Synthesis of 1,2-diketones by mercury-catalyzed alkyne oxidation

Article abstract of DOI:10.1080/00397911.2021.1946082

The first mercury-catalyzed synthesis of 1,2-diketones by alkyne oxidation has been developed. This inexpensive method extends the potential of mercury catalysis and allows the rapid construction of various 1,2-diketones and α-carbonyl amides in good yields with high functional group tolerance.

Full text of DOI:10.1080/00397911.2021.1946082

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
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Synthesis of 1,2-diketones by mercury-catalyzed
alkyne oxidation
Xiaochuan Mei, Weican Hu, Kexin Gao, Haotian Gao, Chaoyang Wang,
Guoying Qian & Zhouting Rong
To cite this article: Xiaochuan Mei, Weican Hu, Kexin Gao, Haotian Gao, Chaoyang Wang,
Guoying Qian & Zhouting Rong (2021): Synthesis of 1,2-diketones by mercury-catalyzed alkyne
oxidation, Synthetic Communications, DOI: 10.1080/00397911.2021.1946082
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https://doi.org/10.1080/00397911.2021.1946082
Synthesis of 1,2-diketones by mercury-catalyzed
alkyne oxidation
Xiaochuan Mei, Weican Hu, Kexin Gao, Haotian Gao, Chaoyang Wang,
Guoying Qian, and Zhouting Rong
College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, PR China
ABSTRACT
ARTICLE HISTORY
Received 18 April 2021
The first mercury-catalyzed synthesis of 1,2-diketones by alkyne oxi-
dation has been developed. This inexpensive method extends the
potential of mercury catalysis and allows the rapid construction of
various 1,2-diketones and a-carbonyl amides in good yields with
high functional group tolerance.
KEYWORDS
Alkyne oxidation;
1,2-diketones;
Mercury catalysis
GRAPHICAL ABSTRACT
Introduction
1,2-Diketones are important building blocks for the construction of many organic
compounds, including a variety of bioactive molecules[1] and natural products.[2]
Huge efforts have been made by chemists to develop methods for the synthesis of
1,2-diketones.[3] Among them, direct oxidation of alkynes has become one of the most
[4]
[6]
studied approaches. Strong oxidants such as KMnO4, oxone,[5] RuO4 and organic
peracids[7] were found to be effective in converting alkynes into 1,2-diketones.
Transition metals such as Au,[8] Pd,[9] Ru[10] and Cu[11] also play major roles in this
transformation, which allow the alkynes to be oxidized by weak oxidants (Scheme 1(a)).
Photochemical or electrochemical methods have also been developed to realize this
transformation.[12]
Mercuric salts are known to be inexpensive transition-metal compounds to effectively
activate alkynes.[13] Jung and coworkers employed stoichiometric mercuric salts as the
oxidant to synthesize 1,2-diketones from internal alkynes (Scheme 1(b)).[14] However, to
CONTACT Guoying Qian
qiangy@zwu.edu.cn; Zhouting Rong
zrong@zwu.edu.cn
College of Biological and
Environmental Sciences, Zhejiang Wanli University, Ningbo, PR China
Supplemental data for this article can be accessed on the publisher’s website.
ß 2021 Taylor & Francis Group, LLC

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X. MEI ET AL.
Scheme 1. Previous work on the synthesis of 1,2-diketones and our work.
the best of our knowledge, mercuric salt has never been used as the catalyst
to transform alkynes into 1,2-diketones. Herein, we report the first mercury-catalyzed
synthesis of 1,2-diketones by alkyne oxidation.
Results and discussion
Our studies commenced with the use of diphenylacetylene 1a as the substrate and
the results were listed in Table 1. When exposing 1a to 10 mol% of Hg(OTf)2 in
dimethyl sulfoxide at room temperature, our desired product 1,2-diketone 2a could
be obtained in 29% yield, with 62% of 1a recovered (entry 1). In this transform-
ation, DMSO served both as the solvent and the oxidant. No better conversion of
1a could be observed after we increased the temperature or catalyst loading. Then
we turned our attention to the screening of oxidants. Sulfoxides 3a–d with different
substituents on the phenyl rings were examined and 2a could be isolated in moder-
ate yields with full consumption of starting material (entries 2–5). We then focused
on pyridine N-oxides, which are commonly used weak oxidants for the oxidation of
alkynes. 2.1 equivalents of 4a in a solution of Hg(OTf)2 (10 mol%) and 1a (1.0 eq)
in CH2Cl2 afforded 2a in 60% yield (entry 6). The yield of 2a could be further
improved when halo-substituted pyridine N-oxides 4c-f were employed (entries
8–11), with 2-Cl-pyridine N-oxide 4c giving the best yield (82%). The effect of solv-
ent in this transformation was also checked and we were excited to find that when
CH3CN was used as the solvent, 2a could be obtained in 95% yield (entry 15).
However, the replacement of 4c with O2 as the oxidant led to no formation of 2a,
with 87% of the starting material recovered (entry 16).

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Table 1. Optimization of the reaction conditionsa.
Entry
Oxidant
Solvent
Yield (%)b
1c
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
DMSO
3a (R ¼ H)
DMSO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
Toluene
THF
CH3CN
CH3CN
29
46
42
40
51
60
55
82
76
80
73
80
79
48
95
0
3b (R ¼ Me)
3c (R ¼ OMe)
3d (R ¼ Cl)
4a (R ¼ H)
4b (R ¼ 2-Me)
4c (R ¼ 2-Cl)
4d (R ¼ 2-Br)
4e (R ¼ 2,6-Cl2)
4f (R ¼ 3,5-Br2)
4c
4c
4c
4c
O2 (balloon)
aReaction conditions: 1a (0.2 mmol), Hg(OTf)2 (0.02 mmol) and 3 or 4 (0.42 mmol) were dissolved in solvent (1 mL) and
the solution was stirred at 23 ꢀC for 3 h.
bIsolated yield.
cReaction time ¼ 24 h.
With the optimal conditions in hand, we decided to test the generality of the method
on a variety of diarylacetylenes. To our delight, this transformation exhibited high func-
tional group tolerance (Table 2). Benzils 2b–d with a Me group at the different posi-
tions of the phenyl ring could be obtained under our standard conditions in 86–92%
yield. Substrates 1e–g bearing electron-rich aromatic rings also gave corresponding
products 2e–g in excellent yields. Cl atom was found to be tolerated in this reaction (2h
and 2i) and substrates bearing electron-withdrawing groups such as CO2Me and NO2
furnished benzils 2j and 2k with a slight decrease of yield. Furthermore, diarylacetylenes
1l–q with substituents on both aromatic rings reacted smoothly to produce benzils 2l–q
after treatment with the standard conditions. Next, we checked our reaction conditions
on substrates with heteroaromatic rings or alkyl groups. We are excited to find that
thienyl phenylacetylene 1r gave 1,2-diketone 2r in 87% yield. The indole moiety can
also survive from our oxidative conditions and corresponding product 2s can be
obtained in 84% yield. However, when substrates with one or two alkyl groups were
used, no desired product was detected, which indicated that alkyl acetylenes are not
appropriate substrates for this method.

4
X. MEI ET AL.
Table 2. Hg(OTf)2-catalyzed synthesis of 1,2-diketones 2b-qa,b
.
aReaction conditions: 1 (1.0 mmol), 4c (2.1 mmol) and Hg(OTf)2 (0.1 mmol) were dissolved in CH3CN (5 mL) and the
solution was stirred at 23 ꢀC for 3 h.
bIsolated yields of 2 are presented.
We then decided to explore more possibilities of our method and various ynamides
were employed. In all cases, after treatment with our standard conditions, the substrates
were transformed into corresponding a-carbonyl amides in good yields (Table 3). Tosyl
ynamides bearing phenyl rings with substituents such as Cl, NO2, Me and OMe all
reacted well to give products 4a–e in 78–94% yield. The reactions of 3f–j with substi-
tuted groups such as 4-nitrobenzenesulfonyl (Ns), methanesulfonyl (Ms), Et and Ph also
proceeded smoothly to furnish corresponding a-carbonyl amides 4f-j in 87–95% yield.
A possible mechanism of this reaction is then proposed (Scheme 2). At the outset,
substrate 1 can be activated by Hg(OTf)2 and attacked by 2-Cl-pyridine N-oxide to

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5
Table 3. Hg(OTf)2-catalyzed synthesis of a-carbonyl amides 4a-ja,b
.
aReaction conditions: 3 (1.0 mmol), 4c (2.1 mmol) and Hg(OTf)2 (0.1 mmol) were dissolved in CH3CN (5 mL) and the solu-
tion was stirred at 23 ꢀC for 3 h.
bIsolated yields of 4 are presented.
Scheme 2. Possible reaction mechanism.

6
X. MEI ET AL.
afford intermediate A. Intermediate A can behave as an electrophilic enolate and
nucleophilic attack by another 2-Cl-pyridine N-oxide takes place to deliver intermediate
B. A subsequent attack by OTfꢁ would give 1,2-diketone 2, liberating Hg(OTf)2 for the
next catalytic cycle.
Experimental procedure
Representative procedures for the synthesis of 1,2-diketones––-synthesis of 2a
To a solution of 1a (178.2 mg, 1 mmol) and 2-Cl-pyridine N-oxide (272.1 mg, 2.1 mmol)
in CH3CN (5 mL) was added Hg(OTf)2 (49.9 mg, 0.1 mmol) and the mixture was stirred
at 23 ꢀC for 3 h. The solvent was evaporated and the residue was purified by flash col-
umn chromatography (hexane/EtOAc 20:1) to give 2a (199.7 mg, 95%). 1H NMR
(400 MHz, CDCl3) d 8.03 ꢁ 7.94 (m, 4H), 7.72 ꢁ 7.61 (m, 2H), 7.56 ꢁ 7.47 (m, 4H). 13C
NMR (101 MHz, CDCl3) d 194.59, 134.91, 132.99, 129.91, 129.04. HRMS-ESI calculated
for C14H11O2 [M þ H]þ: 211.0758; found: 211.0754.
Conclusions
In conclusion, we have reported the first mercury-catalyzed synthesis of 1,2-diketones
by alkyne oxidation. This inexpensive method extends the potential of mercury catalysis
and allows the rapid construction of various 1,2-diketones and a-carbonyl amides in
good yields with high functional group tolerance, which makes it a competitive choice
for the synthesis of these compounds.
Funding
This work was supported by the Natural Science Foundation of Zhejiang Province
[LQ21B020010], Scientific Research Fund of Zhejiang Provincial Education Department
[Y201942345], the Natural Science Foundation of Ningbo [2019A610193], the Zhejiang Provincial
Top Key Discipline of Bioengineering [ZS2017014].
ORCID
Zhouting Rong
http://orcid.org/0000-0001-7811-4890
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