MHz, CDCl3) δ ppm 2.71−2.68 (m, 2H),
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solution
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screw cap glass tube, catalyst A (100 µL of a stock solution; 0.01
mmol of CuCl2, 2.1 mg, 0.01 mmol of neocuproine), 2,6-di-tert-
butyl-4-methylphenol (308.0 mg, 1.4 mmol), fluorene (33.9 mg,
0.2 mmol) were added. Then 0.7 mL of H2O and 70% aq. tert-
butyl hydroperoxide, (200 µL, 1.4 mmol) was added in the above
reaction tube. The mixture was stirred vigorously at room
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