Iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with KOAc: Synthesis of α-acetoxy aryl ketones via a Michael-like addition process

Article abstract of DOI:10.1016/j.cclet.2010.11.022

A novel and convenient iron-catalyzed ketonization of 2-aryl-1,1- dibromoalkenes with KOAc has been achieved. A series of α-acetoxy aryl ketones were prepared with moderate yields via 2-carbon position functionalization of 2-aryl-1,1-dibromoalkenes.

Full text of DOI:10.1016/j.cclet.2010.11.022

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 571–574
www.elsevier.com/locate/cclet
Iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with
KOAc: Synthesis of a-acetoxy aryl ketones via a
Michael-like addition process
a
b
Ming Zhao a, Chun Xiang Kuang a, , Xue Zhi Cheng , Qing Yang
*
a Department of Chemistry, Tongji University, Shanghai 200092, China
b Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai 200433, China
Received 14 September 2010
Available online 3 March 2011
Abstract
A novel and convenient iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with KOAc has been achieved. A series of a-
acetoxy aryl ketones were prepared with moderate yields via 2-carbon position functionalization of 2-aryl-1,1-dibromoalkenes.
# 2010 Chun Xiang Kuang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Iron catalyst; Ketonization; Dibromoalkene; a-Acetoxy ketone; Potassium acetate
Ketonization of olefins and alkynes is a very important strategy to import carbonyl in organic synthesis. Transition
metal oxides are prevalent and effective ketonization reagents for unsaturated compounds. Bernd reported RuO4-
catalyzed selective oxidations of C–C double bonds to a-hydroxy ketones [1] and ketohydroxylation of 1-aryl-1-
alkenes with H2O2 catalyzed by 12-tungstophosphoric acid/cetylpyridinium chloride system [2]. Metal-catalyzed
ketonization of C–C triple bonds is a dominant strategy for oxidation of alkynes. Originally the use of
(cetylpyridinium)3PM12O40 (M = Mo(VI), W(VI)) [3a] and (2,6-dicarboxylatopyridine) iron(II) [Fe(DPA)] [3b] was
reported. Yamamoto and co-workers [3c] developed palladium-catalyzed hydroamination of alkynes affording
ketones or aldehydes. Gold-catalyzed intramolecular acyl migration via nucleophilic attack of carbonyl to triple bond
was reported later [3d–f]. Nonetheless, it is worth noting that catalysts used in the above methods are either expensive
or bearing complicated structure.
Although many reports on C–Br bonds activation of 2-aryl-1,1-dibromoalkenes have been reviewed [4],
ketonization of 2-carbon position of 2-aryl-1,1-dibromoalkenes has rarely been reported except the synthesis of aryl
methyl ketones mediated by zinc in near-critical water at a high temperature of 548 K [5]. This method is bound to be
confined because of its harsh reaction conditions. To the best of our knowledge, however, transition metal-catalyzed
ketonization on 2-carbon position of 2-aryl-1,1-dibromoalkenes has not been reported previously.
Herein, we developed a novel iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with KOAc and
synthesized a variety of a-acetoxy aryl ketones (Scheme 1).
* Corresponding author.
E-mail address: kuangcx@tongji.edu.cn (C.X. Kuang).
1001-8417/$ – see front matter # 2010 Chun Xiang Kuang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.11.022

[()TD$FIG]
572
M. Zhao et al. / Chinese Chemical Letters 22 (2011) 571–574
O
Br
[Fe]/ligand
base
Ar
+KOAc
OAc
Ar
Br
Scheme 1. Iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with KOAc.
Table 1
Iron-catalyzed ketonization of 2-aryl-1,1-dibromoalkenes with KOAc.
[TD$INLE]
Entry
[Fe] (20 mol%)/ligand (1 equiv)
Base (2 equiv)
Solvent
Temperature/time
Yield of 2a (%)a
1
2
3
4
5
6
7
FeCl3/acac
FeCl2/acac
FeCl3Á6H2O/acac
Fe(acac)3/acac
–
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
125 8C/8 h
125 8C/8 h
125 8C/8 h
125 8C/8 h
125 8C/8 h
125 8C/12 h
125 8C/6 h
28
26
0
0
0
FeCl3/acac
FeCl3/acac
28
50
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU).
a
Isolated yield.
Table 2
Synthesis of 2a–f from 2-aryl-1,1-dibromoalkenes 1a–f.
Entry
1
Dibromide 1
Product 2
Time (h)
Yield (%)a
50
1a
1b
1c
2a
2b
2c
6
4
6
[TD$INLINE]
[DT$INLE]
2
3
55
52
[TD$INLINE]
[DT$INLE]
[TD$INLINE]
[DT$INLE]
4
5
1d
1e
1f
2d
2e
2f
4
4
6
40
47
67
[TD$INLINE]
[DT$INLE]
[TD$INLINE]
[DT$INLE]
6
[TD$INLINE]
[DT$INLE]
a
Isolated yields.

[()TD$FIG]
M. Zhao et al. / Chinese Chemical Letters 22 (2011) 571–574
573
O
OAc
FeCl3(20 mol%),acac(1.0 equiv)
+
KOAc
Br
DBU(1.0 equiv), DMF,125 oC, 5 h
(5.0equiv)
3
2a
(47% isolated yield)
Scheme 2. Synthesis of 2a from (4-tolyl)ethynyl bromide 3.
At the outset of our studies, 2-(4-tolyl)-1,1-dibromoethylene 1a was chosen as a model substrate to screen suitable
reaction conditions (Table 1). Treatment of 1a and KOAc with FeCl3 in the presence of 2,4-pentanedione, Cs2CO3 in
DMF at 125 8C for 8 h, 2-(4-tolyl)-2-oxoethyl acetate 2a was isolated in 28% yield (entry 1). Encouraged by this
result, other reaction parameters like catalysts and bases were also screened (for some other examples, see supporting
information). The results showed that FeCl2 resulted in a similar yield as FeCl3, FeCl3Á6H2O and Fe(acac)3 did not
show any catalytic activity (entries 2–4). It was worth noting that no desired product was detected when iron catalyst
was absent (entry 5). The bases, such as K2CO3 and DBU were also investigated. Much to our delight, when DBU was
used, 2a was obtained in 50% yield after 6 h (entries 6–7).
Under the optimized conditions, the substrate scope of the reaction was investigated (Table 2, for some other
examples, see supporting information). The ketonization of 2-aryl-1,1-dibromoalkenes bearing both electron-rich
arenes and haloarenes proceeded smoothly. Substrates with electron-donating group on aromatic ring or without
substituent like 1a–c afforded moderate yields of 50–55% (entries 1–3). Substrates with halogen substituent like 1d–f
gave similar yields of 40–67% (entries 4–6).
To elucidate the reaction mechanism of this novel iron-catalyzed ketonization, (4-tolyl)ethynyl bromide 3 was used
instead of 1a under the same reaction conditions. The expected 2a was also obtained in 47% yield (Scheme 2). This
result is a demonstration that elimination of hydrogen bromide from 2-aryl-1,1-dibromoalkenes under base may be
initially attributed to be responsible for whole iron-catalyzed ketonization process.
A plausible mechanism for the ketonization of 2-aryl-1,1-dibromoalkenes is proposed in Scheme 3. Elimination of
dibromide 1 under base condition initially gives alkynyl bromide A1, which coordinates with iron(III) catalyst to
afford complex A2. The subsequent Michael-like addition of complex A2 on the triple bond occurs, gives rise to B,
which undergoes nucleophilic attack by acetate anion to form C. The simultaneous nucleophilic substitution of Br by
acetate anion would then give the desired product 2.
In summary, we have developed a novel and convenient protocol on the ketonization of 2-aryl-1,1-dibromoalkenes
with acetate salts catalyzed by iron(III) chloride, which affords a strategy for 2-carbon position functionalization of 2-
aryl-1,1-dibromoalkenes. A Micheal-like nucleophilic addition mechanism is presented for the conversion.
1. Experimental
1H NMR spectra were recorded using a Bruker AM-500 spectrometer.
General procedure for the synthesis of 2a–f: A mixture of 1,1-dibromoalkene 1 (0.3 mmol), KOAc (1.5 mmol),
FeCl3 (0.06 mmol), 2,4-pentanedione (0.3 mmol), DBU (0.6 mmol) and 5 mL of DMF was stirred in a sealing reactor
at 125 8C for 4–6 h. After cooling to room temperature, the reaction mixture was filtered to remove deposit and washed
with ethyl acetate (60 mL). The organic phase was then washed with soft water (3 Â 20 mL) and brine (50 mL), and
[()TD$FIG]
Ln
OAc
Br
H
Br
Br
OAc
Fe
base
Michael-like addition
Br
Ar
Br
Ar
Ar
Ar
A1
A2
1
B
OAc
Ac2O
O
O
OAc
Br
OAc
Ar
Ar
2
C
Scheme 3. Plausible mechanism for the reaction.

574
M. Zhao et al. / Chinese Chemical Letters 22 (2011) 571–574
dried over anhydrous Na2SO4. The solvent was evaporated in vacuum and the residue was purified by silica gel column
chromatography (ethyl acetate/petroleum ether) to afford the title compounds 2a–f [6].
Acknowledgments
The work was supported by Natural Science Foundation of China (No. 30873153), the Key Projects of Shanghai in
Biomedical (No. 08431902700) and the Scientific Research Foundation of State Education Ministry for the Returned
Overseas Chinese Scholars. We would like to thank the Center for Instrumental Analysis, Tongji University, China.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/
j.cclet.2010.11.022.
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[6] 1H NMR spectra were recorded using a Bruker AM-500 spectrometer. 2-(4-Tolyl)-2-oxoethyl acetate 2a. 1H NMR (500 MHz, CDCl3): d 2.23 (s,
3H), 2.43 (s, 3H), 5.32 (s, 2H), 7.28 (d, 2H, J = 7.95 Hz), 7.81 (d, 2H, J = 8.25 Hz). 2-Phenyl-2-oxoethyl acetate 2b. 1H NMR (500 MHz,
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1
7.77 (d, 2H, J = 8.60 Hz). 2-(4-Chlorophenyl)-2-oxoethyl acetate 2e. H NMR (500 MHz, CDCl3): d 2.23 (s, 3H), 5.30 (s, 2H), 7.46 (d, 2H,
J = 8.45 Hz), 7.85 (d, 2H, J = 8.45 Hz). 2-(4-Fluorophenyl)-2-oxoethyl acetate 2f. 1H NMR (500 MHz, CDCl3): d 2.23 (s, 3H), 5.30 (s, 2H),
7.15–7.19 (m, 2H), 7.94–7.97 (m, 2H).