Copper/Selectfluor-System-Catalyzed Dehydration-Oxidation of Tertiary Cycloalcohols: Access to β-Substituted Cyclohex-2-enones, 4-Arylcoumarins, and Biaryls

Article abstract of DOI:10.1002/ejoc.201500610

A route to β-substituted cyclohex-2-enones, 4-arylcoumarins, and biaryls has been developed. This approach involves a one-pot Cu⁰/Selectfluor-catalyzed dehydration-oxidation of tertiary cycloalcohols. Thus, by using 2 equiv. of Selectfluor at 25 C, the dehydration-oxidation of tertiary cyclohexanols and oxabenzocyclohexanols gave β-substituted cyclohex-2-enones and 4-arylcoumarins, respectively; whereas the dehydration-oxidation of tertiary cyclohexanols gave biaryls as the final products by using 2.5 equiv. of Selectfluor at 80 C. A route to β-substituted cyclohex-2-enones, 4-arylcoumarins, and biaryls has been developed. This approach involves a one-pot Cu⁰/Selectfluor-catalyzed dehydration-oxidation of tertiary cycloalcohols.

Full text of DOI:10.1002/ejoc.201500610

FULL PAPER
DOI: 10.1002/ejoc.201500610
Copper/Selectfluor-System-Catalyzed Dehydration–Oxidation of Tertiary
Cycloalcohols: Access to β-Substituted Cyclohex-2-enones, 4-Arylcoumarins,
and Biaryls
Shaobo Ren,[a] Jian Zhang,[a] Jiahui Zhang,[a] Heng Wang,[a] Wei Zhang,[a] Yunkui Liu,*[a]
and Miaochang Liu[b]
Keywords: Synthetic methods / Oxidation / Copper / Enones / Oxygen heterocycles / Biaryls
A route to β-substituted cyclohex-2-enones, 4-arylcoumarins,
and biaryls has been developed. This approach involves a
one-pot Cu0/Selectfluor-catalyzed dehydration–oxidation of
tertiary cycloalcohols. Thus, by using 2 equiv. of Selectfluor
at 25 °C, the dehydration–oxidation of tertiary cyclohexanols
and oxabenzocyclohexanols gave β-substituted cyclohex-2-
enones and 4-arylcoumarins, respectively; whereas the de-
hydration–oxidation of tertiary cyclohexanols gave biaryls as
the final products by using 2.5 equiv. of Selectfluor at 80 °C.
Hoesch reactions,[16] and others.[17] The second involves
transition-metal-catalyzed cross-couplings of coumarin
frameworks (coumarin-derived bromides, triflates, tosylates,
phosphonates, carbonates, or even unactivated coumarins)
with various aryl reagents (organoboron, -tin, -zinc, -bis-
muth, and -indium organometallic reagents, and even unac-
tivated aromatics).[18] Despite significant progress in this
area, the exploration of alternative strategies for the con-
struction of 4-arylcoumarins remains a challenging task,
and therefore merits further consideration.
Furthermore, the biaryl scaffold is also an important and
frequently occurring structural element in a large number
of biologically active natural products and synthetic mol-
ecules,[19] polymers, functional materials, and liquid crys-
tals.[20] To date, established methods for the construction
of biaryls mainly focus on transition-metal-catalyzed cross-
coupling reactions between an aryl halide and an aryl orga-
nometallic reagent.[21] Despite the effectiveness of this ap-
proach, it has some drawbacks: fact that both coupling
partners require prefunctionalization, a large amount of or-
ganic and/or inorganic waste is generated, and expensive
ligands and transition-metal catalysts are used. In the past
few decades, benefiting from the remarkable advances in
the field of C–H activation,[22] a new and promising strategy
for the construction of biaryls has been developed that in-
volves C–C bond formation based on the C–H activation
of either one or both of the aromatic coupling partners.[23]
However, this strategy suffers from harsh reaction condi-
tions, tedious procedures for the installation and removal
of the directing groups, and the need to use expensive tran-
sition-metal catalysts. Recently, Li,[24a] Jasti,[24b] and It-
ami[24c] reported an alternative strategy for the construction
of biaryl scaffolds starting from non-aromatic precursors.
This strategy enabled direct access to biaryl compounds
Introduction
β-Substituted cyclohex-2-enones are widely used as ver-
satile synthetic intermediates in Michael reactions,[1] cyclo-
additions,[2] dehydrogenation reactions,[3] and other reac-
tions.[4] This motif is also an essential component of a vari-
ety of biologically active molecules.[5] Thus, a number of
synthetic methods for the construction of this important
unit have been developed in recent decades.[6] Some repre-
sentative methods include allylic oxidation of substituted
cyclohexenes,[6a–6d] oxidative rearrangement of tertiary
cyclohex-2-enols,[6e–6i] transition-metal-catalyzed oxidative
Heck reactions[2b,6j,6k] and cross-coupling reactions,[6l] and
others.[6m–6q] Although much progress has been made in
this field, the development of new methods for the mild and
efficient synthesis of β-substituted cyclohex-2-enones from
easily available starting materials is still in great demand.
On the other hand, 4-arylcoumarins,[7] known as neoflav-
ones, are very important members of the flavonoid family.
They show a variety of biological activities, including cyto-
toxic,[8] antibacterial,[9] antimalarial,[10] anti-HIV,[11] antitu-
mor,[12] antiprotozoal,[13] antidiabetic,[14] and antiviral ac-
tivities.[15] Existing methods for their synthesis generally fo-
cus on two conventional strategies. The first involves the
formation of benzopyranone rings through cyclization reac-
tions such as Pechmann, Perkin, Ponndorf, Houben–
[a] State Key Laboratory Breeding Base of Green Chemistry –
Synthesis Technology, Zhejiang University of Technology,
Hangzhou 310014, P. R. China
E-mail: ykuiliu@zjut.edu.cn
http://www.zjut.edu.cn
[b] College of Chemistry & Materials Engineering, Wenzhou
University, Zhejiang Province,
Wenzhou 325027, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500610.
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FULL PAPER
from non-aromatic precursors, thereby extending the range Table 1. Optimization of reaction conditions for the synthesis of 2a
and 3a.[a]
of starting materials that could be used. This strategy for
the construction of biaryls remains underexplored.[24]
As part of our continuing efforts towards the develop-
ment of highly efficient tandem reactions,[25] in this paper
we present a new, efficient, and one-pot route to β-substi-
tuted cyclohex-2-enones, 4-arylcoumarins, or biaryls involv-
ing a Cu0/Selectfluor-catalyzed dehydration–oxidation of
tertiary cycloalcohols as the key process.
Results and Discussion
Entry
Cat.
Oxidant
[equiv.]
T
[°C]
Yield [%][b]
2a
3a
Initially, 1-phenylcyclohexanol (1a), easily prepared by
the addition of phenylmagnesium bromide to cyclohexan-
one, was selected as the model substrate to investigate the
dehydration–oxidation reaction (Table 1). When 1a was
treated with copper powder (5 mol-%) and Selectfluor
(1 equiv.) in anhydrous MeCN at 25 °C for 24 h, β-phenyl-
cyclohex-2-enone 2a was chemoselectively obtained in 49%
yield (Table 1, entry 1). When 2 equiv. of Selectfluor was
used, the reaction gave 2a in a yield as high as 97%
(Table 1, entry 2). Further increasing the amount of Se-
lectfluor slightly decreased the yield of 2a (Table 1, entry 3).
A series of additional parameters including other F+ rea-
gents (Table 1, entries 4 and 5), solvents (Table 1, entries 6),
and copper catalysts (Table 1, entries 7–10) were investi-
gated, but we found that the reaction generally gave poor
yields of 2a under these reaction conditions. When the reac-
tion temperature was increased, the yield of biphenyl 3a
significantly increased (Table 1, entries 11–13). To our de-
light, 3a could be chemoselectively obtained in 96% yield
when the reaction was carried out using 5 mol-% of Cu0
and 2.5 equiv. of Selectfluor at 80 °C for 24 h (Table 1, en-
1
2
3
4
Cu0
Cu0
4 (1)
4 (2)
4 (3)
5 (2)
6 (2)
4 (2)
4 (3)
4 (3)
4 (3)
4 (3)
4 (3)
4 (2)
4 (2)
4 (2.5)
4 (2.5)
25
25
25
25
25
25
25
25
25
25
40
50
60
80
60
25
80
49
97
92
Ͻ10
Ͻ10
0
23
0
Ͻ5
0
82
64
15
0
9
0
–
trace
Ͻ 10
28
19
–
–
–
–
–
4
16
83
96
87[d]
0
Cu0
Cu0
5
Cu0
6[c]
7
Cu0
CuBr
CuI
8
9
Cu2O
CuSO4
Cu0
10
11
12
13
14
15
16
17
Cu0
Cu0
Cu0
Cu0
conditions[e]
conditions[f]
0
0
[a] Reaction conditions: 1a (0.2 mmol), catalyst (5 mol-% based on
1a), oxidant, and dehydrated MeCN (2 mL) under an air atmo-
sphere for 24 h, unless otherwise noted. [b] GC yield. [c] Anhydrous
1,4-dioxane, 1,2-dichloroethane, CH2Cl2, MeOH, acetone, and
DMF were each used as the solvent; all gave identical results.
[d] The reaction was carried out under an O2 atmosphere (1 atm,
balloon). [e] In the presence of either Cu0 (5 mol-%) or Selectfluor
try 14). When the reaction was carried out at 60 °C under (2 equiv.) only. [f] In the presence of either Cu0 (5 mol-%) or Se-
lectfluor (2.5 equiv.) only.
a dioxygen atmosphere (1 atm, balloon), 3a could be ob-
tained in 87% yield (Table 1, entry 15). Control experiments
showed that both Cu0 and Selectfluor were indispensable also compatible with this transformation, and could be con-
for the efficient formation of both 2a and 3a (Table 1, en- verted into the corresponding β-substituted cyclohex-2-en-
tries 16 and 17).
ones (i.e., 2) in moderate yields. Unfortunately, substrates
Having established the optimized reaction conditions in bearing methoxy and ethoxycarbonyl groups on the cyclo-
hand, a study to evaluate the scope and generality of this hexanol core (4-position) gave complicated results. Note
method for the chemoselective synthesis of β-substituted that for substrate 1q, the reaction regioselectively gave 4-
cyclohex-2-enones 2 was carried out (Scheme 1). Under the methyl-3-phenyl-cyclohex-2-enone (2q) in moderate yield,
optimized reaction conditions for the synthesis of 2 as and the regioisomer, i.e., 2-methyl-3-phenyl-cyclohex-2-en-
shown in the Table 1, entry 2, it we found that a variety of one, was not detected. When phenylcycloheptan-1-ol (1x)
substrates 1 bearing different substituents on the aromatic was used as a substrate, 1-phenylcyclohepta-1,4-diene (2xЈ)
rings (R1) (1a–1m, 1r except 1h) were smoothly converted was obtained in 56% yield, and the desired 3-phenyl-
into the corresponding β-substituted cyclohex-2-enones cyclohept-2-enone (2x) was not detected. Phenylcyclo-
(i.e., 2) in moderate to excellent yields (50–90%, Scheme 1) pentan-1-ol (1y) only gave a complex mixture under the
under very mild reaction conditions (25 °C). When sub- standard reaction conditions.
strate 1h was used, the reaction needed a higher tempera-
Encouraged by the successful synthesis of β-substituted
ture (60 °C) to go to completion. A series of functional cyclohex-2-enones from tertiary cyclohexanols, we envi-
groups, including electron-donating and electron-with- sioned that the dehydration–oxidation reaction could also
drawing groups, such as halogen (F, Cl, and Br), methyl, work with tertiary oxabenzocyclohexanols 7, and thereby
ether, and even ester groups, were tolerated under the reac- provide an alternative approach for the synthesis of 4-aryl-
tion conditions. Substrates 1o–1q and 1s, with methyl, ethyl, coumarins 8 (Table 2).[16–18] To our delight, when 4-phen-
or phenyl substituents (R2) on the cyclohexane ring, were ylchroman-4-ol (7a) was subjected to the standard condi-
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Dehydration–Oxidation of Tertiary Cycloalcohols
Table 2. Dehydration–oxidation of 7 for the synthesis of 4-aryl-
coumarins 8.[a]
Scheme 1. Dehydration–oxidation of 1 for the synthesis of substi-
tuted cyclohex-2-enones 2.[a,b] [a] Reaction conditions:
1
(0.2 mmol), Cu powder (0.01 mmol), Selectfluor (2 equiv. based on
1), anhydrous MeCN (2 mL), under air at 25 °C for 24 h. [b] Iso-
lated yields. [c] The reaction was carried out at 60 °C.
tions for the synthesis of 2, 4-phenylcoumarin (8a) was in-
deed produced in 86% yield (Table 2, entry 1). Further in-
vestigation demonstrated that the present dehydration–
oxidation process could be used with a variety of arene
types, including benzene rings bearing alkyl, aryl, and
chloro groups (Table 2, entries 2–8). In addition, several
functional groups (e.g., isopropyl, tert-butyl, and chloro
groups) on the oxabenzocyclohexanol core were compatible
with the dehydration–oxidation conditions, and the desired
products were obtained in moderate to good yields (Table 2,
entries 9–11). Finally, the dehydration–oxidation of a thia-
benzocyclohexanol (i.e., 7l) was also successful, and the cor-
responding thia-4-arylcoumarin (i.e., 8l) was produced in
51% yield (Table 2, entry 12).
Under the optimized reaction conditions for the synthe-
sis of 3 as shown in Table 1, entry 14, the dehydration–oxid-
ation of 1 to give biaryls 3 was also examined, and the re-
sults are listed in Table 3. We found that a variety of tertiary
cyclohexanols having different substituents (R1) on the aro-
matic rings, including electron-donating and -withdrawing
groups, could undergo the dehydration–aromatization
smoothly to give the desired biaryl products in moderate
to excellent yields (41–94%; Table 3, entries 1–19). Tertiary
cyclohexanols 1s, with a phenyl substituent, and 1t, with a
tert-butyl substituent on the cyclohexanol core, could be
chemoselectively transformed into the corresponding bi-
aryls (i.e., 3s and 3t) in 77 and 85% yields, respectively
(Table 3, entries 15 and 16). Substrate 1w, derived from the
addition of phenylmagnesium bromide to 3,4-dihydro-
naphthalen-1(2H)-one, was also converted into the desired
1-phenylnaphthalene (i.e., 3w) in a high yield of 94%
[a] Reaction conditions: 1a (0.2 mmol), catalyst (5 mol-% based on
1a), oxidant, and dehydrated MeCN (2 mL) under an air atmo-
sphere for 24 h, unless otherwise noted. [b] Isolated yields.
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Table 3. Dehydration–oxidation of 1 for the synthesis of biaryls 3.[a]
[a] Reaction conditions: 1 (0.2 mmol), Cu powder (0.01 mmol), Selectfluor (2.5 equiv. based on 1), anhydrous MeCN (2 mL), under air
at 80 °C for 24 h. [b] Isolated yields.
(Table 3, entry 19). Similarly, a series of functional groups obtained in 85% yield, but no formation of 2a-18O was de-
such as halogen, methyl, ether, and even ester groups were tected [Equation (3), Scheme 2]. The results in Equa-
tolerated under the reaction conditions.
tions (2) and (3) revealed that the oxygen atom in 2a origi-
To gain insight into the mechanism of the dehydration– nated from dioxygen rather than water. When 1a was al-
oxidation process, several additional experiments were car- lowed to react under an 18O2 atmosphere, the formation of
ried out (Scheme 2).
2a-18O was indeed detected [Equation (4), Scheme 2]. When
During the formation of 2a, we were able to detect cyclo- 1a was subjected to the standard conditions for the forma-
hexenylbenzene 9 as an intermediate. When isolated 9 was tion of 2a, but in the presence of TEMPO, a radical scaven-
subjected to the standard reaction conditions for the syn- ger,[26] the formation of 2a was suppressed [Equation (5),
thesis of 2, 2a was obtained in 87% yield [Equation (1), Scheme 2]. This supports a radical process. Treatment of 2a
Scheme 2]. When 1a was subjected to the standard reaction under the standard conditions for the synthesis of 3 failed
conditions for the synthesis of 2 but using degassed MeCN, to give 3a [Equation (6), Scheme 2]. However, when 9 was
and running the reaction under an argon atmosphere, only subjected to the same conditions, 3a was formed in 90%
a trace amount of 2a was detected, and cyclohexenylbenz- yield [Equation (7), Scheme 2], which suggests that 9 is also
ene 9 was obtained in 90% yield [Equation (2), Scheme 2]. an intermediate in the formation of 3a.
This suggests that dioxygen is indispensable for the forma-
On the basis of the above experiments and previous lit-
tion of 2a. Under the standard reaction conditions, but erature results,[6b,25a,27–30] a proposed mechanism for the de-
using a MeCN/H218O (400:1) solvent system, 2a was also hydration–oxidation of 1a to give 2a is shown in Scheme 3.
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Dehydration–Oxidation of Tertiary Cycloalcohols
per species HOCuIIBF4 (C) through the action of the base
(i.e., A). Allylic C–H activation of 9 by C followed by di-
oxygen insertion gives an intermediate F.[6b,29,30] Proton-
ation of F by the HF generated in the catalytic cycle releases
an intermediate G, and regenerates the catalyst (i.e., B). Al-
ternatively, G could be produced from 9 via an allylic radi-
cal intermediate H. Finally, G is further oxidized (probably
by Selectfluor) to give 2a.[6b,31]
Conclusions
In summary, for the first time we have developed an ef-
ficient and chemoselective method for the construction of
β-substituted cyclohex-2-enones, 4-arylcoumarins, and bi-
aryls from easily prepared tertiary cycloalcohols promoted
by a Cu0/Selectfluor system. The reaction is characterized
by the ready availability of the starting materials, the use of
inexpensive copper as a catalyst, mild reaction conditions
(for the synthesis of β-substituted cyclohex-2-enones and 4-
arylcoumarins), tunable synthesis of different products with
high chemoselectivity using a single catalytic system (for the
synthesis of β-substituted cyclohex-2-enones and biaryls),
and simple operation.
Scheme 2. Mechanistic studies.
Experimental Section
General Information: 1H and 13C NMR spectra were recorded with
a Bruker AVANCE III 500 instrument at 25 °C in CDCl3 at 500
and 125 MHz, respectively, using tetramethylsilane as an internal
standard. Chemical shifts (δ) are expressed in ppm, and coupling
Firstly, the redox reaction between copper powder and
Selectfluor[27] produces a cationic copper species FCuIIBF4
(B) and releases a base A.[25a,28] Then 1a undergoes de-
hydration to give cyclohexenylbenzene 9, A·HF, and a cop- constants (J) are given in Hz. IR spectra were recorded with an
Scheme 3. Proposed mechanism.
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FULL PAPER
FTIR spectrometer. GC–MS experiments were carried out with an
Agilent 6890N GC system equipped with a 5973N mass-selective
detector with an EI source. Low- and high-resolution mass spectra
(LRMS and HRMS) were obtained with a TOF MS instrument
with an EI source. The characterization of all known compounds
is presented in the Supporting Information.
m/z (%) = 264 (18) [M]+. HRMS (EI): calcd. for C18H16O2 [M]+
264.1150; found 264.1143.
6-Chloro-4-phenyl-2H-thiochromen-2-one (8l): Purified by column
chromatography (petroleum ether/EtOAc, 6:1) to give 8l (27.8 mg,
51%) as a yellow solid, m.p. 192–194 °C. IR (neat): ν = 1635 (C=O)
˜
1
cm–1. H NMR (500 MHz, CDCl3): δ = 7.56–7.48 (m, 6 H), 7.41–
7.39 (m, 2 H), 6.58 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 184.0, 154.5, 137.7, 136.1, 132.4, 130.1, 130.0, 129.4, 129.0, 128.6,
128.3, 127.6, 125.7 ppm. MS (EI, 70 eV): m/z (%) = 272 (44) [M]+.
HRMS (EI): calcd. for C15H9ClOS [M]+ 272.0063; found 272.0056.
Typical Experimental Procedure for the Synthesis of 2 by De-
hydration–Oxidation of Tertiary Cyclohexanols 1: Compound 1
(0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor (141.7 mg,
0.4 mmol, 2 equiv.), and anhydrous CH3CN (2 mL) were added to
a 10 mL flask. The reaction mixture was stirred at room tempera-
ture for 24 h. Upon completion, the mixture was diluted with
CH2Cl2 (10 mL), and filtered through Celite. The solvent was evap-
orated under vacuum, and the residue was purified by column
chromatography on silica gel (100–200 mesh; petroleum ether/
EtOAc, 6:1) to give pure 2.
Typical Experimental Procedure for the Synthesis of 3 by De-
hydration–Oxidation of Tertiary Cyclohexanols 1: Compound 1
(0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor (177.1 mg,
0.5 mmol, 2.5 equiv.), and anhydrous CH3CN (2 mL) were added
to a 10 mL flask. Then the reaction mixture was stirred at 80 °C
for 24 h. Upon completion, the mixture was diluted with CH2Cl2
(10 mL), and filtered through Celite. The solvent was evaporated
under vacuum, and the residue was purified by column chromatog-
raphy on silica gel (100–200 mesh; petroleum ether) to give pure 3.
3,6-Diphenyl-2-cyclohexen-1-one (2s): Purified by column
chromatography (petroleum ether/EtOAc, 6:1) to give 2s (38.7 mg,
78%) as a yellow solid, m.p. 78–80 °C. IR (neat): ν = 1688 (C=O)
˜
1
cm–1. H NMR (500 MHz, CDCl3): δ = 7.61–7.59 (m, 2 H), 7.46–
Mechanistic Studies
7.22 (m, 8 H), 6.61 (s, 1 H), 3.71–3.68 (m, 2 H), 2.93–2.90 (m, 2
H), 2.48–2.42 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
199.4, 159.1, 139.5, 138.6, 130.1, 128.9, 128.6, 128.4, 127.0, 126.2,
125.8, 52.5, 30.8, 27.5 ppm. MS (EI, 70 eV): m/z (%) = 248 (31) [M]+.
HRMS (EI): calcd. for C18H16O [M]+ 248.1201; found 248.1209.
Conversion of 9 into 2a Under the Standard Conditions: Compound
9 (31.6 mg, 0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor
(141.7 mg, 0.4 mmol, 2 equiv.), and anhydrous CH3CN (2 mL)
were added to a 10 mL flask. Then the reaction mixture was stirred
at room temperature for 24 h. Upon completion, the mixture was
diluted with CH2Cl2 (10 mL), and filtered through Celite. The sol-
vent was evaporated under vacuum, and the residue was purified
by column chromatography on silica gel (100–200 mesh; petroleum
ether/EtOAc, 6:1) to give pure 2a (30.0 mg, 87%).
Typical Experimental Procedure for the Synthesis of 8 by De-
hydration–Oxidation of Tertiary Oxacyclohexanols 7: Compound 7
(0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor (141.7 mg,
0.4 mmol, 2 equiv.), and anhydrous CH3CN (2 mL) were added to
a 10 mL flask. The reaction mixture was stirred at room tempera-
ture for 24 h. Upon completion, the mixture was diluted with
CH2Cl2 (10 mL), and filtered through Celite. The solvent was evap-
orated under vacuum, and the residue was purified by column
chromatography on silica gel (100–200 mesh; petroleum ether/
EtOAc, 6:1) to give pure 8.
Reaction of 1a in Degassed MeCN Under an Argon Atmosphere:
Compound 1a (35.3 mg, 0.2 mmol), Cu0 powder (0.64 mg, 5 mol-
%), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv.), and anhydrous
CH3CN (2 mL) were added to a 10 mL flask equipped with a high-
vacuum PTFE (polytetrafluoroethene) valve-to-glass seal. Then the
mixture in the sealed tube was frozen by immersion of the flask in
liquid N2. When solvent was completely frozen, the flask was
opened to the vacuum (high vacuum) and pumped for 2–3 min,
with the flask still immersed in liquid N2. The flask was then
closed, and warmed until the solvent had completely melted. This
process was repeated three times, and after the last cycle the flask
was backfilled with inert Ar gas. Then the reaction mixture was
stirred at room temperature for 24 h. Upon completion, the mix-
ture was diluted with CH2Cl2 (10 mL), and filtered through Celite.
The solvent was evaporated under vacuum, and the residue was
purified by column chromatography on silica gel (100–200 mesh;
petroleum ether/EtOAc, 6:1) to give pure 9 (28.5 mg, 90%). Only
a trace amount of 2a was detected.
4-(3,5-Dichlorophenyl)-2H-chromen-2-one (8g): Purified by column
chromatography (petroleum ether/EtOAc, 6:1) to give 8g (43.7 mg,
75%) as a yellow solid, m.p. 167–169 °C. IR (neat): ν = 1732 (C=O)
˜
1
cm–1. H NMR (500 MHz, CDCl3): δ = 7.63–7.55 (m, 2 H), 7.45–
7.40 (m, 4 H), 7.37–7.30 (m, 1 H), 6.39 (s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 164.0, 154.2, 152.9, 138.0, 135.8, 132.5,
129.8, 126.9, 126.4, 124.6, 117.6, 116.0 ppm. MS (EI, 70 eV): m/z
(%) = 290 (40) [M]+. HRMS (EI): calcd. for C15H8Cl2O2 [M]+
289.9901; found 289.9909.
4-(3,4-Dichlorophenyl)-2H-chromen-2-one (8h): Purified by column
chromatography (petroleum ether/EtOAc, 6:1) to give 8h (46.0 mg,
79%) as a yellow solid, m.p. 197–199 °C. IR (neat): ν = 1734 (C=O)
˜
1
cm–1. H NMR (500 MHz, CDCl3): δ = 7.65–7.58 (m, 3 H), 7.45–
Analytical data for 9: Purification by column chromatography (pe-
troleum ether/EtOAc, 10:1) gave 9 as a yellow oil. 1H NMR
(500 MHz, CDCl3): δ = 7.42 (d, J = 7.5 Hz, 2 H), 7.34 (t, J =
7.5 Hz, 2 H), 7.25 (t, J = 7.5 Hz, 1 H), 6.16–6.15 (m, 1 H), 2.46–
2.44 (m, 2 H), 2.25–2.23 (m, 2 H), 1.84–1.79 (m, 2 H), 1.72–1.67
(m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 142.7, 136.6,
128.2, 126.5, 124.9, 124.8, 27.4, 25.9, 23.1, 22.2 ppm. GC–MS (EI,
70 eV): m/z (%) = 158 (82) [M]+, 129 (100).
7.42 (m, 2 H), 7.33–7.27 (m, 2 H), 6.38 (s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 160.1, 154.2, 153.1, 135.0, 134.3, 133.5,
132.4, 131.1, 130.3, 127.7, 126.5, 124.5, 118.4, 117.6, 115.8 ppm.
MS (EI, 70 eV): m/z (%) = 290 (38) [M]+. HRMS (EI): calcd. for
C15H8Cl2O2 [M]+ 289.9901; found 289.9907.
6-Isopropyl-4-phenyl-2H-chromen-2-one (8i): Purified by column
chromatography (petroleum ether/EtOAc, 6:1) to give 8i (45.5 mg,
1
86%) as a yellow oil. IR (neat): ν = 1723 (C=O) cm–1. H NMR
Reaction of 1a in MeCN/H218O (400:1, v/v): Compound 1a
˜
(500 MHz, CDCl3): δ = 7.57–7.56 (m, 3 H), 7.49–7.44 (m, 3 H), (35.3 mg, 0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor
7.38–7.36 (m, 1 H), 7.32 (d, J = 2.5 Hz, 1 H), 6.38 (s, 1 H), 2.95– (141.7 mg, 0.4 mmol, 2 equiv.), and CH3CN/H218O (400:1, v/v;
2.87 (m, 1 H), 1.21 (d, J = 7.0 Hz, 6 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 160.9, 155.8, 152.5, 145.0, 135.2, 130.3, 129.7, 128.9,
128.5, 124.4, 118.7, 117.3, 115.1, 33.7, 24.0 ppm. MS (EI, 70 eV):
2 mL) were added to a 10 mL flask. Then the reaction mixture was
stirred at room temperature for 24 h. Upon completion, the mix-
ture was diluted with CH2Cl2 (10 mL), and filtered through Celite.
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Eur. J. Org. Chem. 2015, 5381–5388

Dehydration–Oxidation of Tertiary Cycloalcohols
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The solvent was evaporated under vacuum, and the residue was
purified by column chromatography on silica gel (100–200 mesh;
petroleum ether/EtOAc, 6:1) to give pure 2a (29.3 mg, 85%). No
formation of 2a-18O was detected by GC–MS analysis.
Reaction of 1a Under an 18O2 Atmosphere: Compound 1a (35.3 mg,
0.2 mmol), Cu0 powder (0.64 mg, 5 mol-%), Selectfluor (141.7 mg,
0.4 mmol, 2 equiv.), and anhydrous CH3CN (2 mL) were added to
a 10 mL flask equipped with a high-vacuum PTFE valve-to-glass
seal. The mixture was opened to the vacuum (high vacuum) and
pumped for 2–3 min. Then the flask was backfilled with 18O2 gas.
The reaction mixture was stirred at room temperature for 24 h.
Upon completion, the mixture was diluted with CH2Cl2 (10 mL),
and filtered through Celite. The solvent was evaporated under vac-
uum, and the residue was purified by column chromatography on
silica gel (100–200 mesh; petroleum ether/EtOAc, 6:1) to give pure
2a (28.6 mg, 83%). GC–MS analysis showed that the 18O-en-
richment in 2a was 48 %.
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Effect of the Radical Scavenger TEMPO on the Model Reaction:
Compound 1a (35.3 mg, 0.2 mmol), Cu0 powder (0.64 mg, 5 mol-
%), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv.), TEMPO (15.6 mg,
0.5 equiv.; or 62.5 mg, 2 equiv.), and anhydrous CH3CN (2 mL)
were added to a 10 mL flask. The reaction mixture was stirred at
room temperature for 24 h. Upon completion, the mixture was di-
luted with CH2Cl2 (10 mL), and filtered through Celite. The solvent
was evaporated under vacuum, and the residue was purified by
column chromatography on silica gel (100–200 mesh; petroleum
ether/EtOAc, 6:1) to give pure 2a. In the presence of 0.5 and
2 equiv. of TEMPO, 2a was obtained in 22 and 0% yield, respec-
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Received: May 13, 2015
Published Online: July 20, 2015
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