Iron(iii) chloride hexahydrate-promoted selective hydroxylation and chlorination of benzyl ketone derivatives for the construction of hetero-quaternary scaffolds

Article abstract of DOI:10.1039/c6ob01733a

A novel and tunable α-hydroxylation/α-chlorination of benzyl ketone derivatives has been developed for the construction of hetero-quaternary carbon centers by iron(iii) chloride hexahydrate mediated selective transformations through the application of dif

Full text of DOI:10.1039/c6ob01733a

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DOI: 10.1039/C6OB01733A
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ARTICLE
Iron (III) chloride hexahydrate-promoted selective hydroxylation
and chlorination of benzyl ketone derivatives for construction
hetero-quaternary scaffolds
Received 00th January 20xx,
Accepted 00th January 20xx
Tao Chen, Rui Peng, Wenxin Hu, and Fu-Min Zhang*
DOI: 10.1039/x0xx00000x
A novel and tunable α-hydroxylation/α-chlorination of benzyl ketone derivatives has been developed for the construction
of hetero-quaternary carbon center by Iron(III) chloride hexahydrate mediated selective transformations through the
application of different oxidants, especially the crystal water in catalyst as OH source is firstly reported in this hydroxylation.
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Introduction
Selective functionalization of C-H bond at the α-position of
ketones has been a classical and important research topic in
organic synthesis.1 Especially, the construction of tertiary α-
heteroatom-substituted carbonyl compound through direct
functionalization of ketones has attracted the interests of
synthetic communities.2 Among the resulting products, two
motifs are of great importance to academic research and
industrial field: one is the tertiary α-hydroxyl ketones, and the
other is the tertiary α-chloro ketones.
The tertiary α-hydroxyl ketones not only exist in many bioactive
compounds (Figure 1), but also serve as the building block for
the syntheses of functional molecules.3 Especially, the
rearrangement of these scaffolds and their variants could
provide various products via the migration of corresponding
alkyl or aryl groups.4 Although many methods for the
preparation of these unique scaffolds have been explored,
direct oxidation of the activated C-H bond at the α-position of
the easily available ketones is one of the most common
strategy.5 For example, Ritter5a and Schoenebeck5b reported
hydroxylation of C-H bond through Pd- or Cu-catalyzed
oxidation of ketone, respectively, while Jiao5c and Zhao5d
independently have developed the base catalyzed similar
transformations. However, some drawbacks are involved in
these transformations, such as the application of precious metal
catalyst, the requirement of relative poisonous reductant, and
the preformation under the basic reaction conditions.
Therefore, the development of new synthetic method
especially under acidic reaction conditions for the preparation
of these important units is highly needed.
Fig. 1 The selective natural products containing tertiary α-hydroxyl-
or α-chloro- ketone scaffold.
In analogy to the tertiary α-hydroxyl ketones, the tertiary α-
chlorinated ketones have been used as valuable intermediates
and ligands in organic synthesis6 and are also common scaffolds
in numerous bioactive molecules7 (Figure 1), so the
construction of these challenging units has also been an active
area in organic synthesis. In many developed synthetic methods,
the direct introduction of a chlorine atom in the corresponding
ketones is a commonly used approach.8 However, some
shortcomings still exist. Consequently, the exploitation of new
approach for the preparation of the tertiary α-chlorinated
ketones is of great necessary.
Considering two abovementioned valuable synthetic motifs,
and our continuing research interests in “three birds with one
stone” chemical reagents,9 we speculated that FeCl3·6H2O,10
which has shown excellent properties, such as inexpensiveness,
easily availability, low-toxicity, insensitivity for moisture and air
in organic synthesis, could be used as both Lewis acid and OH or
Cl source for the construction of the tertiary α-hydroxyl ketones
or the tertiary α-chlorinated analogues under suitable reaction
conditions. Herein, we report FeCl3·6H2O mediated selective
hydroxylation/chlorination of benzyl ketones through the
switch of reaction conditions.
Results and discussion
Initially, we started our research for the hydroxylation of the
commercially available 2-phenylcyclohexanone. However,
there were some tough problems to be solved in this
State Key Laboratory of Applied Organic Chemistry and Department of Chemistry,
Lanzhou University, Lanzhou, 730000(P.R. China).
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Table 1. Selected optimization of reaction conditiona
Journal Name
strong coordinating effect between iron (III) and VoiexwygAretincleaOtnolimne
in DMSO, DMF, THF, and CH3NO2 which rDeOduI:c1e0.d10t3h9e/CL6eOwBi0s17a3c3idA
activity of Iron (III), resulting in the suppressing of the initial
enloted process, while product 2a could be isolated with 19%
yield in CH3CN (entry 13, Table 1). Other oxidants did not give
better result.14 When the acidic additives were introduced to
o
the reaction systems at 65 C, no obvious improvement of the
entry cat. (0.5 equiv) solv.
ox. (equiv) additives (equiv) temp. yieldb
DDQc (1.0) -
RT 48%
yield was observed, however, the additives were beneficial for
this reaction at 55 oC, in which the best yield of 73% was
obtained by the use of acetic acid (entries 14-19, Table 1); So
the amount of acetic acid was further investigated, however, no
superior results were obtained (entries 20-22, Table 1). The
loading of FeCl3·6H2O did not affect obviously the yield of
product.14 In the absence of FeCl3·6H2O or DDQ, no desired
product 2a was isolated (entries 23-24, Table 1). Other Iron salt
hydrates were also tested.14 Among them, 50% Fe(OTs)3·6H2O
could promote the reaction in 35% yield, while Fe(NO3)3·9H2O
was inefficient (entries 25-26, Table 1). Further screening other
metal salt hydrates or the addition of water (entry 28, table 1)
could not improve the yield.14 So 50% FeCl3·6H2O, DDQ (1.0 eq.)
and AcOH (1.0 eq.) in DCE at 55oC under an argon atmosphere
were selected as the optimal reaction conditions.
1
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
-
DCE
DCE
DCE
DCE
DCE
DCE
DMF
2
3
4
5
DDQ (1.0)
DDQ (1.0)
DDQ (1.0)
DDQ (1.0)
DDQ (1.0)
DDQ (1.0)
-
-
-
-
-
-
-
-
-
-
-
-
45oC 55%
55 oC 56%
65 oC 61%
75 oC 57%
85 oC 36%
6
7
8
9
65 oC
65 oC
65 oC
0
0
0
DMSO DDQ (1.0)
THF DDQ (1.0)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
CH3NO2 DDQ (1.0)
toluene DDQ (1.0)
hexane DDQ (1.0)
CH3CN DDQ (1.0)
65 oC trace
65 oC trace
65 oC trace
65 oC 19%
55 oC 70%
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DDQ (1.0) PhCO2H (1.0)
DDQ (1.0) Picolinic acid(1.0) 55 oC 18%
DDQ (1.0) Me3CCO2H (1.0) 55 oC 64%
DDQ (1.0) HCO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CF3CO2H (1.0)
DDQ (1.0) CH3CO2H (0.5)
DDQ (1.0) CH3CO2H (2.0)
DDQ (1.0) CH3CO2H (4.0)
55 oC 71%
55 oC 73%
55 oC 70%
55 oC 56%
55 oC 48%
55 oC 40%
55 oC trace
With the optimal reaction conditions in hand, we turned our
attention to expand the substrate scope, and the reaction
results were shown in Scheme 1. The substituents on the aryl
ring had an obvious effect on the reaction results. For examples,
the substrates bearing the slight electronic-withdrawing F, Cl or
-
CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
DDQ (1.0) CH3CO2H (1.0)
55 oC
0
Fe(OTs)3·6H2O
Fe(NO3)3·9H2O
55 oC 35%
55 oC trace
55 oC trace
55 oC 62%
55 oC 29%
d
FeCl3
FeCl3
Scheme 1 Scope of hydroxylation substrates a
e
FeCl3·6H2Of
a) Reactions were performed using 2-phenylcyclohexanone (0.2 mmol) in 2.0
mL solvent at the noted temperature under an argon atmosphere; b)
isolated yield; c) DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; d) the
anhydrous FeCl3 was prepared according the reported method; e) 0.5 equiv
FeCl3 and 3.0 equiv H2O was used; f) Reaction was performed under air
atmosphere.
transformation: 1) the competitive C-C bond cleavage of the α-
position of the ketone other than C-H bond hydroxylation or
chlorination have been reported;2d,5b,11 2) the intermolecular
oxidative self-coupling product would be produced in the
presence of FeCl3;12 3) to our best knowledge, crystal water
contained in the hydrated metal salt serves as OH source was
seldom investigated,13 although free water has been
extensively studied and applied as the same purpose; 4)
especially, how to control the selectivity of hydroxylation and
chlorination through the adjustment of experimental
parameters is a challenging issue. To our delight, the desired
product 2a was isolated in 48% yield in the presence of 50%
FeCl3·6H2O in 1,2-dichloroethane (DCE) under an argon
atmosphere at room temperature after 2 days (entry 1, Table 1).
Encouraged by this initial result, we conducted the reaction at
various temperatures, and the results indicated that the
product 2a was obtained with 61% yield at 65 oC, and decreasing
or increasing reaction temperature are adverse for this
transformation (entries 2-6, Table 1). Then the reaction were
performed in different solvents, and it was revealed that solvent
strongly affected this transformation; no reaction occurred in
DMF, DMSO and THF (entries 7-9, Table 1), might be due to the
a) Unless noted, reactions were performed using 2-phenylcyclohexanone
derivatives (0.2 mmol) in 2.0 mL DCE at 55 oC under an argon atmosphere;
b) the reaction was performed at 18 oC; c) the reaction was performed at 0
oC; d) the reaction was performed at rt.
2 | J. Name., 2012, 00, 1-3
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Br group at the p-position afforded the expected product 2b
ARTICLE
(entry 1, Table 2). Therefore, after completing tVhieew sAurtbicsletOrantlienes
DOI: 10.1039/C6OB01733A
investigation of the hydroxylation, we turned our efforts to explore
-
2d
in good yield. Similarly, the electronic-donating OMe or
piperonyl group on the aryl ring were tolerated, led to the
desired product 2e and 2f in 48% and 50% yield, respectively.
However, strong electronic-withdrawing NO2 group on the aryl
ring didn’t afford the desired product 2g. Substrates with a
naphthyl ring reacted smoothly, although the yield of 1-
naphthyl product 2h was slightly lower than that of 2-naththyl
analogue 2i, which might be due to the steric hindrance effect.
Interestingly, the mono-hydroxylated product 2j was isolated in
49% yield, even though dual reaction positions existed in 2, 6-
the optimal conditions for chlorination of 2-phenylcyclohexanone
(Table 2). Solvents screening demonstrated that the best result was
obtained in a mixture solvent (ethyl acetate/AcOH = 1：1) at room
temperature, while no product 3a was isolated when the reaction
was conducted in THF, DMSO, or CF3CO2H (entries 2-9, Table 2).
Further screening of oxidants indicated that the similar result was
obtained using IBX to replace DMP, while only trace amount of
product 3a was observed using Na2IO4, K2S2O8 or H2O2 as oxidant
(entries 11-13, Table 2). Notably, O2 or air using as oxidant led to the
unexpected C-C bong cleavage process, resulting in the cycle-
opening product2d,
(entries 14-15, Table 2). The amount of
diphenylcyclohexanone.
When
2-phenyl-3,
4-
5b
dihydronaphthalen-1(2H)-one was subjected to the optimal
conditions, the expected product 2k was obtained in 65% yield.
α-Methyl-β-tetralone also afforded the α-hydroxy-α-methyl-β-
tetralone 2l at room temperature. The derivative of
cycloheptanone gave the expected product 2m, albeit with 40%
yield. It is noteworthy that non-cyclic 1-(9H-fluoren-9-yl) ethan-
1-one was also an ideal substrate, producing the desired
product 2n in 48% yield.
FeCl3·6H2O obviously affected the yield of product 3a (entries 16-19,
Table 2). Replacement of FeCl3·6H2O with other metal hydrate were
inefficient for this transformation (entries 20-22, Table 2), but the
product 3a was isolated in 13% yield in the presence of FeCl2·4H2O
(entry 23, Table 2). Increasing or lowing the amount of DMP was not
beneficial for this transformation (entries 24-26, Table 2). Therefore,
200% FeCl3·6H2O, DMP (1.2 equiv) in EA/AcOH at room temperature
under an argon atmosphere (entry 9, Table 2) were used as the
optimal chlorination conditions for the next investigation.
Under the optimal reaction conditions, a series of substrates were
tested, and the results are summarized in Scheme 2. Among the
substrates tested, the corresponding products 3a-3d and 3f-3i were
isolated in moderate to good yield. The slight electronic-drawing
groups on the aryl ring did not affect the reaction results, and the
desired products bearing p-F, p-Cl, and p-Br on the aryl ring could be
isolated in good yields. It is noteworthy that the product 3e bearing
strong electron-donating OMe at meta-position was not isolated,
while the product 3f bearing strong electron-withdrawning NO2 on
aryl ring was obtained in 34% yield, which are different from the
results of hydroxylation. Similar to the hydroxylation, the mono-
chlorinated product 3g was also isolated as a major product. Non-
cyclic ketone could afford the products 3h under the optimal
Interestingly, the chlorinated product 3a was isolated in 52% yield
using Dess-Martin periodinane (DMP) as oxidant and DCE as solvent
in the investigative processes of the hydroxylation reaction
a
Table 2. Selected optimization of reaction condition
Entry Metal hydrate (equiv)
Oxidant (equiv) Solvent
Yield (%)b
52
45
31
trace
trace
1
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (1.0)
FeCl3·6H2O (1.5)
FeCl3·6H2O (2.5)
FeCl3·6H2O (3.0)
CoCl2·6H2O (2.0)
NiCl2·6H2O (2.0)
CuCl2·2H2O (2.0)
FeCl2·4H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
FeCl3·6H2O (2.0)
DMPc (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
IBX (1.2)
DCE
2
3
4
5
6
7
8
9
hexane
toluene
DMSO
THF
ethyl acetate 63
AcOH
a
Scheme 2. Scope of hydroxylation substrates
71
trace
72
70
trace
57
13
trace
trace
58
60
66
57
0
trace
trace
13
CF3CO2H
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
EA/AcOH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
H2O2 (1.2)
Na2IO4 (1.2)
K2S2O8 (1.2)
O2
air
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2))
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (1.2)
DMP (0.8)
DMP (1.5)
DMP (2.0)
-
66
72
62
trace
a) Unless noted, reactions were performed using 2-phenylcyclohexanone
derivatives (0.2 mmol) in 2.0 mL EA/HOAc (v/v = 1:1) at rt under an argon
atmosphere; b) Isolated by HPLC; c) the complex mixture was observed.
a) Reactions were performed using 2-phenylcyclohexanone (0.2 mmol) in 2.0
mL solvent at the room temperature under an argon atmosphere; b) the
NMR yield; c) DMP = Dess-Martin periodinane; d) IBX = 2-Iodoxybenzoic acid;
e) EA = Ethyl acetate
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chlorination results (entry 9, Table 3), demonstrating that the IBX-Ac,
serves as the possible active oxidant, involveDthOeI:c1h0l.o10ri3n9a/tCio6nOBp0ro17c3e3sAs.
conditions. Notably, 1,3-dicarboyl compound was also an ideal
substrate, providing the expected product 3i in 80% yield. Because
some functional groups such as F, Cl, Br, NO2 on the aryl ring could
be tolerated in this transformation, the resulting products could be
further convert to other valuable synthetic intermediates or couple
with other reaction partner for the construction of more complex
functional molecules.
In order to elucidate the reaction mechanism, some control
experiments were carried out. When FeCl3·6H2O was replaced by
anhydrous FeCl315 (entry 27, Table 1), only trace amount of product
2a was observed, and the result proved that the hydroxyl group in
product 2a should be derived from the crystal water in FeCl3·6H2O.
Moreover, the product 2a was isolated in 62% yield when the
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Based on these experiment results and the previous studies,17
a
plausible reaction mechanism is proposed, although other possible
mechanisms cannot be excluded at this stage. The substrate 1a is
enolized inspired by FeCl3, which serves as Lewis acid, and the
intermediate enolate is oxidized by DDQ to give α-keto radical II. The
resulted radical II could be further oxidized to anion IV17e by oxidant
V derived from DDQ, and the anion IV is trapped by H2O to provide
the hydroxylation product 2a. For the chlorination process, the DMP
reacted with water to produce compound VI (IBX-Ac),18 which act as
active oxidant to oxidize the enolized intermediate I, and the α-keto
radical III is generated through a SET process. The resulting radical III
additional water was introduced in reaction system (entry 27, Table could be further oxidized by FeCl3 to give the product 3a, in which
FeCl3 serves as a ligand transfer reagent.6a, 17a-d
1). In order to further prove the source of hydroxyl group, the isotope
experiment was performed. When the combination of FeCl3 (0.5
equiv) and H2O18 (3.0 equiv) was used under the optimal
hydroxylation reaction conditions, the product 2a-O18 could be
isolated (eq. 1, Scheme 3). This result confirmed that the OH group
was derived from water. While the model reaction was conducted
under air atmosphere, the product 2a was isolated in only 29% yield
(entry 28, Table 1), stating that air suppress obviously the
hydroxylation reaction, hence a radical process maybe involve in this
transformation. Moreover, in the presence of radical scavenger
2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), the desired product
2a or 3a was observed only in trace amount (eq. 2, Scheme 3),
indicating a radical intermediate could be involved in the both of
hydroxylation and chlorination processes. Furthermore, the obvious
substituent effect on the aryl ring demonstrated that the
hydroxylation and chlorination might go through two different
approaches (Scheme 1 and 2). Replacing FeCl3·6H2O with weak Lewis
acid CoCl2·6H2O, CuCl2·2H2O, or NiCl2·6H2O were inefficient for both
of the hydroxylation and the chlorination transformation,14 revealing
that the enolization process would be vital in above two
transformations. Importantly, the replacement FeCl3·6H2O with
FeBr3 and H2O, the hydroxylation product 2a was isolated in 60%
yield under the optimal hydroxylation conditions (eq. 3, Scheme 3),
while the bromation product 416 was also obtained under the optimal
chloronation conditions, albeit with 15% yield. Additionally, o-
iodoxybenzoic acid (IBX) as oxidant couldn’t obviously effect the
Scheme 4. The proposed reaction mechanism.
Conclusions
In summary, we have developed a controllable and direct
FeCl3·6H2O mediated α-hydroxylation/α-chlorination of
benzylketone derivatives through the switch of different
oxidants, in which the FeCl3·6H2O serves as both Lewis acid and
OH or Cl source. The procedure could provide the products
bearing a hetero-quaternary motif in moderate to good yield.
Especially, the crystal water in catalyst as OH source is firstly
reported in the hydroxylation process.
Experimental section
General Information
All solvents were purified using standard techniques and
distilled prior to use. All reagents obtained from commercial
sources and were directly used without further purification,
unless otherwise noted.
All reactions were monitored by thin-layer chromatography
(TLC). Flash chromatography was carried out on 200‒300 mesh
silica gel, eluting with a mixture of petroleum ether (b.p. 60‒
90 °C) and ethyl acetate or petroleum ether (b.p. 60‒90 °C) and
dichloromethane, unless otherwise noted.
Scheme 3. Some control experiments.
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+
1H NMR and 13C NMR spectra were recorded in CDCl3 solution (12); HRMS (ESI) m/z calculated for C12H17BrO2N [M+NHVie4w]A2rt8ic6le.0O4n3lin7e,
DOI: 10.1039/C6OB01733A
on 400 spectrometer or a 300BB spectrometer. Coupling found 286.0433.
constants (J) were reported in hertz (Hz). Electron ionization 2-hydroxy-2-(3-methoxyphenyl) cyclohexan-1-one (2e). 48% yield,
mass spectra (EI-MS) were measured on a spectrometer by 21.2 mg, colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.33-7.29 (m, 1 H),
direct inlet at 70 eV and signals were given in m/z with relative 6.89-6.85 (m, 3 H), 4.50 (s, 1 H), 3.80 (s, 3 H), 3.00-2.95 (m, 1 H), 2.55-
intensity (%) in brackets. High-resolution mass spectra (HRMS) 2.40 (m, 2 H), 2.08-2.02 (m, 1 H), 1.88-1.67 (m, 4 H); 13C NMR (100
were measured on a Mass Spectrometer by means of the ESI MHz, CDCl3): δ 212.7, 160.3, 141.5, 130.3, 118.7, 113.5, 112.5, 80.0,
technique. High Performance Liquid Chromatography (HPLC) 55.4, 39.0, 38.9, 28.4, 23.2; MS (EI) m/z (%): 55 (100), 65 (27), 77 (58),
equipped with a UV-detector.
Preparation of substrates
107 (42), 135 (94), 150 (64), 163 (83), 192 (47), 220 (34); HRMS (ESI)
m/z calculated for C13H16O3Na [M+Na+] 243.0992, found 243.0989.
Besides commercially available 2-phenylcyclohexan-1-one, 2- 2-(benzo[d][1,3]dioxol-5-yl)-2-hydroxycyclohexan-1-one (2f). The
(3-methoxyphenyl)cyclohexan-1-one, 2,6-diphenylcyclohexan- reaction was performed at 18oC. 50% yield, 23.4 mg, colorless oil. 1H
1-one, 1-methyl-3,4-dihydronaphthalen-2(1H)-one and 2- NMR (400 MHz, CDCl3): δ 6.83-6.75 (m, 3 H), 5.97 (s, 2 H), 4.45 (s, 1
benzoylcyclohexan-1-one, other substrates were prepared H), 2.93-2.89 (m, 1 H), 2.54-2.43 (m, 2 H), 2.09-2.03 (m, 1 H), 1.87-
according to the reported procedures.19-26
General Hydroxylation Procedure.
1.69 (m, 4 H); 13C NMR (100 MHz, CDCl3): δ 212.7, 148.5, 147.6, 134.0,
120.2, 108.8, 107.0, 101.4, 79.9, 39.2, 38.9, 28.4, 23.2; MS (EI) m/z
Under an argon atmosphere, to a stirred suspension of 2- (%): 55 (50), 65 (33), 91 (22), 149 (100), 164 (73), 177 (60), 206 (35),
phenylcyclohexan-1-one (34.9 mg, 0.20 mmol), DDQ (45.4 mg, 234 (34); HRMS (ESI) m/z calculated for C13H14O4Na [M+Na+]
0.20 mmol, 1.0 equiv) and FeCl3·6H2O (27.0 mg, 0.10 mmol, 0.5 257.0784, found 257.0782.
equiv) in DCE (2.0 mL) was added acetic acid (11.4 μL, 0.20 mmol, 2-hydroxy-2-(naphthalen-1-yl)cyclohexan-1-one (2h). The reaction
1.0 equiv) at room temperature, then the mixture was stirred at was performed at 0 oC. 34% yield, 16.5 mg, colorless oil. 1H NMR (400
55 °C. After the starting material disappeared, the reaction MHz, CDCl3): δ 7.96-7.94 (m, 1 H), 7.87-7.85 (m, 2 H), 7.81-7.79 (m, 1
mixture was allowed to cool to room temperature, and diluted H), 7.53-7.44 (m, 3 H), 4.61 (s, 1 H), 3.30-2.48 (m, 1 H), 2.47-2.44 (m,
with 1.0 mL petroleum ether. The crude product was directly 1 H), 2.26-2.19 (m, 1 H), 2.10-2.05 (m, 1 H), 1.98-1.76 (m, 4 H); 13C
purified by flash column chromatography with petroleum NMR (100 MHz, CDCl3): δ 216.2, 134.9, 134.1, 132.0, 129.9, 129.2,
ether/ethyl acetate as eluent to afford the desired product 2a
.
126.8, 125.84, 125.80, 124.9, 124.8, 82.0, 43.6, 39.4, 30.3, 23.7; MS
2-hydroxy-2-phenylcyclohexan-1-one (2a).5c 73% yield, 27.8 mg, (EI) m/z (%): 127 (38), 141 (29), 155 (100), 165 (42), 183 (43), 212 (27),
1
colorless oil. H NMR (400 MHz, CDCl3): δ 7.41-7.38 (m, 2 H), 7.34- 240 (28); HRMS (ESI) m/z calculated for C16H16O2Na [M+Na+]
7.30 (m, 3 H), 4.48 (s, 1 H), 3.02-2.98 (m, 1 H), 2.56-2.52 (m, 1 H), 263.1043, found 263.1040.
2.47-2.39 (m, 1 H), 2.09-2.03 (m, 1 H), 1.90-1.82 (m, 2 H), 1.81-1.68 2-hydroxy-2-(naphthalen-2-yl)cyclohexan-1-one (2i). 44% yield,
(m, 2 H); 13C NMR (100 MHz, CDCl3): δ 212.9, 140.1, 129.3, 128.5, 21.2 mg, colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.88-7.81 (m, 4 H),
126.5, 80.2, 39.1, 39.0, 28.5, 23.2; MS (EI) m/z (%): 55 (42), 77 (72), 7.52-7.50 (m, 2 H), 7.37-7.34 (m, 1 H), 4.61 (s, 1 H), 3.17-3.13 (m, 1
91 (28), 105 (81), 120 (100), 190 (24).
H), 2.60-2.55 (m, 1 H), 2.50-2.42 (m, 1 H), 2.09-2.04 (m, 1 H), 1.99-
2-(4-fluorophenyl)-2-hydroxycyclohexan-1-one (2b). 60% yield, 25.1 1.75 (m, 4 H); 13C NMR (100 MHz, CDCl3): δ 213.0, 137.3, 133.4, 133.1,
1
mg, colorless oil. H NMR (400 MHz, CDCl3): δ 7.30-7.27 (m, 2 H), 129.3, 128.4, 127.7, 126.8, 126.6, 125.7, 124.2, 80.3, 39.13, 39.07,
7.10-7.06 (m, 2 H), 4.51 (s, 1 H), 2.97-2.93 (m, 1 H), 2.56-2.52 (m, 1 28.5, 23.3; MS (EI) m/z (%): 127 (50), 141 (21), 155 (92), 170 (78), 183
H), 2.44-2.36 (m, 1 H), 2.11-2.04 (m, 1 H), 1.91-1.83 (m, 2 H), 1.77- (100), 212 (50), 240 (36); HRMS (ESI) m/z calculated for C16H16O2Na
1.71 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ 212.6, 162.2 (d, J = 246 [M+Na+] 263.1043, found 263.1041.
Hz), 136.0 (d, J = 3 Hz), 128.4 (d, J = 8 Hz), 116.2 (d, J = 22 Hz), 79.6, 2-hydroxy-2,6-diphenylcyclohexan-1-one9 (2j).5f 49% yield, 25.9 mg,
39.2, 38.9, 28.5, 23.2; MS (EI) m/z (%): 123 (53), 138 (40), 151 (100), colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.47-7.43 (m, 2 H), 7.39-
180 (62), 208 (15); HRMS (ESI) m/z calculated for C12H13FO2Na 7.33 (m, 5 H), 7.31-7.27 (m, 1 H), 7.11-7.09 (m, 2 H), 4.64 (s, 1 H),
[M+Na+] 231.0792, found 231.0789.
3.79-3.74 (m, 1 H), 3.17-3.13 (m, 1 H), 2.28-2.22 (m, 1 H), 2.15-1.96
2-(4-chlorophenyl)-2-hydroxycyclohexan-1-one (2c). 67% yield, 30.1 (m, 4 H); 13C NMR (100 MHz, CDCl3): δ 211.7, 140.2, 137.3, 129.5,
mg, colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 8.4 Hz, 2 H), 128.61, 128.56, 127.5, 126.5, 80.5, 53.9, 39.2, 36.4, 22.9; MS (EI) m/z
7.24 (d, J = 8.4 Hz, 2 H), 4.51 (s, 1 H), 2.96-2.91 (m, 1 H), 2.57-2.53 (m, (%): 51 (13), 77 (43), 91 (28), 105 (81), 120 (100), 133 (33), 266 (34).
1 H), 2.43-2.35 (m, 1 H), 2.10-2.05 (m, 1 H), 1.91-1.83 (m, 2 H), 1.77- 2-hydroxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one (2k).27 65%
1.68 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ 212.3, 138.7, 134.4, 129.4, yield, 30.8 mg, colorless oil. 1H NMR (400 MHz, CDCl3): δ 8.19-8.17
128.0, 79.6, 39.1, 38.9, 28.4, 23.2; MS (EI) m/z (%): 111 (11), 139 (61), (m, 1 H), 7.54-7.50 (m, 1 H), 7.41-7.37 (m, 1 H), 7.30-7.26 (m, 5 H),
154 (48), 167 (100), 169 (35), 196 (31), 224 (12); HRMS (ESI) m/z 7.21-7.19 (m, 1 H), 4.20 (s, 1 H), 2.94-2.88 (m, 1 H), 2.76-2.67 (m, 2
calculated for C12H13ClO2Na [M+Na+] 247.0496, found 247.0494.
H), 2.49-2.41 (m, 1 H); 13C NMR (100 MHz, CDCl3): δ 200.9, 144.5,
2-(4-bromophenyl)-2-hydroxycyclohexan-1-one (2d). 64% yield, 141.1, 134.4, 131.8, 129.2, 128.7, 128.3, 127.8, 127.2, 126.2, 77.9,
34.5 mg, colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 8.4 Hz, 36.7, 26.7; MS (EI) m/z (%): 77 (22), 90 (32), 105 (100), 118 (95), 133
2 H), 7.18 (d, J = 8.4 Hz, 2 H), 4.51 (s, 1 H), 2.96-2.91 (m, 1 H), 2.57- (36), 150 (64), 220 (64), 238 (34).
2.53 (m, 1 H), 2.43-2.34 (m, 1 H), 2.10-2.06 (m, 1 H), 1.89-1.82 (m, 2 1-hydroxy-1-methyl-3,4-dihydronaphthalen-2(1H)-one (2l).5a The
H), 1.76-1.70 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ 212.3, 139.2, reaction was performed at rt. 50% yield, 17.5 mg, colorless oil. 1H
132.4, 128.3, 122.6, 79.7, 39.0, 38.9, 28.4, 23.2; MS (EI) m/z (%): 25 NMR (400 MHz, CDCl3): δ 7.67-7.65 (m, 1 H), 7.34-7.30 (m, 1 H), 7.27-
(25), 77 (27), 132 (100), 183 (35), 198 (34), 211 (31), 240 (18), 268 7.24 (m, 1 H), 7.17-7.15 (m, 1 H),3.94 (s, 1 H), 3.35-3.27 (m, 1 H), 3.11-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
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ARTICLE
3.04 (m, 1 H), 2.98-2.91 (m, 1 H), 2.69-2.60 (s, 1 H), 1.55 (s, 3 H); 13
Journal Name
+
C
226 (18); HRMS (ESI) m/z calculated for C12H16ClFVOieNw A[Mrtic+leNOHnl4ine]
DOI: 10.1039/C6OB01733A
NMR (100 MHz, CDCl3): δ 213.1, 140.9, 133.9, 127.81, 127.77, 127.65, 244.0899, found 244.0893.
125.5, 76.2, 33.6, 28.0, 27.9; MS (EI) m/z (%): 77 (28), 91 (46), 105 2-chloro-2-(4-chlorophenyl)cyclohexan-1-one (3c). 63%
(26), 121 (58), 133 (100), 158 (54), 176 (9).
yield, 30.4 mg, amorphous solid. Isolated by HPLC (SunFireTM
2-hydroxy-2-phenylcycloheptan-1-one (2m).28 40% yield,16.2 mg, Prep C18 OBDTM, 10 μm, 19×150mm Column, H2O-CH3CN 60:40,
colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.46-7.44 (m, 2 H), 7.38- 20 mL/min, tr = 59.6 min, 210 nm.). 1H NMR (400 MHz, CDCl3): δ
7.34 (m, 2 H), 7.31-7.27 (m, 1 H), 4.57 (d, J = 1.2 Hz, 1 H), 2.87-2.80 7.38-7.33 (m, 4 H), 2.97-2.92 (m, 1 H), 2.79-2.75 (m, 1 H), 2.49-
(m, 1 H), 2.51-2.46 (m, 1 H), 2.37-2.25 (m, 2 H), 2.05-1.99 (m, 3 H), 2.39 (m, 2 H), 2.10-2.07 (m, 1 H), 1.98-1.97 (m, 1 H), 1.90-1.80 (m,
1.54-1.36 (m, 3 H); 13C NMR (100 MHz, CDCl3): δ 213.9, 141.8, 128.8, 2 H); 13C NMR (100 MHz, CDCl3): δ 203.1, 137.5, 134.7, 128.90,
128.1, 125.9, 82.5, 39.7, 36.6, 30.7, 28.0, 23.8; MS (EI) m/z (%): 55 128.85, 75.7, 41.9, 38.8, 27.3, 22.5; MS (EI) m/z (%): 101 (22), 125
(38), 77 (37), 105 (46), 133 (100), 176 (15), 204 (6).
(100), 153 (52), 179 (43), 198 (40), 242 (30); HRMS (ESI) m/z
1-(9-hydroxy-9H-fluoren-9-yl)ethan-1-one (2n).3g 48% yield, 21.7 mg, calculated for C12H12Cl2ONa [M+Na+] 265.0157, found 265.0153.
colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.75-7.73 (m, 2 H), 7.48- 2-(4-bromophenyl)-2-chlorocyclohexan-1-one (3d). 65%
7.44 (m, 2 H), 7.35-7.31 (m, 4 H), 5.11 (s, 1 H), 1.65 (s, 3 H); 13C NMR yield, 37.1 mg, amorphous solid. Isolated by HPLC (SunFireTM
(100 MHz, CDCl3): δ 207.2, 144.5, 141.6, 130.0, 128.6, 124.0, 120.7, Prep C18 OBDTM, 10 μm, 19×150 mm Column), H2O-CH3CN 60:40,
88.4, 22.6; MS (EI) m/z (%): 152 (28), 165 (15), 181 (100), 199 (18), 20 mL/min, tr = 71.1 min, 210 nm.). 1H NMR (400 MHz, CDCl3): δ
224 (8).
7.53-7.50 (m, 2 H), 7.30-7.27 (m, 2 H), 2.98-2.92 (m, 1 H), 2.78-
2.74 (m, 1 H), 2.49-2.39 (m, 2 H), 2.10-2.07 (m, 1 H), 1.99-1.97 (m,
1 H), 1.90-1.80 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ 203.0,
General Chlorination Procedure.
Under an argon atmosphere, to a stirred suspension of 2- 138.0, 131.9, 129.2, 122.9, 75.7, 41.9, 38.7, 27.3, 22.5; MS (EI) m/z
phenylcyclohexan-1-one (34.9 mg, 0.20 mmol) and DMP (101.8 (%): 102 (60), 115 (100), 128 (65), 179 (43), 169 (60), 244 (88),
mg, 0.24 mmol, 1.2 equiv) in the mixed solvent (EtOAc /AcOH = 288 (62); HRMS (ESI) m/z calculated for C12H12BrClONa [M+Na+]
1:1, 2.0 mL) was added FeCl3·6H2O (108.1 mg, 0.40 mmol, 2.0 308.9652, found 308.9649.
equiv) at room temperature. The mixture was then stirred at 2-chloro-2-(4-nitrophenyl)-3,4-dihydronaphthalen-1(2H)-
this temperature. After the starting material disappeared, the one (3f). 34% yield, 20.6 mg, amorphous solid.1H NMR (400 MHz,
reaction mixture was quenched with a saturated aqueous CDCl3): δ 8.23 (d, J = 8.8 Hz, 2 H), 8.18 (d, J = 8.0 Hz, 1 H), 7.72 (d,
solution of Na2CO3. The mixture was extracted with EtOAc (40 J = 8.8 Hz, 2 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.41 (t, J = 7.6 Hz, 1 H), 7.29
mL × 2) and the combined organic layers were washed (d, J = 7.6 Hz, 1 H), 3.47-3.39 (m, 1 H), 3.00-2.90 (m, 2 H), 2.76-
successively with water and brine, dried over Na2SO4, filtered, 2.70 (m, 1 H); 13C NMR (100 MHz, CDCl3): δ 190.1, 147.8, 146.5,
and concentrated under vacuum. The mixture was preliminarily 142.7, 134.6, 130.4, 129.4, 129.0, 128.7, 127.6, 123.5, 72.3, 39.5,
purified by flash column chromatography with petroleum 26.5; MS (EI) m/z (%): 90 (38), 118 (100), 266 (15), 301 (28).
ether/ethyl acetate as eluent to afford crude product 3a, and HRMS (ESI) m/z calculated for C16H13ClNO3 [M+H+] 302.0578,
continuously isolated by HPLC with acetonitrile/water as eluent found 302.0574.
to afford the product 3a (27.1 mg, 65% yield, an amorphous 2-chloro-2,6-diphenylcyclohexan-1-one (3g). 36% yield, 20.3
solid). The pure products 3b
same procedure for preparation of 3a, while the pure products 2 H), 7.37-7.30 (m, 5 H), 7.27-7.23 (m, 1 H), 7.18-7.16 (m, 2 H),
3f 3i could be isolated by flash column chromatography with 4.71 (dd, J = 13.6 Hz, J = 5.6 Hz, 1 H), 2.71-2.66 (m, 2 H), 2.52-2.48
petroleum ether/ethyl acetate as eluent.
(m, 1 H), 2.36-2.32 (m, 1 H), 2.12-2.00 (m, 2 H); 13C NMR (100
2-chloro-2-phenylcyclohexan-1-one (3a).29 65% yield, 27.0 mg, MHz, CDCl3): δ 202.9, 139.2, 138.2, 128.9, 128.4, 128.3, 128.2,
amorphous solid. Isolated by HPLC (SunFireTM Prep C18 OBDTM
127.9, 127.3, 75.8, 52.3, 42.0, 35.3, 21.9; MS (EI) m/z (%): 77 (12),
-
3d were obtained through the mg, amorphous solid. 1H NMR (400 MHz, CDCl3): δ 7.48-7.45 (m,
-
,
10 μm, 19×150 mm Column, H2O-CH3CN 60:40, 20 mL/min, tr = 91 (23), 117 (84), 129 (26), 221 (100), 248 (15), 284 (44); HRMS
26.3 min, 210 nm.). 1H NMR (400 MHz, CDCl3): δ 7.41-7.33 (m, 5 (ESI) m/z calculated for C18H17ClONa [M+Na+] 307.0860, found
H), 2.99-2.92 (m, 1 H), 2.89-2.83 (m, 1 H), 2.48-2.41 (m, 2 H), 2.04- 307.0859.
2.00 (m, 1 H), 1.94-1.89 (m, 2 H), 1.86-1.80 (m, 1 H); 13C NMR (100 1-(9-chloro-9H-fluoren-9-yl)ethan-1-one (3h). 87% yield, 42.1
MHz, CDCl3): δ 203.5, 138.7, 128.9, 128.7, 127.2, 41.9, 39.2, 27.5, mg, amorphous solid. 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 7.6
22.8; MS (EI) m/z (%): 77 (32), 91 (93), 103 (50), 115 (87), 129 Hz, 2 H), 7.52-7.47 (m, 4 H), 7.38 (td, J = 7.6 Hz, J = 0.8 Hz, 2 H),
(100), 145 (40), 164 (20), 173 (19), 208 (10).
1.77 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ 198.5, 143.8, 140.6,
2-chloro-2-(4-fluorophenyl)cyclohexan-1-one (3b). 50% 130.4, 129.0, 125.2, 120.9, 78.2, 24.5; MS (EI) m/z (%): 81 (8), 163
yield, 22.7 mg, amorphous solid. Isolated by HPLC (SunFireTM (36), 199 (100), 242 (18); HRMS (ESI) m/z calculated for
Prep C18 OBDTM, 10 μm, 19×150 mm Column, H2O-CH3CN 60:40, C15H11ClONa [M+Na+] 265.0391, found 265.0390.
20 mL/min, tr = 31.3 min, 210 nm.). 1H NMR (400 MHz, CDCl3): δ 2-benzoyl-2-chlorocyclohexan-1-one (3i).8g 80% yield, 37.6
7.41-7.37 (m, 2 H), 7.10-7.06 (m, 2 H), 2.96-2.91 (m, 1 H), 2.82- mg, amorphous solid. 1H NMR (400 MHz, CDCl3): δ 7.98-7.96
2.78 (m, 1 H), 2.51-2.40 (m, 2 H), 2.06-1.81 (m, 4 H); 13C NMR (100 (m, 2 H), 7.57-7.53 (m, 1 H), 7.44-7.40 (m, 2 H), 3.09-3.05 (m,
MHz, CDCl3): δ 203.3, 162.7 (d, J = 247 Hz), 134.8 (d, J = 3 Hz), 1 H), 2.81-2.77 (m, 1 H), 2.25-2.19 (m, 1 H), 2.15-2.09 (m, 1 H),
129.3 (d, J = 8 Hz), 115.7 (d, J = 21 Hz), 75.8, 42.0, 38.8, 27.4, 22.6; 2.02-1.98 (m, 1 H), 1.94-1.85 (m, 3 H); 13C NMR (100 MHz,
MS (EI) m/z (%): 57 (18), 109 (100), 147 (60), 163 (40), 182 (33), CDCl3): δ 203.6, 190.9, 134.4, 133.7, 130.2, 128.7, 77.2, 41.5,
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
Hu, Y. Guan and H. Jiang, Green Chem., 2014, 16, 3729; (k) M.
41.3, 28.5, 23.1. MS (EI) m/z (%): 77 (32), 105 (100), 173
(10), 201 (4), 236 (0.5).
2-bromo-2-phenylcyclohexan-1-one (4).16 15% yield, 7.7 mg,
View Article Online
R. Witten and E. N. Jacobsen, Org. Lett., 2015, 17, 2772; (l) Y.-
F. Liang, K. Wu, S. Song, X. Li, X. HuangDaOnId: 1N0..10Ji3a9o/,C6OOrgB.01L7e3t3tA.,
2015, 17, 876; (m) C. Yin, W. Cao, L. Lin, X. Liu, X. Feng, Adv.
Synth. Catal., 2013, 355, 1924. (n) X. Lin, S. Ruan, Q. Yao, C.
Yin, L. Lin, Xi. Feng, and X. Liu, Org. Lett., 2016, 18, 3602.
(a) J. Suffert, α-heterosubstitued ketones, Science of synthesis
(J. Cossy Ed.), 2004, 26, 869. (b) D. Yang, Y.-C. Yip, J. Chen and
K. K. Cheung, J. Am. Chem. Soc., 1998, 120, 7659; (c) M. G.
amorphous solid. Isolated by HPLC (SunFireTM Prep C18 OBDTM
,
10 μm, 19×150 mm Column, H2O-CH3CN 40:60, 20 mL/min, tr =
6.7 min, 210 nm.).1H NMR (600 MHz, CDCl3): δ 7.43-7.31 (m, 5 H),
3.02-2.95 (m, 2 H), 2.65-2.61 (m, 1 H), 2.51-2.46 (m, 1 H), 2.00-
1.83 (m, 4 H); 13C NMR (150 MHz, CDCl3): δ 202.8, 139.3, 128.7,
128.5, 127.5, 72.5, 42.5, 38.7, 27.3, 23.3; MS (EI) m/z (%): 55
(100), 69 (85), 81 (75), 91 (76), 115 (70), 172 (41), 173 (45).
HRMS (ESI) m/z calculated for C12H13BrONa [M+Na+] 275.0042,
found 275.0043.
6
Banwell and D. W. Lupton, Org. Biomol. Chem., 2005, 3, 213.
W.-j. Chung and C. D. Vanderwal, Angew. Chem. Int. Ed., 2016,
55, 4396.
For selective examples of direct chlorination of benzylic
ketone, see: (a) S. Klimczyk, X. Huang, C. Farès and N. Maulide,
Org. Biomol. Chem., 2012, 10, 4327; (b) Q. Yin, S.-G.Wang, X.-
W. Liang, D.-W. Gao, J. Zheng and S.-L. You, Chem. Sci., 2015,
7
8
6
, 4179; (c) H, Sakurai, I. Kamiya, H. Kitahara, H. Tsunoyama
Acknowledgements
We gratefully acknowledge financial support from the NSFC
(Grant Nos. 21272097, and 21290181.), PCSIRT of MOE (No. IRT-
15R28) and lzujbky-2016-ct02.
and T. Tsukuda, Synlett, 2009, 245. For selective examples of
direct chlorination of 1,3-dicarbonyl compounds, see: (d) M.
Marigo, N. Kumaragurubaran and K. A. Jørgensen, Chem. Eur.
J., 2004, 10, 2133; (e) M. J. Galligan, R. Akula and H. Ibrahim,
Org. Lett., 2014, 16, 600; (f) R. Akula, M. J. Galligan and H.
Ibrahim, Synthesis, 2011, 347; (g) S. Chong, Y. Su, L. Wu, W.
Zhang, J. Ma, X. Chen, D. Huang, K.-H. Wang and Y. Hu,
Synthesis, 2016, 48, 1359; (h) M. L. Meketa, Y. R. Mahajan and
S. M. Weinreb, Tetrahedron Lett., 2005, 46, 4749.
Notes and references
1
For selective reviews: (a) A. Russo, C. D. Fusco and A. Lattanzi,
RSC Adv., 2012, , 385; (b) A. M. R. Smith, and K. K. (M.) Hii,
9
H. Lu, F.-M. Zhang, J.-L. Pan, T. Chen and Y.-F. Li, J. Org. Chem.,
2014, 79, 546.
2
Chem. Rev., 2011, 111, 1637; (c) G. Guillena and D. J. Ramon,
Curr. Org. Chem., 2011, 15, 296; (d) B. Plietker, Tetrahedron:
Asymm., 2005, 16, 3453; (e) J. M. Janey, Angew. Chem. Int. Ed.,
2005, 44, 4292.
10 For selective reviews, see: (a) I. Bauer and H.-J. Knölker, Chem.
Rev., 2015, 115, 3170; (b) N. Guo and S.-F. Zhu, Chin. J. Org.
Chem., 2015, 35, 1383; (c) A. Correa, O. G. Mancheño and C.
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DOI: 10.1039/C6OB01733A
Graph Abstract
A
tunable α-hydroxylation/α-chlorination of benzylketone
derivatives for the construction hetero-quaternary units have
been developed by Iron(III) chloride hexahydrate-mediated
selective transformations.
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