Enantio-and diastereoselective oxidation of N-alkylimines using chiral-bromonitriles and hydrogen peroxide system

Article abstract of DOI:10.1080/00397911.2011.573611

Chiral-bromonitriles were prepared with good chemical and optical yields starting from natural-amino acids by dehydrating the corresponding α-bromoamides with thionyl chloride. The combined system-bromonitriles/ hydrogen peroxide was examined for the enantio-and diastereoselective oxidation of N-alkylimines in basic media at room temperature. The oxidation of N-tertiobutylarylimines leads to optically active oxaziridines with moderate enantiomeric excess. However, the oxidation of (S)-1-phenylethylarylimines affords the corresponding oxaziridines with good diasteromeric excess up to 97/3 as proved by gaseous-phase chromatography.

Full text of DOI:10.1080/00397911.2011.573611

This article was downloaded by: [Stanford University Libraries]
On: 22 June 2012, At: 15:20
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Enantio- and Diastereoselective
Oxidation of N-Alkylimines Using Chiral
α-Bromonitriles and Hydrogen Peroxide
System
Najeh Tka a , Jamil Kraïem a & Béchir Ben Hassine a
a Laboratoire de Synthèse Organique Asymétrique et Catalyse
Homogène, Faculté des Sciences de Monastir, Monastir, Tunisia
Available online: 10 Jan 2012
To cite this article: Najeh Tka, Jamil Kraïem & Béchir Ben Hassine (2012): Enantio- and
Diastereoselective Oxidation of N-Alkylimines Using Chiral α-Bromonitriles and Hydrogen Peroxide
System, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 42:20, 2994-3003
To link to this article: http://dx.doi.org/10.1080/00397911.2011.573611
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 2994–3003, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.573611
ENANTIO- AND DIASTEREOSELECTIVE OXIDATION OF
N-ALKYLIMINES USING CHIRAL a-BROMONITRILES
AND HYDROGEN PEROXIDE SYSTEM
´
Najeh Tka, Jamil Kra¨ıem, and Bechir Ben Hassine
Laboratoire de Synthese Organique Asymetrique et Catalyse Homogene,
`
´
`
´
Faculte des Sciences de Monastir, Monastir, Tunisia
GRAPHICAL ABSTRACT
Abstract Chiral a-bromonitriles were prepared with good chemical and optical yields start-
ing from natural a-amino acids by dehydrating the corresponding a-bromoamides with thio-
nyl chloride. The combined system a-bromonitriles/hydrogen peroxide was examined for
the enantio- and diastereoselective oxidation of N-alkylimines in basic media at room tem-
perature. The oxidation of N-tertiobutylarylimines leads to optically active oxaziridines
with moderate enantiomeric excess. However, the oxidation of (S)-1-phenylethylarylimines
affords the corresponding oxaziridines with good diasteromeric excess up to 97/3 as proved
by gaseous-phase chromatography.
Keywords Chiral a-bromonitriles; chiral bromoalkylperoxyimidic acids; chiral
oxaziridines; oxidation of N-alkylimines
Received February 17, 2011.
Address correspondence to Bechir Ben Hassine, Laboratoire de Synthese Organique Asymetrique
´
et Catalyse Homogene, (01 UR 1201), Faculte des Sciences de Monastir, Avenue de l’Environment, 5019,
`
´
`
Monastir, Tunisia. E-mail: bechirbenhassine@yahoo.fr
´
2994

OXIDATION OF N-ALKYLIMINES
2995
INTRODUCTION
Oxaziridines are a topic of increasing interest in medicinal chemistry. They
have received attention as antitumour agents[1,2] and analogs of penicillin.[3] Further-
more, the oxaziridine ring has been the focus of several studies mainly because of the
presence of an inherently weak N–O bond, which makes the molecule unusually
reactive. As a result, oxaziridines have been used as both oxygenating[4–7] and ami-
nating[8–11] agents in reactions with a wide variety of nucleophiles. Furthermore,
oxaziridines constitute a highly reactive functional group that can serve as versatile
synthetic intermediates for the synthesis of many heterocyclic compounds.[12]
Recently, Marilene et al. have described an efficient cycloaddition reaction of a var-
iety of aryl alkenes with 2-tert-butyl-3-aryloxaziridines leading to 3,5-diarylisoxazo-
lidines.[13] We have recently shown that cycloaddition of 2-alkyl-3-aryloxaziridines
with chlorosulfonylisocyanate occurs with cleavage of the C–N bond of the oxazir-
idine ring and gives the corresponding 1,2,4-oxadiazolidin-3-one.[14]
Several synthetic methods have been employed for the synthesis of oxaziri-
dines.[15–18] Among them, the oxidation of imines with different oxidizing agents
continues to be the favored method. The commercially available m-chloroperbenzoic
acid (MCPBA) is one of the most widely used reagents.[19] However, we have pre-
viously reported that the trichloroacetonitrile–hydrogen peroxide system can com-
pete with MCPBA at the levels of costs reactivity, and yields of oxaziridines.[20,21]
As part of our work to synthesize optically pure oxaziridines and investigate
the preparation of new chiral heterocyclic compounds, herein we report the investi-
gation of an optically active a-bromonitriles=hydrogen peroxide system for the enan-
tio- and diastereoselective oxidation of N-alkylimines and the study of the
asymmetric induction of in situ formed chiral bromoalkylperoxyimidic acids when
transferring oxygen to N-tertiobutylarylimines and (S)-1-phenylethylarylimines. This
oxidant system can compete at the levels of cost and reactivity with chiral peroxy
acids, which have been widely used since 1968.
RESULTS AND DISCUSSION
The synthetic route to the target a-bromonitriles 1a–d from the corresponding
a-amino acids is outlined in Scheme 1. Optically pure a-bromoacids prepared
[22]
ˆ
according to the procedure described by Larcheveque and petit
were easily con-
verted to a-bromoamids by treatment with thionyl chloride followed by aqueous
ammonia and then dehydrated with thionyl chloride to afford the corresponding
a-bromonitriles 1a–d with good yields and enantiomeric purity.
Scheme 1. Synthesis of a-bromonitriles 1a–d from the corresponding natural amino acids. a: R ¼ Me; b:
R ¼ i-Pr; c: R ¼ i-Bu; d: R ¼ sec-Bu.

¨
N. TKA, J. KRAIEM, AND B. BEN HASSINE
2996
Scheme 2. Synthesis of prochiral and chiral N-alkylarylimines 2a–d. a: R ¼ tBu-, X ¼ H; b: R ¼ tBu-,
X ¼ OCH3; c: R ¼ PhMeHCꢀ-, X ¼ H; d: R ¼ PhMeHCꢀ-. X ¼ OCH3.
The synthetic route to the prochiral and chiral imines 2a–d is outlined in
Scheme 2.
N-Alkylimines 2a–d were obtained as one geometrical isomer by reacting
tertiobutylamine or optically pure (S)-1-phenylethylamine with the corresponding
aryl aldehydes in the presence of molecular sieves.
The synthetic route to oxaziridines 4a and b is outlined in Scheme 3. The chiral
a-bromonitriles 1a–d react with hydrogene peroxide under basic media to generate in
situ the corresponding chiral bromoalkylperoxyimidic acids 3a-d, which oxidize the
N-tertiobutylarylimines 2a and b to provide the corresponding optically active oxa-
ziridines 4a and b. The latter compounds were obtained as a mixture of two enantio-
mers with good chemical yields and moderate enantiomeric excesses.
The synthetic route to oxaziridines 4c,d is outlined in Scheme 4. The
a-bromonitriles=hydrogene peroxide system is used to oxidize chiral (S)-1-phenyl-
ethylarylimines 2c and d under basic media to afford the corresponding oxaziridines
4c and d with good diastereomeric excesses.
The activation of the nitrile by hydrogen peroxide to form peroxycarboximidic
acid was first described by Payne et al.[23] Since that, an interesting variation of
the Payne system has been introduced.[24] We have previously reported the use of
a trichloroacetonitrile–hydrogen peroxide system to oxidize several imines in a sym-
metric manner, giving racemic oxaziridines. Our dual objective in the present study is
to develop an efficient, inexpensive, asymmetric, oxidizing reagent based upon chiral
a-bromonitriles and 30% H2O2 that could lead to chiral oxaziridines with good
optical purity.
We have already reported the synthesis of new enantiomerically pure amino-
nitriles[25] and their application to prepare some chiral biologically active hetero-
cyclic compounds.[26–28] Following the same strategy, we have prepared four new
Scheme 3. Enantioselective synthesis of oxaziridines 4a and b from the corresponding prochiral imines 2a
and b. a: R ¼ Me; b: R ¼ i-Pr; c: R ¼ i-Bu; d: R ¼ sec-Bu. X ¼ OCH3.

OXIDATION OF N-ALKYLIMINES
2997
Scheme 4. Diastereoselective synthesis of oxaziridines 4c and d from the corresponding chiral imines 2c
and d. R ¼ Me; b: R ¼ i-Pr; c: R ¼ i-Bu; d: R ¼ sec-Bu. X ¼ OCH3.
enantiomerically enriched a-bromonitriles from natural aminoacids by dehydrating
the corresponding a-bromoamides with thionyl chloride. Desired a-bromonitriles
were obtained with chemical yields ranging from 88% to 92% and good enantiomeric
excess. Enantiomeric ratios were measured by high-performance liquid chromato-
graphy (HPLC), showing in all cases a slight racemization of less than 5%.
This asymmetric oxidation of N-alkyl imines involves two steps. The first step
is the in situ formation of chiral peroxycarboximidic acid by adding hydrogen per-
oxide to optically active a-bromonitriles in basic media. This step is promoted by
NaHCO3, which is added in an appropriate amount to the aqueous H2O2 to adjust
the pH to 8. This pH favors the increase of concentration of ion HOOꢁ, which acti-
vates the a-bromonitriles 1a–d to form in situ the chiral bromoalkylperoxyimidic
acids 3a–d. The second step is the electrophilic transfer of oxygen from peroxycar-
boximidic acids to imines 2a–d.
As described in the literature,[29] prochiral and chiral imines were prepared by
reacting tertiobutylamine or optically pure (S)-1-phenylethylamine with the corre-
sponding aryl aldehydes in the presence of molecular sieves in anhydrous methylene
chloride. Imines 2a and d were obtained as one geometrical isomer, presumably the
thermodynamically favored anti-imine. Oxaziridines 4a and d were obtained with good
yields in a reasonably short time, ranging from 4 to 6 h by oxidizing the corresponding
imines 2a and d using 1.2 equivalents of a-bromonitriles and 6 equivalents of H2O2.
As shown in Scheme 3, the enantioselective oxidation of N-tertiobutylaryli-
mines 2a and b using the combined system of a-bromonitriles 1a and d and hydrogen
peroxide leads to a mixture of two enantiomeric oxaziridines 4a and b with good
chemical yields. We note that both enantiomers were obtained exclusively in a
trans-configuration and the less stable (Z)-isomer could not be obtained because
of the bulkiness of the substituents. Unfortunately, we have found that oxaziridines
were formed with relatively low enantiomeric excess not exceeding 18%, as shown in
Table 1. The enantiomeric excess of obtained oxaziridines were found to be moder-
ate because the central chirality of the peroxyimidic acid is relatively far from the
site of oxygen transfer. Therefore, the interaction between the stereocentre and the
substituents of the imines remains too low as shown in Figure 1.
Unlike N-tertiobutylarylimines 2a and b, the oxidation of (S)-1-phenylethyl-
arylimines 2c and d proceeded with fairly good stereoselectivity. This high stereo-
selectivity of the reaction is the outcome of asymmetric induction exerted by two

¨
N. TKA, J. KRAIEM, AND B. BEN HASSINE
2998
Table 1. Chemical yields and enantiomeric excess of obtained oxaziridines 4a and b
MeC ꢂ HBrCN
iPr-C ꢂ HBrCN
tBu-C ꢂ HBrCN
Sec-BuC ꢂ HBrCN
Oxaziridines
R
Yield (%)
Eea
Yield (%)
Eea
Yield (%)
Eea
Yield (%)
Eea
Ph
4-CH3O-C6H4
71
74
55:45
57:43
72
70
58:42
56:44
75
76
57:43
54:46
78
74
59:41
57:43
aThe enantiomeric ratios have been assigned by NMR using chiral solvating agents as reported by Pirkle
and Rinaldi.[30]
Figure 1. Electrophilic oxygen transfer from chiral bromoalkylperoxyimidic acid to imines.
stereocenters present in the chiral imines and the chiral peroxycarboximidic acids.
From each optically pure imine 2c and d, two diastereomeric oxaziridines were gen-
erated with good diastereomeric ratios ranging from 74% to 94% as shown in Table 2.
However, Troisi et al.[31] have shown that diastereoselective oxidation of imines 2c,
and d using achiral oxidant (MCPBA) gives the corresponding oxaziridines with
diastereomeric ratios ranging from 20% to 60%.
Both diastereomers were obtained with good chemical yields in a trans-
configuration and the less stable cis-isomer has not been obtained because of the
bulkiness of the substituents. For example, the addition of hydrogen peroxyde
to the (2S)-2-bromopropane nitrile 1a generates in situ the (2S)-2-bromo-
propylperoxyimidic acid 2a, which oxidizes chiral imine 2c to afford a mixture of
both nonequimolar oxaziridines 4c and 4c0. The diastereomeric excess of the
obtained oxaziridines was measured by gaseous-phase chromatography, showing a
Table 2. Chemical yields and diastereomeric excess of obtained oxaziridines 4c and d
MeC ꢂ HBrCN
iPr-C ꢂ HBrCN
tBu-C ꢂ HBrCN
Sec-BuC ꢂ HBrCN
Oxaziridines
R
Yield (%)
Dea
Yield (%)
Dea
Yield (%)
Dea
Yield (%)
Dea
Ph
4-CH3O-C6H4
80
82
87:13
88:12
81
83
89:11
86:14
85
86
92:8
90:10
88
84
97:3
95:5
aThe diastereomeric excess of obtained oxaziridines was measured by gaseous-phase chromatography.

OXIDATION OF N-ALKYLIMINES
2999
Figure 2. Analyses by gaseous-phase chromatography of the mixture of oxaziridines 4c and 4c0 obtained
using (a) (2S)-2-bromopropane nitrile–hydrogen peroxyde system and (b) (2S,3S)-2-bromo-3-methylpen-
tanenitrile–hydrogen peroxyde system.
diastereomeric excess of 73% (Fig. 2). The best result was observed with chiral
(2S,3S)-2-bromo-3-methylpropylperoxyimidic acid formed in situ by adding hydro-
gen peroxyde to the (2S,3S)-2-bromo-3-methylpentanenitrile. As shown in the gas
chromatogram (Fig. 2), both oxaziridine diastereoisomer 4c and 4c0 were isolated
with a diastereomeric ratio of 94%.
The absolute configuration of major diastereomers isolated in the enantiomeri-
cally pure form after column chromatography on silica gel is given by comparing the
specific rotation values with the known products described in the literature. As a
result, we suggest that imines 2c and d were attacked by the oxygen of the bromoalk-
ylperoxyimidic acid from the upper side affording a new stereogenic carbon of oxa-
ziridinic ring having the R configuration. However, an attack from the bottom leads
to the minor diastereomer having the S configuration.
Finally, the investigated method for asymmetric oxidation of imines was found
to be more stereoselective with chiral N-alkylimines. This method seems to be simple
and inexpensive because available amino acids were used as starting materials.
CONCLUSION
We reported the enantioselective and diastereoselective synthesis of oxaziri-
dines by oxidation of the corresponding imines using the combined system of chiral
a-bromonitriles and hydrogen peroxide. The enantiomeric excesses of the prepared
oxaziridines were moderate, whereas the diastereomeric excesses were high, up to
97=3, as proved by gaseous-phase chromatography. We intend to optimize experi-
mental conditions to further improve the chemical and optical yields of the obtained
oxaziridines and their use to synthesize new biologically active compounds.
EXPERIMENTAL
Chiral a-Bromonitriles 1a–d
General procedure. A mixture of a-bromoacid (10 mmol), SOCl2 (50 mmol),
and three drops of dry DMF in anhydrous dichloromethane was stirred overnight at

¨
N. TKA, J. KRAIEM, AND B. BEN HASSINE
3000
room temperature. After removal of the excess of SOCl2 under vacuum, the residue
was added slowly to a cold solution of aqueous ammonium hydroxide and stirred for
2 h. The mixture was filtered, and the resultant a-bromoamides were collected, pur-
ified, and dissolved in 20 mL of freshly distilled thionyl chloride. The mixture was
refluxed for 2 h, the excess of thionyl chloride was removed, and the reaction residue
was mixed with crushed ice, and extracted with ethylacetate, and dried with anhy-
drous MgSO4. After removing the solvent, the crude product was purified by column
chromatography on a neutral alumina gel to afford the chiral a-bromonitriles 1a–d.
HPLC analysis of a-bromonitriles 1a–d were carried out using a chiral
Chirobiotic V column 4.6 mm ꢃ 250 mm under the following conditions: heptane=
isopropanol (98:2) as mobile phase, rt, k ¼ 254 nm, flow rate ¼ 0.6 mL=min. Reten-
tion times of a-bromonitriles 1a–d are 1a, 15.25 min; 1b, 17.66 min, 1c, 19.01 min,
and 1d, 21.81 min.
(2S)-2-Bromopropanenitrile 1a. Yield ¼ 90%; colorless oil; [a]D ꢁ50.0 (c
0.25%, CHCl3); HRMS-ESI calcd. for C3H4BrN 132.95274; found 132.95279; IR
1
(cmꢁ1); nCN ¼ 2249; H NMR (300 MHz, CDCl3): d 1.97(d, 3H, J ¼ 7.2 Hz); 4.38
(q, 1H, J ¼ 6.9 Hz); 13C NMR (75 MHz, CDCl3), d d 21.21; 23.91; 118.26 (CN).
(2S)-2-Bromo-3-methylbutanenitrile 1b. Yield ¼ 88%; colorless oil; [a]D
ꢁ
55.0 (c 0.25%, CHCl3); HRMS-ESI calcd. for C5H8BrN 160.98403; found 160.98408;
IR (cmꢁ1); nCN ¼ 2239; 1H NMR (300 MHz, CDCl3): d1.15 (d, 3H, J ¼ 2.4 Hz); 1.18
(d, 3H, J ¼ 2.4 Hz), 2.16 (m, 1H), 4.24 (d, 1H, J ¼ 5.1 Hz); 13C NMR (75 MHz,
CDCl3), d 19.09, 19.59, 33.89, 35.75, 116.60 (CN).
(2S)-2-Bromo-4-methylpentanenitrile 1c. Yield ¼ 92%; color less oil; [a]D
ꢁ60.0 (c 0.25%, CHCl3); HRMS-ESI calcd. for C6H10BrN 174.99969; found
1
174.99972; IR (cmꢁ1); nCN ¼ 2242; H NMR (300 MHz, CDCl3): d 0.93 (m, 6H);
1.87–2.02 (m, 3H); 4.29 (m, 1H); 13C NMR (75 MHz, CDCl3), d 21.64, 25.66,
26.63, 45.17, 52.65, 117.66 (CN).
(2S,3S)-2-Bromo-3-methylpentanenitrile 1d. Yield ¼ 90%; color less oil;
[a]D ꢁ65.0 (c 0.25%, CHCl3); HRMS-ESI calcd. for C6H10BrN 174.99969; found
1
174.99974; IR (cmꢁ1); nCN ¼ 2240; H NMR (300 MHz, CDCl3): d 0.97 (t, 3H,
J ¼ 7.5 Hz); 1.17 (d, 3H, J ¼ 6.6 Hz), 1.48 (m, 1H), 1.69 (m, 1H), 1.97 (m, 1H);
4.33 (d, 1H, J ¼ 4.8 Hz); 13C NMR (75 MHz, CDCl3), d 11.38, 16.03, 26.98, 34.22,
40.39, 116.43 (CN).
Chiral Oxaziridines 4a–d from the Corresponding Imines 2a–d
General procedure. A solution of H2O2 (30%) (30 mmol) over a period of
5 min was added to a stirred solution of imines 2a–d (5 mmol) and a-bromonitrile
1 (5.5 mmol) in CH2Cl2 (30 ml) at 0 ꢄC. The pH of the 30% aqueous H2O2 was
adjusted to 8 prior to addition with the appropriate amount of NaHCO3. The
reaction mixture was allowed to come to room temperature and then stirred until
the imine was consumed (TLC). Then, the mixture was washed with water
(250 mL) and extracted with three 50-mL portions of CH2Cl2. The combined organic
phases were dried (MgSO4) and concentrated under reduced pressure (T < 30 ꢄC).
The crude residue was cooled, diluted with 100 mL hexane, and filtered to remove

OXIDATION OF N-ALKYLIMINES
3001
precipitated a-bromoamide. The solvant was evaporated, and the residue was puri-
fied by flash chromatography on silica gel (cyclohexane=acetate 85:15) to afford pure
(E) oxaziridines 4a–d. All oxaziridines mentioned have previously been reported: 4a,
b[32] and 4c, d.[31]
Analysis of different oxaziridines was performed using a gas chromatograph
type HP 5890 equipped with a flame ionization detector and a polar capillary column
50 m long and 0.32 mm in diameter. The carrier gas used was nitrogen at a pressure
of 0.552 bar and chromatography is developed with temperature programming from
180 to 250 ꢄC.
(E)-2-tert-Butyl-3-phenyloxaziridine 4a. Yield ¼ 71–78%; yellow oil; ee
1
10–18%. H NMR (300 MHz, CDCl3): d 1.25 (s, 9H), 4.69 (s, 1H), 7.38–7.44 (m,
5H); 13C NMR (75 MHz, CDCl3), d 25.34, 58.51, 73.71, 127.56, 128.52, 129.83.
(E)-2-tert-Butyl-3-paramethoxyphenyloxaziridine
4b. Yield ¼ 70–76%;
1
yellow oil; ee 08–14%; H NMR (300 MHz, CDCl3): d 1.16 (s, 9H), 3.81 (s, 3H)
4.64 (s, 1H) 6.31 (d, 2H, J ¼ 8.7 Hz); 6.89 (d, 2H, J ¼ 8.7 Hz). 13C NMR (75 MHz,
CDCl3), d 25.32, 55.38, 58.34, 73.53, 113.93, 127.66, 128.98, 160.89.
(E)-(1’S,3R)-2-(1’-Phenylethyl)-3-phenyloxaziridine 4c. Yield ¼ 80–88%;
1
yellow oil; de 74–94%; H NMR (300 MHz, CDCl3): d 1.66 (d, 3H, J ¼ 6.3 Hz)
3.29 (q, 1H); 4.56 (s, 1H); 7.29–7.33 (m, 5H); 7.41–7.54 (m, 5H). 13C NMR
(75 MHz, CDCl3), d 21.84, 71.36, 79.54, 124.21, 127.12, 128.02, 128.85, 129.21,
131.69, 133.75, 139.97.
(E)-(1’S,3R)-2-(1’-Phenylethyl)-3-paramethoxyphenyloxaziridine 4d.
1
Yield ¼ 82–86%; yellow oil; de 72–90%; H NMR (300 MHz, CDCl3): d 1.71 (d,
3H, J ¼ 6.3 Hz) 3.37 (q, 1H) 3.85 (s, 3H) 4.67 (s, 1H); 7.12 (d, 2H, J ¼ 8.4 Hz)
7.30–7.34 (m, 7H). 13C NMR (75 MHz, CDCl3), d 20.54, 56.24, 71.34, 80.55,
113.84, 125.55, 127.74, 128.55, 128.97, 129.45, 137.77, 160.94.
ACKNOWLEDGMENT
´ ´
The authors thank the Direction Generale de la Recherche Scientifique of the
Tunisian Ministry of Higher Education and Scientific Research for the financial sup-
port of this research.
REFERENCES
1. Mlochowski, J.; Kubiez, E.; Kloc, K.; Mordarski, M.; Peczyuska, W.; Syper, L. Synthesis
of oxaziridinylquinones and oxaziridinylazines as potential antitumor agents. Liebigs Ann.
Chem. 1988, 455.
2. Said, S. B.; Molchowski, J.; Skarzewski, J. Synthesis of 2-alkyl-3-vinyloxaziridines as
potential antitumor agents. Liebigs Ann. Chem. 1990, 461.
3. Marchant-Brynaert, J.; Bounkhala-Khrouz, Z.; Vanlierde, H.; Ghosez, L. Oxaziridines
and nitrones as potential inhibitors of bacterial D,D-peptidases. Heterocycles 1990, 30,
971–982.
4. Evans, D. A.; Morrissey, M. M.; Dorow, R. L. Asymmetric oxygenation of chiral imide
enolates: A general approach to the synthesis of enantiomerically pure a-hydroxy
carboxylic acid synthons. J. Am. Chem. Soc. 1985, 107, 4346–4348.

¨
N. TKA, J. KRAIEM, AND B. BEN HASSINE
3002
5. Anderson, D. R.; Woods, K. W.; Beak, P. The endocyclic restriction test: Oxygen transfer
from N-sulfonyl oxaziridines to alkenes. Org. Lett. 1999, 1, 1415–1417.
6. Bethell, D.; Bulman Page, P. C.; Vahedi, H. Catalytic asymmetric oxidation of sulfides to
sulfoxides mediated by chiral 3-substituted-1,2-benzisothiazole 1,1-dioxides. J. Org.
Chem. 2000, 65, 6756–6760.
7. Arnone, A.; Cavicchioli, M.; Montanari, V.; Resnati, G. Direct oxyfunctionalization at
unactivated sites: Synthesis of 5b-hydroxysteroids by perfluorodialkyloxaziridines. J.
Org. Chem. 1994, 59, 5511–5513.
8. Choong, I. C.; Ellman, J. A. Synthesis of alkoxylamines by alkoxide amination with
3,30-di-tert-butyloxaziridine. J. Org. Chem. 1999, 64, 6528–6529.
9. Armstrong, A.; Cooker, R. S. Efficient amination of sulfides with a ketomalonate-derived
oxaziridine: Application to [2,3]-sigmatropic rearrangements of allylic sulfimides. J. Chem.
Soc., Chem. Commun. 2002, 904.
10. Vidal, J.; Guy, L.; Sterin, S.; Collet, A. Electrophilic amination: Preparation and use of
N-Boc-3-(4-cyanophenyl)oxaziridine, a new reagent that transfers a N-Boc group to N-
and C-nucleophiles. J. Org. Chem. 1993, 58, 4791–4793.
11. Enders, D.; Poiesz, C.; Joseph, R. Enantioselective synthesis of protected a-aminoketones
via electrophilic amination of a-silylketones with an oxaziridine. Tetrahedron: Asymmetry
1998, 9, 3709–3716.
12. Davis, F. A.; Sheppard, A. C. Applications of oxaziridines in organic synthesis. Tetra-
hedron 1989, 45, 5703–5742.
13. Marilena, F.; Ludovico, R.; Luigino, T. Synthesis of new 3,5-diarylisoxazolidines by
cycloaddition of oxaziridines and alkenes. Tetrahedron 2007, 63, 12896–12902.
14. Kraiem, J.; Grosvalet, L.; Perrin, M.; Hassine, B. B. Synthesis of new 1,2,4-
oxadiazolidin-3-ones by cycloaddition of 2-alkyl-3-aryloxaziridines with chlorosulfonyli-
socyanate. Tetrahedron Lett. 2001, 42, 9131.
15. Iesce, M. R.; Cermola, F.; Guitto, A. Stereoselective synthesis of N-hydroperoxyalkylox-
aziridines: A new class of heterocyclic hydroperoxides. Synthesis 1997, 657.
16. Damavandi, J. A.; Karami, B.; Zolfigol, M. A. Selective oxidation of N-alkyl imines to
oxaziridines using UHP=Maleic anhydride system. Synlett. 2002, 933.
17. Martiny, L.; Jorgensen, K. A. Oxidation of imines to oxaziridines catalysed by transition
metal complexes using molecular oxygen as the terminal oxidant. J. Chem. Soc., Perkin
Trans. 1 1995, 699.
18. Boyd, D. R.; Malone, J. F.; McGuckin, M. R.; Jennings, W. B.; Rutherford, M.; Saket, B.
M. Imines and derivatives, part 20: N-Phosphinoyloxaziridines: Synthesis and structural
characterisation by nuclear magnetic resonance spectroscopy and a crystal structure of
3-(4-chlorophenyl)-2-(diphenylphosphinoyl)oxaziridine. J. Chem. Soc., Perkin Trans. 2
1988, 1145.
19. Emmons, W. D. The synthesis of oxaziranes. J. Am. Chem. Soc. 1956, 78, 6208–6209.
20. Kra¨ıem, J.; Ben Othman, R.; Ben Hassine, B. Synthesis of oxaziridines by oxidation of
imines with the trichloroacetonitrile–hydrogen peroxide system. C. R. Chim. 2004, 7,
1119–1126.
21. Kra¨ıem, J.; Kacem, Y.; Khiari, J. D.; Ben Hassine, B. Stereospecific synthesis of 2-alkyl-
3-aryloxaziridines from prochiral and chiral N-arylidenealkylamines by use of the
benzonitrile–hydrogen peroxide system. Synth. Commun. 2001, 31, 263.
´
´
´
22. Larcheveque, M.; Petit, Y. Preparation d’a-hydroxyesters et d’a-hydroxyaldehydes enan-
´
`
`
´
´
´
tiomeriquement purs: Application a la synthese enantiospecifique de la phermone sexuelle
de la cochenille Pseudococus comstoki. Bull. Soc. Chim. Fr. 1989, 1, 130.
23. Payne, G. B.; Deming, P. H.; Williams, P. H. Reactions of hydrogen peroxide, VII:
Alkali-catalyzed epoxidation and oxidation using a nitrile as co-reactant. J. Org. Chem.
1961, 26, 659.

OXIDATION OF N-ALKYLIMINES
3003
24. Arias, L. A.; Adkins, S.; Nagel, C. J.; Bach, R. D. Epoxidation of alkenes with
trichloroacetonitrile=hydrogen peroxide in a neutral biphasic solvent system. J. Org.
Chem. 1983, 48, 888.
25. Tka, N.; Kraiem, J.; Kacem, Y.; Hajri, A.; Ben Hassine, B. Synthesis of new enantiomeri-
cally pure N-methyl-Narylsulfonyl-a-aminonitriles from amino acids. C. R. Chim. 2009,
12, 1066–1071.
26. Tka, N.; Jegham, N.; Ben Hassine, B. Synthesis, antibacterial and antifungal, activities of
new chiral 5-alkyl-3-(10-benzenesulfonylpyrrolidin-20-yl)-4,5-dihydro-1,2,4-oxadiazin-6-
ones. C. R. Chim. 2010, 131278–1283.
27. Tka, N.; Ben Hassine, B. One-pot synthesis of new biologically active
3,5-disubstituted-1,2,4-oxadiazoles. Synth. Commun. 2010, 40, 3168–3176.
28. Tka, N.; Ben Hassine, B. New chiral aminoamidoximes: Synthesis and investigation of
heterocyclic compounds. Synth. Commun. 2012, 42, 828–835.
29. Westheimer, F. H.; Taguchi, K. Catalysis by molecular sieves in the preparation of keti-
mines and enamines. J. Org. Chem. 1971, 36, 1570–1572.
30. Pirkle, W. H.; Rinaldi, P. L. Nuclear magnetic resonnance determination of enantiomeric
compositions of oxaziridines using chiral solvating agents. J. Org. Chem. 1977, 42, 3217–
3220.
31. Troisi, L.; De Lorenzis, S.; Fabio, M.; Rosato, F., Granito, C. Chiral oxaziridines in the
enantioselective synthesis of isoxazolidines. Tetrahedron: Asymmetry 2008, 19, 2246–2251.
32. Pirkle, W. H.; Rinaldi, P. L. Nuclear magnetic resonance determination of absolute con-
figuration and enantiomeric compositions of chiral oxaziridines using chiral solvating
agents. J. Org. Chem. 1978, 43, 4475–4480.