Intramolecular acceleration effect of a tosylamide group on the electrochemical oxidation of N-α-silylalkyl amides

Article abstract of DOI:10.1039/b111106j

In electrochemical oxidation, N-alkyl-N-α-silylalkyl (N-tosyl)amino acid amides react faster than N-alkyl-N-α-silyl-alkyl aliphatic amides. This phenomenon is due to the two roles of the tosylamide moiety. One is the assistance in release of the silyl cat

Full text of DOI:10.1039/b111106j

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Intramolecular acceleration effect of a tosylamide group on the
electrochemical oxidation of N-ꢀ-silylalkyl amides
Tohru Kamada* and Akira Oku
1
Department of Chemistry and Materials Technology, Faculty of Engineering and Design,
Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
E-mail: kamada@chem.kit.ac.jp; Fax: 81-75-724-7580; Tel: 81-75-724-7528
Received (in Cambridge, UK) 5th December 2001, Accepted 11th March 2002
First published as an Advance Article on the web 26th March 2002
In electrochemical oxidation, N-alkyl-N-α-silylalkyl (N-tosyl)amino acid amides react faster than N-alkyl-N-α-silyl-
alkyl aliphatic amides. This phenomenon is due to the two roles of the tosylamide moiety. One is the assistance in
release of the silyl cation by the tosylamide moiety to transform the cation radical, which possesses a higher oxidation
potential, to the radical which possesses a lower oxidation potential. Another is the stabilization of the cation radical
by the coordination of the tosylamide moiety to the positively charged silyl atom of the cation radical to shift the
equilibrium of the first one-electron oxidation to the more stable side.
Introduction
Organonitrogen compounds are important as precursors in the
synthesis of biologically active compounds such as alkaloids,
pharmaceuticals and agrochemicals. In the chemical trans-
formation of organonitrogen compounds to such chemicals,
activation of a carbon atom alpha to nitrogen is often neces-
sary. For this purpose, alkoxylation on an α-carbon atom of
an amide or carbamate nitrogen atom by electrochemical oxid-
ation is a versatile method.1 We modified this method, and
succeeded in stereoselective electrochemical alkoxylation on the
α-carbon of an amide nitrogen atom by use of lactic acid
derivatives as the acid part of the amides (Chart 1).2
Chart 2
to the positively charged silyl atom to lower its oxidation poten-
tial.4 The amino acid amides shown in Chart 2 are also silyl
compounds which possess nitrogen substituents. For these
compounds, we examined whether the same coordination effect
would be observed, and if an acceleration effect in the electro-
chemical oxidation would be observed. We will report in this
paper about the acceleration effect in detail.
Results and discussion
In the generation of imines and iminium cations by electro-
chemical oxidation, the protection of amines with electron-
withdrawing groups as amides or carbamates prior to oxidation
is necessary.5 In the use of an amino acid as a protecting group
for amines, the amino group of the amino acid must also be
Chart 1
In this reaction, the stereoselectivity is affected by the relative
nucleophilic strength of the methoxy group of the lactic acid as
the internal nucleophile compared with the external nucleo-
philic alcohol. For alkoxylation to proceed stereoselectively,
the internal nucleophilic methoxy group should attack the
electrochemically generated iminium cation to yield the cyclic
oxonium ion intermediate in preference to any attack by the
external nucleophile. Therefore, in order to improve the stereo-
selectivity, a stronger internal nucleophile is necessary. On the
basis that a nitrogen atom is more nucleophilic than an oxygen
atom, the nitrogen-homologue of lactic acid derivatives, i.e.,
amino acid derivatives, was examined as the acid part of the
amides (Chart 2).3
protected. The protecting group must be resistant to electro-
chemical oxidation, and stable under acidic and basic con-
ditions, because the vicinity of electrodes is usually acidic
or basic. The tosylamide group should be stable under such
conditions, and was proved to be more nucleophilic than carb-
amates by our previous study.3 For these reasons, tosylation was
adopted as protection for the amino group of amino acids.
First, in order to confirm the effectiveness of tosylation to
protect the amino group of amino acids in electrochemical
oxidation, a competitive electrochemical oxidation between 1
and 2 was carried out; 2 was oxidized to decomposition pro-
ducts selectively, whereas 1 was recovered quantitatively (Table
1, entry 1).
Yoshida et al. reported that in electrochemical oxidation of
silyl compounds, an intramolecular pyridinyl group coordinates
The electron-withdrawing character of the tosyl group is
stronger than that of the acetyl group. Therefore, the oxidation
DOI: 10.1039/b111106j
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Table 1 Competitive reactions in the absence of methanola
Entry
1
Substrates (recovered ratio)
2
3
4
2 (99%)
2 (92%)
3 (59%)
4 (100%)
a Conditions: see experimental part.
potential of an N-alkyltosylamide should be higher than that of
an N-alkylacetamide. Furthermore, the interaction between a
3d-orbital of a silyl atom and the π electrons of amide nitrogen
atom in 2 lowers the oxidation potential of amides.6 As a result
of these two factors, the oxidation potential of 2 becomes lower
than that of 1, and only 2 was oxidized.
To confirm that the oxidation potential of 1 is higher than
that of 2, the cyclic voltammetry for 1 and 2 was measured
(Fig. 1).
Substrate 2 showed a peak of oxidative current at 1.3 V
vs. Ag/Agϩ, while 1 showed no oxidative current below 1.8 V vs.
Ag/Agϩ.
From the above results, the effectiveness of tosylation to
protect the amino group in the electrochemical oxidation of
N-α-silylalkyl aliphatic amide has been proved.
Next, in order to examine the electrochemical effect of an
intramolecular tosylamide moiety,
a competitive electro-
chemical oxidation between 2 and 3 was carried out (Table 1,
entry 2).
After 1.5 F molϪ1 of electricity for 2 and 3 was passed, 30%
of 3 was oxidized, and 2 was recovered quantitatively. These
two substrates have the same reaction center, N-α-(dimethyl-
phenyl)silylalkyl amide structure.7 The presence or absence
of an intramolecular tosylamide moiety, causes the different
electrochemical behavior between 2 and 3.
Fig. 1 Cyclic voltammetry of 1, 2, 3 and 4 in the absence of methanol.
Conditions; [sub] = 0.01 M, [Et4NBF4] = 0.05 M in acetonitrile, scan
rate = 50 mV sϪ1, working electrode (W.E.); 2 × 1 cm2 Pt plate, counter
electrode (C.E.); 2 × 1 cm2 Pt plate, reference electrode (R.E.); Ag/
AgNO3/MeCN (BAS RE-5).
In order to confirm this hypothesis, another competitive reac-
tion between 2 and 4 was carried out, and resulted in selective
oxidation of 4 (Table 1, entry 3).
In another competitive reaction between 3 and 4, 3 was
oxidized preferentially (Table 1, entry 4).
To summarize these competitive reactions, the order in the
reactivities of 2, 3 and 4 under electrochemical oxidation is
revealed as shown in Fig. 2.
In the absence of external nucleophiles, electrochemical
oxidation of 2, 3 and 4 yielded tarry compounds. In order to
obtain products, a competitive reaction between 2 and 3 in the
presence of methanol as an external nucleophile was carried
out (Chart 3). In addition to a small amount of tarry com-
pounds, N-methylacetamide 58 from 2, and a methoxylated
compound 6 from 3 were obtained, whereas the selectivity
observed in the absence of external nucleophiles disappeared.
Some selective electrochemical oxidations proceed as the
result of the selective adsorption of substrates onto the elec-
trode surface.9 In our cases, the disappearance of the selectivity
in the presence of methanol means that the selective adsorption
of substrates onto the electrode surface is not the main factor
for the selectivity.
Fig. 2 The order of reactivities and 1H-NMR chemical shift of the
methyl on the silyl atom.
Substrates 3 and 4, which possess a tosylamide moiety, were
electrochemically oxidized predominantly over 2, which does
not possess a tosylamide moiety. This fact indicates that the
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This explanation is supported by the experiments in the
presence of methanol, in which the selectivity disappeared.
Because methanol is more silanophilic than the tosylamide
moiety, the cation radicals of 2 and 3 are equally stabilized. The
fact that substrate 3 was oxidized predominantly over 4 means
that the cation radical of 3 in a six-membered cyclic structure is
more stable than that of 4 in a seven-membered cyclic structure
(Fig. 3).
Chart 3
intramolecular tosylamide moiety makes the reaction center
more sensitive to electrochemical oxidation.
Fig. 3 Intramolecular interaction between the tosylamide moiety and
Substrate 3 was oxidized in preference to 4, which indicates
that the reactivity is affected by the spatial distance between the
tosylamide moiety and the reaction center. In such a case, the
tosylamide moiety may act as an electron carrier from anode
to the reaction center. However, oxidation at the tosylamide
moiety does not occur prior to the oxidation of the reaction
center, because the cyclic voltammetry measurement of 1 and 2
suggests that the oxidation potential of the tosylamide moiety
should be higher than that of the reaction center (Fig. 1).
It is reported that an intramolecular interaction toward the
reaction center at which electron transfer occurs, affects the
redox potential of the molecule.10 If such an interaction exists
between the tosylamide moiety and the reaction center, the
tosylamide moiety should interact with the silyl atom, the most
positive atom in the reaction center. As a result, the environ-
ment around the silyl substituent of 3 and 4 should alter com-
the silyl atom.
Todd et al. reported that in photochemical oxidation of
benzyltrialkylsilane, a nucleophile assists carbon–silane bond
cleavage via an SN2-like mechanism to suppress the back-
electron transfer process and accelerate the photochemical
oxidation process.13
Certain N-silylamides are used as silylating reagents.14
Analogously, the tosylamide moiety must be a good silanophile
and N-silyltosylamide should be stable. It is therefore also
possible that the intramolecular tosylamide moiety attacks the
positively charged silyl atom in the cation radical via an SN2-like
mechanism to assist the carbon–silane bond cleavage.
The cation radicals of 3 and 4, which possess the tosylamide
moiety, are quickly converted to the iminium radical to
suppress the back-electron transfer; in the case of 2 the
back-electron transfer is not suppressed. Consequently, via an
electron scrambling among the substrates in the first oxidation,
the substrate in which the back-electron transfer is effectively
suppressed is converted to the iminium radical preferentially
(Scheme 1).
1
pared with 2. To evaluate this interaction, H-NMR chemical
shifts of the methyl group on the silyl atom in 2, 3 and 4 were
measured (Fig. 2).11
Although the extent of the upfield shift was small, the upfield
shift effect was in the same order as the reactivity. The extent of
upfield shift of the most reactive 3 compared with 2 is one order
larger than that of 4. This result shows that the tosylamide
moiety interacts weakly with the silyl atom in the same
molecule, and it is not clear whether such a weak interaction
could alter the reactivity.
Yoshida et al. reported the effect of “dynamic coordination”:
if the electrostatic interaction is weak before the electron trans-
fer process, the larger the charge increases in the process, the
stronger the interaction becomes.12 In his case, the stabilization
of the electron-transfer product by the dynamic coordination
makes the oxidation potential of the substrate lower. Similarly,
if the dynamic coordination occurs in the cases of 3 and 4, their
oxidation potentials should be appreciably different from that
of 2.
Once the iminium radical, which possesses a more negative
oxidation potential than the starting material, is selectively
produced, the subsequent oxidation to an iminium cation
proceeds.
This is also the reason why the selectivity disappeared in the
presence of methanol. In this case, the carbon–silane bond
cleavage is assisted by the more silanophilic methanol, not by
the tosylamide moiety.
In the absence of an external nucleophile, electrochemical
oxidation of 2, 3 and 4 yielded tarry products. In the presence
of trifluoroethanol possessing lower nucleophilicity than
methanol, 3 yielded 7 where the tosylamide moiety attacked
the electrochemically generated iminium ion as an internal
nucleophile (Chart 4).
To examine this, cyclic voltammetry of 3 and 4 was measured
(Fig. 1). Substrates 3 and 4 showed a peak of oxidative current
at 1.3 V vs. Ag/Agϩ, therefore, there is no difference in oxidation
potential among 2, 3 and 4. This means that in the case of 3 and
4, there is no “dynamic coordination effect” on the oxidation
potentials.
Although a clear deviation of the oxidation potentials was
not observed, the electrostatic interaction between the tosyl-
amide moiety and the silyl atom in the reaction center would
become stronger after the first single electron oxidation. There-
fore, the first intermediate, a cation radical, would be stabilized
in the oxidation of 3 and 4, while the cation radical of 2 would
not be stabilized. Because of the similar oxidation potentials
of 2, 3 and 4 as shown in Fig. 1, an intersubstrate electron
transfer “electron scrambling” between the starting materials
and their cation radicals may occur, so that the substrate which
yields more stable cation radical is oxidized selectively in the
competitive oxidation (Scheme 1).
Chart 4
Thus, the tosylamide moiety exhibits nucleophilicity in the
presence of trifluoroethanol in the electrochemical oxidation of
3 to give 7.15 These results suggest that in the cation radical
J. Chem. Soc., Perkin Trans. 1, 2002, 1105–1110
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Scheme 1 Mechanism for the substrate selectivity in the competitive electrochemical oxidation in the absence of external silanopholes.
intermediate, the tosylamide moiety attacks the intramolecular
positively charged silyl atom to assist the carbon–silyl bond
cleavage resulting in an iminium radical, and the tosylamide
moiety traps the silyl cation released in the reaction process, so
that the nucleophilicity of the tosylamide moiety is decreased
(Scheme 1). In the presence of trifluoroethanol, which is more
silanophilic but less nucleophilic than the tosylamide moiety,
the silyl cation trapped by the tosylamide moiety is removed
by trifluoroethanol, and the tosylamide moiety recovers its
nucleophilicity to yield 7.
radical preferentially. These two factors have been proven, in
this study, to govern the substrate selectivity in the competitive
electrochemical oxidation.
The effect of the tosylamide moiety disappeared in the
presence of external nucleophiles (silanophiles). For the pur-
pose of synthetic applications, the selectivity must appear in the
presence of external nucleophiles. We anticipate this problem
will be solved by the use of a multiphase method: the electro-
chemical phase is separated from the chemical phase where an
external nucleophile reacts with an electrochemically generated
reactive intermediate.
This selective electrochemical oxidation will be applicable for
diastereomer separation of N-alkyl-N-α-(dimethylphenyl)silyl-
alkyl amino acid amides. In diastereomers, the magnitude of
the intramolecular interaction between the tosylamide moiety
and the positively charged silyl atom is different for each
diastereomers.
Conclusion
A substrate-selective electrochemical oxidation proceeds in the
competitive reaction between an N-alkyl-N-α-(dimethylphenyl)-
silylalkyl aliphatic amide and its analogous compounds owing
to thermodynamic control and/or kinetic control. The thermo-
dynamic control occurs in the first oxidation, the cation radical
is stabilized more effectively by the intramolecular electrostatic
interaction between the tosylamide moiety and the positively
charged silyl atom, produced predominantly via an electron-
scrambling. For the kinetic control, the cation radical in which
the intramolecular assistance by the tosylamide moiety acceler-
ates the release of the silyl cation is converted to the iminium
Experimental
Tetrahydrofuran (THF), dichloromethane (DCM), dimethyl-
formamide (DMF) and triethylamine (TEA) were purified by
the usual methods16 and other commercially available chem-
1
icals were used without further purification. H NMR and 13C
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NMR spectra were measured in CDCl3 solutions using CHCl3
(δH 7.26) and CDCl3 (δC 77.0) as the internal standards.
Chemical shifts (δ) are given in ppm and the coupling constants
(J) are given in Hz. IR spectra were recorded on a grating IR
spectrometer. High resolution mass spectra were measured by
EI or CI or FAB methods. Cyclic voltammetry was measured
on a potentiostat equipped with a function generator. An Ag/
AgNO3/MeCN electrode (BAS RE-5) was used as a refer-
ence electrode, and platinum plates (2 × 1 cm2) were used as a
working and a counter electrode.
organic extracts were combined, dried over MgSO4, and evap-
orated to give a residue, which was subjected to flash column
chromatography (eluent 20 to 40% ethyl acetate–hexane) to
afford 3 (1.02 g, 61%); δH (a major isomer) 7.76 (2 H, d, J 8.3),
7.44 (2 H, m), 7.32 (2 H, d, J 8.3), 7.34 (3 H, m), 5.70 (1 H, br s),
3.94 (1 H, t, J 7.8), 3.53 (2 H, d, J 16.1), 2.57 (3 H, s), 2.43 (1 H,
s), 1.58 (2 H, dt, J 7.8 and 7.2), 0.70 (3 H, t, J 7.2), 0.29 (3 H, s),
0.26 (3 H, s); δC (a major isomer) 166.3, 143.4, 133.9, 133.8,
133.6, 129.6, 129.4, 127.8, 127.2, 50.9, 43.7, 43.6, 31.9, 20.4,
12.1, Ϫ4.0; νmax/cmϪ1 (KBr) 3230, 2960, 1640, 1390, 1170, 820,
710, 560; m/z (CI) (Found: Mϩ. 419.1822. C21H30N2O3SSi ϩ Hϩ
requires M, 419.1824).
Materials
N-(4-Methylphenyl)sulfonylglycine methyl ester 1
N-1-(Dimethylphenylsilyl)propyl-N-methyl-N’-(4-methylphenyl)-
sulfonyl-ꢁ-alaninamide 4
Compound 1 was obtained from glycine methyl ester by a
general procedure.17
β-Alanine was converted to N-(4-methylphenyl)sulfonyl-β-
alanine by a general procedure.17 A solution of DCC (1.01 g,
4.92 mmol) in dry DCM (4.7 cm3) was added to a suspended
solution of N-(4-methylphenyl)sulfonyl-β-alanine (1.17 g, 4.83
mmol) in dry DCM (60 cm3) at 0 ЊC under N2 atmosphere.
After stirring for 15 min, a solution of N-methyl-1-(dimethyl-
phenylsilyl)propylamine (1.01 g, 4.85 mmol) in dry DCM
(4.7 cm3) was added to the solution. After stirring at ambient
temperature overnight, the resulting white solid was filtered off,
and washed with DCM (30 cm3). The filtrate and the washings
were collected, and washed with water (50 cm3). The organic
portion was dried over MgSO4, and evaporated to give a resi-
due, which was subjected to flash column chromatography
(eluent 20 to 80% ethyl acetate–hexane) to afford the title com-
pound (1.99 g, 95%); δH (a major isomer) 7.76 (2 H, d, J 8.1),
7.49 (2 H, m), 7.37 (3 H, m), 7.32 (2 H, d, J 8.1), 5.70 (1 H, br s),
4.06 (1 H, t, J 9.0), 3.13 (2 H, t, J 5.5), 2.68 (3 H, s), 2.44 (3 H,
s), 2.38 (2 H, t, J 5.5), 1.61 (2 H, m), 0.82 (3 H, t, J 7.0), 0.35
(3 H, s), 0.34 (3 H, s); δC (a major isomer) 170.8, 143.1, 137.1,
135.8, 133.8, 129.6, 129.3, 127.8, 127.0, 51.4, 49.0, 39.3, 33.0,
21.4, 20.6, 12.3, Ϫ3.7, Ϫ4.0; νmax/cmϪ1 (liq. film) 3220, 2960,
1620, 1330, 1160, 1100, 820, 720; m/z (CI) (Found: Mϩ.
433.1979. C22H32N2O3SSi ϩ Hϩ requires M, 433.1981).
N-1-(Dimethylphenylsilyl)propyl-N-methylacetamide 2
To a solution of N-methyl-1-(dimethylphenylsilyl)propylamine2
(1.01 g, 4.86 mmol) and dry TEA (1.10 cm3, 7.89 mmol) in
dry DCM (20 cm3), a solution of acetyl chloride (0.37 cm3,
5.26 mmol) in dry DCM (2 cm3) was added at 0 ЊC under a
N2 atmosphere. The solution was refluxed for 1 h. Then
sat. aq. NaHSO4 solution (30 cm3) was added to the solution.
The organic layer was separated, and the aqueous layer was
extracted with DCM (3 × 20 cm3). The organic layer and the
organic extracts were combined, dried over MgSO4, and evap-
orated to give a residue, which was subjected to flash column
chromatography (eluent 30 to 50% ethyl acetate–hexane) to
afford the title compound (0.99 g, 81%): δH (a major isomer)
7.55 (2 H, m), 7.38 (3 H, m), 4.07 (1 H, dd, J 11.3 and 4.2), 2.78
(3 H, s), 2.06 (3 H, s), 1.6 (2 H, m, dqd J 11.3, 7.3 and 4.2), 0.86
(3 H, t, J 7.3), 0.38 (3 H, s), 0.35 (3 H, s); δC (a major isomer)
170.6, 137.5, 133.9, 129.1, 127.7, 49.0, 34.4, 21.6, 20.7, 12.3,
Ϫ3.8, Ϫ3.9; νmax/cmϪ1 (liq. film) 2960, 1640, 1250, 1140,
840; m/z (EI) (Found: Mϩ. 249.1512. C14H23NOSi requires M,
249.1549).
N-[1-(Dimethylphenylsilyl)propyl]-N-methyl-N’-(4-methyl-
phenyl)sulfonylglycinamide 3
Competitive electrolysis of amides in the presence or absence of
methanol
To a solution of chloroacetyl chloride (0.57 cm3, 7.16 mmol) in
dry DCM (11.4 cm3), a solution of N-methyl-1-(dimethyl-
phenyl)silylpropylamine (1.38 g, 6.65 mmol) and dry TEA (1.39
cm3, 9.97 mmol) in dry DCM (11.4 cm3) was added at 0 ЊC
under N2 atmosphere. After stirring at ambient temperature
overnight, water (30 cm3) was added to the solution. The
organic layer was separated, and the aqueous layer was
extracted with DCM (2 × 30 cm3). The organic layer and the
organic extracts were combined, dried over MgSO4, and evap-
orated to give a residue, which was subjected to flash column
chromatography (eluent 20 to 40% ethyl acetate–hexane) to
afford N-[1-(dimethylphenylsilyl)propyl]-N-methylchloroacet-
amide (1.14 g, 60%); δH (a major isomer) 7.50 (2 H, m), 7.36
(3 H, m), 3.99 (2 H, s), 3.98 (1 H, t, J 6.6), 2.85 (3 H, s), 1.64
(2 H, m, containing td, J 7.2 and 6.6), 0.85 (3 H, t, J 7.2), 0.38
(3 H, s), 0.34 (3 H, s); δC (a major isomer) 166.4, 137.1, 133.9,
129.3, 127.8, 49.9, 41.4, 33.9, 20.6, 12.2, Ϫ3.8, Ϫ4.0; νmax/cmϪ1
(liq. film) 2960, 1650, 1400, 1255, 1140, 700; m/z (EI) (Found:
Mϩ. 283.1150. C14H22NOClSi requires M, 283.1159).
To a suspended solution of sodium hydride (60% in mineral
oil) (0.25 g, 6.27 mmol) in dry DMF (2.5 cm3), a solution of
tosylamide (0.83 g, 4.82 mmol) in dry DMF (6.3 cm3) was
added at ambient temperature under N2 atmosphere. The sol-
ution was stirred at 60 ЊC for 2 h, and cooled to ambient
temperature. To the solution, a solution of N-[1-(dimethylphen-
ylsilyl)propyl]-N-methylchloroacetamide (1.14 g, 4.01 mmol)
in dry DMF (2.6 cm3) was added. The solution was stirred at
60 ЊC for 2 h. Water (30 cm3) was added to the solution. The
solution was extracted with diethyl ether (3 × 30 cm3). The
A solution of an amide (0.25 mmol), another amide (0.25
mmol), and tetraethylammonium tetrafluoroborate (0.043 g,
0.2 mmol) in dry DCM (4 cm3) was placed in an undivided cell
equipped with two platinum plate electrodes (2 × 1 cm2). A
constant current (20 mA) was passed in the presence of
methanol (0.080 g, 2.5 mmol) or in the absence of methanol at
ambient temperature under N2 atmosphere. After 36.2 C of
electricity (1.5 F molϪ1) was consumed, volatiles were evapor-
ated to give a residue, which was subjected to flash column
chromatography (eluent 20 to 40% ethyl acetate–hexane) to
afford the unreacted amides, 518 and 6. The results were
summarized in Table 1 and Chart 3.
N-(1-Methoxypropyl)-N-methyl-N’-(4-methylphenyl)sulfonyl-
glycinamide 6
δH 7.75 (2 H, d, J 8.2), 7.28 (2 H, d, J 8.2), 5.72 (1 H, br s), 5.34
(1 H, t, J 6.8), 3.76 (2 H, d, J 3.5), 3.05 (3 H, s), 2.64 (3 H, s),
2.38 (3 H, s), 1.61 (2 H, m), 0.72 (3 H, t, J 7.5); δC 168.1, 143.6,
136.0, 129.7, 127.3, 86.1, 55.6, 43.8, 25.9, 25.2, 21.4, 8.9;
νmax/cmϪ1 (liq. film) 3250, 2980, 2950, 1660, 1400, 1360,
1340, 1170, 1100, 1070, 920, 820, 740; m/z (FABϩ, matrix;
m-NBA) (Found: Mϩ. 315.1368. C14H22N2O4S ϩ Hϩ requires
M, 315.1379).
Electrolysis of 3 in the presence of trifluoroethanol
A solution of 3 (0.19 g, 0.458 mmol), trifluoroethanol (0.50 g,
5.01 mmol), and tetraethylammonium tetrafluoroborate (0.043 g,
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0.2 mmol) in dry DCM (4 cm3) was placed in an undivided cell
equipped with two platinum plate electrodes (2 × 1 cm2).
Constant current (20 mA) was passed at ambient temperature
under N2 atmosphere. After 7 F molϪ1 was consumed, volatiles
were evaporated to give a residue, which was subjected to flash
column chromatography (eluent 10 to 80% ethyl acetate–
hexane) to afford 3 (99.1 mg, 48%) and 1,4-diaza-1-methyl-2-
ethyl-3-(4-methylphenylsulfonyl)cyclopentan-5-one 7 (17.6 mg,
26% to the consumed 3): δH 7.70 (2 H, d, J 8.3), 7.34 (2 H, d,
J 8.3), 4.97 (1 H, t, J 2.8), 3.86 (2 H, s), 2.67 (3 H, s), 2.44 (3 H,
s), 2.04 (1 H, dtd, J 22.1, 7.4 and 2.8), 1.76 (1 H, dtd, J 22.1, 7.4
and 2.8), 0.88 (3 H, t, J 7.4); δC 167.2, 144.7, 133.3, 130.2, 127.5,
77.2, 49.6, 26.7, 26.1, 21.6, 5.9; νmax/cmϪ1 (KBr) 2980, 1720,
1350, 1170, 950, 680, 600; m/z (CI) (Found: Mϩ. 283.1099.
C13H18N2O3S ϩ Hϩ requires M, 283.1117).
5 (a) T. Shono, Y. Matsumura and S. Kashimura, J. Org. Chem., 1983,
48, 3338; (b) M. Mitzlaff, K. Warning and H. Rehling, Synthesis,
1980, 315; (c) M. Okita, T. Wakamatsu and Y. Ban, Heterocycles,
1983, 20, 401; (d ) M. Okita, T. Wakamatsu and Y. Ban,
Heterocycles, 1983, 20, 129; (e) Z. Blum and K. Nyberg, Acta Chem.
Scand. Ser. B, 1982, 36, 165.
6 J. Yoshida and S. Isoe, Tetrahedron Lett., 1987, 28, 6621.
7 In the presence of alcohol, an N-α-alkoxylated product such as 6
(Chart 3) and a cyclic product such as 7 (Chart 4) were obtained.
These results show that N-α-(dimethylphenyl)silylalkyl amide
moiety is the reaction center.
8 The first methoxylated product analogous to 6 was changed to 8 via
methanolysis. See Ref. 2.
9 T. Nonaka and T. Fuchigami, in Organic Electrochemistry, 4th edn.,
ed. H. Lund and H. Ole, Marcel Dekker, Inc., New York, 2001,
p. 1051–1102; and references are cited therein.
10 (a) S. Sankararaman, W. Lau and J. K. Kochi, J. Chem. Soc., Chem.
Commun., 1991, 396; (b) J. A. Olabe and A. Haim., Inorg. Chem.,
1989, 28, 3277.
11 Average values of the two methyl substituents on the silyl atom are
shown.
12 (a) J. Yoshida and M. Izawa, J. Am. Chem. Soc., 1997, 119, 9361;
(b) M. Watanabe, S. Suga and J. Yoshida, Bull. Chem. Soc. Jpn.,
2000, 73, 243.
13 K. P. Dockery, J. P. Dinnocenzo, S. Farid, J. L. Goodman, I. R.
Gould and W. P. Todd, J. Am. Chem. Soc., 1997, 119, 1876.
14 (a) L. Birkofer, A. Ritter and F. Bentz, Ber., 1964, 97, 2196; (b)
C. Palomo, Synthesis, 1981, 809.
15 J. Yoshida, Y. Ishichi, K. Nishikawa, S. Shiozawa and S. Isoe,
Tetrahedron Lett., 1992, 33, 2599.
References and notes
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Chem. Soc., 1981, 103, 1172; (c) T. Shono, Y. Matsumura and
K. Tsubata, Tetrahedron Lett., 1981, 22, 2411; (d ) T. Shono, Y.
Matsumura and K. Tsubata, Tetrahedron Lett., 1981, 22, 3249; (e)
T. Shono, Y. Matsumura, K. Tsubata and J. Takata, Chem. Lett.,
1981, 1121; ( f ) T. Shono, Y. Matsumura, K. Tsubata, Y. Sugihara,
S. Yamane, T. Kanazawa and T. Aoki, J. Am. Chem. Soc., 1982, 104,
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2 T. Kamada and A. Oku, J. Chem. Soc., Perkin Trans. 1, 1998, 3381.
3 T. Kamada and A. Oku, The 76th Annual Meeting of Chemical
Society of Japan, Proceedings II, Yokohama, 1999, 1B2 28, p. 832.
4 J. Yoshida, S. Suga, K. Fuke and M. Watanabe, Chem. Lett., 1999,
251.
16 D. D. Perrin, L. F. Armarego and D. R. Perrin, Purification of
Laboratory Chemicals, 2nd edn., Pergamon Press, Oxford, 1990.
17 T. W. Greene, Protective Groups in Organic Synthesis, John Wiley &
Sons, Inc., New York, 1981.
1
18 H-NMR spectrum of 5 was consistent with that of commercially
available N-methylacetamide.
1110
J. Chem. Soc., Perkin Trans. 1, 2002, 1105–1110