K. Tahara et al.
Journal of Inorganic Biochemistry xxx (xxxx) xxx–xxx
−
3
−1
the disproportionation to the Co(I) species and the dialkylated complex
trap adduct was also observed (g = 2.01, A
N
= 1.37 × 10
cm
,
−
4
−1
(
Eq. (8)) [21]. The B12 model complex 1 does not form a dialkylated
H
A = 2.7 × 10
cm ) as shown in Fig. S2b [30]. These results
complex because of the steric hindrance of the corrin with the cobalt
center during the second alkylation. While the anodic electrochemistry
of the dialkylated complex of 2 is critical for the electrolysis of 3, the
cathodic electrochemistry of the monoalkylated complex of 1 is a key
process in the electrolysis of 3 as discussed below.
imply the involvement of a radical intermediate for the formations of A
and B. This is consistent with a previous study on the radical-involved
reaction of 3 using conventional methods with n-Bu SnH and AIBN,
3
leading the hydrodebromination of the β-carbon of the alkyl bromide 3
as well as the 1,2-phenyl migration in the β-phenyl carbon centered
radical, as expressed in Eq. (9). The present selectivity for B in DMF was
about 27–35% lower than the previous one in benzene in a former study
because DMF is a good hydrogen radical donor [31]. The radical in-
termediate in the present study results from the photolysis or the one-
electron reduction of the monoalkylated complex of 1. This is consistent
with the reported reactivity of alkylcobalamin and derivatives as ra-
dical forming reagents [32].
(
(
6)
7)
(
9)
To obtain a mechanistic insight into the 1-mediated electrolysis of 3
at −2.0 V vs. Ag-AgCl, the electrolysis was carried out in the presence
(
8)
of acetic acid‑d
chromatography and identified as a mixture of C and the carboxylic
ester migrated product containing one deuterium, (H C)CH CD
)(CO ), by NMR. The deuterium incorporation ratio was
9%. This result implies that the protonation of an anionic intermediate
1 3
(CH COOD). The main product was isolated by gas
5 2
C O
2
2
3.2. Controlled-potential electrolysis of 3 mediated by 1
(
C
6
H
5
2 2 5
C H
2
Based on the investigation by cyclic voltammetry, the controlled-
is a possible pathway of the formation of C. The relatively low in-
potential electrolysis of 3 in the presence of a catalytic amount of 1 was
carried out in DMF under several conditions. The products were ana-
lyzed by GC as summarized in Table 2. When the electrolysis was car-
ried out at −1.0 V vs. Ag-AgCl along with light irradiation (Entry 1),
the phenyl migrated product B was obtained in a 24% product ratio,
and the simple reduced product A was obtained as the major product.
When the electrolysis was carried out at −1.5 V vs. Ag-AgCl (Entry 2),
the phenyl migrated product B was also obtained and the product
contribution was not changed. On the other hand, when the electrolysis
was carried out at −2.0 V vs. Ag-AgCl (Entry 3), the conversion of 3
was significantly increased. This is probably because the reactivity of
the Co(III) alkyl intermediate complex varies at the applied potential.
Interestingly, the formation of B decreased and the product ratio of the
carboxylic ester migrated product C was obtained in a 63% product
ratio as the major product. It is noticeable that the selectivity for the
migrating group (phenyl vs. carboxylic ester group) was tuned by
controlling the electrolysis potential.
In our previous 2-mediated electrolysis, the participation of the
anodic process during the 1,2-migration of the carboxylic ester group
was confirmed by the fact that the selectivity for C was enhanced by
removing the cell partition (Entry 5 vs. Entry 6) and was dependent on
the type of the counter (Zn or Pt) electrodes (Entry 5 vs. Entry 7) [21].
This enabled the duet redox process between the reduction of the
monoalkylated complex and oxidation of the dialkylated complex. On
the other hand, during the present 1-mediated electrolysis, the parti-
cipation of the anodic process in the 1,2-migration of the carboxylic
ester group is ruled out because the electrolysis cell was divided into
two internal compartments with a polypropylene membrane.
corporation ratio of the deuterium ion is probably due to the proton-
exchange between CH
proton donation from formic acid formed by the decomposition of DMF
33], and/or the proton donation from the Hofmann elimination of the
n-Bu salt [35]. The participation of the anionic intermediate in the 1,2-
carboxylic ester migration is consistent with our previous study on the
-mediated electrolysis of diethyl 2-bromomethyl-malonate 4 [24,25].
3
COOD and water involved in DMF [33,34], the
[
4
1
Based on previous and present studies, the participation of a radical
intermediate in the 1,2-migration of the carboxylic ester group is ruled
out. Furthermore, we clarified that the key processes of the 1,2-mi-
gration are the electrochemical reactivity of the monoalkylated com-
plexes of 1 as expressed by Eq. (10).
(
10)
Based on the mechanistic investigation, mechanisms at −1.0, −1.5
and −2.0 V vs. Ag-AgCl are proposed as shown in Fig. 3. The electro-
chemically generated Co(I) species of 1 induces the oxidative addition
of the alkyl bromide 3 to the cobalt center with debromination. The
resulting Co(III) monoalkylated complex reacts in three different ways.
(i). Electrolysis −1.0 V vs. Ag-AgCl; upon the light irradiation, the
CoeC bond of the monoalkylated complex is homolytically
cleaved to form 1 and a radical intermediate. The radical inter-
mediate abstracts a hydrogen atom before and after the 1,2-mi-
gration of a phenyl group via a radical mechanism to afford A and
B, respectively.
(
ii). Electrolysis −1.5 V vs. Ag-AgCl; the one-electron-reduction of the
monoalkylated complex results in cleavage of the CoeC bond to
form the Co(I) species and a radical intermediate. The radical
intermediate abstracts a hydrogen atom before and after the 1,2-
migration of a phenyl group via a radical mechanism to afford A
and B, respectively.
3.3. Mechanistic aspects
To obtain a mechanistic insight into the 1-mediated electrolysis of 3
at −1.0 V and −1.5 V vs. Ag-AgCl, the electrolysis in the presence of a
spin trap agent, α-phenyl N-tertiary-butyl nitrone (PBN) (0.83 equiva-
lent vs. 3), was monitored by ESR. When the electrolysis
was carried out at −1.0 V vs. Ag-AgCl along with light irradiation, a
spin trap adduct was observed in the ESR spectrum (g = 2.01,
(
iii). Electrolysis −2.0 V vs. Ag-AgCl; the two-electron-reduction of the
monoalkylated complex results in the cleavage of the CoeC bond to
form the Co(I) species and an anionic intermediate, consistent with
the mass and charge balance. The 1,2-migration of a carboxylic
ester group proceeds via an anionic mechanism to afford C.
−
3
−1
−4
−1
A
N
= 1.37 × 10
cm , A
H
= 2.7 × 10
cm ) as shown in Fig.
S2a. When the electrolysis was carried out at −1.5 V vs. Ag-AgCl, a spin
4