Substrate-Dependent Electrochemical Dimethoxylation of Olefins

Article abstract of DOI:10.1002/adsc.201801173

A general and direct electrochemical dimethoxylation of olefins is reported, which enables a divergent route to different products depending on the structure of olefins. The present protocol features mild conditions and broad substrate scope (49 examples) obviating the usage of transtion-metals and external oxidants. More importantly, to rationalize the divergent route of the transformation, an ionic-like pathway involving carbocation intermediate is proposed and the diverse products is attributed to the different stability of carbocations. (Figure presented.).

Full text of DOI:10.1002/adsc.201801173

Title: Substrate-Dependent Electrochemical Dimethoxylation of Olefins
Authors: Sheng Zhang, Lijun Li, Ping Wu, Pengjuan Gong, Rui Liu, and
Kun Xu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801173
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Substrate-Dependent Electrochemical Dimethoxylation of
Olefins
Sheng Zhang,*a Lijun Li,a Ping Wu,a Pengjuan Gong,a Rui Liub and Kun Xu*a
a
Engineering Technology Research Center of Henan Province for Solar Catalysis, College of Chemistry and
Pharmaceutical Engineering, Nanyang Normal University, Nanyang, 473061 P. R. China
E-mail: shengzhang@nynu.edu.cn; xukun@nynu.edu.cn
b School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032 P. R. China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
strategy towards dioxygenation of olefins (Scheme 1,
Abstract:
A
general and direct electrochemical
dimethoxylation of olefins is reported, which enables a process c), which could obviate the participation of
divergent route to different products depending on the
structure of olefins. The present protocol features mild
conditions and broad substrate scope (49 examples)
obviating the usage of transtion-metals and external
oxidants. More importantly, to rationalize the divergent
route of the transformation, an ionic-like pathway involving
carbocation intermediate is proposed and the diverse
transition-metals and external oxidant.
products is attributed to the
carbocations.
different stability of
Keywords: Electrochemistry; Oxidation; Dimethoxylation;
Olefins;
Scheme 1. Approaches toward the dioxygenation of
olefins
Olefins as one of the most accessible and abundant
chemical feedstocks are considered as appealing
substrates in organic synthesis from an academic and
Recently, electro-oxidation has proved to be a
powerful tool in difunctionalization of alkenes,[7]
especially for the formation of C-O bonds. Very
recently, an efficient electrochemical oxidative
radical oxysulfuration was independently reported by
Lei and Han (Scheme 2a).[8] Notably, a remarkable
breakthrough in the electrocatalytic synthesis of 1,4-
dioxane and 1,4-dioxepane was achieved by Xu et al
(Scheme 2b).[9] Lin also unveiled a prominent work
of electrochemical azidooxygenation of alkenes
(Scheme 2c).[10] Nevertheless, the dimethoxylation of
olefins was still considered as an illusive issue due to
the undesired olefin dimerization.[7],[11] In this context,
a direct electro-oxidation was selected as a strategy to
solve the dimethoxylation of olefins (Scheme 2d).
More importantly, we found that the electrochemical
dimethoxylation delivered different products largely
dependent on the stability of the carbocation
intermediate i (Scheme 2d). It also demonstrated that
the reaction proceed through an ionic-like pathway.
Furthermore, the utility of this efficient protocol
could readily expand to the synthesis of lactones,
industrial
perspective.
Particularly,
direct
dioxygenation of olefins has received tremendous
attention since the pioneering work of Sharpless.[1],[2]
The classical Sharpless asymmetric dihydroxylation
involves the usage of toxic osmium together with
oxidants, which provides the impetus to develop
alternative environmentally benign methods. For
instance, some alternative transition metals, including
ruthenium, manganese, palladium, have been
reported for the dioxygenation of olefins (Scheme 1,
process a).[3] To further improve the process, some
metal-free strategies have also been achieved by
using stoichiometric peroxides, hypervalent iodine
and selenium (Scheme 1, process b).[4] Despite the
tremendous progress, a greener and more practical
dioxygenation method is still highly demanded.
Organic electrochemistry represented as an ideal
synthetic technology has experienced a renaissance,[5]
owning to the reason that electrons can be directly
manipulated via the electrochemical oxidation and
reduction. As our ongoing work on organic
electrosynthesis,[6] we envisaged that direct
electrochemical oxidation might be an appealing
1
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
7 [d,e]
8[d,e]
9[d,f]
60
60
60
guanidine
TMG
-
66/ trace
69/trace
68/trace
lactams and indolines via an intramolecular
difuctionalization of olefins.
[a] Reaction conditions: undivided cell, platium electrodes
(1.5 × 1.5 cm2, J = 8.9 mA/cm2), 1a (0.5 mmol),
CH3CN/MeOH (7/1 mL, v/v), n-Bu4NBF4 (0.8 mmol)
under argon for 2 h, 3.0 F. [b] Isolated yield. 0.5mL H2O
[c]
[d]
was added as an additive. Anhydrous solvent was used.
[e] DBU (0.1 mmol) was added as an additive. Graphite
[f]
electrodes were used.
Table 2. Substrate scope of olefins in the dimethoxylation
of olefins [a]
Scheme 2. Electrooxidative C-O bonds formation of
alkenes
Initially, 1,1-diphenylethylene was selected as a
pilot substrate in the electrochemical dimethoxylation
using platinum plate as electrodes in an undivided
cell under constant current conditions (Table 1).
Increasing reaction temperature could afford the
product 2a with higher yield, albeit with a higher
yield of byproduct 3a (Entry 1-3). To further improve
the reaction performance, the byproduct 3a had to be
suppressed. Interestingly, the generation of 3a was
attributed to water residue in the solvent according to
result of Entry 4. Subsequently, anhydrous solvent
was tested and the dimethoxylated product 2a was
exclusively obtained with a satisfactory yield (Entry
5). Further evaluation on additives showed that DBU
as a base had little effect on the yield of the reaction,
while guanidine and tetramethylguanidine (TMG)
resulted in much lower yields (Entry 6-8). Replacing
the platinum electrodes with graphite electrodes
caused significant erosion on the yield (Entry 9).
[a]
Reaction conditions: undivided cell, platium electrodes
(1.5 × 1.5 cm2, J = 8.9 mA/cm2), 1 (0.5 mmol),
Table 1. Optimization of electrochemical dimethoxylation
n-
CH3CN/MeOH (7/1 mL, v/v), Bu4NBF4 (0.8 mmol) at 60
of olefins [a]
ºC under argon for 2 h, 3.0 F. [b] Lower current density (J =
4.4 mA/cm2) and prolonged reaction time (3h, 2.2 F) were
required. [c] DBU (0.1 mmol) was added as an additive.
Having identified the optimal conditions, a broad
spectrum of olefin was investigated (Table 2). It was
found that the electronic property and the substitution
pattern of 1,1-diphenylethylenes marginally affected
the reaction performance resulting in the
corresponding products (2a-2m) with good yields
(63-89%). Next, 2-substituted propenes were
subjected to the optimal conditions and relative lower
yields were observed (2n-2x), which were partially
due to the volatility of the products. Remarkably, the
Entry
1
2
T/ºC
30
50
60
60
Additive
Yield (2a/3a)[b]
46/n.d.
-
-
-
63/n.d.
65/16
trace/76
80/trace
79/trace
3
4[c]
5[d]
6 [d,e]
H2O
-
DBU
60
60
2
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
substrates 1u and 1v containing multiple reactive
sites were well tolerated in this electrochemical
method, thereby giving the products (2u-2v) with
good selectivity. In the case of substrates containing
fused ring, DBU was added to facilitate the
nucleophilic addition of methanol. Additionally, other
alkyl and cyclo-alkenes were also tested and proved
to be amenable in the reaction (2y-2ae). It was
particularly noteworthy that a radical-clock substrate
type reactions[8b] (2ar-2av) was achieved, which
made this protocol a complementary method to
construct lactones, lactams and indolines. Notably,
ethanol proved to be a compatible nucleophile as well,
although only 32% yield was observed (2as').
Nevertheless, the substrates bearing hydroxyl (1aw)
and amino groups (1ax) failed to give the desired
product.
Furthermore,
the
gram-scale
dimethoxylation of olefins were achieved with a
modified condition delivering the products 2a with
71% yield.
Next, we turned our attention to the mechanism of
the reaction. To elucidate the reaction process, cyclic
voltammetry of the reactants was explored. As shown
in the Figure 1, no significant oxidation peak of
MeOH was observed (curve b) in the potential
window of interest. In contrast, an obvious peak was
observed in the CV of substrate 1a and 1al (curve c,
[12]
1aa proceeded smoothly in this reaction (2aa)
without giving any ring-expansion products. This
result clearly suggests an ionic-like pathway
involving in the reaction. Finally, we found that
trisubstituted olefins were favoured substrates in this
transformation furnishing the dimethoxylated
products with up to 96% yield (2af-2ak).
To further verify the ionic-like pathway, 1,2-
substituted olefins, which could form less stable
carbocations, were explored (Scheme 3). Surprisingly, d). The comparison indicated that olefin can be
the carbocation-initiated semipinacol rearrangement
was observed, thereby giving access to the acetals
(2al-2aq) with moderate yields (45-74%). It showed
that this electrochemical dimethoxylation delivered
different products largely independent of the
substitution pattern of olefins, due to the different
stability of the carbocations.
oxidized more easily than MeOH under the optimized
conditions, which further excluded the possibility to
generate methoxyl radicals in the presence of olefins.
Further kinetic isotope effect studies verified that the
nucleophilic addition of MeOH might not be the rate-
determining step (for details see SI).
Scheme 3. Semipinacol rearrangement in the
electrochemical dimethoxylation
To demonstrate the synthetic utility of the
electrochemical approach, some specific substrates
and the gram-scale reaction were studied. As shown
in the Scheme 4, the olefins (1ar-1av) bearing
nucleophilic reactive sites (COOH, CONHPh, NHTs)
were employed in the reaction. To our delight, a
different regioselectivity compared with the radical
Figure 1. Cyclic voltammograms of substrates: (a)
background (LiClO4 0.1M in CH3CN), (b) MeOH (10
mmol/L), (c) 1a (5 mmol/L), (d) 1al (5 mmol/L).
On the basis of the observation in the reaction and
the CV experiment, a plausible mechanism was
proposed as shown in the Scheme 5. Firstly, anodic
oxidation of alkene produces a radical cation
intermediate (i1), which subsequently undergoes a
nucleophilic addition affording the radical i2.
Secondly, a further oxidation of transient species i2
leads to the generation of carbocation i3, which can
be considered as the major intermediate in the
process due to the fast steps of nucleophilic addition
and radical oxidation. Ultimately, the in-situ
generated carbocation i3 can experience two different
pathways, depending on the stability nature of i3. The
more stable cation bearing multiple substituents
proceeds through a direct nucleophlic addition (path
I), whereas the less stable one proceeds a semipinacol
rearrangement (path II) delivering the acetal product.
Scheme 4. Synthetic utility of the electrochemical
approach
3
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
In conclusion, an electrochemical dimethoxylation
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wide range of alkenes. In this efficient transformation,
an ionic-like pathway involves in the reaction, which
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products can be obtained depending on the
substitution pattern of alkenes.
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Scheme 5. Proposed mechanism
Experimental Section
Electrochemical dimethoxylation of olefins (1a as
example)：An undivided cell was equipped with a magnet
stirrer, platinum plate (1.5×1.5 cm2) electrode, as the
working electrode and counter electrode. The substrate 1,1-
diphenylethylene 1a (90 mg, 0.5 mmol) and electrolyte n-
Bu4NBF4 (263 mg, 0.8 mmol) was added to the anhydrous
solvent CH3CN/MeOH (7/1 mL) under argon atmosphere.
The resulting mixture was allowed to stir and electrolyze at
constant current conditions (J = 8.9 mA/cm2) at 60 ºC for 2
hours. Then the solvent was removed with a rotary
evaporator and the residue was purified by column
chromatography (EA/PE = 1/50-1/30) on silica gel to
afford the desired product (1,2-dimethoxyethane-1,1-
diyl)dibenzene 2a with 80 % yield.
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Acknowledgements
We are grateful to the Natural Science Foundation of China
(21702113, 21602119, U1504208), the financial support from
He’nan Provincial Department of Science and Technology
(182102310608) and acknowledged University Natural Science
Research Project of Anhui Province (KJ2016A334).
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4
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
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5
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10.1002/adsc.201801173
Advanced Synthesis & Catalysis
COMMUNICATION
Substrate-Dependent Electrochemical
Dimethoxylation of Olefins
Adv. Synth. Catal. Year, Volume, Page – Page
Sheng Zhang,* Lijun Li, Ping Wu, Pengjuan Gong
and Kun Xu*
6
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