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DOI: 10.1039/C8CC00794B
COMMUNICATION
Journal Name
applying a low current density (j: 0.7 mA cm‒2) and a small following the loss of a proton. This radical species
amount of electricity (Q: 0.2 F referring ). Table 1 summarizes solvated by HFIP and trapped by another to afford the
the anodic oxidation of isoeugenol using BDD electrodes in intermediate In the solvate structure, the dispersion
A can be
1
1
B
.
HFIP. When the amount of applied charge is fixed at a certain interactions as well as the solvation result in a specific
value, isolated yields tend to decrease with increasing current molecular orientation, probably due to an aromatic donor‒
density (e.g., entries 1 vs. 2). In general, better yields were acceptor interaction between the electron-rich aromatic ring
obtained when applying a lower current density. This might be in
attributed to an over-oxidation of isoeugenol or arrangement leads to the unusual addition onto the exocyclic
intermediate neutral radical species leading to completely C,C double bond. The generated carbon-centered radical does
1 and the electron-deficient ring in A This particular
(1)
different reaction pathways.
undergo hydrogen atom transfer maintaining the radical chain
reaction. The new bond destabilizes the solvate and cyclization
reaction occurs between the aromatic ring and the exocyclic
Table 1 Anodic conversion of isoeugenol (1) using BDD / HFIP system.
methylene carbon of the quinone methide in intermediate
the intermediate Subsequent aromatization reaction
accomplishes α-diisoeugenol ( ). The first C–C bond formation
(addition step, is crucial to control the
stereochemistry of . In this step, the orthogonal approach
B in
j[b]
Q[c]
B.
Entry[a]
2[d]
(mA cm−2)
(F)
2
A
+ 1 → B)
1
2
3
4
5
6
7
8
0.7
0.7
1.4
1.4
2.1
2.1
2.8
2.8
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
57
45
55
41
55
42
52
40
2
would be favored due to an aromatic donor‒acceptor
interaction. The second C–C bond formation proceeds again
with an aromatic donor‒acceptor interaction in the
intermediate
B to form the five-membered ring with α-
configuration. In this cyclization process, the aromatic donor‒
acceptor interaction can be expressed as the Newman
projection in Fig. 3 (inset), in which two methoxy groups face
opposite side to each other.
[a] Reaction conditions: BDD anode and cathode, 5 mL HFIP, 0.09 M N-methyl-
N,N,N-tributylammonium methylsulfate, undivided beaker-type cell, 50 °C.
[b] Current density.
Here, the roles of HFIP are rationalized as follows. First,
[c] Amount of charge referring 1.
[d] Isolated yields.
HFIP strongly enhances the stability of the radical species A
and suppresses carbonization of isoeugenol (1), due to its non-
nucleophilic and protic nature.15 These solvent effects can be
seen in our previous studies of the anodic reactions: homo-
In further experiments, different solvents such as
acetonitrile or dichloromethane were tested. Here, we could
coupling of phenol,19 phenol-arene cross-coupling,20 and N
−N
bond formation.21 Second, HFIP forms a unique hydrogen-
bonding network, where fluorine atoms are excluded and
not observe a complete consumption of isoeugenol (1). This
indicates the unique ability of HFIP as fluorinated solvent to
stabilize radical species.15,16 Addition of small amounts of
strong acid (sulfuric acid or trifluoroacetic acid) did not
improve the situation. However, the small peak derived from
cluster together.22 In this occasion, the radical species
A
forms
small clusters surrounded by the fluorous moieties of HFIP.
Therefore, confinement of in the HFIP solvate cage is
A
supposed to induce the specific molecular orientation that is
favorable to the stereoselective conversion in α-configuration.
In conclusion, we demonstrated the first solvent-directed
stereoselective and electrocatalytic synthesis of α-
diisoeugenol by the anodic oxidation of isoeugenol. Using the
particularly powerful electrolytic system based on the HFIP
solvent and BDD as very stable and inert electrode material is
the key for this stereoselective electrosynthesis.
Electrosynthesis is a sustainable, scalable, and cost-efficient
protocol; a specific catalyst is not required and reagent wastes
can be avoided. In addition, the present work offers new
perspectives for an electro-synthetic strategy toward complex
molecules with stereocenters: electrosynthesis of biologically
active lignan and neolignan compounds by oxidative coupling
of phenolic substrates exhibiting the phenylpropanoid
skeleton. The initiation of the radical chain reaction might be
also achieved photochemically, whereby this finding can be
exploited as well.23
the coupling product of isoeugenol (1) was detected in the GC-
MS (m/z: 328).
Furthermore, electrolysis was carried out not only with
BDD but also with glassy carbon as an electrode material in
HFIP. The stereoselectivity of the anodic conversion is
maintained due to the solvent effect of HFIP, but the yield
obtained is significantly lower (Table S1, ESI†).
Upon isolation of the product we could unequivocally
assign molecular structure of the coupling product. The normal
1D 1H NMR and 13C NMR spectra and the ESI-MS measurement
revealed the
1 represents a diisoeugenol, which was identical
regardless of the electrolytic conditions. As there are four
potential diastereomers of diisoeugenol (Fig. 2), we performed
2D NMR measurements to confirm the stereochemistry of the
product. The obtained NMR spectra were in good agreement
with the reported data,17,18 and the coupling product was
determined to be α-diisoeugenol (
Fig. 3 displays a mechanistic rationale for the anodic
electrocatalytic conversion of isoeugenol using the
BDD/HFIP system. In the initial step, is oxidized at the BDD
2).
(1)
1
anode to generate the corresponding radical species
A
2 | J. Name., 2012, 00, 1-3
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Yamamoto, Takashi
