Generation of carbon free radicals by reduction of the cation pool

Article abstract of DOI:10.1246/bcsj.77.1545

The electrochemical reduction of N-acyliminium ions, which were generated by the "cation pool" method, led to the formation of carbon free radicals. Carbon radicals thus generated underwent homo-coupling reactions and the reactions with activated olefins, such as methyl acrylate. In the latter case, a mechanism involving the addition of a carbon radical to the carbon-carbon double bond, followed by one-electron reduction to give carbanions, has been proposed. The present study opens a new possibility for radical-mediated carbon-carbon bond formation based on the reduction of carbocations.

Full text of DOI:10.1246/bcsj.77.1545

Ó 2004 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 77, 1545–1554 (2004) 1545
Generation of Carbon Free Radicals by Reduction of the Cation Pool
ꢀ
ꢀ
Seiji Suga, Shinkiti Suzuki, Tomokazu Maruyama, and Jun-ichi Yoshida
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510
Received February 27, 2004; E-mail: yoshida@sbchem.kyoto-u.ac.jp
The electrochemical reduction of N-acyliminium ions, which were generated by the ‘‘cation pool’’ method, led to the
formation of carbon free radicals. Carbon radicals thus generated underwent homo-coupling reactions and the reactions
with activated olefins, such as methyl acrylate. In the latter case, a mechanism involving the addition of a carbon radical to
the carbon–carbon double bond, followed by one-electron reduction to give carbanions, has been proposed. The present
study opens a new possibility for radical-mediated carbon–carbon bond formation based on the reduction of carbocations.
Carbon free radicals are important reactive intermediates in
organic chemistry, and are widely utilized in organic synthesis
and polymer synthesis.1 Carbon radicals are usually generated
by the homolytic cleavage of the C–X (X = H, halogen, hetero-
atom, etc.) bond (Eq. 1), but redox-mediated bond cleavage al-
so serves as a useful method for the generation of carbon radi-
cals. For example, one-electron oxidation of neutral com-
pounds having a C–X bond produces radical cation intermedi-
ates that decompose to give carbon radicals and Xþ (Eq. 2).
Carbon radicals can also be generated by one-electron reduc-
tion followed by bond cleavage (Eq. 3).
In our previous work, 1,3-diketones were oxidized by the
electrochemical method to give the corresponding radicals.3
The oxidation presumably takes place at the enol form, and
the O–H bond cleavage gives the carbon radical adjacent to
the carbonyl group. This radical adds to olefins to produce an-
other radical. This radical formation has been successfully ap-
plied to oxygenation reactions to form cyclic peroxides.
Oxidative generation, however, often suffers from the prob-
lem of over-oxidation. Carbon radicals generated by the de-
composition of radical cations are often oxidized to the corre-
sponding carbocations under the conditions. The over-oxida-
tion problem is especially serious for the generation of elec-
tron-rich radicals. For example, organic compounds having a
heteroatom, such as nitrogen, are easily oxidized to generate
the radical cations (Scheme 2, Y = N), and cleavage of ꢀ C–
H bond produces carbon radicals ꢀ to nitrogen. However, these
radicals are easily oxidized to give the corresponding iminium
ion.4 Therefore, it is difficult to stop the oxidation at the free
radical stage. The oxidation of other heteroatom compounds
(Y = O, S) also suffers from a similar over-oxidation problem.5
In order to generate free radical species by electron transfer,
we envisioned that the following two-step procedure is effec-
tive (Scheme 3). In the 1st step, carbocations are generated
by the two-electron oxidation of heteroatom compounds. The
+
ð1Þ
ð2Þ
C
X
X
X
C
X
X
X
- e
+
+
C
C
C
C
C
C
X
X
+ e
ð3Þ
Extensive work by Schmittel revealed that the one-electron
oxidation of metal enolates leads to the generation of free radi-
cal species (Scheme 1).2 Metal enolates are easily oxidized to
give the corresponding radical cations, which collapse to give
carbon radical and metal cation. In some cases the O–M bond
cleavage in radical cation leads to the formation of carbocation
and metal radical. Although the bond-cleavage mode depends
upon the nature of the metal enolates, this reaction serves as
a good example that free radicals are generated by the electron
transfer-driven bond cleavage.
Scheme 2.
R1
R2
O M
R3
1st step
- e
- e
Y C
H
Y
Y
C H
Y
C
Y C
- H
- e
2nd step
R1
R2
O M
R3
R1
R2
O
R1
R2
O
+
M
+
+ e
M
Y
C
C
R3
R3
Scheme 1.
Scheme 3.
Published on the web August 6, 2004; DOI 10.1246/bcsj.77.1545

1546 Bull. Chem. Soc. Jpn., 77, No. 8 (2004)
Reduction of the Cation Pool
initially formed radical cations collapse to give the carbon rad-
icals, which are further oxidized to give the corresponding car-
bocations. In the 2nd step, the thus-generated carbocations are
reduced to generate free radicals.
The reduction of the cation to the radical takes place at a less
negative potential than the reduction of the radical to an anion.
As described above, the conversion of carbocations to car-
bon radicals can be definitely accomplished by one-electron re-
duction. Although such a relationship between carbocations
and carbon radicals has been well recognized,12 experimental
work has been rather limited to analytical studies on highly sta-
bilized species. The manipulation of such a redox process with
complete control still remains as one of the challenging goals of
synthetic organic chemistry. Thus, we initiated our project on
the reduction of cation pools to generate carbon radicals that
can be used for synthetically useful reactions. In a preliminary
study, we have already found that the electrochemical reduc-
tion of N-acyliminium ion 2 generated from 1 gave homo-cou-
pling product 4, presumably via free radical 3 (Scheme 6).13
We also revealed that the reduction of 2 in the presence of
methyl acrylate and an excess amount of proton gave the cou-
pling product 5. A mechanism involving the addition of radical
3 to the carbon–carbon double bond of methyl acrylate was pro-
posed. Herein, we report on the full details of this study.
In order to accomplish this two-step transformation, it is nec-
essary to accumulate a carbocation as a solution that is used for
the 2nd step. Carbocations, however, are usually trapped imme-
diately after generation in situ by a nucleophile that is present in
the reaction medium. This is because carbocations are general-
ly unstable and difficult to accumulate in a solution.6 Recently,
however, we have developed the ‘‘cation pool’’ method, which
involves the generation and accumulation of reactive carbo-
cations in the absence of nucleophiles.7 In the ‘‘cation pool’’
method, carbocations are generated by two-electron oxidation
using low-temperature electrolysis, and are accumulated as a
solution. Carbocations thus generated are easily characterized
by NMR and IR at low temperature. The ‘‘cation pool’’ method
has already been successfully applied for N-acyliminium ions
and alkoxycarbenium ions. Thus, we envisaged that the one-
electron reduction of ‘‘cation pool’’ serves as an efficient meth-
od for the generation of carbon radicals (Scheme 4).
Results and Discussion
It is well known that one-electron reduction of carbocation
leads to the formation of the corresponding free radical. Pio-
neering work of Conant revealed that the one-electron reduc-
tion of pyridinium ion by low-valent vanadium produces the
Reduction Potential of Cation Pool. We first studied the
redox behavior of the N-acyliminium ion, which is generated
by the ‘‘cation pool’’ method, using cyclic voltammetry. The
reduction potentials were determined in Bu4NBF4/CH2Cl2 us-
ing a glassy carbon electrode. A Ag/Agþ (CH3CN) electrode
was used as a reference electrode. The N-acyliminium ion
2 was generated by the anodic oxidation of N-(methoxycar-
corresponding carbon radical, which dimerizes to give a homo-
8
´
coupling product. Saveant has studied the electrochemical re-
duction of stable iminium salts extensively, and observed two
reduction waves in the polarograms (Scheme 5).9 The first
wave corresponds to the one-electron reduction process for
which dimerization occurs. This process presumably involves
the carbon radical. The second wave is concerned with the for-
mation of the amine by two-electron reduction. When the car-
bon is substituted by two aromatic groups, stable free radicals
are obtained, as indicated by the color of the solution and the
EPR spectrum.
Wayner accomplished extensive work on oxidation and re-
duction potentials of carbon radicals.10 A modulated photolysis
technique was used for radical generation, and phase-sensitive
voltammetry was used for their detection. The oxidation poten-
tial of the benzyl radical is 0.73 V and the reduction potential is
ꢁ1:45 V. The oxygen- and nitrogen-substituted radicals exhibit
oxidation waves at ꢁ0:24 V and ꢁ1:03 V, respectively. Arnet
studied the redox potentials of the xanthyl system, where the
cation and the anion can be generated in the same solvent.11
- 2e
- H+
+ e
N
N
N
CO2Me
2
CO2Me
3
CO2Me
1
O
H
OMe
OMe
N
N
N
O
CO2Me
CO2Me CO2Me
4
5
Scheme 6.
µA
400
- 2e
- H+
+ e
Y
C
H
Y
C
Y C
300
200
100
cation pool
Scheme 4.
0
0
-2.0
-1.0
V vs. Ag/Ag+(CH3CN)
Fig. 1. Cyclic voltammogram for the reduction of N-acyl-
iminium ion 2.
Scheme 5.

S. Suga et al.
Bull. Chem. Soc. Jpn., 77, No. 8 (2004) 1547
bonyl)pyrrolidine 1 as a precursor in Bu4NBF4/CH2Cl2 at ꢁ78
ꢂC, and accumulated as a solution. As shown in Fig. 1, N-acyl-
iminium ion 2 exhibited a major reduction wave at Ep ¼ ꢁ0:85
to ꢁ0:90 V, although a small peak was observed at ꢁ0:5 V, pre-
sumably due to the reduction of an impurity that is difficult to
remove. It should be noted that this reduction potential is much
less negative than that reported for the reduction of the N,N-di-
alkyliminium ion (E1=2 ¼ ꢁ1:95 V).9 A significant positive
shift of the reduction potential seems to be attributed by the
electron-withdrawing effect of methoxycarbonyl group on the
nitrogen atom.
N-Acyliminium ion 7 was generated by the low-temperature
oxidation of 6, which has a silyl group as an electroauxiliary14
(Scheme 7). Electroauxiliary is a group that facilitates electron
transfer and controls the follow-up chemical processes. N-Ac-
yliminium ion 7 exhibited a reduction wave at a less negative
potential (ꢁ0:75 V) than that of 2, as shown in Fig. 2.
Preparative Electrochemical Reduction of Cation Pool
from ꢂ1 was carried out under a constant-current condition at
ꢁ78 C in a divided cell equipped with a carbon-rod anode.
As expected, the homo-coupled product 4 was obtained as
shown in Scheme 8.
At first, the effect of the electrode material was examined
(Table 1). The use of a carbon-rod cathode gave rise to the for-
mation of 4 in 31% yield together with 1, which was the same
as the starting material for the generation of the cation pool 2, in
13% yield (run 1). Because the solution of 2 did not contain 1
(conversion of 1 was ca. 100%), 1 was definitely produced dur-
ing the course of the electrochemical reduction. The yield
slightly increased when the cathode was switched to carbon felt
(run 2). In order to facilitate the anodic reaction, some com-
pounds that might play the role of a substrate for anodic oxida-
tion seemed to be needed. Thus, THF, which is easily oxidized
and should not affect cathodic reduction, was added as a sub-
strate for oxidation in the anodic chamber. This caused a slight
increase in the yield of 4 (run 3), although it was not clear that
THF was oxidized anodically. The increase in the amount of
electricity did not affect the yield of 4 significantly (run 4).
The use of a platinum cathode suppressed the formation of 1
(runs 5, 6), although the reason is not clear at present. In any
case, the formation of a significant amount of 1 is disadvanta-
geous from a synthetic point of view. Therefore, the use of a
platinum electrode seems to be better from a synthetic point
of view. With a platinum electrode, the yield of 4 could be im-
proved up to 75% (a mixture of two diastereomers (51:49)) by
increasing the electricity (run 7), although 1 was also formed in
7% yield. In this case, the excess electricity may be consumed
for the reduction of protons generated during the course of the
anodic oxidation of 1.
in the Absence of Radical Acceptor.
Homo-Coupling
Reaction: Next, we examined the preparative electrochemical
reduction of the cation pool in the absence of a radical acceptor.
The electrochemical reduction of acyliminium ion 2 generated
SiMe3
- 2e
C4H9
C4H9
N
N
+"
- "SiMe3
CO2Me
CO2Me
7
6
Scheme 7.
µA
200
The present result implies that the one-electron reduction of
2 produced carbon-centered radical 3, which homo-coupled to
give 4 (Scheme 9). It is also reasonable to consider that radical
3 reacts with 2 to give a dimeric radical cation 8, the one-elec-
tron reduction of which gives a homo-coupled product 4. It
seems to be difficult, however, to distinguish these two mecha-
nisms experimentally at present. Another possibility to be con-
sidered is that the two-electron reduction of N-acyliminium ion
100
0
0
-2.0
-1.0
- 2e
- H+
+ e
1
+
N
N
N
N
V vs. Ag/Ag+(CH3CN)
CO2Me
2
CO2Me
CO2Me CO2Me
1
4
Fig. 2. Cyclic voltammogram for the reduction of N-acyl-
iminium ion 7.
Scheme 8.
Table 1. Electrochemical Reduction of 2aÞ
Run
Cathode
Additive to
anodic solution
Electricity
/F molꢁ1
Yield of 4
Yield of 1
1
2
3
4
5
6
7
C (rod)
C (felt)
—
—
1.25
1.25
1.25
1.75
1.25
1.25
2.0
31
47
62
65
49
47
75
13
18
13
22
0
THF (10 equiv)
THF (10 equiv)
—
THF (10 equiv)
THF (10 equiv)
Pt (plate)
0
7
a) The cathodic reduction was usually carried out with 0.4 mmol scale with 8 mA of electric
current.

1548 Bull. Chem. Soc. Jpn., 77, No. 8 (2004)
Reduction of the Cation Pool
+ e
+ e
- 2e
- H+
+ e
N
N
N
+
10
Pt cathode
2.0 F/mol
N
N
N
N
CO2Me
2
CO2Me
3
CO2Me
9
20%
CO2Me
11
CO2Me CO2Me
CO2Me
10
2
2
12
homo-
coupling
H+
39%
Scheme 12.
+ e
N
N
N
N
N
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
- 2e
- H+
8
4
1
+ e
Pt cathode
2.0 F/mol
+
13
N
N
N
N
Scheme 9.
0%
CO2Me CO2Me
CO2Me
13
CO2Me
14
15
68%
Zn
(excess)
+
Scheme 13.
N
N
N
N
CO2Me
2
CO2Me CO2Me
CO2Me
1
4
SiMe3
(16%)
(54%)
- 2e
+ e
C4H9
C4H9
N
N
+"
Pt cathode
2.0 F/mol
- "SiMe3
Scheme 10.
CO2Me
7
CO2Me
6
SmI2
(3 eq)
C4H9
C4H9
N
C4H9
N
N
+
N
+
N
N
N
CO2Me CO2Me
CO2Me
CO2Me
2
CO2Me CO2Me
CO2Me
16
17
1
4
(4%)
40%
20%
(10%)
Scheme 14.
Scheme 11.
2 took place to give carbanion 9, which reacted with the origi-
nal N-acyliminium ion 2 to produce the dimer. Simply reduced
product 1 was probably formed via protonation of the carbanion
9. Presumably, two-electron reduction also took place with a
carbon cathode to give a significant amount of 1, whereas with
a platinum cathode one-electron reduction is more favorable to
give the homo-coupled product 4 selectively.
C4H9
+ e
N
N
Pt cathode
2.0 F/mol
CO2Me
2
CO2Me
7
(0.171 mmol) (0.160 mmol)
The reduction of the N-acyliminium ion 2 with chemical re-
ducing agents was also studied.15 When zinc powder was used
as a reducing agent, 1 was obtained as the major product (54%)
together with the homo-coupled product 4 (16%) (Scheme 10).
Two-electron reduction of the acyliminium ion seemed to take
place predominantly to produce the corresponding carbanion 9,
which is trapped by a proton in the reaction media to give 1.
When SmI2 was used as a reducing agent, 1 was also formed
as the major product (10%) together with a small amount of
4 (4%), although the material balance was not good
(Scheme 11). These results suggest that two-electron reduction
is the major pathway in the chemical reduction, whereas one-
electron reduction is predominant in electrochemical reduction.
It is reasonable to consider that metal ions in the chemical re-
duction system coordinate to stabilize carbanion 9 and facilitate
the two-electron reduction process, although the detailed mech-
anism is not clear at present.
We next examined the electrochemical reductive homo-cou-
pling of other N-acyliminium ions. The electrochemical reduc-
tion of N-acyliminium ion 11 generated from the six-membered
ring carbamate 10 also gave the corresponding homo-coupled
product 12 in 39% together with a simply reduced product 10
(20%) (Scheme 12). The reduction of 14 generated from acy-
clic carbamate 13 also proceeded smoothly to give homo-cou-
C4H9
N
C4H9
C4H9
N
N
N
N
N
CO2Me
CO2Me CO2Me
CO2Me CO2Me
CO2Me
16
4
18
(0.043 mmol)
(0.027 mmol)
(0.041 mmol)
Scheme 15.
pled product 15 in 68% yield (Scheme 13). In this case, the cor-
responding simply reduced product was not obtained. The
cathodic reduction of N-acyliminium ion 7 generated from a
silyl-substituted carbamate 6 was also carried out to obtain
the homo-coupled product 16 in 40% yield together with a sim-
ply reduced product 17 in 20% yield (Scheme 14).
In order to obtain a deeper insight into the reaction mecha-
nism, a mixture of two cation pools (2 and 7) was reduced elec-
trochemically (Scheme 15). Although the reduction potential
(Ep ¼ ꢁ0:75 V) of 7 is slightly less negative than that of 2,
the reduction took place almost non-selectively to give a mix-
ture of three coupling products (4, 16, and 18). The result is
consistent with the mechanism involving radical coupling,
but mechanisms involving radical–cation coupling and anion–
cation coupling are also possible.
Cathodic Reduction of Cation Pool in the Presence of
Radical Acceptor. Next, we focus on the reduction of the cat-

S. Suga et al.
Bull. Chem. Soc. Jpn., 77, No. 8 (2004) 1549
ion pool in the presence of radical acceptors.16 The radical that
is formed by one-electron reduction of the cation is expected to
add to a carbon–carbon double bond, as shown in Scheme 16.
We also expected that the resulting radical undergoes a subse-
quent one-electron reduction to generate a carbanion species,
which is trapped by a proton. The overall transformation serves
as a formal addition reaction of C–H to C=C.17
Thus, we examined the electrochemical reduction of the N-
acyliminium ion pool (2) in the presence of methyl acrylate
(5 equiv) in order to achieve the addition of the radical inter-
mediate to the carbon–carbon double bond (Scheme 17).18
THF (10 equiv) was added to the anodic solution in order to fa-
cilitate the anodic reaction. We first examined the effect of the
cathode material. As the anode, a carbon rod was used through-
out this study. Surprisingly, a carbon-felt cathode is much bet-
ter than a platinum-plate cathode. When a platinum cathode
was used, the desired product 19 was obtained in 41% yield to-
gether with homo-coupled product 4 in 19% yield. The use of a
platinum cathode resulted in the formation of a significant
amount of homo-coupled product. The use of a zinc rod cathode
gave rise to lower yields of 19 (8%) and 4 (6%).
(Scheme 18). The one-electron reduction of acyliminium ion
2 gives radical 3. Because 3 is a rather electron-rich radical,
it adds to the electron-deficient carbon–carbon double bond
of methyl acrylate (path A). The resulting carbon radical (20)
is an electron-deficient radical, and is therefore easily reduced
to give the corresponding carbanion (21), which is trapped by a
proton to give the final product (19). Another possibility to con-
sider is the pathway via carbanion 9 (path B). Carbanion 9 at-
tacks the carbon–carbon double bond of methyl acrylate to give
carbanion 21.
This reaction, however, suffered from the formation of a 2:1
coupling product (22) (20–40% yield), which might be pro-
duced by the reaction of 21 with 2. A mechanism involving
the reaction of radical 20 with 2 to give 22 seems to be less like-
ly, because 20 is an electron-deficient radical. The addition of
such an electron-deficient radical to an electron-deficient car-
bon–nitrogen double bond does not take place easily.
The problem concerning the formation of 22 was overcome
by the addition of trifluoromethanesulfonic acid (TfOH) as a
proton source (Table 2). Prior to a study of the reduction in
the presence of TfOH, we confirmed that the addition of TfOH
did not affect the N-acyliminium ion 2 appreciably by NMR
spectroscopy. Thus, the reaction was carried out with 50 equiv
of TfOH. The amount of 22 produced was negligible, and the
yield of 19 increased up to 88%. Presumably, the carbanion
intermediate 21 was selectively trapped by a proton to give
19. As for the amount of the radical acceptor, the use of 5 equiv
of methyl acrylate gave the best result.
The following mechanism seems to be reasonable
C
H
- 2e - H+
+ e
C
C
As described previously, the two-electron reduction of 2 to
C
C
C
C
+ e
+ e
N
N
N
N
+ e
path B
C
C
C
C
CO2Me
CO2Me
CO2Me
CO2Me
2
3
9
1
H+
path A
CO2Me
CO2Me
C
H
C
+ e
C
CO2Me
CO2Me
N
N
CO2Me
CO2Me
21
Scheme 16.
20
H+
+ e
2
2
+ 2e
CO2Me
N
CO2Me
CO2Me
CO2Me
N
+
4
N
N
CO2Me
CO2Me
N
CO2Me
19%
CO2Me
2
19
CO2Me
19
41%
22
Scheme 18.
Table 2. Electrochemical Reduction of 2 in the Presence of Methyl AcrylateaÞ
Scheme 17.
Run
TfOH
Methyl acrylate
/equiv
ProductsbÞ/%
/equiv
19
4
22
1
1
2
3
4
5
0
10
50
50
50
5
5
2
5
8
34
66
78
88
83
11
3
0
0
0
28
17
0
0
0
2
1
4
0
0
a) The reactions were carried out in a divided cell using a carbon felt cathode. 0.01 M cation pool
was used. b) GC yields.

1550 Bull. Chem. Soc. Jpn., 77, No. 8 (2004)
Reduction of the Cation Pool
Table 3. Redox-Mediated Coupling of Carbamates and
Activated Olefins via Cation PoolaÞ
that free radical species can be generated by the electrochemi-
cal reduction of a ‘‘cation pool’’ and that they are utilized for
homo-coupling reactions and coupling reactions with activated
olefins. The present work establishes a new strategy for radical-
mediated carbon–carbon bond formation, which opens new op-
portunities to manipulate reactive carbon species using redox
processes in organic synthesis.
Carbamate Activated olefin
Product
YieldbÞ/%
84 (88)
CO2Me
N
N
CO2Me
CO2Me
CO2Me
75
i
CO2 Bu
i
N
CO2 Bu
Experimental
CO2Me
General Remarks. GC analysis was performed on a gas chro-
matograph (SHIMADZU GC-14B) equipped with a flame ioniza-
tion detector using a fused-silica capillary. 1H and 13C NMR spec-
tra were recorded in CDCl3 on a Varian Gemini 2000 spectrometer
or a JEOL ꢀ-500 spectrometer with Me4Si as an internal standard,
unless otherwise noted. NMR spectra of the carbamates were usu-
ally very broad and sometimes separated into two signals due to
their rotamers. Especially in cases where two diastereomers exist,
the 13C NMR spectra were complicated and a few signals were oc-
casionally missing. Mass spectra were obtained on a JEOL JMS
SX-102A mass spectrometer. Elemental analyses were carried
out at the Kyoto University Elemental Analysis Center. IR spectra
were measured with a SHIMADZU FTIR 8100 spectrometer.
Thin-layer chromatography (TLC) was carried out by using Merck
precoated silica gel F254 plates (thickness 0.25 mm). Gel permenta-
tion chromatography (GPC) was carried out on a Japan Analytical
Industry LC-908 equipped with JAIGEL-1H and 2H using CHCl3
as an eluant. All reactions were carried out under an Ar atmo-
sphere, unless otherwise noted.
Materials. Tetrabutylammonium tetrafluoroborate was pur-
chased from TCI and dried at 50 ꢂC/1 mmHg overnight before
use. Dichloromethane was washed with water, distilled from P2O5,
redistilled from dried K2CO3 to remove a trace amount of acid, and
stored over molecular sieves 4A. THF was purchased from Kanto
as a dehydrated solvent.
Cyclic Voltammetry. The cyclic voltammetry of cation pools
was carried out with BAS100B in Bu4NBF4/CH2Cl2 at ꢁ20 ꢂC. A
glassy carbon electrode was used as the cathode and a Pt wire elec-
trode was used as the anode. Ag/Agþ (CH3CN) was used as the
reference electrode. The scan rate was 100 mV/s.
77
CO2Me
CO2Me
N
dr = 59:41c)
CO2Me
CO2Me
CO2Me
32
N
dr = 64:36c)
CO2Me
MeO2C
CO2Me
41d)
CO2Me
CO2Me
N
dr = 48:52c)
CO2Me
39
dr = 48:52c)
CO2Me
CO2Me
MeO2C
CO2Me
O
N
CO2Me
O
71
dr = 73:27c)
N
O
O
CO2Me
12
CN
N
CN
CO2Me
53
63
CO2Me
CO2Me
N
N
COOMe
CO2Me
CO2Me
N
N
COOMe
CO2Me
CO2Me
a) The reaction was carried out with 5–8 equiv of an activated
olefin and 50 equiv of TfOH. The carbon felt was used as the
anode for the generation of the cation pool and as the cathode
for the subsequent reduction of the cation pool (0.01 M). b) Iso-
lated yields. Yield in parentheses was GC yield. c) Diastereom-
er ratio. d) 0.05 M cation pool was used.
N,N0-Bis(methoxycarbonyl)-2,20-bipyrrolidine (4). Typical
Procedure of Homo-Coupling: The electrochemical homo-cou-
pling was carried out in an H-type divided cell (4G glass filter) hav-
ing two chambers: chamber A equipped with a carbon felt elec-
trode (Nippon Carbon JF-20-P7, ca. 320 mg, dried at 250 ꢂC/
1 mmHg for 2 h before use) and a platinum plate electrode (30
mm ꢃ 25 mm); chamber B equipped with a platinum plate elec-
trode (30 mm ꢃ 25 mm) and a carbon-rod electrode (Touhou
Tanso Kougyou ER-38H, diameter 7 mm). In chamber A were
placed 1 (52.6 mg, 0.407 mmol) and 0.3 M Bu4NBF4/CH2Cl2
(8.0 mL). In chamber B were placed trifluoromethanesulfonic acid
(169.8 mg, 1.13 mmol) and 0.3 M Bu4NBF4/CH2Cl2 (8.0 mL).
Constant-current electrolysis (8 mA) was carried out by using a
carbon-felt electrode in chamber A as an anode and a platinum
plate electrode in chamber B as a cathode at ꢁ78 ꢂC with stirring
until 2.5 F/mol of electricity was consumed. Thus, the cation pool
of 2 was generated. After the anodic oxidation of 1 was completed,
to the solution in chamber B was added THF (275.5 mg, 3.82
mmol), which would serve as a substrate for oxidation during the
reduction of 2 in chamber A. Constant-current electrolysis (8
mA) was carried out by using the platinum plate electrode in cham-
ber A as a cathode and the carbon-rod electrode in chamber B as an
generate carbanion 9, followed by nucleophilic addition to the
carbon–carbon double bond to give 19, might be an alternative
pathway (path B), but this possibility is denied by the fact that
the yield of simply reduced product 1 did not increase by the
addition of a large excess amount of TfOH, which should trap
the carbanion 9 to give 1 (Table 2).
The present reaction with activated olefins is generally appli-
cable to other cyclic (1 and 10) and acyclic (13) carbamates, as
shown in Table 3. The corresponding coupling product was ob-
tained in good yields. As an activated olefin, acrylates, meth-
acrylate, crotonate, fumarate, maleate, and ꢀ,ꢁ-unsaturated
lactone were effective, although the yields of the cross-coupled
products depended on the structure of the substrates. The use of
acrylonitrile gave the desired coupling product, but the yield
was very low. The use of methyl vinyl ketone and other ꢀ,ꢁ-
unsaturated ketones resulted in the formation of complex mix-
tures, although the reason is not clear at present.
Conclusion
In conclusion, the research described above demonstrates

S. Suga et al.
Bull. Chem. Soc. Jpn., 77, No. 8 (2004) 1551
ꢂ
ꢂ
1
anode at ꢁ78 C with stirring until 2.0 F/mol of electricity was
consumed. The reaction mixture in chamber A was transferred to
a flask and the solvent was removed under reduced pressure. The
residue was quickly filtered through a short column (10 cm) of sili-
ca gel to remove Bu4NBF4. The silica-gel was washed with ether
(300 mL). The GC analysis of the combined filtrate indicated that 4
was produced in 75% yield. Purification with flash chromatogra-
phy (hexane/EtOAc 2:1 to 1:2) gave the two diastereomers (dia-
stereomer ratio was 51:49). a: GC (tR 11.5 min, column, OV-1;
crease, 10 C/min); TLC Rf 0.25 (hexane/EtOAc 3:1); H NMR
(300 MHz, CDCl3) ꢂ 1.02–1.25 (m, 12H), 2.96–3.40 (m, 4H),
3.66 (s) and 3.70 (s) (total 6H), 3.90–4.41 (m, 2H); 13C NMR (75
MHz, CDCl3) ꢂ 14.3 and 14.6 and 15.0 and 15.1, 15.7 and 16.2
and 16.9 and 17.4, 36.9 and 38.6, 52.0 and 52.2, 53.5, 156.0 and
156.3 and 156.6 and 156.9; IR (neat) 1700, 1456, 1271 cmꢁ1
;
LRMS (EI) m=e 260 (Mþ), 130 (Mþ ꢁ C6H12NO2); HRMS (EI)
calcd for C12H24N2O4 260.1736, found 260.1732.
N,N0-Dibutyl-N,N0-bis(methoxycarbonyl)-1,2-ethanediamine
(16). Prepared from cation pool 7 (8.0 mL, 0.426 mmol) and pu-
rified by flash chromatography (hexane/EtOAc 10:1 to 5:1) (24.0
mg, 39%). TLC Rf 0.27 (hexane/EtOAc 3:1); 1H NMR (300
MHz, CDCl3) ꢂ 0.91 (t, J ¼ 7:2 Hz, 6H), 1.17–1.40 (m, 4H),
1.40–1.59 (m, 4H), 3.15–3.43 (m, 8H), 3.67 (s, 6H); 13C NMR
(100 MHz, CDCl3) ꢂ 13.9, 20.0, 30.4 and 30.9, 45.0 and 45.6
and 45.7 and 46.3, 47.8 and 48.0, 52.5, 156.6 and 156.7; IR (neat)
2959, 1699, 1480, 1229 cmꢁ1; LRMS (FAB) m=e 289 (MHþ), 257
(Mþ ꢁ OMe), 158 (Mþ ꢁ C6H12NO2); HRMS (FAB) calcd for
C14H29N2O4 (MHþ) 289.2127, found 289.2122.
ꢂ
0.25 mm ꢃ 25 m; oven temperature, 100 C; rate of temperature
increase, 10 ꢂC/min); TLC Rf 0.33 (hexane/EtOAc 1:1); 1H NMR
(300 MHz, CDCl3) ꢂ 1.58–2.10 (m, 8H), 3.21–3.44 (m, 4H), 3.69
(s, 6H), 3.86–4.26 (m, 2H); 13C NMR (125.65 MHz, CDCl3) ꢂ 22.8
and 23.0 and 23.3 and 23.5, 26.6 and 27.6 and 28.0 and 28.8, 46.4
and 47.3, 52.2, 58.3 and 59.4 and 59.8 and 60.4, 155.9 and 156.0
and 156.7; IR (KBr) 1694, 1377, 1113 cmꢁ1; LRMS (EI) m=e
256 (Mþ), 128 (Mþ ꢁ C6H10NO2); HRMS (EI) calcd for
C12H20N2O4 256.1423, found 256.1422; Anal. Calcd for
C12H20N2O4: C, 56.23; H, 7.87; N, 10.93%. Found: C, 56.02; H,
7.90; N, 10.65%. b: GC (tR 11.2 min, column, OV-1; 0.25 mm
Methyl 2-[(N-Butyl-N-methoxycarbonyl)aminomethyl]pyr-
rolidine-1-carboxylate (18). Prepared from mixture of cation
pools 2 (3.2 mL, 0.171 mmol) and 7 (3.2 mL, 0.160 mmol) and pu-
rified by flash chromatography (hexane/EtOAc 10:1 to 5:1) (11.1
ꢂ
ꢃ 25 m; oven temperature, 100 C; rate of temperature increase,
10 ꢂC/min); TLC Rf 0.23 (hexane/EtOAc 1:1); 1H NMR (300
MHz, CDCl3) ꢂ 1.57–2.20 (m, 8H), 3.21–3.59 (m, 4H), 3.68 (s,
6H), 3.80–4.13 (m, 2H); 13C NMR (125.65 MHz, CDCl3) ꢂ 22.5
and 22.7 and 23.2 and 23.5, 27.6 and 28.4 and 28.5 and 28.7,
46.0 and 46.5 and 46.7 and 47.0, 52.0 and 52.2 and 52.4, 58.8
and 59.1 and 59.5 and 59.7, 155.5 and 155.6 and 155.8 and
155.9; IR (KBr) 1690, 1383, 1111 cmꢁ1; LRMS (EI) m=e 256
(Mþ), 128 (Mþ ꢁ C6H10NO2); HRMS (EI) calcd for C12H20N2O4
256.1423, found 256.1419.
1
mg, 0.0409 mmol): TLC Rf 0.25 (hexane/EtOAc 3:1); H NMR
(300 MHz, CDCl3) ꢂ 0.91 (t, J ¼ 7:2 Hz, 3H), 1.16–1.37 (m,
2H), 1.37–1.62 (m, 2H), 1.62–2.05 (m, 4H), 3.01–3.52 (m, 6H)
3.68 (s, 6H), 3.96–4.07 (m, 1H); 13C NMR (100 MHz, CDCl3) ꢂ
13.9, 20.1, 22.8 and 23.7, 28.1 and 28.8, 30.1 and 30.7, 46.4 and
46.6, 46.9 and 47.2, 47.7 and 48.1, 49.0 and 49.3, 52.3 and 52.5,
55.8 and 56.6, 155.5, 156.6 and 157.6; IR (neat) 2957, 1700,
N,N0-Bis(methoxycarbonyl)-2,20-bipiperidine (12). Prepared
from the cation pool generated from methyl 1-piperidinecarboxyl-
ate (10) (58.4 mg, 0.408 mmol), and purified by flash chromatog-
raphy (hexane/EtOAc 5:1 to 2:1) to give the two diastereomers
(total 22.6 mg, 39%, diastereomer ratio was 42:58). a: GC (tR
15.8 min, column, OV-1; 0.25 mm ꢃ 25 m; oven temperature,
100 ꢂC; rate of temperature increase, 10 ꢂC/min); TLC Rf 0.25
(hexane/EtOAc 3:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.24–1.96
(m, 12H), 2.67–2.88 (m, 2H), 3.69 (s) and 3.71 (s) (total 6H),
3.93–4.20 (m, 2H), 4.49–4.79 (m, 2H); 13C NMR (75 MHz,
CDCl3) ꢂ 18.9 and 19.0 and 19.2 and 19.3, 24.4 and 24.6 and
24.7 and 24.9, 25.1 and 25.4, 39.5 and 39.8, 47.7 and 47.7 and
48.1 and 48.1, 52.6, 156.1 and 156.2; IR (KBr) 1685, 1441, 1380
cmꢁ1; LRMS (EI) m=e 284 (Mþ), 142 (Mþ ꢁ C7H12NO2); HRMS
(EI) calcd for C14H24N2O4 284.1736, found 284.1728. b: GC (tR
15.8 min, column, OV-1; 0.25 mm ꢃ 25 m; oven temperature,
100 ꢂC; rate of temperature increase, 10 ꢂC/min); TLC Rf 0.13
(hexane/EtOAc 3:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.24–1.86
(m, 12H), 2.92–3.23 (m, 2H), 3.64 (s, 6H), 3.84–4.12 (m, 2H),
4.44–4.80 (m, 2H); 13C NMR (75 MHz, CDCl3) ꢂ 18.9 and 19.0,
25.1 and 25.2 and 25.4, 25.8 and 25.9 and 26.3, 39.1 and 39.4
and 39.6 and 39.8, 48.1 and 48.2 and 48.6 and 48.7, 52.4 and
52.5, 156.2 and 156.4; IR (neat) 1700, 1455, 1260 cmꢁ1; LRMS
(EI) m=e 284 (Mþ), 142 (Mþ ꢁ C7H12NO2); HRMS (EI) calcd
for C14H24N2O4 284.1736, found 284.1730.
1456, 1385 cmꢁ1; LRMS (FAB) m=e 273 (MHþ), 241 (Mþ
ꢁ
OMe), 128 (Mþ ꢁ C7H14NO2); HRMS (FAB) calcd for
C13H25N2O4 (MHþ) 273.1814, found 273.1813.
Methyl 2-[2-(Methoxycarbonyl)ethyl]pyrrolidine-1-carbox-
ylate (19). Typical Procedure of Reductive Coupling of Cation
Pool and Activated Olefin: Electrochemical reductive coupling
was carried out in an H-type divided cell (4G glass filter) having
two chambers: chamber A equipped with a carbon-fꢂelt electrode
(Nippon Carbon JF-20-P7, ca. 320 mg, dried at 250 C/1 mmHg
for 2 h before use); chamber B equipped with a platinium plate
electrode (30 mm ꢃ 25 mm) and a carbon-rod electrode (Touhou
Tanso Kougyou ER-38H, diameter 7 mm). In chamber A were
placed 1 (51.4 mg, 0.398 mmol) and 0.06 M Bu4NBF4/CH2Cl2
(40.0 mL). In chamber B were placed trifluoromethanesulfonic
acid (143.8 mg, 0.958 mmol) and 0.06 M Bu4NBF4/CH2Cl2
(40.0 mL). Constant-current electrolysis (8 mA) was carried out
by using the carbon-felt electrode in chamber A as an anode and
the platinum-plate electrode in chamber B as a cathode at ꢁ78
ꢂC with stirring until 2.5 F/mol of electricity was consumed. Thus,
the cation pool of 2 was genarated. After the anodic oxidation of 1
was completed, methyl acrylate (171.5 mg, 1.99 mmol) and tri-
fluoromethanesulfonic acid (3.124 g, 20.8 mmol) were added to
the solution in chamber A. To the solution in chamber B was added
THF (261.3 mg, 3.62 mmol), which would serve as a substrate for
oxidation during the reduction of 2 in chamber A. Constant-current
electrolysis (8 mA) was carried out using the carbon felt electrode
in chamber A as a cathode and the carbon-rod electrode in chamber
B as an anode at ꢁ78 ꢂC with stirring until 2.5 F/mol of electricity
was consumed. Et3N (2.157 g, 21.3 mmol) was added to the solu-
tion in chamber A to neutralize the reaction mixture and the mix-
ture was warmed to room temperature. The reaction mixture in the
chamber A was transferred to a flask and the solvent was removed
N,N0-Diethyl-N,N0-bis(methoxycarbonyl)-2,3-butanediamine
(15). Prepared from the cation pool generated from methyl dieth-
ylcarbamate (13) (54.5 mg, 0.415 mmol), and purified by flash
chromatography (hexane/EtOAc 5:1) (36.6 mg, 68%). This com-
pound was characterized as a mixture of two diastereomers
(48:52 by GC): GC (tR 10.4 and 11.0 min, column, OV-1; 0.25
ꢂ
mm ꢃ 25 m; oven temperature, 100 C; rate of temperature in-

1552 Bull. Chem. Soc. Jpn., 77, No. 8 (2004)
Reduction of the Cation Pool
under reduced pressure. The residue was quickly filtered through a
short column (10 cm) of silica-gel to remove Bu4NBF4. The silica-
gel was washed with ether (300 mL). The GC analysis of the com-
bined filtrate indicated that 6 was produced in 88% yield. The
crude product was purified by flash chromatography (hexane/
EtOAc 7:1 to 5:1): GC (tR 8.2 min, column, OV-1; 0.25 mm ꢃ
155.6, 176.8; IR (neat) 1730, 1700, 1387 cmꢁ1; LRMS (EI) m=e
229 (Mþ), 142 (Mþ ꢁ C4H7O2), 128 (Mþ ꢁ C5H9O2); HRMS
(EI) calcd for C11H19NO4 229.1314, found 229.1307; Anal. Calcd
for C11H19NO4: C, 57.62; H, 8.35; N, 6.11%. Found: C, 57.53; H,
8.11; N, 6.01%.
Methyl 2-(2-Methoxycarbonyl-1-methylethyl)pyrrolidine-1-
carboxylate. Prepared from the cation pool that was generated
from 1 (52.9 mg, 0.410 mmol) and methyl crotonate (792.4 mg,
7.91 mmol), and purified by flash chromatography (hexane/EtOAc
7:1) (29.9 mg, 32%). This compound was characterized as a mix-
ture of two diastereomers (64:36 by GC): GC (tR 8.5 and 8.7 min,
column, OV-1; 0.25 mm ꢃ 25 m; oven temperature, 100 ꢂC; rate of
ꢂ
25 m; oven temperature, 100 C; rate of temperature increase, 10
ꢂC/min); TLC Rf 0.45 (hexane/EtOAc 1:1); 1H NMR (300
MHz, CDCl3) ꢂ 1.60–2.12 (m, 6H), 2.25–2.43 (m, 2H), 3.27–
3.56 (m, 2H), 3.68 (s, 3H), 3.68 (s, 3H), 3.79–3.94 (m, 1H);
13C NMR (125.65 MHz, CDCl3) ꢂ 22.6 and 23.4, 29.1 and 29.3,
29.7, 30.4 and 30.7, 45.9 and 46.2, 51.1, 51.8, 56.0 and 56.8,
155.4, 173.3 and 173.4; IR (neat) 1748, 1700, 1385 cmꢁ1; LRMS
(EI) m=e 215 (Mþ), 128 (Mþ ꢁ C4H7O2); HRMS (EI) calcd for
C10H17NO4 215.1158, found 215.1159; Anal. Calcd for
C10H17NO4: C, 55.80; H, 7.96; N, 6.51%. Found: C, 55.67; H,
8.10; N, 6.29%.
Methyl 1,2-Bis(N-carbomethoxypyrrolidin-2-yl)propanoate
(22). This compound was obtained as a by-product in the reduc-
tive coupling of the cation pool 2 and methyl acrylate. Purified by
flash chromatography (hexane/EtOAc 1:1 to 1:2) and GPC: TLC
Rf 0.23 (hexane/EtOAc 1:1); 1H NMR (300 MHz, CDCl3) ꢂ
1.37–2.21 (m, 9H), 2.21–2.46 (m, 2H), 3.20–3.55 (m, 4H), 3.65
(s, 3H), 3.65 (s, 3H), 3.70 (s, 3H), 3.81–4.23 (m, 2H); 13C NMR
(125.65 MHz, CDCl3) ꢂ 22.6 and 22.8 and 22.9 and 23.1, 23.4
and 23.5 and 23.7 and 27.9 and 28.1, 29.4 and 29.7, 30.4 and
30.6 and 30.8 and 31.1, 32.7 and 33.3 and 33.5 and 33.6 and
34.0, 43.1 and 43.4 and 44.0 and 44.3 and 44.5 and 44.6 and
45.1, 46.0 and 46.2 and 46.4, 46.9 and 47.4, 51.5, 51.9 and 52.0,
52.1 and 52.3, 55.4 and 55.6 and 55.9 and 56.2, 58.2 and 58.8
and 59.0 and 59.2 and 60.1, 155.3, 155.4, 173.8 and 174.3; IR
(neat) 1732, 1700, 1387 cmꢁ1; LRMS (EI) m=e 342 (Mþ), 128
ꢂ
temperature increase, 10 C/min); TLC Rf 0.52 (hexane/EtOAc
1:1); 1H NMR (300 MHz, CDCl3) ꢂ 0.78–0.94 (m, 3H), 1.56–
1.98 (m, 4H), 1.98–2.17 (m, 1H), 2.24–2.70 (m, 2H), 3.14–3.27
(m, 1H), 3.27–3.46 (m, 1H), 3.64 (s, 3H), 3.68 (s, 3H), 3.72–
3.90 (m, 1H); 13C NMR (125.65 MHz, CDCl3) ꢂ 15.6 and 15.9
and 16.7, 23.2 and 23.6 and 23.9 and 24.3, 26.3 and 27.2 and
27.6, 32.8 and 33.2 and 36.4 and 36.7, 33.6 and 38.5, 46.4 and
46.9 and 47.1 and 47.6, 51.4, 52.2, 60.9 and 61.2 and 61.7 and
61.9, 156.0, 173.4 and 173.5; IR (neat) 1738, 1699, 1379 cmꢁ1
;
LRMS (EI) m=e 229 (Mþ), 128 (Mþ ꢁ C5H9O2); HRMS (EI)
calcd for C11H19NO4 229.1314, found 229.1316; Anal. Calcd for
C11H19NO4: C, 57.62; H, 8.35; N, 6.11%. Found: C, 57.75; H,
8.06; N, 5.88%.
Methyl
2-[1,2-Bis(methoxycarbonyl)ethyl]pyrrolidine-1-
carboxylate. Prepared from the cation pool that was generated
from 1 (51.0 mg, 0.395 mmol) and dimethyl fumarate (455.7
mg, 3.16 mmol), and purified by flash chromatography (hexane/
EtOAc 3:1) (41.8 mg, 39%). This compound was characterized
as a mixture of two diastereomers (53:47 by GC): GC (tR 13.4
and 13.6 min, column, OV-1; 0.25 mm ꢃ 25 m; oven temperature,
100 ꢂC; rate of temperature increase, 10 ꢂC/min); TLC Rf 0.44
(hexane/EtOAc 1:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.63–2.00
(m, 4H), 2.24–2.53 (m, 1H), 2.64–2.82 (m, 1H), 3.08–3.32 (m,
1H), 3.32–3.78 (m, 2H), 3.62 (s, 3H), 3.66 (s, 3H), 3.66 (s, 3H),
4.02–4.30 (m, 1H); 13C NMR (125.65 MHz, CDCl3) ꢂ 22.7 and
23.5 and 24.1, 27.2 and 28.1 and 29.2, 30.5 and 30.9 and 33.0
and 33.4, 42.2 and 43.5 and 44.2 and 44.5, 46.3 and 46.8 and
47.0 and 47.6, 51.7, 52.0, 52.4, 57.2 and 57.6 and 58.2 and 58.8,
155.6, 172.2, 173.5; IR (neat) 1737, 1700, 1383 cmꢁ1; LRMS
(EI) m=e 273 (Mþ), 200 (Mþ ꢁ C3H5O2), 128 (Mþ ꢁ C6H9O4);
HRMS (EI) calcd for C12H19NO6 273.1212, found 273.1206.
Methyl 2-(2-Oxooxolane-2-ylmethyl)pyrrolidine-1-carbox-
ylate. Prepared from the cation pool that was generated from 1
(51.8 mg, 0.401 mmol) and ꢀ-methylene-ꢃ-butyrolactone (196.8
mg, 2.01 mmol), and purified by flash chromatography (hexane/
EtOAc 3:1) (65.0 mg, 71%). This compound was characterized
as a mixture of two diastereomers (73:27 by GC): GC (tR 14.2
and 14.3 min, column, OV-1; 0.25 mm ꢃ 25 m; oven temperature,
100 ꢂC; rate of temperature increase, 10 ꢂC/min); TLC Rf 0.23
(hexane/EtOAc 1:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.32–1.77
(m, 2H), 1.77–2.27 (m, 5H), 2.34–2.88 (m, 2H), 3.20–3.57 (m,
2H), 3.64 (s, 3H), 3.76–4.11 (m, 1H), 4.11–4.25 (m, 1H), 4.25–
4.41 (m, 1H); 13C NMR (125.65 MHz, CDCl3) ꢂ 22.6 and 22.8
and 23.5, 28.5 and 31.1, 29.3 and 29.5, 35.1 and 36.6, 35.6 and
37.3, 46.0 and 46.4, 52.2, 55.2 and 55.5 and 56.3, 66.4 and 66.6,
155.5 and 155.7 and 156.5, 179.1 and 179.2 and 179.7; IR (neat)
(Mþ
ꢁ
C10H16NO4); HRMS (EI) calcd for C16H26N2O6
342.1791, found 342.1785; Anal. Calcd for C16H26N2O6: C,
56.13; H, 7.65; N, 8.18%. Found: C, 55.95; H, 7.67; N, 7.92%.
Methyl
2-[2-(Isobutoxycarbonyl)ethyl]pyrrolidine-1-car-
boxylate. Prepared from the cation pool that was generated from
1 (51.5 mg, 0.399 mmol) and isobutyl acrylate (407.5 mg, 3.18
mmol), and purified by flash chromatography (hexane/EtOAc
7:1) (77.3 mg, 75%): TLC Rf 0.65 (hexane/EtOAc 1:1); 1H NMR
(300 MHz, CDCl3) ꢂ 0.91 (d, J ¼ 6:6 Hz, 6H), 1.57–1.76 (m, 2H),
1.76–2.06 (m, 5H), 2.24–2.39 (m, 2H), 3.25–3.53 (m, 2H), 3.66 (s,
3H), 3.77–3.93 (m, 1H), 3.83 (d, J ¼ 6:6 Hz, 2H); 13C NMR
(125.65 MHz, CDCl3) ꢂ 19.0, 22.9 and 23.7, 27.6, 29.4 and 29.6,
29.9 and 30.6, 31.0 and 31.2, 46.1 and 46.5, 52.1, 56.4 and 57.1,
70.5, 155.7, 173.3 and 173.4; IR (neat) 1734, 1700 1385 cmꢁ1
;
LRMS (EI) m=e 257 (Mþ), 128 (Mþ ꢁ C7H13O2); HRMS (EI)
calcd for C13H23NO4 257.1627, found 257.1633.
Methyl 2-[2-(Methoxycarbonyl)propyl]pyrrolidine-1-car-
boxylate. Prepared from the cation pool that was generated from
1 (51.4 mg, 0.398 mmol) and methyl methacrylate (314.3 mg, 3.14
mmol), and purified by flash chromatography (hexane/EtOAc 7:1)
(70.7 mg, 77%). This compound was characterized as a mixture of
two diastereomers (59:41 by GC): GC (tR 8.3 and 8.5 min, column,
OV-1; 0.25 mm ꢃ 25 m; oven temperature, 100 ꢂC; rate of temper-
ature increase, 10 ꢂC/min); TLC Rf 0.52 (hexane/EtOAc 1:1);
1H NMR (300 MHz, CDCl3) ꢂ 1.08–1.43 (m, 3H), 1.51–1.68 (m,
1H), 1.68–1.97 (m, 4H), 1.97–2.22 (m, 1H), 2.38–2.63 (m, 1H),
3.24–3.50 (m, 2H), 3.65 (s, 3H), 3.66 (s, 3H), 3.76–4.02 (m,
1H); 13C NMR (125.65 MHz, CDCl3) ꢂ 17.6, 22.8 and 23.7, 29.9
and 30.5 and 30.9, 36.6 and 37.8 and 38.4 and 38.6 and 38.8,
36.9, 46.0 and 46.3, 51.5, 52.0 and 52.1, 55.2 and 55.6 and 56.2,
1770, 1695, 1385 cmꢁ1; LRMS (EI) m=e 227 (Mþ), 196 (Mþ
ꢁ
OCH3), 128 (Mþ ꢁ C5H7O2); HRMS (EI) calcd for C11H17NO4
227.1158, found 227.1160.
Methyl 2-[2-(Methoxycarbonyl)ethyl]piperidine-1-carbox-

S. Suga et al.
Bull. Chem. Soc. Jpn., 77, No. 8 (2004) 1553
ylate. Prepared from the cation pool that was generated from N-
(methoxycarbonyl)piperidine (51.8, 0.362 mmol) and methyl acry-
late (151.2 mg, 1.756 mmol), and purified by flash chromatography
(hexane/EtOAc 10:1) (45.4 mg, 53%): TLC Rf 0.39 (hexane/
EtOAc 3:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.28–1.47 (m, 1H),
1.50–1.76 (m, 6H), 2.02–2.21 (m, 1H), 2.23–2.35 (m, 2H), 2.72–
2.87 (m, 1H), 3.66 (s, 3H), 3.66 (s, 3H), 3.84–4.12 (m, 1H),
4.12–4.41 (m, 1H); 13C NMR (75 MHz, CDCl3) ꢂ 18.9, 24.8,
25.4, 28.7, 30.8, 38.8, 50.1, 51.5, 52.4, 156.1, 173.8; IR (neat)
Chemical oxidation: For example, see: i) C.-K. Chen, A. G.
Hortmann, and M. R. Marzabadi, J. Am. Chem. Soc., 110, 4829
(1988).
5
For example, T. Shono, ‘‘The Chemistry of Ethers, Crown
Ethers, Hydroxyl Groups and Their Sulphur Analogues,’’ ed by
S. Patai, Wiley, New York (1980), Chap. 8.
6
Chemistry of Carbocations: For example, a) ‘‘Stable Carbo-
cation Chemistry,’’ ed by G. K. S. Prakash and P. v. R. Schleyer,
Wiley, New York (1997). b) G. A. Olah, K. K. Laali, Q. Wang,
and G. K. S. Prakash, ‘‘Onium Ions,’’ Wiley, New York (1998).
1741, 1700, 1444 cmꢁ1; LRMS (EI) m=e 229 (Mþ), 170 (Mþ
ꢁ
C2H3O2), 142 (Mþ ꢁ C4H7O2); HRMS (EI) calcd for C11H19NO4
7
a) J. Yoshida, S. Suga, S. Suzuki, N. Kinomura, A.
229.1314, found 229.1318.
Yamamoto, and K. Fujiwara, J. Am. Chem. Soc., 121, 9546
(1999). b) S. Suga, M. Okajima, and J. Yoshida, Tetrahedron Lett.,
42, 2173 (2001). c) S. Suga, S. Suzuki, and J. Yoshida, J. Am.
Chem. Soc., 124, 30 (2002). d) S. Suga, M. Watanabe, and J.
Yoshida, J. Am. Chem. Soc., 124, 14824 (2002). e) S. Suga, A.
Nagaki, and J. Yoshida, Chem. Commun., 2003, 354. f) S. Suga,
A. Nagaki, Y. Tsutsui, and J. Yoshida, Org. Lett., 5, 945 (2003).
See also for cation flow method: g) S. Suga, M. Okajima, K.
Fujiwara, and J. Yoshida, J. Am. Chem. Soc., 123, 7941 (2001).
For review, see; h) J. Yoshida and S. Suga, Chem.—Eur. J., 8,
2650 (2002).
Methyl 4-[(N-Ethyl-N-methoxycarbonyl)amino]pentanoate.
Prepared from the cation pool that was generated from N-(methoxy-
carbonyl)diethylamine (53.2 mg, 0.406 mmol) and methyl acrylate
(181.5 mg, 2.11 mmol), and purified by flash chromatography
(hexane/EtOAc 10:1) (56.0 mg, 63%): TLC Rf 0.33 (hexane/
EtOAc 3:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.07–1.21 (m, 3H),
1.17 (d, J ¼ 6:9 Hz, 3H), 1.68–1.92 (m, 2H), 2.28 (t, J ¼ 7:4
Hz, 2H), 2.96–3.39 (m, 2H), 3.66 (s, 3H), 3.68 (s, 3H), 3.87–
4.25 (m, 1H); 13C NMR (125.65 MHz, CDCl3) ꢂ 14.7 and 15.4,
19.0 and 19.5, 29.5, 31.1, 37.3 and 37.9, 51.2, 51.4, 52.1, 156.4
and 156.8, 173.6; IR (neat) 1736, 1700, 1439 cmꢁ1; LRMS (EI)
m=e 217 (Mþ), 158 (Mþ ꢁ C2H3O2), 130 (Mþ ꢁ C4H7O2); HRMS
(EI) calcd for C10H19NO4 217.1314, found 217.1317.
8
a) J. B. Conant and A. W. Sloan, J. Am. Chem. Soc., 45,
2466 (1923). b) J. B. Conant, L. F. Small, and B. S. Taylor, J.
Am. Chem. Soc., 47, 1959 (1925). c) J. B. Conant and B. F. Chow,
J. Am. Chem. Soc., 55, 3752 (1933). See also, d) H. Volz and W.
Lotsch, Tetrahedron Lett., 10, 2275 (1969). e) K. Okamoto, K.
Komatsu, O. Murai, and O. Sakaguchi, Tetrahedron Lett., 13,
4989 (1972).
Methyl 2-(2-Cyanoethyl)pyrrolidine-1-carboxylate.
Pre-
pared from cation pool 2 (8.0 mL, 0.390 mmol) and acrylonitrile
(107.0 mg, 2.017 mmol), and purified by flash chromatography
(hexane/EtOAc 2:1) (8.6 mg, 12%). TLC Rf 0.33 (hexane/EtOAc
1:1); 1H NMR (300 MHz, CDCl3) ꢂ 1.54–2.11 (m, 6H), 2.29–2.47
(m, 2H), 3.27–3.58 (m, 2H), 3.69 (s, 3H), 3.87–3.99 (m, 1H);
13C NMR (100 MHz, CDCl3) ꢂ 14.6, 23.2 and 23.9, 30.5 and
30.9, 30.7, 46.6, 52.5, 56.9, 119.6, 155.5; IR (neat) 2957, 1696,
1456, 1385 cmꢁ1; LRMS (EI) m=e 182 (Mþ), 128 (Mþ ꢁ C3H4N);
HRMS (EI) calcd for C9H14N2O2 182.1055, found 182.1054.
´
a) C. P. Andrieux and J. M. Saveant, Bull. Soc. Chim. Fr.,
1968, 4671. b) C. P. Andrieux and J. M. Saveant, J. Electroanal.
9
´
´
Chem., 26, 223 (1970). c) C. P. Andrieux and J. M.Saveant, J. Elec-
troanal. Chem., 28, 446 (1970). See also, d) J. B. Kerr and P. E.
Iversen, Acta Chem. Scand., Ser. B, 32, 405 (1978).
10 a) D. D. M. Wayner, D. J. McPhee, and D. Griller, J. Am.
Chem. Soc., 110, 132 (1988). b) B. A. Sim, D. Griller, and D. D.
M. Wayner, J. Am. Chem. Soc., 111, 754 (1989). c) B. A. Sim,
P. H. Milne, D. Briller, and D. D. M. Wayner, J. Am. Chem.
Soc., 112, 6635 (1990). See also, d) H. Lund, K. Daasbjerg, T.
Lund, D. Occhialini, and S. U. Pedersen, Acta Chem. Scand., 51,
135 (1997).
11 a) E. M. Arnett, K. E. Molter, E. C. Marchot, W. H.
Donovan, and P. Smith, J. Am. Chem. Soc., 109, 3788 (1987).
b) E. M. Arnett, R. A. Flowers, II, A. E. Meekhof, and L. Miller,
J. Am. Chem. Soc., 115, 12603 (1993).
This work is partially supported by Grants-in-Aid for Scien-
tific Research from the Ministry of Education, Culture, Sports,
Science and Technology.
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4
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1554 Bull. Chem. Soc. Jpn., 77, No. 8 (2004)
Reduction of the Cation Pool
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