Electrocatalytic reactivity of imine/oxime-type cobalt complex for direct perfluoroalkylation of indole and aniline derivatives

Article abstract of DOI:10.1039/d0dt01377c

Imine/Oxime-type cobalt complexes, regarded as simple vitamin B₁₂model complexes, were utilized as catalysts for direct C-H perfluoroalkylations of indole and aniline derivatives with nonafluorobutyl iodide (n-C₄F₉I) as the readily available perfluoroalkyl source. The synthetic approach described herein was performed under mild reaction conditions driven by controlled-potential electrolysis at ?0.8 Vvs.Ag/AgCl in organic solvents. The mechanistic investigations suggest that a nonafluorobutyl radical is mediated by homolytic cleavage of the cobalt(iii)-carbon bond in the catalytic cycle. This is the first report concerning a fluoroalkylation reaction of (hetero)aromatics catalyzed by the simple vitamin B₁₂model complex. The convenient electrocatalytic method employing a simple cobalt complex provides a facile synthesis method toward novel fluoroalkylated compounds, demonstrating potential applications in the fields of pharmaceutical chemistry and materials science.

Full text of DOI:10.1039/d0dt01377c

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DOI: 10.1039/D0DT01377C
ARTICLE
Electrocatalytic Reactivity of Imine/Oxime-type Cobalt Complex
for Direct Perfluoroalkylation of Indole and Aniline Derivatives
‡
Luxia Cui,a Toshikazu Ono,*a, b Yoshitsugu Morita and Yoshio Hisaeda*a, b
c
Received 00th January 20xx,
Accepted 00th January 20xx
Imine/oxime-type cobalt complexes, regarded as simple vitamin B12 model complexes, were utilized as catalysts for direct
C–H perfluoroalkylations of indole and aniline derivatives with nonafluorobutyl iodide (n-C4F9I) as the readily available
perfluoroalkyl source. The synthetic approach described herein was performed under mild reaction conditions driven by
controlled-potential electrolysis at –0.8 V vs. Ag/AgCl in organic solvents. The mechanistic investigations suggest that a
nonafluoroalkyl radical is mediated by homolytic cleavage of the cobalt(III)–carbon bond in the catalytic cycle. This is the
first report concerning a fluoroalkylation reaction of (hetero)aromatics catalyzed by the simple vitamin B12 model complex.
The convenient electrocatalytic method employing a simple cobalt complex provides a facile synthesis method toward novel
fluoroalkylated compounds, demonstrating potential applications in the fields of pharmaneutical chemistry and materials
science.
DOI: 10.1039/x0xx00000x
materials science,21-23 and there is a gradually increasing interest in
synthetic methods for fluoroalkylation of organic compounds.24-26
Compared to fluoroalkyl cation or anion intermediates with poor
Introduction
Organocobalt(III) complexes featuring a cobalt–carbon bond
(Co–C) have attracted much attention in bioinorganic and
organometallic chemistry due to the ability to produce carbon-
centered radicals from homolytic cleavage of the Co–C bond in a
controlled manner by photolysis, electrolysis, or thermolysis.1-3
Vitamin B12 derivatives represent the most familiar biological source
of radicals resulting from thermal homolysis; hence, vitamin B12-type
alkylcobalt complex is important as the most studied organometallic
28
stabilization, radical methods for fluoroalkylation stand out.27,
Nonetheless, catalytic radical fluoroalkylation assisted by Co–C bond
is still less studied.29-31 Soper’s group has reported the (hetero)arene
C–H trifluoromethylation activated by the new Co(III)–
trifluoromethyl complex in stoichiometric protocols rather than the
catalytic method.29 Togni and co-workers reported a series of
perfluoroalkyl cobaloximes and characterized their properities.
However, the authors didn’t explore the reactivity for
fluoroalkylation of (hetero)arenes.30 In 2019, Cobaloxime-catalyzed
C−H monofluoroalkylation of styrenes was performed by Feng et al.
group under photoinduced conditions.31 These works promoted us
to explore other cobalt-mediated catalytic fluoroalkylations. From
the viewpoint of expanding the Co–C chemistry, naturally derived
and simple vitamin B12 model complexes9, 10, 32, 33 for fluoroalkylation
of non-functionalized substrates have been of interest to us. In 2017,
our group developed a Co(III)–C bond-mediated catalytic radical
fluoroalkylation of (hetero)arenes under controlled-potential
electrolysis catalyzed by a naturally derived vitamin B12 model
complex, heptamethyl cobyrinate perchlorate [Cob(II)7C1ester]ClO4
compound, promoting many bio-molecular transformations under
mild conditions.1,
4-6
Additionally, the imine/oxime-type cobalt
complexes such as [Co(III){(C2C3)(DO)(DOH)pn}Br2] (C1) and
[Co(III){(DO)(DOH)pn}Br2] (C2) (Figure 1 (a)), namely Costa-type
complexes,7, 8 are useful models for the vitamin B12 family.9, 10 They
contain an analogous square planar monoanionic ligand as the
suitable model for the corrin framework and exhibit similar redox
behaviors of Co(III)/Co(II) and Co(II)/Co(I) to those in natural vitamin
B12.11-16 Nevertheless, the imine/oxime-type B12 models are less
studied except for the main application in hydrogen evolution with a
proton source.17-20
Fluoroalkyl-substituted organic compounds have been found in
a range of fields including medicinal chemistry, agrochemistry, and
(C3) (Figure
1
(a)).34 This finding encouraged us to design
fluoroalkylation of non-functionalized aromatic compounds based
on the imine/oxime-type cobalt complexes (C1 and C2) as catalysts
due to the economic effect and versatile reactivity of the Co–C bond.
Here we designed fluoroalkylation reactions based on the non-
functionalized indole and aniline derivatives as radical acceptors
because that indole and aniline moiety are both useful building block
for the preparation of functional products,35-39 along with
commercially available n-C4F9I as the fluoroalkylating reagent. The
reactions were mediated by the simple vitamin B12 model complex,
[Co(III){(C2C3)(DO)(DOH)pn}Br2] (C1) as the catalyst through
controlled-potential electrolysis under mild reaction conditions
a. Department of Chemistry and Biochemistry, Graduate School of Engineeing,
Kyushu University 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. E-mail:
tono@mail.cstm.kyushu-u.ac.jp, yhisatcm@mail.cstm.kyushu-u.ac.jp.
b. Center for Molecular Systems (CMS), Kyushu University 744 Motooka, Nishi-ku,
Fukuoka 819-0395, Japan.
c. Institute for Materials Chemistry and Engineering, Kyushu University, Nishi-ku,
Fukuoka 819-0395, Japan
† 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
‡ Current address: Department of Applied Chemistry, Faculty of Science and
Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
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(Figure 1 (b)). This is the first example of a Co–C mediated radical temperatures were 250 °C, the oven temperature was initially held
View Article Online
DOI: 10.1039/D0DT01377C
perfluoroalkylation of (hetero)arenes catalyzed by simple vitamin B12 at 100 °C for 2 min, then increased to 240 °C at the rate of 10 °C /min.
model complex using an electrochemical approach.
A 200 W tungsten lamp with a 420 nm cut-off filter (Sigma Koki, 42L)
and a heat cut-off filter (Sigma Koki, 30H) purchased from
TechnoSigma were used as the visible light irradiation experiment.
Gel permeation chromatography (GPC) was carried out by a Japan
Analytical Industry Co. Ltd., LC-908 apparatus equipped with a UV-
3702 attachment using three connected columns, JAIGEL-1H, 2H, and
2.5H with a chloroform (CHCl3) eluent. The high-resolution mass
spectra (HRMS, EI-MS) were performed with a JEOL JMS-700
instrument. MALDI-TOF-MS spectrum was obtained on Autoflex III
(Bruker Daltonics) under the linear/positive mode with dithranol as
matrix. All the products were isolated by silica-gel column
(a) Cobalt catalysts
H3CO2C
R1
CO2CH3
N
Br
N
H3CO2C
R1
R2
N
N
N
N
Co
Br
CO2CH3
Co
N
N
R2
O
H3CO2C
H3CO2C
C3:
O
H
CO2CH3
[Cob(II)7C1ester]ClO4
C1:
C2:
[Co(III){(C2C3)(DO)(DOH)pn}Br2]
(R1 = C3H7, R2 = C2H5)
[Co(III){(DO)(DOH)pn}Br2]
(R1 = R2 = CH3)
ClO4
chromatography (Kanto Chemicals, 60N) and GPC; and then isolated
1
products were identified by GC-MS, HRMS (EI-MS), H, 19F and 13
C
(b) This work: perfluoroalkylations of indole (or aniline) derivatives NMR.
NR1R2
Rf
NR1R2
X-ray crystal structure analysis. The crystals were mounted on a loop.
Diffraction data of crystal samples were collected at 93 K or 123 K
using a Rigaku XtaLABmini CCD diffractometer equipped with
graphite-monochromated Mo Kαr di tion (λ = 0.71073 Å).
Collected data were integrated, corrected, and scaled using
CrysAlisPro.40 The structures were refined using SHELXT (Sheldrick,
2015)41 Intrinsic phasing and SHELXL (Sheldrick, 2015).42 All
nonhydrogen atoms were refined anisotropically. Hydrogen atoms
were located at calculated positions and included in the structure
factor calculation but were not refined. The program Olex 2 was used
as a graphical interface.43 Crystallographic data have been deposited
with the Cambridge Crystallographic Data Centre. The data can be
obtained free of charge on application to CCDC, 12 Union Road,
Canbridge CB21EZ, UK (fax: (+44) 1223-336-033; email:
deposit@ccdc.cam.ac.uk). The CCDC numbers for crystal structures
of C1 and 3•C4F9 are 1951624, and 1966854, respectively.
Rf
C1
RfI
R2
R2
or
or
Electrolysis
N
R1
N
R1
R3
R3
Figure 1. (a) Molecular structures of C1, C2 and C3. (b) This work:
method for perfluoroalkylation of indole and aniline derivatives
catalyzed by C1.
Experimental Section
Materials and measurements. All chemical reagents and solvents
used in this study were obtained from commercial sources and used
as received unless otherwise stated. The imine/oxime-type cobalt
complex, [Co(III){(C2C3)(DO)(DOH)pn}Br2] (C1), was prepared
according to the literature.15 1H NMR and 19F NMR spectra were
recorded by using a JEOL JNM-ECZ400 NMR spectrometer at the
Centre of Advanced Instrumental Analysis, Kyushu University. The
General procedure for catalytic perfluoroalkylation reaction under
electrochemical conditions.34 Controlled-potential electrolysis were
carried out in dry acetonitrile at –0.8 V vs. Ag/AgCl under N2
atmosphere in an undivided electrolysis cell. The electrolysis cell was
equipped with three electrodes; i.e., a platinum mesh cathode (7 mm
× 25 mm × 0.07 mm thick), a sacrificial Zn-plate anode (5 mm × 20
mm × 0.1 mm thick), and an Ag/AgCl (3.0 M NaCl aq.) as a reference
electrode. For a typical reaction, a 5 mL acetonitrile solution of C1
(5.0 × 10-4 M) (1 mol%), 1,2-dimethylindole (1) (5.0 × 10-2 M), TBAP
(n-Bu4ClO4) (0.1 M) and decafluorobiphenyl (C12F10) as the internal
standard was degassed by N2 gas and stirred at room temperature.
N2 gas was passed over the solution during the measurement to
remove O2 from the reaction system. Fluoroalkylating reagent (n-
C4F9I, 3 eq. of substrate) dissolved in acetonitrile was taken into a 5
ml diameter syringe pump and then it was connected to a reaction
cell. A constant flow (0.5 eq. of substrate per 1 h) of this solution was
added into the reaction mixture for about 6 h. After the catalytic
reaction, the reaction mixture was passed through a short silica-gel
column to remove the catalyst and TBAP, and then analyzed by GC-
MS. All the products were purified by silica-gel column
chromatography and GPC. The authentic samples were characterized
by NMR and mass spectrometry.
1
chemical shifts (in ppm) of H NMR were referenced relative to
tetramethylsilane (CH3)4Si, with the residual solvent peak of
chloroform-d (CDCl3) at 7.26 ppm and methanol-d4 at 3.31 ppm as an
internal standard. The chemical shifts (in ppm) of 19F NMR were
referenced relative to hexafluorobenzene (C6F6) at –162.90 ppm in
CDCl3 and methanol-d4. 13C NMR spectra were recorded by using a
Bruker Avance 500 NMR spectrometer and the chemical shifts (in
ppm) were referenced relative to the residual solvent peak of CDCl3
at 77.2 ppm. The coupling constants, J are reported in Hertz (Hz).
Multiplicity is abbreviated as follows: s = singlet, brs = broad singlet,
d = doublet, t = triplet, q = quartet, m = multiplet. Cyclic voltammetry
(CV) was carried out using a BAS ALS-630C electrochemical analyzer
at a scan rate of 100 mV s-1. The cell was equipped with three
electrodes: an Ag/AgCl (3 M NaCl aq.) reference electrode, a
platinum working electrode, and a platinum wire counter electrode.
The experiments were performed in different solvents under N2
atmosphere with tetrabutylammonium perchlorate (TBAP, 0.1 M) as
the electrolyte. The concentrations of the analytes were 1 × 10-3 M.
The gas chromatography-mass spectra (GC-MS) were obtained using
a Shimadzu GCMS-QP2010SE equipped with an Agilent J&W DB-1
column (length: 30 m; ID: 0.25 mm; film: 0.25 μm) and helium as the
carrier gas. For the measurement, the injector and detector
2 | J. Name., 2012, 00, 1-3
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Results and Discussion
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DOI: 10.1039/D0DT01377C
Table 1. Optimization of the reaction conditions for the
perfluoroalkylation of indole derivativesa
The structure of C1 was unambiguously confirmed by X-ray
crystallography analysis for the first time (Figure S1 and Table S1).
Firstly, the redox behavior of n-C4F9I was characterized by cyclic
voltammetry (CV) at a scan rate of 100 mV s-1 by using
tetrabutylammonium perchlorate (TBAP, n-Bu4NClO4) as the
supporting electrolyte in acetonitrile (CH3CN) (Figure 2 (a)). As
shown in Figure 2 (a), n-C4F9I can be directly reduced over –1.0 V vs.
Ag/AgCl in CH3CN. The result indicated that electrocatalytic potential
for fluoroalkylation should be controlled below this value to avoid
the reduction of n-C4F9I. To further confirm the formation of the Co(I)
species, the redox behavior of C1 was investigated under analogous
conditions using CV with/without n-C4F9I in the described solvent
(Figure 2 (b)). The reduction potentials for Co(III)/Co(II) and
Co(II)/Co(I) couples in CH3CN were observed at –0.15 V and –0.64 V
vs. Ag/AgCl, respectively. In the presence of n-C4F9I, a new
irreversible reduction peak at –1.10 V vs. Ag/AgCl appeared, which
was attributed to the one-electron reduction of the Co–C4F9
complex.44 Additionally, the solvent effect is critical for catalytic
reactions since the polarity and reagent solubilizing ability of the
solvent affect the rate and selectivity of reactions.45 In other solvents,
such as methanol (CH3OH), dimethyl sulfoxide (DMSO) and 1-
propanol, the similar CV results can be observed with slight shift of
reduction potentials, exhibiting the solvent effect on the catalytic
system (Figure S2).
C4F9
C1 (1 mol%)
n-C4F9I
CH3
CH3
Solvent
Potential (V) vs. Ag/AgCl
N
N
CH3
CH3
1 C4F9
1
Potential (V) vs.
Entry
Solventb
Yield (%)c
Ag/AgCl
1
2
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.6 V
–0.9 V
–1.2 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
–0.8 V
CH3OH
1-propanol
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
58
55
30
85
81
69
70
10
64
50
76
75
44
78
0
3
4
5
6
7
8d
9e
10f
11g
12h
13i
14j
15k
16l
-0.15 V
-0.64 V
(a)
(b)
0
5 A
a Reaction conditions: [C1] = 5.0 × 10-4 M; [1,2-dimethylindole (1)] = 5.0 × 10-2
M; [n-C4F9I] = 0.5 eq. of substrate per 1 h, 3 eq. in total; [n-Bu4NClO4] = 0.1 M;
Decafluorobiphenyl (C12F10) as the internal standard; Reaction time: 6 h.
20 A
b
Abbreviations: CH3OH, methanol; CH3CN, acetonitrile; DMSO, dimethyl
c
sulfoxide.
The yields are based on the initial concentration of 1,2-
Catalyst
Catalyst + 2 eq. n-C4F9I
2 eq. n-C4F9I
dimethylindole (1) and were determined by gas chromatography-mass
spectrometry (GC-MS). d In the absence of the C1 catalyst. e [n-C4F9I] = 1.0 eq.
of substrate per 1 h, 3 eq. in total. f 3 eq. of n-C4F9I were added initially without
the syringe pump. In the dark. With visible light (≥ 420nm). C2 as the
catalyst. j C3 as the catalyst. k In the presence of [TEMPO] (5.0 × 10-2 M) as the
radical trapping reagent. l In the presence of [PBN] (5.0 × 10-1 M) as the radical
trapping reagent.
-1.5 -1.0 -0.5
0.0
0.5
1.0
1.5 -1.5 -1.0 -0.5
0.0
0.5
1.0
1.5
Potential (V) vs. Ag/AgCl
Potential (V) vs. Ag/AgCl
g
h
i
Figure 2. (a) CV of nonafluorobutyl iodide (n-C4F9I) (2 mM) and (b)
[Co(III){(C2C3)(DO)(DOH)pn}Br2] (C1) as the catalyst (1 mM)
with/without n-C4F9I (2 mM) in CH3CN.
Ag/AgCl achieved a slightly reduced yield of the desired compound
1•C4F9 (Table 1, entries 6 and 7) due to by-product formation (Figure
S4). Only 10% yield of the desired product 1•C4F9 was achieved in the
absence of the C1 catalyst (Table 1, entry 8). The flow rate of the n-
C4F9I reagent was also measured to check the reactivity. We found
that increased speed of n-C4F9I addition and even adding the same
amount of n-C4F9I at first without the use of the syringe pump both
led to a lower yield of 1•C4F9 (Table 1, entries 9 and 10). In the
present study, we also evaluate the reactivity under the dark and
visible-light conditions (Table 1, entries 11 and 12) and found no
obvious differences with the previously obtained outcomes.
Furthermore, another imine/oxime-type cobalt complex, C2,
exhibited low reactivity for the described perfluoroalkylation
reaction (Table 1, entry 13), possibly due to its low solubility in the
organic solvent. Additionally, an optimized reaction catalyzed by C3
was also conducted and afforded 78% yield of 1•C4F9 (Table 1, entry
14). Although the yield was slightly lower than the result mediated
Based on our previous work and the CV results,34 we commenced
our investigation of direct perfluoroalkylation of (hetero)arenes at –
0.8 V vs. Ag/AgCl using 1,2-dimethylindole (1) as the model substrate
and n-C4F9I as the perfluoroalkyl source in the presence of C1 (1
mol%) at room temperature employing an electrochemical approach
(Figure S3). The results are summarized in Table 1. Following a series
of examinations using various solvents (Table 1, entries 1–4), we
found that CH3CN (Table 1, entry 4) was most optimal for this
catalytic transformation. It resulted in increased yield of the desired
product 1•C4F9 to 85% (Table 1, entry 4), accompanied by a relatively
high turnover number (TON) of 85. Using other solvents led to
incomplete conversions and lower yields (Table 1, entries 1–3).
Moreover, the potential of –0.6 V vs. Ag/AgCl was also chosen for the
catalytic reaction and resulted in a yield of 81% for 1•C4F9 (Table 1,
entry 5) while more negative potentials such as –0.9 V and –1.2 V vs.
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by C1, good reactivity of C3 for the direct C–H perfluoroalkylation of conditions. Thus, this general and cost-effective method offers
View Article Online
DOI: 10.1039/D0DT01377C
aromatic substrate was demonstrated. Besides, in the presence of access to highly functionalized fluoroalkylated aniline molecules.
2,2,6,6-trtramethylpiperidine 1-oxyl free radical (TEMPO) and N-tert-
butyl-α-phenylnitrone (PBN), exhibiting radical scavenging activity, Table 2. Substrate scope of electrochemical fluoroalkylation of
the reaction was inhibited and no formation of the desired product various indole and aniline derivativesa
1•C4F9 was observed (Table 1, entries 15 and 16). Notably, the
NR1R2
NR1R2
adduct of TEMPO and the nonafluorobutyl radical (•C4F9) generated
Rf
C1
RfI
Rf
in situ was detected by GC-MS (Figure S5). Similarly, we can also
monitor the adducts of PBN and •C4F9 by GC-MS (Figure S6). These
results indicated that some radical intermediates were essential for
the formation of the product. Based on these results, the standard
conditions were optimized at –0.8 V vs. Ag/AgCl for the controlled-
potential electrolysis using the substrate (100 eq. to catalyst) with 3
eq. of n-C4F9I in the presence of the catalyst C1 (1 mol%) in CH3CN for
6 h at room temperature (Table 1, entry 4).
Utilizing these optimized conditions, the reactions of different
non-prefunctionalized indole derivatives, such as 1-ethyl-2-
methylindole (2), 1-methyl-2-phenylindole (3), and ethyl indole-2-
carboxylate (4), mediated by C1 with fluoroalkylating reagent (n-
C4F9I) provided perfluoroalkylated products in good to excellent
yields (Table 2). The obtained yields for 2•C4F9 and 3•C4F9 were 87%
and 64% corresponding to the TON of 87 and 64, respectively. A
crystal structure of 3•C4F9 was successfully determined (Figure S7
and Table S2). Under the optimized conditions, no formation of any
significant amounts of side products was observed. Additionally, the
compound 4 could also be performed in the reaction, affording 45%
yield of the desired 4•C4F9 product. All these transformations
exhibited that this method provided a straightforward and versatile
route for synthesizing perfluoroalkylated indole derivatives.
R2
R2
or
or
Solvent, r.t.
–0.8 V vs. Ag/AgCl
N
R1
N
R1
R3
R3
C4F9
CH3
C4F9
C4F9
CH3
C2H5
N
N
N
CH3
1 C4F9
85%
CH3
2 C4F9
87%
3 C4F9
64%
(from Table 1)
C4F9
OC2H5
N
H
O
4 C4F9
45%
Crystal structure of 3•C4F9
NH2
NH2
NHCH3
C4F9
N(CH3)2
C4F9
C4F9
C4F9
OCH3
CH3
CH3
CH3
To continue investigations in this area, we decided to extend our
electrocatalytic protocol to explore the perfluoroalkylation of aniline
derivatives. Similarly, various amounts of the catalyst, different
solvents and light irradiation were screened to improve the reaction
efficiency using p-toluidine (5) as the model substrate (Table S3 and
Figure S8). Finally, –0.8 V vs. Ag/AgCl was chosen as the controlled
potential for the electrolysis with the aniline substrates with 3 eq. of
n-C4F9I in the presence of C1 (3 mol%) in DMSO for 6 h under visible-
light irradiation. The above standard conditions led to the desired
product 5•C4F9 in a yield of 48% (Table 2). Then, we undertook the
perfluoroalkylation reactions of a series of aniline derivatives
employing C1 as the catalyst (Table 2). The reaction of p-anisidine (6)
afforded 65% yield of the substitution product 6•C4F9. In addition, N-
methyl-p-toluidine (7) was subjected to reaction with n-C4F9I,
providing perfluoroalkylated product 7•C4F9 in 34% yield.
Furthermore, the fluoroalkylation of N,N-dimethyl-p-toluidine (8)
resulted in the formation of 8•C4F9 in a low yield of 10%. The
disappointing outcome of this reaction was associated with the 8%
yield of side product 7•C4F9, possibly resulting from the instability of
light-sensitive N,N-dimethyl-p-toluidine (8) under visible-light
irradiation. Moreover, special electron-rich aniline of 1,2,3,4-
tetrahydroquinoline (9) was also amenable to the transformation,
affording the desired product 9•C4F9 in 18% yield in the presence of
another isomer product 9•C4F9* in 29% yield, achieving a total yield
of 47%. Additionally, it is also possible to prepare
trifluoromethylated aniline derivatives through this method. Herein,
2DMSO•CF3I was chosen as the trifluoromethylated source46 and led
to corresponding product 6•CF3 in 21% yield with further optimized
5 C4F9
48%b
6 C4F9
65%b
7 C4F9
34%b
8 C4F9
10%b
NH2
C4F9
H
N
H
N
CF3
C4F9
9 C4F9
18%b
9 C4F9*
29%b
Total yield: 47%b
OCH3
6 CF3
13%b; 21%c
a Reaction conditions: [C1] = 5.0 × 10-4 M (1 mol%); [substrate] = 5.0 × 10-2 M;
[n-C4F9I] = 0.5 eq. of substrate per 1 h, 3 eq. in total; [n-Bu4NClO4] = 0.1 M;
Internal standard: C12F10; Reaction time: 6 h; Solvent: CH3CN; The yields are
based on the initial concentration of the indole substrate and were determined
by GC-MS. b [C1] = 1.5 × 10-3 M (3 mol%); Solvent: DMSO; With visible light (≥
420nm). c [C1] = 1.0 × 10-3 M (4 mol%); [substrate 6] = 2.5 × 10-2 M; [2DMSO•
CF3I] = 1.0 eq. of substrate per 1 h, 12 eq. in total; Reaction time: 12 h; Solvent:
DMSO; With visible light (≥ 420nm).
According to the above investigations and the previously
reported studies,34, 47 a plausible reaction mechanism is illustrated in
Scheme 1. Initially, the supernucleophilic Co(I) species was
generated under electrolysis at –0.8 V vs. Ag/AgCl. Subsequently, the
intermediate Co(III)–Rf complex was formed by the reaction of
fluoroalkylating iodide and Co(I) with the removal of an iodide ion.48
The homolytic dissociation of the Co(III)–Rf bond then leads to the
formation of the key •Rf species, which reacts with the non-activated
indole and aniline derivatives. One-electron oxidation and a proton
loss result in the formation of the desired fluoroalkylated product.49
Isolation of the Co(III)–Rf intermediate was not possible at this stage
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due to the low stability at ambient conditions. Therefore, we
performed DFT calculation to estimate the bond dissociation energy
(BDE) of Co(III)–Rf bond (See Supporting Information Table S4).50 For
simplicity, C2 was used as imine/oxime-type cobalt complex and
corrin cobalt complex (corrin) was used as a model for vitamin B12
derivative (C3). The results show that BDEs of C2(III)–CF3 and C2(III)–
C4F9 complexes are 46.0 and 40.0 kcal/mol, respectively. These BDEs
agree well with values obtained by C2(III)–CH3 and corrin(III)–CH3
(36.0 and 42.3 kcal/mol). These results supported the fact that
Co(III)–Rf complex exhibits similar reactivity as the Co(III)–CH3
complex. The mass peak corresponding to the C1 catalyst was
detected using matrix-assisted laser desorption/ionization-time of
flight-mass spectrometry (MALDI-TOF-MS), indicating the stability of
the catalyst during the process (Figure S9). Although the catalytic
fluoroalkylation reactions using naturally derived vitamin B12
derivatives have been previously reported by our group34 and some
perfluoroalkyl cobaloximes have been synthesized and described by
the Togni et al.,30 electrocatalytic fluoroalkylation of the indole and
aniline derivatives mediated by imine/oxime-type cobalt complexes
has not been reported so far.
Acknowledgements
View Article Online
This work was supported by JSPS KAKDENOIH: 1I0.G10r3a9n/tD0NDuTm01b37e7rCs
JP17H04875, JP16H06514, JP18H04265 and JP19K22204. This
work was also supported Izumi Science and Technology
Foundation and Nissan Chemical Corporation.
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Conflicts of interest
There are no conflicts to declare.
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