Synthesis and reactivity of two new trichloromethyl substituted dihydroisoquinoline-derived oxaziridines

Article abstract of DOI:10.1080/00397911.2015.1122808

N-Alkyl oxaziridines may be used as reagents for the oxidation of sulfides in acid-promoted reactions. This article reports on a simple and efficient synthesis of two new trichloromethyl substituted dihydroisoquinoline oxaziridines, a new family of organi

Full text of DOI:10.1080/00397911.2015.1122808

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Synthesis and Reactivity of Two New
Trichloromethyl Substituted Dihydroisoquinoline-
Derived Oxaziridines
Aydi Rihab & Majed Kammoun
To cite this article: Aydi Rihab & Majed Kammoun (2015): Synthesis and Reactivity of Two
New Trichloromethyl Substituted Dihydroisoquinoline-Derived Oxaziridines, Synthetic
Communications, DOI: 10.1080/00397911.2015.1122808
To link to this article: http://dx.doi.org/10.1080/00397911.2015.1122808
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Date: 11 December 2015, At: 05:32

Synthesis and Reactivity of Two New Trichloromethyl Substituted
Dihydroisoquinoline-Derived Oxaziridines
1
1
Aydi Rihab , Majed Kammoun
1
Laboratory of Chemistry of Natural Products, Faculty of Science, Sfax University, Sfax,
Tunisia
Corresponding author: Majed Kammoun, Laboratory of Chemistry of Natural Products,
Sfax University, Faculty of Science BP 1171, 3000 Sfax, Tunisia.
E-mail: majed_kammoun@yahoo.fr
Supplemental data for this article can be accessed on the publisher’s website.
Abstract
N-alkyl oxaziridines may be used as reagents for the oxidation of sulfides in acid-
promoted reactions. This paper reports on a simple and efficient synthesis of two new
trichloromethyl substituted dihydroisoquinoline oxaziridines, a new family of organic
oxidizing agents. Their oxygen transfer capability with respect to sulfides as model
substrates and in the absence of acid is investigated.
1

KEYWORDS: Synthesis; Oxaziridine; Sulfoxidation.
INTRODUCTION
Oxaziridines, which were first reported in the mid-fifties by Emmons, are heterocyclic
[
1]
compounds containing oxygen, nitrogen and carbon atoms in a three-membered ring .
The literature indicates that these compounds have unusual reactivity particularly due to
the presence of the strained three-membered ring and a relatively weak N-O bond.
These heterocycles have been shown to represent promising reagents for application as
[
2, 3]
[4]
[5]
[6]
anti-tumour
, anti-malaria and anti-fungal agents and penicillin analogs . They
have also been widely used as reagents and intermediates in the preparation of
[
7, 8]
biologically active molecules
.
Several methods have been proposed for the preparation of oxaziridines, including the
[
9]
oxidation of imines with cobalt-mediated molecular oxygen or urea–hydrogen
[
10]
[11]
[12]
peroxide,
photolysis of nitrones. The oxidation of an imine with a peracid, usually meta-
chloroperbenzoic acid (m-CPBA), represents the most widely employed method for
amination of ketenes,
addition of hydroxamic acid to propiolates,
and
[
13]
[
14]
oxaziridine preparation
.
The strained oxaziridine ring offers an unusually high reactivity due to the inherently
weak N–O bond and has received considerable attention particularly due to the chirality
2

of the nitrogen atom, which shows an inversion barrier of 25–32 kcal/mol in N-alkyl
[15]
substituted oxaziridines.
[
1]
Since their discovery, oxaziridines have increasingly been employed as oxygen or
nitrogen donors in organic synthesis, depending on their structural electronic features and
[
16-17]
the nature of the nucleophile.
However, although N-alkyl and N-aryl oxaziridines are only weak oxidants, the
analogues bearing an electron-withdrawing group, such as N-sulfonyl and N-phosphinoyl
oxaziridines, react with a broad array of nucleophiles, including enolates, silyl enol
ethers, organometallic compounds, alkenes, arenes, tertiary amines, thiols, thioethers, and
[
16]
selenides. A remarkably useful property of these heterocyclic compounds is the
configurational stability of the nitrogen atom, due to the combined effects of the ring
strain and the presence of the electron-withdrawing oxygen atom, so that it is possible to
[
18]
synthesize enantio enriched oxaziridines. Moreover, chiral oxaziridines, especially the
N-sulfonyl derivatives commonly known as Davis reagents, have successfully been
employed in several enantio-selective oxidations, such as α-hydroxylation of enolates,
[19-22]
oxidation of sulfides, selenides, alkenes, and sulfenimines.
The oxidation of sulfides to sulfoxides is a highly important synthetic transformation that
[
23]
has received much attention in recent years. Asymetric sulfoxides are highly useful as
[
24]
synthons and chiral auxiliaries in asymmetric synthesis. Some of the most successful
techniques that are currently available for asymmetric sulfoxidation include the
3

[
25]
stoicheiometric or catalytic
use of enantiomerically pure oxaziridine reagents and the
[26]
use of oxaziridium salts, which give the greatest eanatio-selectivities for the oxidation
of sulfides.
The dihydroisoquinolines oxaziridines 1a-c (Scheme 1) have previously been reported to
represent promising agents for the transfer of oxygen on organosulfides if the oxygen
[
27,28,29]
transfer is promoted by an acid.
In this case, N-protonated oxaziridines play the
role of the active oxidizing species, which enables the transfer of its oxygen to a sulfide
in the presence of acid.
In the absence of sulfide, oxaziridine, which is equally O-protonated, isomerizes into
nitrone 2a-c (Scheme 2).
However, the structural modification of oxaziridine, most notably the substitution at
[
28]
position 1, can result in useful reagents for the electrophilic oxidation of nucleophiles
.
Considering the promising opportunities that novel oxaziridines might open for the
development of various applications, the present study aimed to synthesize two new
oxaziridines, namely 3 and 4. We also examine the effect of the introduction of a nitro
group in position 7 and of a tichloromethyl substitute in position 1 on the oxidation of
sulfides into sulfoxides.
RESULTS AND DISCUSSION
4

Synthesis Of Oxaziridines 3 And 4
The two new oxaziridines presented in this study were synthesized starting from the
commercial tertiary alcohol 5 (Scheme 3). The imine 6 from step (a) was obtained by the
cyclization of the tertiary alcohol 5 by Ritter-type procedure. The nitration of imine 6
[
30, 31]
under soft conditions
selectively led to the derived imine 7. The peracidic oxidation
of imines 6 and 7 led to good yields of oxaziridines 3 and 4, respectively (Scheme 3).
Oxygen Atom Transfer Onto Sulfides
In order to check the oxidizing properties of the two new oxaziridines 3 and 4, the results
of oxygen transfer of thioanisole into the corresponding sulfoxide was examined as a
model reaction in the presence and absence of acid (Table 1).
The oxidation of thioanisole with 3 and 4 were first performed under the conditions
[
29]
previously described elsewhere
at room temperature in the presence of
methanesulfonic acid (MSOH) in dichloromethane (entry 1).
The results presented in Table 1 revealed that the oxidation of thioanisole with
oxaziridines 3 and 4 was not total; the data indicated a conversion of 65% (with 4) and
4
0% (with 3) (entry 1) into the corresponding sulfoxide, respectively.
The presence of a nitro group in position 7 increased the electrophile of oxaziridine, thus
increasing the conversion rate. This is consistent with the results reported in our
[
28, 29]
previously work.
5

The introduction of a nitro group onto the dihydroisoquinoline skeleton could be
stipulated to induce a significant variation in the reactivity of oxaziridine. However, the
oxidation of the same reagent (thioanisole) by oxaziridines 3 and 4 was performed,
without acid, at reflux for 7h in different solvents (entries 2-4).
Oxaziridine 4 oxidized thioanisole quantitatively to the corresponding sulfoxide with
variable yields in different solvents. The best sulfoxide production yield was obtained
using chloroform as a solvent (Table 1, entry 2).
When the oxidation of thioanisole was performed using oxaziridine 3 under the same
conditions, no reaction was observed and the starting reagent was recovered.
Without a nitro group (oxaziridine 3), no oxygen transfer was observed by increasing the
basicity of the function. Hence, the presence of a nitro group increased the electrophile of
oxaziridine, thus making the reaction of the oxygen transfer onto sulfide easier.
It should be noted, when the oxidation of thioanisole was performed using oxaziridines
[29]
[28]
1
b
and 1c
under the same conditions, in absence of acid and at reflux in
chloroform for 7 h, no oxygen transfer was observed and the starting reagent was
recovered (Table 1, entries 5 and 6).
6

The oxidation of other sulfides, such as p-tolyl methyl sulfide, dimethyl , diphenyl ,
dibenzyl, benzyl phenyl and aryl benzyl sulfides, was then examined using oxaziridine 4
under the optimized reaction conditions, in the absence of acid, in chloroform, and with
heating at reflux for 7 h (Table 2).
The results of oxygen transfer are listed in Table 2. The results revealed that the presence
of sulfide led to oxygen transfer.
Oxaziridine 4 oxidized sulfides quantitatively upon heating at reflux and in the absence
of acid, giving a good sulfoxide conversion rate without over oxidation into sulfones. The
reaction yield was noted to depend on the nucleophilicity of the sulfides. In fact, the
yields required for the oxidation of sulfides 1 and 2 into the corresponding sulfoxides
were the same.
It can be observed that the efficiency of the oxidation is related with the electronic
property of substrates. Compared with the electron-withdrawing groups at p- position of
phenyl ring, the electron-donating groups were more favorable to the conversion of
sulfides (entries 1-5).
The influence of steric effects could be observed. Using diphenyl , dibenzyl, benzyl
phenyl and aryl benzyl sulfides, the yields of the reaction of oxygen transfer was slightly
decreased (entries 6-9).
7

Conversely, the best rates of dimethylsulfide oxidation were obtained by oxaziridine 4
(entry 10).
The introduction of the two attractor groupings, trichloromethyl in position 1 and nitro
group in position 7, onto the dihydroisoquinoline skeleton of the function was noted to
bring a significant variation in terms of oxaziridine reactivity, with the resulting
oxaziridine 4 being able to oxidize sulfide into sulfoxide in the absence of acid.
Accordingly, the steric hindrance around the oxygen atom resulted from the presence of
the strong electron-withdrawing trichloromethyl substitute of oxaziridine 4 was
compatible with the oxygen transfer, and does not block it.
Overall, this study is the first to report on a dihydroisoquinoline-derived oxaziridine able
to oxidize a sulfide into sulfoxide in the absence of acid.
CONCLUSION
The present study aimed to investigate the effect of introducing trichloromethyl and nitro
groups on the dihydroisoquinoline skeleton. The results revealed that the oxaziridine
became more electrophilic and that the reaction of oxygen transfer onto sulfide became
possible in the absence of acid. This reactivity, which is actually novel for
dihydroisoquinoline-derived oxaziridine, can be considered promising because it offers
interesting possibilities for future applications.
8

EXPERIMENTAL
Preparation Of Imine 6
To a cooled (0°C) solution (7. 5 mL) of sulfuric acid H SO (95%) was added dropwise
2
4
and under magnetic stirring, 2 mL of trichloroacetonitrile in 28 mL of hexane. Then, (1.5
g, 9.98 mmol) of tertiary alcohol 1 (commercial product) in 15 mL of hexane was added
to the solution. After return to room temperature, the resulting mixture was stirred under
reflux for 2.5 h. Then, the solution is cooled at room temperature and versed on ice-cold
water (50 mL) under magnetic stirring. The solution is alkalized with ammonia. The
organic layer was extracted with dichloromethane (100 mL), washed with a saturated
aqueous NaCl solution, dried over sodium sulfate and filtered. The solvent was removed
in vacuo and the crude material was then purified by chromatpgraphy (silica gel, eluent
dichloromethane/ methanol 95:5) to afford the imine 6 as pure compound.
1
Yield: 90%. Mp: 74 °C. H NMR (CDCl , 300 MHz): δ (ppm) 1.27 ( s, 6H, 2-CH ) ,2.74
3
3
(
s, 2H , CH ),7.22 (d, J= 8.7Hz ,1H),7.30 (m,1H),7.38 (m,1H), 8.11 ( d, J= 7.8 Hz ,1H).
2
¹
³C NMR (CDCl , 75 MHz): δ 26.75 (2C), 39.02, 55.74, 97.67, 122.79, 126.16, 127.60,
3
-1
-1
1
28.70, 131.20, 138.31, 157.90. IR (KBr): υ 2970 cm (CH ), 1690 cm (C=N), 1618
3
-1
+
cm (Ar). HRMS-ES [M+Na] calc for C H NCl Na 297.9933 found 297.9929.
1
2
12
3
Preparation Of Imine 7
The cold imine 6 (980 mg, 3.56 mmol) was added dropwise to 21.5 mL of concentrated
sulfuric acid. A solution of 827mg potassium nitrate in 5.5 mL of sulfuric acid is added
dropwise by maintaining the temperature at less than 0°C. The reactional medium was
9

stirred at room temperature for 2h and then at 60°C for 4h. After return to room
temperature, the reaction mixture is poured into ice-cold water and alkalized with
ammonia. The organic phase was extracted with the dichloromethane, washed with brine,
dried over sodium sulfate, and filtered. The solvent was removed in vacuo. The residue
was purified by chromatography (silica gel, eluent dichloromethane/ methanol 95:5) to
afford the imine 7 as pure compound.
1
Yield: 77%. Mp: 115 °C; H NMR (CDCl , 400 MHz): δ (ppm) 1,33 (s, 6H, 2-CH ), 2.89
3
3
(
s, 2H, CH ), 7.44 (d, J=8.3 Hz, 1H), 8.30 (dd , J= 2.2, 8.3 Hz , 1H ), 9.04 (d , J= 1.9 Hz,
2
1
1
1
H).¹³C NMR (CDCl , 100 MHz): δ 26.77 (2C), 39.00, 55.98, 96.68, 122.79, 125.77,
3
-1
-1
26.64, 129.61,145.54, 146.45, 156.16. IR (KBr): υ 1342 cm (NO ), 1514 cm (Ar),
2
-1
622 (C=N), 2966 cm (CH ). Anal.calc. for C H N O Cl : C, 44.82; H, 3.45; N, 8.71.
3
12 11
2
2
3
Found: C, 44.88; H, 3.33; N, 8.96.
Preparation Of Oxaziridine 3
To a solution of imine 6 (300 mg, 1.09 mmol) in methanol (10 mL) was added in small
portions, an excess of m-chloroperbenzoic acid (537.2 mg, 3.11 mmol, 2 equiv of active
oxygen) under magnetic stirring and at room temperature. The reaction was followed by
TLC (dichloromethane/methanol: 9:5). The solvent was evaporated and the residue
obtained was taken up in dichloromethane. The solution was washed with a solution of
sodium bicarbonate then with a saturated aqueous NaCl solution. The organic phase was
dried over sodium sulfate, filtered, and concentrated. The residue was then purified by
crystallization from ether/ hexane (1:1) to afford crystals of oxaziridine 3.
1
0

1
Yield = 63%. Mp: 110°C. H NMR (CDCl , 400 MHz): δ (ppm) 1.00 (s, 3H, CH ),1.56
3
3
(
s, 3H,CH ), 2.49 (d, J=15.4 Hz,1H), 2.87 (d, J=15.4 Hz,1H), 7.19 (d, J=7.4 Hz, 1H),7.34
3
(
m, 1H), 7.40 (m, 1H), 8.40 (dd, J=1.2, 7.9 Hz, 1H); ¹³C NMR (CDCl , 100 MHz): 22.29,
3
2
8.58, 37.93, 57.41, 81.66, 99.10, 124.14, 125.96, 129.31, 129.72, 130.93,136.74. MS
+
.
-1
(
EI): 291 (M , base peak), 174 (291- 117), 77 (291-214). IR (KBr): υ 768 cm (C-N),
-
1
-1
1
4
577 cm (Ar), 2972 cm (CH ). Anal. calc. for C H NOCl C, 49.26; H, 4.13; N,
3
12 12
3:
.79. Found: C, 49.36; H, 4.10; N, 4.65.
Preparation Of Oxaziridine 4
To a solution of imine 7 (200 mg, 0.62mmol) in methanol (7 mL) was added in small
portions, an excess of m-chloroperbenzoic acid (280 mg, 1.62 mmol, 2 equiv of active
oxygen) under magnetic stirring at room temperature. The reaction was followed by TLC
(dichloromethane/methanol: 9:5). The solvent was evaporated and the residue obtained
was taken up in dichloromethane. The solution was washed with a solution of sodium
bicarbonate and then with a saturated aqueous NaCl solution. The organic phase was
dried over sodium sulfate, filtered, and concentrated. The residue was then purified by
crystallization from ether/ hexane (1:1) to afford crystals of oxaziridine 4.
1
Yield = 70 %. Mp: 127 °C. H NMR (CDCl , 400 MHz): δ (ppm) 1.01 (s, 3H, CH ), 1.60
3
3
(
s, 3H, CH ), 2.65 (d, J=15.9 Hz, 1H, CH ), 2.93 (d, J=16 Hz,1H, CH ), 7.39 (m, 1H),
3 2 2
8
1
.28 (dd, J=2.2, J=8.3 Hz, 1H), 9.35 (d, J=2.2 Hz, 1H). ¹³C NMR (CDCl , 100 MHz):
3
7.52, 23.60, 33.29, 52.95, 76.57, 93.34, 119.71, 121.68, 125.42, 128.99, 139.40, 141.57.
1
1

-1
-1
-1
-1
IR (KBr): υ 771 cm (C-N), 1383 cm (NO ), 1521 cm (Ar), 2871 cm (CH ). Anal.
2
3
calc. For C H N O Cl C, 42.69; H, 3.28; N, 8.30. Found: C, 42.40; H, 3.28; N, 8.08.
1
2
11
2
3
3:
Oxygen Transfer To Sulfides With Oxaziridines 3 And 4 In Presence Of Acid
A solution of the oxaziridine 3 and 4 (0.50 mmol) in methylene chloride (2 mL) was
added to a solution of thioanisole (0.50 mmol) and methanesulfonic acid (1.5 mmol) in
methylene chloride (2 mL). The reaction mixture was stirred at room temperature until
the disappearance of the active oxygen, as monitored by TLC and potassium iodide test,
and then diluted with methylene chloride and washed with an aqueous sodium
bicarbonate solution. The organic phase was dried with Na SO and concentrated in
2
4
vacuo. The sulfoxide was purified by chromatography on silica gel. The sulfoxide was
purified by chromatography in silica gel using dichloromethane/ methanol 95:5 as eluent.
The sulfoxide obtained is compared and identified with commercial samples. The results
obtained are presented in Table 1 (entry 1).
Oxygen Transfer To Sulfides With Oxaziridines In Absence Of Acid
A solution of oxaziridine 3, 4, 1b and 1c (1 mmol) in chloroform (20 mL) was heated at
reflux in the presence of sulfide (1 mmol). The reaction was taken under magnetic
stirring and heating for 7 h and monitored by TLC. Then, the reaction products were
1
identified by H NMR spectroscopic analysis. All The isolated sulfoxide compounds
were purified by chromatography over silica gel using dichloromethane/ methanol 95:5
1
2

as eluent. The sulfoxides obtained are compared and identified with commercial samples.
The results obtained are presented in Table 1 (entries 2, 5-6).
This reaction was carried out using also acetonitrile (20 mL) and methanol (20 mL) as
solvent. The results obtained are presented in Table 1 (entries 3-4).
Characterization Data For Sulfoxides (Table 1)
[
32] 1
Methyl phenyl sulfoxide (entry 1) : H NMR (400 MHz, CDCl ) δ (ppm): 7.65-7.63
3
1
3
(
m, 2H), 7.55-7.47 (m, 3H), 2.72 (s, 3H). C NMR (100 MHz, CDCl ) δ (ppm): 145.8,
3
1
31.2, 129.5, 123.6, 44.1.
[
32] 1
p-Tolylmethyl sulfoxide (entry 2) : H NMR (400 MHz, CDCl ) δ (ppm): 7.54 (d, J=
3
1
3
8
.0 Hz, 2H), 7.33 (d, J= 8.0 Hz, 2H), 2.69 (s, 3H), 2.40 (s, 3H). C NMR (100 MHz,
CDCl ) δ (ppm): 142.5, 141.6, 130.2, 130.1, 123.6, 44.1, 21.5.
3
[
32] 1
4
-Methoxyphenyl methyl sulfoxide (entry 3) : H NMR (400 MHz, CDCl ) δ (ppm):
3
1
3
7
.57 (d, J= 8.0 Hz, 2H), 7.01 (d, J= 8.0 Hz, 2H), 3.82 (s, 3H), 2.67 (s, 3H). C NMR
(
100 MHz, CDCl ) δ (ppm): 162.0, 136.6, 125.5, 114.9, 55.6, 44.0.
3
[
32] 1
p-Chlorophenyl methyl sulfoxide (entry 4) : H NMR (400 MHz, CDCl ) δ (ppm):
3
1
3
7
.59 (d, J= 8.0 Hz, 2H), 7.50 (d, J= 8.0 Hz, 2H), 2.70 (s, 3H). C NMR (100 MHz,
CDCl ) δ (ppm): 144.3, 137.3, 129.8, 125.1, 125.0, 44.1.
3
[
33] 1
p-Nitrophenyl methyl sulfoxide (entry 5) : H NMR (300MHz, CDCl , 278K, TMS):
3
1
3
2
.56 (s, 3H, Me), 7.84 (d, 2H), 8.34(d 2H); C NMR (75MHz, CDCl , 278K, TMS):
3
4
7.7, 124.5, 149.3, 153.1.
1
3

[
32] 1
Diphenyl sulfoxide (entry 6) : H NMR (400 MHz, CDCl ) δ (ppm): 7.65-7.63 (m,
3
1
3
4
1
H), 7.47-7.43 (m, 6H). C NMR (100 MHz, CDCl ) δ (ppm): 145.7, 131.2, 129.4,
3
24.9.
[
34] 1
Dibenzyl sulfoxide (entry 7) : H NMR (300 MHz, CDCl ) δ (ppm): 3.89 (d, 4H),
3
1
3
7
.21-7.40 (m, 10 H). C NMR (75 MHz, CDCl ) δ (ppm): 130.10, 129.01, 128.02, 57.10.
3
[
35] 1
Benzyl phenyl sulfoxide (entry 8) : H NMR (400 MHz, CDCl ) δ (ppm): 7.47-7.36
3
(m, 5H), 7.29-7.23 (m, 3H), 6.99 (d, J= 8.0 Hz, 2H), 4.12 (d, J= 16.0 Hz, 1H), 4.01 (d, J=
1
3
1
1
2.0 Hz, 1H). C NMR (100 MHz, CDCl ) δ (ppm): 131.2, 130.4, 129.1, 128.9, 128.5,
3
28.3, 124.5.
[
36] 1
Benzyl cyclohexyl sulfoxide (entry 9) : H NMR (300 MHz, CDCl ) δ (ppm): 1.29
3
(m, 3H), 1.51 (m, 2H) ), 1.69 (m, 1H), 1.88 (m, 3H), 2.09 (m, 1H) , 2.48 (m, 1H), 3.90
1
3
(
m, 2H) 7.34 (m, 5 H). C NMR (75 MHz, CDCl ) δ (ppm): 130.85, 129.90, 128.50,
3
1
27.90, 56.98, 54.50, 26.98, 25.01, 24.87, 23.99.
[
37] 1
Dimethyl sulfoxide (entry 10) : H NMR (300 MHz, CDCl ) δ (ppm): 2.62 (s, 6H).
3
1
3
C NMR (75 MHz, CDCl ) δ (ppm): 40.76.
3
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3
3
1
7

Table 1. Oxidation of thioanisole with oxaziridines 3, 4, 1b and 1c
a
Entry R'
Acid
Temperature Solvent
°C)
Time Yield of thioanisole
b
(
(%) (conversion)
R"=NO2
R"=H
c
1
2
3
4
5
CCl3 MsOH 25
CH Cl2
24 h
7 h
7 h
7 h
7 h
7 h
40 (65) 20 (40)
2
c
CCl3 No
CCl3 No
CCl3 No
61
81
68
61
61
CHCl3
82 (100)
0
c
CH CN
76 (100)
0
0
-
3
c
MeOH
CHCl3
CHCl3
74 (100)
H
No
No
0
0
6
Me
-
a
Determined by TLC.
b
c
1
Determined by H NMR spectroscopy in CDCl .
3
Isolated product.
1
8

a
Table 2. Oxidation of sulfides with oxaziridine 4 in the absence of acid
b
Entry Sulfides
1
Yield of sulfoxide (%) (conversion)
c
82 (100)
c
2
3
80 (100)
c
80 (100)
c
4
5
6
77 (100)
c
75 (100)
c
65 (100)
c
7
8
68 (100)
c
70 (100)
c
9
72 (100)
d
1
0
quantitative
a
Reaction performed at reflux in CHCl3
1
9

b
c
d
1
Determined by H NMR spectroscopy in CDCl .
3
Isolated product
Reaction performed in CDCl3
2
0

Scheme 1. Oxaziridines 1a-c.
2
1

Scheme 2. Reactivity of oxaziridines 1a-c
2
2

Scheme 3. Synthesis of oxaziridines 3 and 4
2
3