Metal-free synthesis of ketones by visible-light induced aerobic oxidative radical addition of aryl hydrazines to alkenes

Article abstract of DOI:10.1039/c7gc01083d

A green and cost-effective method has been developed for the conversion of alkenes to ketones under metal-free conditions. The reaction involves the oxidative addition of alkenes with aryl radicals, which are generated by visible-light induced aerobic oxidation of arylhydrazines. The key features of this reaction include broad substrate scope, readily available reagents and amenability to gram-scale synthesis.

Full text of DOI:10.1039/c7gc01083d

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DOI: 10.1039/C7GC01083D
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Metal-free synthesis of ketones by visible-light induced aerobic
oxidative radical addition of aryl hydrazines to alkenes
Ya Ding,a Wenkai Zhang, a Hao Li, Yunge Meng, a Te Zhang, a Qiu-Yun Chen a and Chunyin Zhu*ab
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
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A green and cost-effective method has been developed for the efficiency and generality for the conversion of alkenes to
conversion of alkenes to ketones under metal-free conditions. The carbonyl compounds is highly desirable.
reaction involves the oxidative addtion of alkenes with aryl radicals,
The Wacker-type reactions generally rely on the interaction
which are generated by visible-light induced aerobic oxidation of of palladium(II) salts with the π-orbitals of an alkene, as an
arylhydrazines. The key features of this reaction include broad alternative, visible light photoredox catalysis9 can engage
substrate scope, readily available reagents and amenability to alkenes in single-electron-transfer (SET) processes leading to
gram-scale synthesis.
the functionalization of the double bond in the presence of
radical source. Hydrazines have been reported to generate
radical species by treatment with metallic compounds through
the formation of diazenes.10 However, many of these radical
reactions were carried out in the presence of toxic transition
metals. There are only a few examples using photoredox
catalysts to initiate the formation of radical species from
hydrazines. For example Zhou and Mao reported the use of
organic dye eosin B as an efficient initiator for generation of
radical species from hydrazines upon visible-light irradiation in
the open air, which were trapped by 2-isocyanobiphenyls to
give a series of 6-substituted phenanthridines in good yields.11
We reported a visible-light photocatalytic aerobic oxidation of
hydrazine to diazene followed by its addition to Michael
acceptors to form polysubstituted pyrazoles.12 In this respect
we envision that alkenes could be converted to ketones by
reaction with radicals generated from the oxidation of
hydrazines in the presence of photocatalyst (PC) and dioxygen
(Scheme 1).
Carbonyl groups are important moieties for the construction of
organic targets and synthetic intermediates.1 Alkenes are
extremely abundant chemical feedstocks which are produced in
large quantities from petrochemical sources. As a consequence,
they have been exploited as starting materials for the synthesis
of a wide range of fine chemicals, and the oxidation of alkenes
has evolved to be one of the most straightforward routes for
the synthesis of carbonyl compounds. The industrially
important oxidation of ethylene to acetaldehyde promoted by
the combination of palladium with copper, namely the Wacker
process, represents a milestone of alkene utilization.2-5 Since
the discovery of this process, this Pd/Cu catalyst system has
been extended to the oxidation of diverse terminal olefins
(Wacker–Tsuji oxidation), which provides a powerful method
for the synthesis of methyl ketones.6 More recent
developments in this area have focused on the identification of
new conditions that enable broader substrate scope and
efficient catalytic turnover of the palladium catalyst.7 However,
the Wacker-type reactions generally employs expensive
palladium(II) salts as the catalyst and sometimes high catalyst
loading is required8, leading to cost and environmental
concerns and limiting their practical utility. Hence, the
development of metal-free synthetic methods with improved
a.School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang
212013, PR China. E-mail: zhucycn@gmail.com
b.State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University,
Xiamen 361005, P.R. China.
Scheme 1. Synthetic pathways from alkenes to ketones
† 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
J. Name., 2013, 00, 1-3 | 1
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We initiated our studies by examining the model reaction of desired transformation affording yields greater thVaienw8A0rt%icle(O3nalibne
,
DOI: 10.1039/C7GC01083D
1a and 2a (Table 1). After examining a wide array of reaction 3ad
conditions, we determined that the ketone 3aa can be at the ortho position (3ac
,
3ag
,
3al, and 3am). But when steric pressure was applied
3ae 3af, and 3ah), the yield was
,
,
produced in a good yield (81%) in the presence of methylene reduced by 10% approximately. The electronic nature of the
blue (MB+, 2 mol%), DABCO (1 equiv.), and air (open flask) in substrates was shown to have little influence on the reaction
MeCN at room temperature under the irradiation of 7 W blue efficiency, and styrenes with electron-donating or electron-
LEDs for 8 h (Table 1, entry 1).
withdrawing substituents on the phenyl group could be
converted to corresponding ketones in good to excellent yields
Table 1
.
Effect of Reaction Parameters on the oxidative addition of aryl hydrazines to
(3ag and 3al). Interestingly divinylbenzene substrates could
a
alkenes
react with phenylhydrazine to form mono-ketone selectively in
good to excellent yields (3an and 3ao). Notably β-methyl
styrene also worked smoothly under current conditions
affording a yield of 76%. Furthermore, we turned our attention
to the scope of the aryl hydrazine fragment. As shown in bottom
line of Table 2, different aryl hydrazines are amenable to this
strategy, including those that bearing different groups at
entry
1
2
3
4
5
6
7
8
variation from the standard conditions yield/%b
none
no MB+
81
0
different positions on the aromatic ring (3ba-3bf, 70-86% yield).
And steric effect was observed that ortho-substituted
hydrazines gave slightly lower yields (3bb and 3bc). To
demonstrate the synthetic utilities of this strategy, we also
conducted a gram-scale reaction of 1a and 2a, which provided
3aa in 78% yield.
no visible light
0
rhodamine B, instead of MB+
RuII(bpy)3Cl2.6H2O, instead of MB+
eosin Y, instead of MB+
no DABCO
Cs2CO3, instead of DABCO
Et3N, instead of DABCO
iPr2NEt, instead of DABCO
DBU, instead of DABCO
MeOH, instead of MeCN
CH2Cl2, instead of MeCN
DMSO, instead of MeCN
32
56
65
10
25
51
20
60
58
62
45
a
Table 2. Substrate scope of the oxidative addition of aryl hydrazines to alkenes
9
10
11
12
13
14
aStandard conditions: 0.5 mmol of 1a, 1.5 mmol of 2a, 0.01 mmol of methylene
blue, 0.5 mmol of DABCO, air (open flask), and MeCN (1.5 mL) at room
temperature under the irradiation of 7 W blue LEDs; MB+ = methylene blue,
DABCO = 1,4-Diazabicyclo[2.2.2]octane. bisolated yield
The data in Table 1 illuminated the effect of a variety of
parameters on the reaction efficiency. For example, results of
control experiments showed that photocatalyst and visible light
are essential for this reaction (entries 2−3). Replacing of
methylene blue with other commercially available
photocatalysts (i.e., rhodamine B, RuII(bpy)3Cl2.6H2O and eosin
Y), was deleterious to the product yield (entries 4−6).
RuII(bpy)3Cl2.6H2O and eosin Y possess lower oxidation potential
[e.g., E1/2(PC*/PC−) = +0.77 V for Ru(bpy)32+; E1/2(PC*/PC−) =
+0.83 for eosin Y] than methylene blue [E1/2(PC*/PC−) = +0.97].9
Obviously, it is more difficult for RuII(bpy)3Cl2.6H2O and eosin Y
to oxidize hydrazine in this reaction. On the other hand, removal
of DABCO from the reaction mixture resulted in a decreased
yield (entry 7), indicating that base is necessary for the reaction
to achieve a decent yield. Several bases could promote the
reaction (entries 8−11), and DABCO was found to be the best.
When other solvent, such as MeOH, CH2Cl2 or DMSO, was
employed as the reaction media to replace MeCN, a notable
decrease of yield was observed (Table 1 entries 12-14).
After establishing suitable conditions, the scope of the
reaction in terms of hydrazine and alkene was explored (Table
2). Initially, styrene derivatives with various functional groups
a0.5 mmol of
1, 1.5 mmol of 2, 0.01 mmol of methylene blue, 0.5 mmol of DABCO,
air (open flask), and MeCN (1.5 mL) at room temperature under the irradiation of
7 W blue LEDs; MB+ = methylene blue, DABCO = 1,4-Diazabicyclo[2.2.2]octane. b10
mmol of 1a, 30 mmol of 2a, 0.2 mmol of methylene blue, 10 mmol of DABCO, air
(open flask), and MeCN (30 mL)
on the phenyl ring were investigated (3aa−3ap), and most of the
para-substituted styrene substrates were found to undergo the
2 | J. Name., 2012, 00, 1-3
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To further understand this transformation, Stern-Volmer intermediate 12, followed by its decomposition toVfiienwaAlrtpicrleoOdnulicnet
DOI: 10.1039/C7GC01083D
fluorescence quenching experiments were performed to gain 3aa (path b).
an insight into the photoredox catalytic cycle. The luminescence
of methylene blue with excitation at 664 nm could be readily
Scheme 2. Proposed Mechanism
quenched by 1a following Stern−Volmer kinetics (Figure 1), and
styrene 2a cannot serve as the emission quenchers. This
luminescence quenching is most likely due to photoinduced
electron transfer.
700
600
500
400
300
200
100
0
680
700
720
740
760
780
Wavelength (nm)
2.0
1.8
1.6
1.4
1.2
1.0
y = a + b*x
Equation
0.9979
Adj. R-Square
Value
Standard Error
0.01135
Conclusions
Intercept
Slope
0.98849
B
15622.7106 320.54805
In conclusion, we have developed a metal-free protocol for the
conversion of alkenes to ketones through oxidative radical
addition with arylhydrazines. This reaction avoids the need for
the use of aryldiazonium or diaryliodonium which are unstable
and may cause some cost and environmental concerns. Instead,
by using arylhydrazines as the radical source, this visible-light
induced reaction leads to H2O and N2 as the by-products.
Preliminary mechanistic studies suggested the reaction goes
through VLPC-promoted oxidation of arylhydrazine to aryl
radical followed by its addition to alkenes. Taken together with
its operational simplicity, readily available reagents, broad
substrates scope, and amenability to gram-scale synthesis, this
green reaction will find practical application for the utilization
of alkenes.
0.00000
0.00001
0.00002
0.00003
0.00004
0.00005
0.00006
1a (mol/L)
Figure 1. (up) Luminescence quenching of methylene blue with excitation at 664
nm by 1a. (down) The Stern- Volmer plot.
On the basis of these experimental observations, a plausible
mechanism is proposed (Scheme 2). First, methylene blue is
irradiated to the excited state *MB+ using blue LEDs, and this
excited state is then reductively quenched by 1a with
concomitant generation of ionic radical
radical (MB ). Upon deprotonation, ionic radical
to radical
, which can also quench the excited state *MB+ and
lose a proton to form diazene . Another single-electron
oxidation by *MB+, followed by deprotonation, leads to the
formation of phenyl radical . During the course MB is oxidized
back to MB+ by molecular oxygen which is reduced to
4
and methylene blue
Acknowledgments
We acknowledge the Qing Lan Project of Jiangsu Province and
Jiangsu University Foundation (No. 13JDG059) for finance
support.
•
4
is converted
5
6
8
•
hydroperoxyl radical (HOO
which is generated from the addition of phenyl radical
styrene 2a followed by incorporation of dioxygen, could react
with hydroperoxyl radical to form 11. Then 11 decomposes to
afford the desired product 3aa, along with the formation of
molecular oxygen and water through Russell fragmentation13.
•
). Furthermore, intermediate 10
,
Notes and references
8
to
1
H. Siegel, M. Eggersdorfer, Ullmann’s Encyclopedia of
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Another possible pathway from intermediate
9 to 3aa is the
1
combination of with hydroperoxyl radical to form
9
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DOI: 10.1039/C7GC01083D
Metal-free synthesis of ketones by visible-light induced aerobic
oxidative radical addition of aryl hydrazines to alkenes
Ya Ding,a Wenkai Zhang, a Hao Li, Yunge Meng, a Te Zhang, a Qiu-Yun Chen a and Chunyin
Zhu*ab
aSchool of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
E-mail: zhucycn@gmail.com
bState Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005,
P.R. China