Organic Letters
Letter
a
Table 1. α-CF3 Ketone 2a Synthesis via Electrochemical Trifluoromethylation of Enol Acetate 1a
no.
A/C
electrolyte
current (mA)
N (F/mol)
yield 2a (%)
1
2
3
4
5
6
7
8
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
C/Pt
C/SS
GC/GC
Pt/GC
Pt/Cu
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
LiClO4
NaBF4
n-Bu4NClO4
n-Bu4NBF4
n-Bu4NBF4
n-Bu4NBF4
20
20
20
20
40
3
3
3
3
3
0
3
5
2.2
3
3
3
3
3
3
3
3
3
3
3
67
68
68
77
69
n.r.
85
58
70
70
73
72
73
80
51
84
35
79
62
51
20
20
20
20
20
20
20
20
20
20
20
20
20
20
9
10
11
12
13
14
15
16
17
18
b
c
d
e
f
19
20
g
a
General procedure: undivided cell, plate cathode and anode (15 mm × 20 mm × 0.1 mm), constant current 20−40 mA (j = 6.7−13.3 mA/cm2),
1a (1.0 equiv, 1.0 mmol, 162.0 mg), CF3SO2Na (2.0 equiv, 2.0 mmol, 312.0 mg), electrolyte (0.5 equiv, 0.5 mmol), CH3CN/H2O (8 mL/2 mL),
20−25 °C, air atmosphere. Isolated yields. 1.0 equiv of CF3SO2Na. 3.0 equiv of CF3SO2Na. DMSO/H2O (8 mL/2 mL). THF/H2O (8 mL/2
mL). CH3CN (10 mL). CH3OH (10 mL). SS, stainless steel; GC, glassy carbon.
b
c
d
e
f
g
undergo anodic oxidation to form α-acetoxy and α,β-
unsaturated carbonyl compounds (Scheme 1b).27−29
8) or decreasing (entry 9) the electricity passed through the
reaction mixture did not give better results. The reaction
tolerated a wide range of electrode materials (entries 7 and
10−14). The 2a yield was similar to that using 3 equiv of
CF3SO2Na (entries 7 and 16) and dropped with the use 1
equiv of CF3SO2Na (entry 15). The use of DMSO/H2O,
THF/H2O mixtures, CH3CN, or CH3OH as the solvent
resulted in a lower yield of 2a (entries 17−20). The conversion
of enol acetate 1a was >95% in most experiments.
Under the optimized reaction conditions (Table 1, entry 7),
the scope of this electrochemical method for the α-CF3
ketones 2 synthesis via the trifluoromethylation of enol
acetates 1 was tested (Scheme 2).
The enol acetates from aryl ketones with methyl, methoxy,
Cl, F, and Br groups reacted well to give corresponding
products 2b−2f in 63−79% yields. α-Alkyl-substituted α-CF3
ketones 2g−2i were synthesized in 67−81% yields. The
naphthyl-containing enol acetate 1j was converted into α-CF3
ketone 2j in a low 20% yield, probably due to the susceptibility
of the naphthyl ring to oxidation.38,39 (The reaction was
carried out in THF/H2O (8:2) due to the insolubility of
substrate 1j in CH3CN/H2O (8:2).) To our delight, the
reaction was compatible with aliphatic enol acetates 1k−1o to
give good (66−78%) yields of products 2k−2o. It is worth
noting that enol acetates from dicarbonyl compounds 1p and
1q did not react under our reaction conditions. The reaction
with the oxidation-sensitive acetyl furan 1r resulted in a
mixture of inseparable products.
In recent years, more and more attention has been paid to
the use of electrochemistry in redox processes for the following
reasons: the availability and the low cost of the electric current,
the variety of electrochemical reaction mechanisms, and the
decrease in waste.30−32 Electrolysis can be carried out in a
divided or undivided cell under controlled potential (CPE) or
constant current conditions (CCE).33 Using an undivided cell
is more practical, but at the same time, it is more difficult to
implement because of the undesirable processes connected to
the counter-electrode action.34 The advantages of the constant
current (CCE) conditions are the high current density, the
small electrode surface, and the compact reaction vessels.
The study of the electrochemical perfluoroalkylation of enol
acetates began by optimizing the electrosynthesis for the
reaction between 1-phenylvinyl acetate 1a and CF3SO2Na,
resulting in 3,3,3-trifluoro-1-phenylpropan-1-one 2a (Table 1).
The use of silyl enol ether in this process did not lead to good
results. (See the SI.) Silyl enol ethers were found35−37 to have
oxidation potentials significantly lower than those of the enol
acetates. The electron-accepting nature of the ester group in
enol acetates is likely to be helpful in preventing the oxidation
of the enol moiety.
Screening of the supporting electrolytes (entries 1−4)
showed that the best yield of 2a (77%) was achieved with n-
Bu4NBF4 (entry 4). A two-fold increase in the current density
led to a slightly worse 2a yield (69%) (entry 5). Product 2a
was not formed in the absence of an electric current (entry 6).
Surprisingly, in the absence of a supporting electrolyte, the
yield of 2a was 85% (entry 7). Thus all other experiments were
conducted without a supporting electrolyte. Increasing (entry
The established protocol was applied to the reaction of enol
acetates 1 with C4F9 sulfinate (Scheme 3). The electrochemical
perfluoroalkylation proceeded well to afford the corresponding
C4F9-containing ketones 3 in 32−58% yields. The moderate
5108
Org. Lett. 2021, 23, 5107−5112