Development of electrochemical processes for nitrene generation and transfer

Article abstract of DOI:10.1021/jo048591p

(Chemical Equation Presented) An electrochemical strategy for running nitrogen-transfer reactions on chemically inert anode surfaces has been developed. The generation and trapping of highly reactive nitrene-transfer reagents can be accomplished under mild conditions on platinum electrodes. The key factor that accounts for the high levels of chemoselectivity in this process is the phenomenon of overpotential. We have found that molecules that are similar in terms of propensity toward oxidation can be differentiated on the basis of their affinity to a given electrode surface. Thereby, reactive species can be selectively generated in the presence of acceptor molecules of interest. Specifically, a wide range of structurally dissimilar olefins can be transformed into the corresponding aziridines in the presence of N-aminophthalimide. Likewise, nitrene generation in the presence of sulfoxides leads to their chemoselective transformation into the corresponding sulfoximines. In this paper we discuss the underlying mechanistic foundation of these reactions.

Full text of DOI:10.1021/jo048591p

Development of Electrochemical Processes for Nitrene Generation
and Transfer
Tung Siu, Christine J. Picard, and Andrei K. Yudin*
Department of Chemistry, University of Toronto, 80 St. George Street,
Toronto, Ontario M5S 3H6, Canada
ayudin@chem.utoronto.ca
Received August 12, 2004
An electrochemical strategy for running nitrogen-transfer reactions on chemically inert anode
surfaces has been developed. The generation and trapping of highly reactive nitrene-transfer
reagents can be accomplished under mild conditions on platinum electrodes. The key factor that
accounts for the high levels of chemoselectivity in this process is the phenomenon of overpotential.
We have found that molecules that are similar in terms of propensity toward oxidation can be
differentiated on the basis of their affinity to a given electrode surface. Thereby, reactive species
can be selectively generated in the presence of acceptor molecules of interest. Specifically, a wide
range of structurally dissimilar olefins can be transformed into the corresponding aziridines in the
presence of N-aminophthalimide. Likewise, nitrene generation in the presence of sulfoxides leads
to their chemoselective transformation into the corresponding sulfoximines. In this paper we discuss
the underlying mechanistic foundation of these reactions.
Introduction
chemical aspects and mechanistic understanding of olefin
aziridination and sulfoxide imination processes.
Due to the fundamental role of electron transfer in
redox processes, developing an electrochemical under-
standing of oxidative atom-transfer reactions that are
normally driven by metal reagents may help in designing
new, highly efficient processes. The ultimate goal is to
find general and practical electrochemical solutions to
selective functionalization of hydrocarbons with nitrogen-
containing fragments. Another important question is
whether direct electron transfer can find broad applica-
tions in synthetic organic chemistry. In this regard,
understanding ways of electrochemical generation and
subsequent trapping of highly reactive atom-transfer
species has been of particular interest. Our recent studies
defined the scope of electrochemical nitrene transfer to
olefins (Table 1) and sulfoxides (Table 2).1 This strategy
allows one to access a wide range of aziridines and sul-
foximines, respectively. A variety of substituents around
the double bond of the olefin and around the sulfur center
of the sulfoxide can be tolerated in the course of these
reactions. In the present paper we outline the electro-
Results and Discussion
Electrochemical Aziridination of Olefins. The
aziridination of olefins is of significant current interest
due to the enormous synthetic potential of aziridines.2
These nitrogen-containing heterocycles have approxi-
mately 28 kcal/mol of strain3 and are amenable to ring-
opening reactions with a wide range of nucleophiles.
Some of these transformations lead to molecules with
valuable 1,2-heteroatom relationships, commonly found
in natural products and in pharmaceuticals.4
Until recently, there have been no examples of catalytic
oxidation systems based on readily available oxidants
that convert simple amines or amides into active nitrogen-
transfer species in the presence of olefins and leave no
byproducts. On the other hand, a stoichiometric oxidation
(2) McCoull, W.; Davis, F. A. Synthesis 2000, 10, 1347.
(3) Skancke, A.; van Vechten, D.; Liebman, J. F.; Skancke, P. N. J.
Mol. Struct. 1996, 376, 461.
(4) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004.
(1) (a) Siu, T.; Yudin, A. K. J. Am. Chem. Soc. 2002, 124, 530. (b)
Siu, T.; Yudin, A. K. Org. Lett. 2002, 4, 1839.
10.1021/jo048591p CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/07/2005
932
J. Org. Chem. 2005, 70, 932-937

Nitrene Generation and Transfer
TABLE 1. Selected Substrate Scope in Electrochemical
Aziridinations of Olefins
FIGURE 1. Cyclic voltammetry study of N-aminophthalimide
(dashed line) and cyclohexene (solid line) on a platinum
electrode in acetonitrile (0.1 M HEt3N+OAc-).
electrochemical aziridination with a catalytic amount of
Pb(OAc)2. Using 10 mol % Pb(OAc)2 with respect to
N-aminophthalimide, cyclohexene (1.5 equiv) was trans-
formed into the corresponding aziridine at a constant
potential of +1.80 V(Ag wire pseudo reference electrode),
and gave a 75% isolated yield of 1.
Aware of the relative facility with which olefins may
undergo detrimental background oxidation at the anode,7
we recorded the cyclic voltammogram of cyclohexene
under the conditions used in N-aminophthalimide oxida-
tion (0.01 M in acetonitrile). The observed anodic current
was only -1.3 µA at +1.68 V (vs Ag/AgCl), a small
fraction of the current recorded for N-aminophthalimide
(-152 µA, Figure 1). This clearly indicates that the
background oxidation of olefins on platinum electrodes
is disfavored under the reaction conditions due to the
olefin overpotential. By definition, an overpotential is the
“additional potential (beyond the thermodynamic require-
ment) needed to drive a reaction at a certain rate”.8
Under certain conditions, i.e., electrode material and
medium, various substrates possess different overpoten-
tials depending on the nature of the electrode. We
hypothesized that the overpotential phenomenon can be
used as a guiding principle to selectively oxidize a given
species in the presence of a thermodynamically similar
acceptor molecule, thus avoiding detrimental background
reactions. For instance, selective oxidation of N-amino-
phthalimide at the anode at around +1.60 V should be
possible in the absence of Pb(OAc)4. A simple combination
of platinum electrodes, triethylamine, and acetic acid has
led to a highly efficient, soluble metal reagent-free
nitrene transfer from N-aminophthalimide to cyclohexene
at room temperature (Scheme 1). The reaction utilizes
only a small excess of N-aminophthalimide relative to
the olefin and can be performed in a divided cell using
silver wire as a pseudo reference electrode. The pseudo
reference electrode was calibrated against the ferrocene/
TABLE 2. Selected Substrate Scope in Electrochemical
Imination of Sulfoxides
system that generates active nitrene precursors from the
amine species does exist. Valuable aziridines equipped
with an N-N bond can be obtained from olefins using
lead tetraacetate as oxidant (eq 1).5 Unfortunately,
widespread application of this method is hampered by
the use of excess Pb(OAc)4, known for its high toxicity.6
Because of the broad utility of Pb(OAc)4 as a reagent in
organic synthesis, it is desirable to develop systems in
which the Pb(IV) species can be replaced by the less toxic
reagents. As a general approach to our electrochemical
study aimed at understanding the possibilities for ca-
talysis in this system, we first used cyclic voltammetry
(CV) to investigate the Pb(OAc)4-mediated nitrene trans-
fer. CV of Pb(OAc)2 in acetonitrile gives a value of +1.60
V (vs Ag/AgCl) for the peak potential that corresponds
to the oxidation of Pb(II) to Pb(IV). CV of N-amino-
phthalimide (0.01 M in acetonitrile) shows two irrevers-
ible one-electron oxidation processes with anodic peak
potentials at +1.35 and at +1.68 V (vs Ag/AgCl). Clearly,
only the first electron transfer from N-aminophthalimide
occurs at a less positive potential than the oxidation of
Pb(II); the second electron transfer is in fact more
positive. This observation encouraged us to run the
ferricinium couple in the electrolysis medium (Epa
0.47 V, Epc ) 0.30 V).
)
The nature of the electrode material can be critical in
electrosynthesis. For instance, the Kolbe reaction re-
quires smooth platinum or iridium electrodes to give the
(5) Atkinson, R. S. In Azides and Nitrenes; Scriven, E. F. V., Ed.,
Academic Press: Orlando, FL, 1984; see also references therein.
(6) Daland, R. J. Lead and Human Health: An Update; American
Council on Science and Health: New York, 2000; see also references
therein.
(7) For CV data on various olefins, see: Tsuchiya, M.; Akaba, R.;
Aihara, S.; Sakuragi, H.; Tokumaru, K. Chem. Lett. 1986, 1727.
(8) Bard, A. J.; Faulkner, L. R. Electrochemical Methods: Funda-
mentals and Applications, 2nd ed.; Wiley: New York, 2000.
J. Org. Chem, Vol. 70, No. 3, 2005 933

Siu et al.
FIGURE 3. Current/time profiles of aziridination of chalcone
on poisoned (sulfided) platinum (thin line) vs aziridination on
flamed platinum (thick line).
FIGURE 2. Cyclic voltammetry study of N-aminophthalimide
(dashed line) and cyclohexene (solid line) on a glassy carbon
electrode in acetonitrile (0.1 M HEt3N+OAc-).
SCHEME 1. Electrochemical Aziridination of
Olefins
FIGURE 4. Olefins that are inert in electrochemical aziridi-
nation.
In sharp contrast to the metal-based nitrene transfer,
both electron-rich and electron-poor olefins can be con-
verted to aziridines with high efficiency. For certain
monosubstituted terminal olefins (Figure 4), the electro-
chemical aziridination was not successful although the
redox behavior of these olefins is not significantly differ-
ent from that of the others. Surprisingly, dimethyl
maleate was found to be inert toward electrochemical
aziridination, while the corresponding trans-isomer, di-
methyl fumarate, gave an excellent yield of the aziridine.
In all cases with inert olefins, N-aminophthalimide was
completely converted to phthalimide (precipitated from
the reaction mixture) and the olefins were recovered
quantitatively. This observation suggests that the elec-
trochemical oxidation does take place but the active
nitrogen-transfer species is not intercepted by the olefin.
This is clearly a relative rate phenomenon, rather than
a consequence of platinum surface poisoning with “inert”
olefins. Indeed, a 1:1 mixture of 1-hexene and chalcone
gave an 83% yield of chalcone-derived aziridine while
1-hexene remained unreacted.
Electrochemical Imination of Sulfoxides. The ni-
trene transfer to sulfur was investigated similarly to
aziridination.10 The redox behavior of sulfoxides on
platinum was first studied using cyclic voltammetry
(Figure 5). At +1.68 V, tetramethylene sulfoxide (0.01
M in acetonitrile) produces a considerably smaller anodic
current (-7.52 µA) than the current recorded for N-
aminophthalimide (-152 µA). This is a sign of kinetically
sluggish background oxidation of sulfoxides to sulfones
on a platinum anode, which enables direct electrochemi-
cal nitrogen transfer to sulfoxides.
coupling products, whereas the reactions on graphite
lead to products exclusively derived from carbenium
ions.9 In our case, the aziridination reaction did not take
place when platinum was replaced by carbon. The CV
study (Figure 2) on carbon revealed that the anodic
current corresponding to cyclohexene oxidation (-5.3
µA at +1.68 V) was comparable to that of N-amino-
phthalimide (-15.6 µA at +1.68 V). Such a small differ-
ence in electroactivity apparently does not secure high
selectivity in N-aminophthalimide oxidation, supporting
the notion that selectivity can be obtained by maxi-
mizing the difference in overpotentials between the
substrates.
The choice of the separator material turned out to be
crucial to the success of electrochemical nitrene transfer.
In certain cases, the use of glass frits resulted in higher
cell voltages (the voltage needed to be applied across the
cell to maintain the working potential) which exceeded
the instrument compliance voltage limit and caused the
working potential to be lower than the set value of
+1.80 V. In such cases, Nafion membranes allowed us
to construct cells with lower cell voltages, which enabled
scaleup. Aziridination attempts in undivided cells re-
sulted in significant amounts of olefin reduction by-
products.
As a qualitative measure of electroactivity throughout
the reaction, we monitored the current/time profile. The
poisoning of platinum electrodes is a common problem,
and the current/time profile is the easiest and most
reliable way of comparing the reaction runs and ensuring
that the electrode performance is close to optimal and is
reproducible. For instance, Figure 3 features the com-
parison of current/time profiles for the aziridination on
poisoned (sulfided) platinum vs aziridination on flamed
platinum. The current/time profiles also facilitate scaleup
by providing direct comparison of the electrochemical
process efficiency as a function of the electrode surface
area, which is particularly important for scaleup.
The nature of the electrode material is crucial to the
success of this process as well. CV (Figure 6) of tetra-
methylene sulfoxide (0.01 M in acetonitrile) on a glassy
(9) Torii, S.; Tanaka, H. In Organic Electrochemistry, 4th ed.; Lund,
H., Hammerich, O., Eds.; Marcel Dekker: New York, 2001; Chapter
14.
(10) (a) Ohashi, T.; Masunaga, K.; Okahara, M.; Komori, S. Synthesis
1971, 96. (b) Colonna, S.; Stirling, C. J. M. J. Chem. Soc., Perkin Trans.
1 1974, 2120. (c) Kim, M.; White, J. D. J. Am. Chem. Soc. 1977, 99,
1172. (d) Kemp, J. E. G.; Closier, M. D.; Stefanich, M. H. Tetrahedron
Lett. 1979, 3785.
934 J. Org. Chem., Vol. 70, No. 3, 2005

Nitrene Generation and Transfer
SCHEME 3. Mechanism of the Nitrene Transfer to
Olefins
a mixture of products consisting mainly of sulfoxide and
sulfoximine was obtained.
FIGURE 5. Cyclic voltammetry study of N-aminophthalimide
(dashed line) and tetramethylene sulfoxide (solid line) on a
platinum electrode in acetonitrile (0.1 M HEt3N+OAc-).
The electrochemical nitrene-transfer process was found
to be stereospecific. An enantiomerically enriched (93%
ee of the (R)-enantiomer)13 sample of methyl p-tolyl
sulfoxide was electrolyzed under the same conditions as
above. The ee value measured for the product sulfoximine
20 was the same (97%) within the error of HPLC
analysis, and the X-ray structure (see the Supporting
Information) of the product showed retention of config-
uration, indicating that no racemization occurred during
nitrene transfer.
Mechanistic Apects of the Electrochemical Aziri-
dination Process. The mechanism of Pb(OAc)4-medi-
ated olefin aziridination with N-aminophthalimide and
other N-amino heterocycles has been studied by Atkinson
and co-workers.11 It is believed that the oxidation of
N-aminophthalimide by Pb(OAc)4 generates an N-ace-
toxyamino intermediate, which is stable enough to be
observed by NMR at low temperature (<5 °C). Addition
of olefins to this intermediate at elevated temperature
is known to result in aziridines (Scheme 3). In the
absence of olefins, the N-acetoxyamino intermediate
dimerizes to generate tetrazene, which then decomposes
to phthalimide by extrusion of N2. Fuchigami and co-
workers12 showed that electrochemical oxidation of N-
aminophthalimide using Bu4NBF4 or LiClO4 as support-
ing electrolyte at 0 °C gave tetrazene as the main product
and 10-20% phthalimide. It is believed that the electro-
chemically generated N-nitrene intermediate inserts into
the N-H σ-bond of N-aminophthalimide to afford the
tetrazane product (Scheme 4). The tetrazane is further
oxidized to give tetrazene. In our case, the crucial role of
the acetate anion is to prevent the unwanted nitrene
dimerization pathway. The necessity of acetate (or other
carboxylate) anions for the aziridine generation implies
that a similar N-acetoxyamino intermediate is involved
in our reaction. This is also evidenced by the correlation
between aziridine yields and acetate concentrations
(Table 3). In the case of inert olefins (Figure 4), the
nitrene transfer is slow and an alternate path (A, likely
proceeding via two consecutive R-hydride eliminations)
depicted in Scheme 4 predominates to give phthalimide
as the reaction product, leaving the olefin intact. There-
fore, we believe that the key role of the acetate anion is
to intercept the Pt-N species obtained after the first
R-hydride elimination, leading to the N-acetoxy species.
To further probe the involvement of acetate in the
electrochemical aziridination, we performed oxidation of
FIGURE 6. Cyclic voltammetry study of N-aminophthalimide
(dashed line) and tetramethylene sulfoxide (solid line) on a
glassy carbon electrode in acetonitrile (0.1 M HEt3N+OAc-).
SCHEME 2. Electrochemical Imination of
Sulfoxides
carbon electrode shows two irreversible oxidation pro-
cesses with peak potentials at +1.64 and +1.82 V and a
considerably higher anodic current (-272 µA) than that
of N-aminophthalimide at +1.68 V (-15.6 µA). Not
surprisingly, the bulk electrolysis of tetramethylene
sulfoxide in the presence of N-aminophthalimide on
graphite gave tetramethylene sulfone as the major
product with no evidence of sulfoximine formation.
On the other hand, the electrolysis conditions on
platinum were similar to those of aziridination (Scheme
2). A small excess of N-aminophthalimide relative to
sulfoxide was used. The electrolysis was performed in a
divided cell using silver wire as a pseudo reference
electrode. No special precautions to exclude moisture or
air were taken. The reaction was stopped when the cell
current dropped to less than 5% of its original value.
There was no evidence for the background formation of
sulfone byproduct. The oxidative imination of sulfides
(resulting in sulfimines) was also attempted using this
methodology. However, due to the less positive oxidation
potential of sulfides compared to N-aminophthalimide,
(11) Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron 1989,
45, 2875.
(12) Fuchigami, T.; Sato, T.; Nonaka, T. Electrochim. Acta 1986, 31,
365.
(13) Chilmonczyk, Z.; Egli, M.; Behringer, C.; Dreiding, A. S. Helv.
Chim. Acta 1989, 72, 1095.
J. Org. Chem, Vol. 70, No. 3, 2005 935

Siu et al.
SCHEME 4. Electrochemical Oxidation of
N-Aminophthalimide
metric or catalytic amounts of oxidants and metal addi-
tives in organic redox reactions. The differentiation of
substrates is based on their behavior at the electrode/
solution interface. This strategy has been applied to
electrochemical nitrogen transfer to olefins and sulfox-
ides, resulting in synthetically useful aziridines and
sulfoximines, respectively. The electrochemical aziridi-
nation process gives good to excellent yields for both
electron-rich and electron-poor olefins. The range of ole-
fins compares favorably with the metal-catalyzed aziri-
dination processes, which usually have limited substrate
scope.
Identifying other nitrogen sources for electrochemical
nitrene transfer will further broaden the utility of this
process. In this regard, cyclic voltammetry will continue
to be an invaluable tool that can be used to select the
nitrene precursor molecules with higher overpotentials
than the nitrene acceptors (e.g., olefins and sulfoxides).
The parallel electrosynthesis methodology14 may be
promising to further identify appropriate nitrogen sources.
TABLE 3. Cation and Anion Effects in Electrochemical
Aziridination with 1.0 mmol Cyclohexene, 1.3 mmol
N-Aminophthalimide, and Supporting Electrolyte
amt of
Experimental Section
supporting
electrolyte
(mmol)
yield of
aziridine
(%)
amt of
phthalimide
(mmol)
supporting
electrolyte
N-Aminophthalimide.15 To hydrazine monohydrate (4.4
g) in 95% ethanol (80 mL) was added powdered phthalimide
(12 g), and the mixture was stirred at room temperature for 2
min. The resulting spongy mass was quickly heated and
refluxed for 3 min while ammonia was evolved. Cold water
(250 mL) was added at once, and N-aminophthalimide crystal-
lized during 1 h. Recrystallization from 95% ethanol gave
white needles (5.6 g, 43%, mp 223-224 °C).
LiClO4
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.20
0.50
2.0
5.0
0
0
0
1.06
1.11
1.03
0.33
0.33
0.39
0.37
0.37
0.64
0.51
0.40
0.32
Bu4NBF4
Et4NOTs
1:1 Et3N/CF3CO2H
1:1 Et3N/ClCH2CO2H
Me4NOAc
90
87
85
81
83
55
69
83
89
Et4NOAc
Bu4NOAc
1:1 Et3N/HOAc
1:1 Et3N/HOAc
1:1 Et3N/HOAc
1:1 Et3N/HOAc
CV Experiments. A platinum disk (0.07 cm2) electrode, a
platinum wire (0.1 mm diameter) electrode, and a Ag/AgCl
electrode were used as the working, counter, and reference
electrodes, respectively. The substrate concentration of 0.01
M in acetonitrile with 0.1 M Et3HN+OAc- as supporting
electrolyte was used, and the potential was swept between 0.0
and +2.0 V at a rate of 200 mV/s.
Electrochemical Aziridination. (a) A 0.5 mmol Scale.
A two-compartment divided cell with a glass frit was used.
The anodic compartment was charged with 41 mg (0.5 mmol)
of cyclohexene, 105 mg (0.65 mmol) of N-aminophthalimide,
and 10 mL of 0.05 M Et3N/HOAc in acetonitrile. Another 10
mL of 0.05 M Et3N/HOAc in MeCN was added to the cathodic
compartment. Flat platinum foils (1.25 × 2.5 cm, 99.99%) were
used as working and auxiliary electrodes. The platinum
electrode foils were placed parallel to each other (4.5 cm apart),
and this arrangement was rigidly fixed throughout the process
by supporting the electrodes using custom-made Teflon hold-
ers. Silver wire (1.5 mm diameter, 99.99%) was used as a
pseudo reference electrode and was placed 0.5 cm away from
the middle of the anode plate. The electrolysis was performed
at +1.80 V at ambient temperature and was stopped when
the cell current dropped to less than 5% of its initial value.
The contents of the anodic compartment were collected and
concentrated in vacuo. The residue was washed with water
and extracted with dichloromethane (3 × 5 mL). The organic
phases were combined, dried over MgSO4, concentrated,
charged onto a silica gel column, and eluted using EtOAc/
hexane (1:4), which afforded 7-phthalimido-7-azabicyclo[4.1.0]-
heptane (1) as a yellow solid (111 mg, 85%).
N-aminophthalimide in the presence of cyclohexene with
supporting electrolytes other than triethylammonium
acetate. The results are shown in Table 3. With LiClO4,
Bu4NBF4, and Et4NOTs as supporting electrolytes, no
aziridine was detected while phthalimide was isolated
in high yields (80-85%).
More mechanistic evidence has been obtained by com-
paring the stereochemical outcomes of electrochemical
and chemical (Pb(OAc)4-mediated) aziridinations. Dre-
iding and co-workers13 showed that the Pb(OAc)4-pro-
moted aziridination is stereospecific; i.e., (E)-olefins afford
only trans-aziridines and (Z)-olefins only cis-aziridines.
In our study, the NMR analysis and X-ray analysis (see
the Supporting Information) of 1 showed exclusive for-
mation of the trans-aziridine. The electrochemical aziri-
dination of (Z)-1,2-dichloro-2-butene was also stereospe-
cific (Table 4, entries 2 and 3). Furthermore, the
diastereoselectivities of the electrochemical and chemical
approaches were comparable (Table 4, entries 4 and 5).
The syn-aziridine (see the Supporting Information for the
X-ray analysis) was exclusively obtained from olefin 3.
Taken together, these facts provide additional evidence
that speaks in favor of the N-acetoxy intermediate.
(b) A 5 mmol Scale. A three-compartment divided cell
equipped with a Nafion membrane placed between the working
and auxiliary electrode compartments was used. The reference
(14) (a) Siu, T.; Li, W.; Yudin, A. K. J. Comb. Chem. 2001, 3, 554.
(b) Yudin, A. K.; Siu, T. Curr. Opin. Chem. Biol. 2001, 5, 269. (c) Siu,
T.; Yekta, S.; Yudin, A. K. J. Am. Chem. Soc. 2000, 122, 11787. (d)
Siu, T.; Li, W.; Yudin, A. K. J. Comb. Chem. 2000, 2, 545.
Conclusions
The present study illustrates the use of an overpoten-
tial as a means of bypassing the requirement for stoichio-
(15) Drew, H. D. K.; Hatt, H. H. J. Chem. Soc. 1937, 16.
936 J. Org. Chem., Vol. 70, No. 3, 2005

Nitrene Generation and Transfer
TABLE 4. Comparison of Electrochemical and Chemical Aziridinations of Olefins
a All aziridination reactions with Pb(OAc)4 were studied by NMR in CD3CN. The products were not isolated, and their configurations
were determined by comparison with the products from electrochemical reactions. b X-ray structure. c NMR study in CDCl3.
compartment was separated from the anodic (working) com-
partment by a glass frit. The anodic compartment was charged
with 1.04 g (5 mmol) of trans-chalcone, 1.05 g (6.5 mmol) of
N-aminophthalimide, and 100 mL of 0.05 M Et3N/HOAc in
acetonitrile. A 40 mL sample of 0.05 M Et3N/HOAc in MeCN
was added to the cathodic compartment, and 6 mL of 0.05 M
Et3N/HOAc in MeCN was added to the reference compartment.
Platinum foils (anodic, 2.5 × 5 cm; cathodic, 2.5 × 2.5 cm,
99.99%) were used as working and auxiliary electrodes. The
platinum electrode plates were placed parallel to each other
(11 cm apart), and this arrangement was fixed throughout the
process. Silver wire (1.5 mm diameter, 99.99%) was used as a
pseudo reference electrode. Electrolysis was performed at
+1.80 V at ambient temperature and was stopped when the
cell current dropped to less than 5% of its initial value. The
contents of the anodic compartment were collected and con-
centrated in vacuo. The residue was washed with water and
extracted with dichloromethane (3 × 30 mL). The organic
phases were combined, dried over Na2SO4, concentrated,
charged onto a silica gel column, and eluted using EtOAc/
hexane (1:4), which afforded 2-(2-benzoyl-3-phenyl-aziridin-
1-yl)-isoindole-1,3-dione (8) as a yellow solid (1.2 g, 65%).
Electrochemical Sulfoximination Procedure. The
anodic compartment was charged with 1.0 mmol of sulfoxide,
210 mg (1.3 mmol) of N-aminophthalimide, 78 mg (1.3 mmol)
of acetic acid (glacial), 130 mg (1.3 mmol) of triethylamine,
and 20 mL of acetonitrile. Portions of 0.05 M AcOH in MeCN
were added to the cathodic (20 mL) and reference (4 mL)
compartments. Platinum foils (2.5 × 2.5 cm, 99.99%) were used
as working and auxiliary electrodes. Silver wire (1.5 mm
diameter, 99.99%) was used as a pseudo reference electrode.
Electrolysis was performed at +1.80 V at ambient temperature
and was stopped when the cell current dropped to less than
5% of its original value. The contents of the anodic compart-
ment were collected and concentrated in vacuo. The residue
was washed with water and extracted with dichloromethane
(3 × 5 mL). The organic phases were combined, dried over
MgSO4, concentrated, charged onto a silica gel column, and
eluted using EtOAc/hexane to afford the sulfoximine.
Acknowledgment. We thank the Natural Sciences
and Engineering Research Council (NSERC), the Canada
Foundation for Innovation, ORDCF, Affinium Pharma-
ceuticals, and the University of Toronto for financial
support. A.K.Y. is a Cottrell Scholar of the Research
Corp. We also thank Dr. Raymond Hui, Fabien Marino,
and Cliff Lansil for many helpful discussions and en-
gineering efforts. Alan Lough is acknowledged for per-
forming the X-ray analysis. We also gratefully acknowl-
edge DuPont for a generous gift of Nafion membranes.
Supporting Information Available: Experimental pro-
cedures and characterization data for the new compounds
(PDF, CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
JO048591P
J. Org. Chem, Vol. 70, No. 3, 2005 937