Efficient intermolecular carbon-carbon bond-formation reactions assisted by surface-condensed electrodes

Article abstract of DOI:10.1002/ejoc.201101313

Transient radical cation intermediates generated at electrodes were effectively trapped by reaction partners noncovalently condensed at the surface of an electrode, enabling efficient intermolecular carbon-carbon bond-formation reactions. When the reactio

Full text of DOI:10.1002/ejoc.201101313

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201101313
Efficient Intermolecular Carbon–Carbon Bond-Formation Reactions Assisted
by Surface-Condensed Electrodes
Yohei Okada,[a] Yusuke Yamaguchi,[a] and Kazuhiro Chiba*[a]
Keywords: Electrochemistry / Radicals / Cations / Cycloaddition
Transient radical cation intermediates generated at elec-
densed electrodes, high reaction efficiencies remained even
trodes were effectively trapped by reaction partners nonco- in the presence of a significantly smaller amount of olefin
valently condensed at the surface of an electrode, enabling
efficient intermolecular carbon–carbon bond-formation reac-
tions. When the reactions were conducted with surface-con-
nucleophiles. The concept of surface-condensed electrodes
could offer opportunities for rapid intermolecular reactions.
tional group transformations, but also carbon–carbon
bond-formation reactions. We have previously developed
electron-transfer-induced intermolecular carbon–carbon
bond-formation reactions.[6] When such intermolecular re-
actions are addressed, reaction partners noncovalently con-
densed at the electrode surfaces would be efficient to trap
transient intermediates generated at the electrodes
(Scheme 1).
Introduction
Intermolecular reactions are triggered by the collision of
reaction component molecules of which the efficiency is es-
sentially dependent upon the homogeneity of the reaction
solution. Several mixing techniques have been established
to achieve such homogeneity and realize effective intermo-
lecular reactions. In this context, the concept of “flash
chemistry” has been proposed, where extremely fast reac-
tions occur by utilizing microreactors that can benefit from
rapid mass and thermal transfer better than conventional
macroreactors, which leads to enhancement in both the ki-
netics and selectivity of chemical transformations.[1] Micro-
reactors have also been well combined with continuous flow
systems to direct multistep chemical processes.[2] In particu-
lar, flash chemistry enables the use of transient intermedi-
ates prior to their decomposition, because the residence
times can be controlled in the range of milliseconds to sec-
onds by simply adjusting the flow rates and length of the
microchannels.
Scheme 1. Concept of surface-condensed electrodes.
On the other hand, several types of heterogeneous reac-
tion fields have been created to offer unique opportunities
for intermolecular reactions. Both supramolecular[3] and
micellar systems[4] have been noncovalently constructed to
facilitate various intermolecular reactions in their cavities
or at their surfaces. Electrochemical approaches have also
been employed to regulate chemical transformations at the
surfaces of electrodes.[5] From the synthetic aspect, an elec-
trochemical approach can be used to generate transient in-
termediates such as ions, radicals, or radical ions through
electron transfer at the electrodes to afford not only func-
Results and Discussion
The present work began with investigation of an appro-
priate model to demonstrate the concept of surface-con-
densed electrodes. For this purpose, the electron-transfer-
induced intermolecular [2+2] cycloaddition reaction be-
tween 1-(prop-1-en-1-yloxy)-4-propylbenzene (1) and hex-
5-enoic acid (2) in LiClO4/CH3NO2 (LPC/NM) electrolyte
solution was selected. In this reaction, the anodically gener-
ated transient radical cation of 1 is trapped by 2 to give
the corresponding [2+2] cycloadduct 3 in good yield as a
diastereomeric mixture (Scheme 2). The radical cation of 1
[a] Department of Applied Life Science,
Tokyo University of Agriculture and Technology,
3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
Fax: +81-42-360-7167
has
a short lifetime; therefore, an excess amount
E-mail: chiba@cc.tuat.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101313.
(20 mol equiv., 200 mm) of 2 was essential for effective trap-
ping. The yields of 3 decreased rapidly in response to the
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243

Y. Okada, Y. Yamaguchi, K. Chiba
SHORT COMMUNICATION
amount of 2, whereas the use of a higher concentration of Table 1. Electron-transfer-induced intermolecular [2+2] cycload-
dition reaction between 1-(prop-1-en-1-yloxy)-4-propylbenzene (1)
1 resulted in a dimerization reaction. Following these re-
and hex-5-enoic acid (2) with the use of surface-condensed elec-
sults, we attempted to design the surface-condensed condi-
trodes.
tions at the electrodes. To this extent, a multiphase reaction
solution was formed by the combination of a large amount
of cyclohexane (c-Hex) and a small amount of LPC/NM
electrolyte solution, in which the electrodes were soaked
(Scheme 3). Less polar c-Hex and polar LPC/NM electro-
lyte solutions were immiscible, forming a multiphase reac-
tion solution and 2 was expected to selectively dissolve into
a polar electrolyte solution due to its free carboxyl group;
therefore, 2 might be condensed at the surface of the elec-
trodes.
Reaction partner 2
Yield [%]
[equiv.]
Conventional[a]
Surface condensed[b]
20
5
2
71
8
6
85
63 (65)
37 (72)
[a] Yield using monophasic electrolysis. [b] Yield using multiphasic
electrolysis (based on consumed starting material).
Subsequently, the electron-transfer-induced intermo-
lecular [2+2] cycloaddition reaction between 1 and hex-5-
en-1-ol (4) in LPC/NM electrolyte solution was attempted
(Scheme 4). Although the anodic oxidation of 1 in the pres-
ence of an excess amount (20 mol equiv., 200 mm) of 4 gave
the corresponding [2+2] cycloadduct 5 in good yield as a
Scheme 2. Electron-transfer-induced intermolecular [2+2] cycload-
dition reaction between 1-(prop-1-en-1-yloxy)-4-propylbenzene (1)
and hex-5-enoic acid (2).
diastereomeric mixture,
a
relatively small amount
(5 mol equiv.) of 4 was less effective for trapping the tran-
sient radical cation of 1. When this reaction was conducted
with surface-condensed electrodes, 5 was produced in excel-
lent yield as a diastereomeric mixture, even in the presence
of a relatively small amount (5 mol equiv.) of 4 (Table 2).
Furthermore, high reaction efficiency remained even in the
presence of a smaller amount (2 mol equiv.) of 4. In both
cases, more than 99% of 4 was dissolved in a small amount
of the electrolyte solution (ca. 200 mm, respectively), which
indicates that 4 was efficiently condensed at the surface of
the electrodes, whereas more than 95% of 1 was dissolved
in a large amount of c-Hex.
Scheme 3. Surface-condensed conditions based on a multiphase re-
action solution formed by the combination of a large amount of c-
Hex (blue) and a small amount of LPC/NM electrolyte solution
(red).
When the electron-transfer-induced intermolecular [2+2]
cycloaddition reaction between 1 and 2 was conducted with
surface-condensed electrodes, 3 was obtained in high yield
as a diastereomeric mixture (Table 1). It should be noted
that a relatively small amount (5 mol equiv.) of 2 could also
effectively trap the transient radical cation of 1 to afford 3
in good yield as a diastereomeric mixture, which is in
marked contrast to the result achieved through conven-
Scheme 4. Electron-transfer-induced intermolecular [2+2] cycload-
dition reaction between 1-(prop-1-en-1-yloxy)-4-propylbenzene (1)
and hex-5-en-1-ol (4).
With these results in hand, finally the electron-transfer-
tional “nonsurface-condensed” electrolysis. Moreover, the induced intermolecular [2+2] cycloaddition reactions be-
same level of reaction efficiency was maintained even in the tween 1 and hex-5-en-2-one (6) or but-3-en-1-yl acetate (8)
presence of a smaller amount (2 mol equiv.) of 2. In both were attempted with the use of surface-condensed elec-
cases, more than 95% of 2 was dissolved in a small amount trodes (Table 3). Although the polarities of these olefin nu-
of electrolyte solution (ca. 200 mm, respectively), into which cleophiles were expected to be much lower than those of 2
the electrodes were soaked, and therefore, condensed at the or 4, more than 90% (ca. 180 mm) of 6 and 8 were dissolved
surface of electrodes, whereas more than 95% of 1 was dis- in a small amount of electrolyte solution, respectively,
solved in a large amount of c-Hex.
which could still efficiently trap the transient radical cation
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C–C Bond Formation Assisted by Surface-Condensed Electrodes
small amount of 1.0 m LPC/NM electrolyte solution (2–5 mL), in
which carbon felt (CF) electrodes (10 mmϫ10 mm) were soaked
by using an undivided reaction cell capped with a septum. Electrol-
ysis was performed at 1.2 V (vs. Ag/AgCl), which was measured by
cyclic voltammetry with the use of a glassy carbon working elec-
trode, a platinum wire counter electrode, and a Ag/AgCl reference
electrode. After the electrolysis (1–3 F/mol), the reaction mixture
was poured into EtOAc, and the EtOAc solution was successively
washed with brine. The organic layer was dried with anhydrous
MgSO4. After filtration and evaporation under reduced pressure,
the residue was purified by silica gel column chromatography (n-
hexane/EtOAc) to give products. Partition ratios in the multiphase
reaction solution were determined by NMR, based on internal
standards.
Table 2. Electron-transfer-induced intermolecular [2+2] cycload-
dition reaction between 1-(prop-1-en-1-yloxy)-4-propylbenzene (1)
and hex-5-en-1-ol (4) with the use of surface-condensed electrodes.
Reaction partner 4
Yield [%]
[equiv.]
Conventional[a]
Surface condensed[b]
20
5
2
72
17
14
95
97
80 (96)
Supporting Information (see footnote on the first page of this arti-
cle): General information, characterization data, and copies of the
1H NMR and 13C NMR spectra of new compounds.
[a] Yield using monophasic electrolysis. [b] Yield using multiphasic
electrolysis (based on consumed starting material).
of 1. The corresponding cycloadducts 7 and 9 were ob-
tained in good yields as diastereomeric mixtures, respec-
tively, even in the presence of relatively small amounts
(5 mol equiv.) of 6 or 8.
Acknowledgments
This work was partially supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Table 3. Electron-transfer-induced intermolecular [2+2] cycload-
dition reaction between 1-(prop-1-en-1-yloxy)-4-propylbenzene (1)
and hex-5-en-2-one (6) or but-3-en-1-yl acetate (8) with the use of
surface-condensed electrodes.
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[a] Yield using monophasic electrolysis. [b] Yield using multiphasic
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Conclusions
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Received: September 9, 2011
Published Online: November 30, 2011
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Eur. J. Org. Chem. 2012, 243–246