Selective oxygenation of alkynes: A direct approach to diketones and vinyl acetate

Article abstract of DOI:10.1039/c4ob01404a

Arylalkynes can be converted into α-diketones with the use of a copper catalyst, and also be transformed into vinyl acetates under metal-free conditions, both in the presence of PhI(OAc)₂ as an oxidant at room temperature. A series of substituted α-diketones were prepared in moderate to good yields. A variety of vinyl halides could be regio- and stereo-selectively synthesized under mild conditions, and I, Br and Cl could be all easily embedded into the alkynes. This journal is

Full text of DOI:10.1039/c4ob01404a

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Selective oxygenation of alkynes: a direct
approach to diketones and vinyl acetate†
Cite this: DOI: 10.1039/c4ob01404a
Xiao-Feng Xia,* Zhen Gu, Wentao Liu, Ningning Wang, Haijun Wang, Yongmei Xia,
Haiyan Gao and Xiang Liu
Arylalkynes can be converted into α-diketones with the use of a copper catalyst, and also be transformed
into vinyl acetates under metal-free conditions, both in the presence of PhI(OAc)2 as an oxidant at room
temperature. A series of substituted α-diketones were prepared in moderate to good yields. A variety of
vinyl halides could be regio- and stereo-selectively synthesized under mild conditions, and I, Br and Cl
could be all easily embedded into the alkynes.
Received 7th July 2014,
Accepted 9th October 2014
DOI: 10.1039/c4ob01404a
www.rsc.org/obc
Introduction
Alkyne chemistry can be dated back to the early nineteenth
century. From that time, the transformation of alkynes has
been a fundamental method that has been widely used in
organic synthesis.1 Various catalytic systems were developed to
synthesize useful compounds from alkynes. Among these, the
Pd-catalyzed Wacker-type oxidation to generate 1,2-diketones
is one of the most important industrial processes.2 1,2-
Diketones are known as one of the most important skeletons
in biologically active molecules3 and are very useful building
blocks which can easily be transformed into a variety of other
chemicals, especially heterocyclic compounds.4 This fact has
stimulated a growing interest in the development of a large
number of new oxidants and catalytic systems to obtain 1,2-
diketones from alkynes.5 However, these reactions still suffer
from some drawbacks such as harsh conditions, a narrow
substrate scope, and chemo-selectivity. Thus, developing a
mild and efficient protocol for catalytic oxidation of alkynes is
still highly desirable.
Vinyl halides (1-halo-1-alkenes), especially vinyl bromides
and iodides, represent one kind of organic synthetic blocks,
which play important roles in the construction of poly-
substituted alkenes through transition-metal-catalyzed cross-
coupling reactions or halogen-metal exchange reactions.6 Con-
sequently, much attention has been paid to preparing vinyl
halides from different starting materials.7 For instance, the
Jiang group recently reported a silver-catalyzed difunctionali-
Scheme 1 Previous work of halogenation of alkynes.
zation of terminal alkynes to obtain 1-halo-1-alkenes
(Scheme 1a).7b Very recently, the Yanada group reported NIS-
mediated halogenation of alkynes, but only non-terminal
alkynes can be used (Scheme 1b).7c Our group has been com-
mitted to the research on functionalization of alkynes.8 As
a part of this continuing project, herein we found that aryl-
alkynes can be oxidized to 1,2-diketones in the presence of PhI-
(OAc)2 using copper as a catalyst, and when TBAI (tetrabutyl-
ammonium iodide) was used instead of a copper catalyst,
(E)-vinyl halides were prepared in similar reaction systems.
The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education,
School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu
214122, China. E-mail: xiaxf@jiangnan.edu.cn; Fax: +86-510-85917763
†Electronic supplementary information (ESI) available: Experimental procedures
and analysis data for new compounds. CCDC 1002379 for 3e. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c4ob01404a
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Table 1 Optimization of reaction conditions for the difunctionalization of 1,2-diphenylethynea
Entry
Catalyst
Oxidant
Solvent
Yieldb
1
2
3
20% Cu(OAc)2
10% Cu(OAc)2 + 5% Pd(OAc)2
20% Cu(OTf)2
20% Cu(OTf)2
20% Cu(OTf)2
10% Cu(OTf)2
5% Cu(OTf)2
10% Cu(OTf)2
10% Cu(OTf)2
10% Cu(OTf)2
10% [Cu(OTf)]2·Ph
10% Cu(OAc)2
10% Cu(OTf)2
—
2.0 eq. PhI(OAc)2
2.0 eq. PhI(OAc)2
2.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
2.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
3.0 eq. PhI(OAc)2
HFIP
HFIP
HFIP
HFIP
10% 2a
15% 2a
20% 2a
30% 2a
35% 2a
90% 2a
74% 2a
40% 2a
0
81% 2a
50% 2a
10% 2a
0
4
5c
6
HFIP
HOAc–HFIP(1 : 2)
HOAc–HFIP(1 : 2)
HOAc–HFIP(2 : 1)
HOAc
HOAc–HFIP(1 : 2)
HOAc–HFIP(1 : 2)
HOAc–HFIP(1 : 2)
HOAc–HFIP(1 : 2)
HOAc–HFIP(1 : 2)
HOAc–HFIP(2 : 1)
HOAc–HFIP(2 : 1)
HOAc–HFIP(2 : 1)
HOAc–HFIP(2 : 1)
HOAc–HFIP(2 : 1)
7
8
9
10
11
12
13
14
15
16
17
18
19
—
3.0 eq. PhI(OAc)2
2.2 eq. PhI(OAc)2
1.2 eq. TBAI, 2.4 eq. PhI(OAc)2
1.2 eq. TBAI, 3.0 eq. PhI(OAc)2
1.2 eq. TBAI, 1.2 eq. PhI(OAc)2
2.2 eq. TBAI, 2.4 eq. PhI(OAc)2
0
20% TBAI
—
—
—
15% 3a
90% 3a
60% 3a
72% 3a
80% 3a
—
a Reaction conditions: 1a (0.3 mmol), solvent (2.0 mL), at room temperature for 12 h in air. b Isolated yield. c 5 eq. HOAc was used. HFIP =
hexafluoroisopropanol; TBAI = tetrabutylammonium iodide.
Results and discussion
The results from the optimization studies are summarized in
Table 1. Our investigation began with the oxidation of 1,2-
diphenylethyne 1a catalyzed by Cu(OAc)2 using PhI(OAc)2 as
an oxidant in HFIP (hexafluoroisopropanol) at room tempera-
ture. To our delight, the target 1,2-diketones 2a was obtained
(Table 1, entry 1). Consequently, a series of other catalytic
systems were evaluated, wherein Cu(OTf)2 displayed high cata-
lytic activity (entries 1–4). When 5 equivalents of HOAc was
used as an additive, the yield of 2a was increased to 35% (entry
5). So we chose HOAc as a co-solvent, and when a volume ratio
of HOAc : HFIP in 1 : 2 was used, the yield of 2a could reach
90%. However, when the volume ratio of HOAc : HFIP was 2 : 1,
the yield decreased to 40%. Only when HOAc was used as a
solvent, no reaction occurred (entry 9), which meant that HFIP
played an important role in the reaction. In our opinion, HFIP
Scheme 2 Copper-catalyzed synthesis of 1,2-diketones.
can increase the solubility of PhI(OAc)2 in our system, and can
increase the rate of product formation. When 10% [Cu-
(OTf)]2·Ph was tried in our system, a 50% yield was obtained
(entry 11). In addition, in the absence of the copper catalyst or
PhI(OAc)2, no product was detected (entries 13 and 14). When
TBAI was used instead of the copper catalyst, vinyl iodide 3a
was obtained. The yield of 3a could increase to 90%, when 1.2
equivalents of TBAI was used (entry 16). The amounts of TBAI
and PhI(OAc)2 were also screened, and there were no better
results, with 1.2 equivalents of TBAI and 2.4 equivalents of
PhI(OAc)2 being optimal (entries 17–19).
in Scheme 2, a variety of diarylalkynes can easily convert to
the corresponding 1,2-diketones in moderate to good yields.
Several useful functional groups were tolerated, including
chloro, fluoro and ether substituents. The ortho-substituted
substrate gave a lower yield (2e). In addition, the heterocycle-
derived thiophene substrate can be also tolerated in the reac-
tion (2h). It is worth mentioning that 1-phenylpropane-1,2-
dione and 1-phenylbutane-1,2-dione can be synthesized under
these conditions (2i and 2j).
With the optimized conditions in hand (Table 1, entry 6),
the oxidation of arylalkynes was firstly investigated. As shown
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Scheme 3 Control experiment.
Scheme 4 Proposed mechanism.
To study the reaction pathway, one possible intermediate,
deoxybenzoin, was independently synthesized and tested
under the standard conditions and no product was detected,
which meant that the deoxybenzoin was not the intermediate
in this reaction (Scheme 3). On the basis of this result and pre-
vious reports,9 we propose a possible reaction pathway as
shown in Scheme 4. The Cu(II)(OTf)2 is oxidized to the active
Cu(III)(OAc)2(OTf) using the oxidant PhI(OAc)2 which then
coordinates and inserts alkynes forming the intermediate
species iv. Release of A from iv by a SN2-type reductive
elimination leads to Cu(I)OTf, which is oxidized back to
the active Cu(III) species ii by PhI(OAc)2. The reaction of the
intermediate A with acetic acid will then lead to the product
2a. The intermediate A can also react with water to give the
intermediate B, which can convert into the product 2a using
the oxidant PhI(OAc)2.
Scheme 5 Halogenation of arylalkynes.
Next, we went on to study the halogenation of alkynes.
Scheme 5 reveals that the electronic properties of alkyne
substitutions did not show obvious influences on the reaction
efficiency. A series of substituents such as nitro, chloro, fluoro
and ether can be tolerated in the reaction. A series of vinyl
iodides can be obtained in good to excellent yields. It is note-
worthy that only the E-isomer is the major product in most
cases (3a–3i).10 To confirm further the structural assignment
of products under the present oxidative conditions, the struc-
ture of the product 3e was unambiguously assigned by X-ray
crystallography (see the ESI,† Fig. 1).11 The heterocycle-derived
thiophene substrate was also compatible, and the desired
product was isolated in 61% yield (3h). When the alkylated
alkyne such as prop-1-ynylbenzene was used in this system, an
unseparated mixture was obtained. Terminal arylalkynes can
be also involved in this reaction (3j–3m). TBAB (tetrabutyl-
ammonium bromide) and TBAC (tetrabutylammonium
chloride) could afford the corresponding β-haloenol acetates
in moderate to good yields as well (3k and 3l). As the challenging
Fig. 1 The X-ray structure of 3e.
substrates, alkynyl halides, such as alkynyl bromide and
alkynyl iodide, can also react with TBAI or TBAC to obtain
vinyl dihalides in moderate to good yields (3n–3q). Aliphatic
terminal alkynes cannot give any products in this reaction.
According to the above results and the Taniguchi reported
mechanism,12 we proposed a plausible reaction pathway
(Scheme 6). Firstly, AcOI was generated by the reaction
between PhI(OAc)2 and the iodide ion,13 which can work as a
strong electrophile against alkynes to give iodonium ion inter-
mediate C. Then, the nucleophile HOAc attacks the positive
charge density of intermediate C from behind to give the
E-isomer as the major product (Path a). When HOAc attacks
from the front of intermediate C, due to the steric hindrance,
the Z-isomer was obtained as the minor product (Path b).14
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Melting points were determined on a microscopic apparatus
and were uncorrected. All new products were further character-
ized by HRMS (high resolution mass spectra), and high
resolution mass spectrometry (HRMS) spectra were obtained
on a micrOTOF-Q instrument equipped with an ESI† source;
copies of their 1H NMR and 13C NMR spectra are provided.
Commercially available reagents and solvents were used
without further purification.
Typical procedure for the synthesis of product 2
To a solution of 1,2-diphenylethyne (1a, 0.3 mmol, 53.4 mg) in
HOAc–HFIP (V : V = 1 : 2, 2.0 mL) were added Cu(OTf)2
(10.9 mg, 10 mol%) and PhI(OAc)2 (289 mg, 3 equiv.). The reac-
tion mixture was then stirred for 12 h at room temperature in
air. The resulting mixture was quenched with saturated
Na2S2O3 and extracted twice with EtOAc. The combined
organic extracts were washed with brine, dried over Na2SO4
and concentrated. The purification of the crude product
by flash column chromatography afforded the product 2
(petroleum ether–ethyl acetate as an eluent (30 : 1)).
Scheme 6 Proposed mechanism for the formation of vinyl iodide.
Typical procedure for the synthesis of product 3
Scheme 7 Illustrative synthetic transformations.
To a solution of 1,2-diphenylethyne (1a, 0.3 mmol, 53.4 mg)
in HOAc–HFIP (V : V = 2 : 1, 2.0 mL) were added n-Bu4NI
(132.8 mg, 1.2 equiv.) and PhI(OAc)2 (231 mg, 2.4 equiv.). The
reaction mixture was then stirred for 12 h at room temperature
in air. The resulting mixture was quenched with saturated
Na2S2O3 and extracted twice with EtOAc. The combined
organic extracts were washed with brine, dried over Na2SO4
and concentrated. The purification of the crude product
by flash column chromatography afforded the product 3
(petroleum ether–ethyl acetate as an eluent (30 : 1)).
Further synthetic transformations of the haloenol acetate
products were investigated with 3a as a model substrate
(Scheme 7). Take 3a as an example to increase molecular com-
plexity via palladium- and copper-catalyzed Sonogashira reac-
tion with a terminal alkyne affording the corresponding 4a in
50% yield. 4a can undergo a NIS inducing electrophilic cycliza-
tion to generate 3-iodo-2,4,5-triphenylfuran 5a, which is fre-
quently found as a subunit in many bioactive natural products
and pharmaceutically important substances.15
Acknowledgements
Conclusions
We thank the National Science Foundation NSF 21402066, the
Fundamental Research Funds for the Central Universities
(JUSRP11419) and Natural Science Foundation of Jiangsu
Province (SBK201222312 and BK20140139) for financial
support. Financial support from MOE&SAFEA for the 111
project (B13025) is also gratefully acknowledged.
In conclusion, we have developed convenient and expedient
methods for the synthesis of α-diketones and β-haloenol
acetates from arylalkynes using PhI(OAc)2 as an oxidant. In
contrast to previous reports, the (E)-β-haloenol acetates were
obtained regio- and stereo-specifically as the major products in
moderate to good yields. In addition, the (E)-β-haloenol acetate
was briefly transformed to the polysubstituted furans in two
steps.
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Experimental
General information
Column chromatography was carried out on silica gel. Unless
noted 1H NMR spectra were recorded on 400 MHz in CDCl3
and d-DMSO, 13C NMR spectra were recorded on 100 MHz in
CDCl3 and d-DMSO. IR spectra were recorded on an FT-IR
spectrometer, and only major peaks are reported in cm−1
.
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