Highly chemoselective rearrangement of 3-aryloxaziridines to nitrones or amides

Article abstract of DOI:10.1055/s-0029-1216965

An efficient method for the chemoselective ring-opening rearrangement of 3-aryloxaziridines by using silver triflate alone to afford nitrones, or in the presence of a simple Br0nsted acid to yield amides, has been developed. Silver triflate plays an impor

Full text of DOI:10.1055/s-0029-1216965

PAPER
3399
Highly Chemoselective Rearrangement of 3-Aryloxaziridines to Nitrones or
Amides
Chemoselective
R
e
o
arrangemen
n
t
of 3-Arylox
g
a
ziridines Xing, Xinfang Xu, Liping Yang*
Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, P. R. of China
Fax +86(21)62232487; E-mail: lpyang@chem.ecnu.edu.cn
Received 27 April 2009; revised 8 June 2009
Nitrones are important and versatile synthetic intermedi-
Abstract: An efficient method for the chemoselective ring-opening
ates in organic synthesis;11 for example, they can undergo
[3+2]-cycloaddition reactions with alkenes to produce
rearrangement of 3-aryloxaziridines by using silver triflate alone to
afford nitrones, or in the presence of a simple Brønsted acid to yield
isoxazolines, which are important precursors for a variety
of biologically important compounds, such as b-amino
acids, alkaloids, etc. Considering the importance of ni-
trone structures, the simple ring-opening rearrangement
of oxaziridines to yield nitrones is highly desired; howev-
er, besides the above-mentioned literature, methods for
this direct transformation are still quite limited. More re-
cently, it has been found that under different Lewis acid
catalysis, N-sulfonyloxaziridines can act as the precursor
of nitrones to produce isoxazolidines with styrenes via
[3+2] cycloaddition.12 Inspired by this result we decided
to further explore the catalytic abilities of more simple
and general Lewis acids toward this transformation.
amides, has been developed. Silver triflate plays an important role
in both transformations.
Key words: oxaziridines, rearrangement, chemoselectivity, ni-
trones, amides
Oxaziridines have three different bonds (C–N, C–O, N–
O) in one highly strained three-membered ring.1 This
unique structure has gained wide application in a variety
of transformations, among which electrophilic oxygen-
ation and amination have been intensively studied and fur-
ther developed into
a
series of asymmetric
transformations.2–4 In addition, the ring-opening rear-
rangement of oxaziridines has also drawn attention.5 It
can not only yield diversely useful compounds via differ-
ent bond cleavages, but also provide insights into the
strength and reactivity of different bonds under various re-
action conditions, which can direct the further transforma-
tions of oxaziridines. Oxaziridines can undergo ring-
opening rearrangement either via C–O bond cleavage to
produce nitrones or via N–O bond cleavage to afford
amides. The chemoselectivity is greatly affected by the
substitution pattern in the oxaziridines. For example, un-
der thermal or acidic conditions, 3-aryloxaziridines afford
nitrones,6,7 while 3-alkyloxaziridines give amide prod-
ucts.1a,8 Different catalytic systems have also been applied
to achieve highly chemoselective products. For 3-arylox-
aziridines, it has been reported that aluminum trichloride
can catalyze nitrone formation, while manganese or rhod-
ium complexes can catalyze amide formation;9,10 however,
a simple and convenient method for the chemoselective
ring-opening rearrangement of oxaziridines is still lack-
ing. Here, we report a general and efficient method to ful-
fill this purpose, by simply controlling the reaction
conditions. Starting from 3-aryloxaziridines and using sil-
ver triflate as the catalyst, the nitrone product is formed
via C–O bond cleavage, while amide is obtained as the
major product via N–O bond cleavage when silver triflate
catalyst in the presence of a simple Brønsted acid is used.
3-(4-Methoxyphenyl)-2-(2-phenylethyl)oxaziridine (1a),
which was easily prepared by epoxidation of the corre-
sponding imine using m-chloroperoxybenzoic acid, was
chosen as the substrate to conduct our initial investigation.
Thus, oxaziridine 1a was heated in anhydrous 1,2-dichlo-
roethane (DCE) at 70 °C with 20 mol% iron(III) chloride
as the catalyst (Table 1, entry 1). Only a trace amount of
the corresponding nitrone product 2a was formed, while
most of the starting material was decomposed into 4-
methoxybenzaldehyde. Following this result, a series of
other Lewis acids was tested, among which 20 mol% zinc
chloride or aluminum trichloride showed good activity
with moderate to good yield (Table 1, entries 2 and 3);
however, several copper salts, such as copper(II) chloride,
copper(II) acetate and copper(II) triflate, gave even worse
results than iron(III) chloride (Table 1, entries 4–6), and
oxaziridine 1a was almost completely decomposed to 4-
methoxybenzaldehyde, which indicated the poor stability
of 1a in the presence of Lewis acids at high temperature.
The best result was obtained when 10 mol% silver triflate
was used, which afforded nitrone 2a with a 91% isolated
yield (Table 1, entry 7). The yield remained unaffected
when the catalyst loading of silver triflate was reduced to
5 mol%, however, the yield was greatly decreased when
the catalyst loading was further reduced to 1 mol%
(Table 1, entries 8 and 9). The reaction proceeds slowly at
room temperature, giving a relatively poor conversion
even after a prolonged reaction time (Table 1, entry 10).
It is worth mentioning that with copper(II) chloride as the
catalyst, oxaziridine 1a gave the amide product 3a via N–
O bond cleavage in 36% yield, instead of nitrone 2a. With
SYNTHESIS 2009, No. 20, pp 3399–3404
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216965; Art ID: F09109SS
x
x.
x
x
.
2
0
0
9
© Georg Thieme Verlag Stuttgart · New York

3400
D. Xing et al.
PAPER
this unexpected chemoselectivity switch, we decided to Therefore, following the standard reaction conditions ap-
develop an efficient method for amide formation. We plied to nitrone formation, several Brønsted acids were
turned our initial attention to simple Brønsted acids, tested. The results showed that the acidity had a strong ef-
which have been found to be capable of promoting oxy- fect on the outcome of the rearrangement of oxaziridine
gen atom transfer from oxaziridines onto sulfides.13 1a. When the more acidic trifluoromethanesulfonic acid
or trifluoroacetic acid catalyst was used, only nitrone
Table 1 Lewis Acid Catalyzed Rearrangement of Oxaziridine 1a to
product 2a was obtained in moderate yield, along with the
Nitrone 2aa
formation of a small amount of 4-methoxybenzaldehyde
O
(Table 2, entries 1 and 2);7b however, when the less acidic
O–
N+
N
Lewis acid
OMe
acetic acid was used, the amide 3a became the major
product, albeit in low yield (Table 2, entry 3). Increasing
the amount of acetic acid was useful to gain a better yield
of amide 3a (Table 2, entries 4 and 5), however, the de-
composition of oxaziridine 1a into 4-methoxybenzalde-
hyde was also accelerated (1a was completely consumed
under the conditions of both entries 4 and 5). In our above-
mentioned results, the decomposition of oxaziridine 1a
had been greatly inhibited by the efficient formation of ni-
trone 2a with silver triflate catalyst. Therefore, we decid-
ed to test the effect of silver triflate catalyst on amide
formation.
Ph
Ph
OMe
1a
2a
Entry Catalyst
Catalyst Amount Temp
Time Yieldb
(mol%)
20
20
20
20
20
10
10
5
(°C)
70
70
70
70
70
70
70
70
70
r.t.
(h)
(%)
<8c
65c
86
1
2
FeCl3
3
ZnCl2
3
3
AlCl3
3
4
CuCl2
3
<5c,d
<5c
<5c
91
5
Cu(OAc)2
Cu(OTf)2
AgOTf
AgOTf
AgOTf
AgOTf
3
The use of 5 mol% silver triflate with 20 mol% acetic acid
made the rearrangement more complicated, with the for-
mation of both nitrone 2a and amide 3a (Table 2, entry 6);
however, when the amount of acetic acid was increased to
50 mol%, the most satisfactory result was obtained and
amide 3a was exclusively afforded in 78% isolated yield
(Table 2, entry 7). A control experiment showed that both
nitrone 2a and amide 3a could be obtained in poor yield,
without any chemoselectivity, under thermal conditions
(Table 2, entry 8). This result indicated that our reaction
system was not only able to accelerate the reactivity but
also to give a good control in the chemoselectivity for the
ring-opening rearrangement of oxaziridine 1a.
6
3
7
1.5
8
1.5
6
91
9
1
52
10
5
12
22c
a Reactions were carried out on 0.5-mmol scale with the indicated
amount of catalyst in anhydrous DCE (4 mL) for the indicated time.
b Isolated yield unless otherwise stated.
c Yield was determined by 1H NMR spectroscopy.
d The corresponding amide product via N–O bond cleavage was
formed in 36% NMR yield.
Table 2 Brønsted Acid Promoted Chemoselective Rearrangement of Oxaziridine 1a to Amide 3aa,b,c
O
O
O–
N+
N
HN
Ph
+
Ph
Ph
OMe
OMe
OMe
1a
2a
3a
Entry
AgOTf (mol%)
Brønsted acid (mol%) Temp (°C)
Time (h)
Yield (%) of 2a
Yield (%) of 3a
1
2
3
4
5
6
7
8
–
–
–
–
–
5
5
–
TfOH (20)
TFA (20)
AcOH (20)
AcOH (50)
AcOH (100)
AcOH (20)
AcOH (50)
–
70
70
70
70
70
70
70
70
6
6
6
6
2
6
2
6
52
n.d.
n.d.
37
48
n.d.
n.d.
n.d.
18
53
58
20
n.d.
11
78d
27
a Reactions were carried out on 0.5-mmol scale, with the indicated amount of AgOTf and Brønsted acid in anhydrous DCE (4 mL).
b All yields were determined by 1H NMR spectroscopy unless otherwise stated.
c n.d. = not detected.
d Isolated yield.
Synthesis 2009, No. 20, 3399–3404 © Thieme Stuttgart · New York

PAPER
Chemoselective Rearrangement of 3-Aryloxaziridines
3401
With the optimized conditions in hand, we further inves- formations, plays the dominant role in both transforma-
tigated the substrate scope for both transformations. Start- tions.
ing from alkylamines and different aromatic aldehydes, a
We have also considered the possible reaction pathways
series of substituted 3-aryloxaziridines was easily pre-
for this chemoselective rearrangement of 3-aryloxaziri-
pared. In terms of the silver triflate catalyzed C–O bond-
dines. For nitrone formation, the silver triflate catalyst
cleavage transformation, a strong electronic effect was
would coordinate with the oxygen atom in the oxaziridine
shown. Reactions of substrates with strong electron-
three-membered ring to lower the activation barrier for the
donating groups at the para position of the 3-aryl ring run
rearrangement to proceed via C–O bond breakage.9 For
amide formation, we assume that in the presence of acetic
smoothly and fast (Table 3, entries 1–3, 6 and 7), while re-
action of the substrate with a weak electron-donating
acid, the relatively weak N–O bond in the oxaziridine ring
group was less efficient (Table 3, entry 5). Substitution at
would be cleaved by O-protonation, to afford an oxonium
intermediate via a 1,2-H shift from C to N. This interme-
diate would then undergo deprotonation to afford the
amide product. Silver triflate may have a role in acceler-
the ortho position made this transformation less efficient
(Table 3, entry 4), while the meta-substituted substrate
gave a relatively low yield (Table 3, entry 9). The substi-
tution pattern at the N-position was also tested, and sub-
ating the N–O bond cleavage by coordinating with the ox-
strates with more bulky alkyl groups gave better yields
ygen atom, or in stabilizing the oxonium intermediate.
(Table 3, entries 8 and 10). We have also tested for the
Further investigations to understand the mechanism are
formation of amides under the conditions of a combina-
underway.
tion of silver triflate catalyst and 0.5 equivalents of acetic
In summary, we have developed a simple and efficient
acid. Generally, except for the formation of a small
method for the chemoselective ring-opening rearrange-
amount of the corresponding benzaldehyde, the N–O
ment of 3-aryloxaziridines. By applying silver triflate as
bond could be chemoselectively cleaved to afford the
the catalyst, nitrones can be efficiently afforded and, with
amides without nitrone formation, and the substrate scope
the addition of 0.5 equivalents of acetic acid to the system,
showed very similar trends to nitrone formation (Table 3,
the chemoselectivity can be completely switched from the
C–O bond to N–O bond cleavage, to yield amides exclu-
sively.
formation of 3). This similarity indicated that the silver
triflate catalyst, as the same factor applied in both trans-
Table 3 The Chemoselective Rearrangement of 3-Aryloxaziridines 1 to Nitrones 2a or Amides 3b
AgOTf (5 mol%)
AgOTf (5 mol%)
DCE, 70 °C
R2
O
AcOH (0.5 equiv)
DCE, 70 °C
R2
R2
O
O
HN
R1
N
R1
N
conditions A
R1
conditions B
2
1
3
Conditions A
Time (h)
Conditions B
Yieldc,d (%) of 2 Time (h)
Entry
1
R1
R2
Yieldc,e (%) of 3
3a: 78
1
2
1a
1b
1c
1d
1e
1f
1g
1h
1i
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
4-MeOC6H4
4-Tol
1.5
2
2a: 91
2b: 67
2c: 67
2d: 69
2e: 34
2f: 77
2g: 68
2h: 94
2i: 26
2j: 80
1.5
2
3b: 74
3
4-(H2C=CHCH2O)C6H4
2-MeOC6H4
4-PhC6H4
2
2
3c: 65
4
6
6
3d: 42
5
6
2
3e: 40
6
(CH2)2C6H4-p-F
(CH2)3Ph
s-Bu
4-MeOC6H4
4-MeOC6H4
2-MeOC6H4
3-MeOC6H4
2-MeOC6H4
2
2
3f: 82
7
2
2
3g: 66
8
1.5
6
1.5
6
3h: 89
9
s-Bu
3i: 31
10
1j
t-Bu
2.5
6
3j: 46
a Nitrones were afforded under conditions A, in which reactions were carried out on 0.5-mmol scale with AgOTf (5 mol%) in anhydrous DCE
(4 mL).
b Amides were afforded under conditions B, in which reactions were carried out on 0.5-mmol scale with AgOTf (5 mol%) and AcOH (0.25
mmol) in anhydrous DCE (4 mL).
c Isolated yield.
d In all cases the yield based on conversion was greater than 90%.
e The corresponding benzaldehyde was always detected as a byproduct in less than 10% conversion.
Synthesis 2009, No. 20, 3399–3404 © Thieme Stuttgart · New York

3402
D. Xing et al.
PAPER
C-(2-Methoxyphenyl)-N-(2-phenylethyl)nitrone (2d)
Colorless liquid.
IR (KBr): 3206, 1667, 1387, 1248, 1002 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.28 (d, J = 8.1 Hz, 1 H), 7.67 (s,
1 H), 7.38–7.19 (m, 6 H), 7.03 (t, J = 7.2 Hz, 1 H), 6.85 (d, J = 8.1
Hz, 1 H), 4.14 (t, J = 7.5 Hz, 2 H), 3.79 (s, 3 H), 3.32 (t, J = 7.2 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 156.9, 137.8, 131.5, 129.3, 128.8,
128.7, 128.6, 126.7, 120.7, 119.4, 109.8, 68.7, 55.5, 34.2.
All reactions were carried out under nitrogen atmosphere using
standard Schlenk techniques. All reagents were obtained commer-
cially and were used without further purification unless otherwise
noted. 1,2-Dichloroethane was purchased from Acros and was used
directly without further purification. The petroleum ether (PE) used
refers to the fraction boiling in the range of 60–90 °C. The starting
materials were synthesized according to known procedures.14–17 IR
spectra were recorded on a Thermo Nicolet Nexus 670 FTIR instru-
ment. 1H and 13C NMR spectra were recorded in CDCl3 with TMS
as internal standard at ambient temperature on a JEOL AL-300
NMR spectrometer. Mass spectra were recorded with a Finnigan
MAT 95 mass spectrometer for both low-resolution and high-
resolution mass spectra. Melting points were determined using a
Zeiss Axiolab microscope apparatus and are uncorrected.
MS (EI, 70 eV): m/z = 255 [M+].
HRMS (EI): m/z [M+] calcd for C16H17NO2: 255.1259; found:
255.1264.
C-(1,1¢-Biphenyl-4-yl)-N-(2-phenylethyl)nitrone (2e)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 122–
123 °C.
IR (KBr): 3067, 1607, 1459, 1226, 1150, 1081 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.24 (d, J = 8.7 Hz, 2 H), 7.66–
7.22 (m, 12 H), 7.18 (s, 1 H), 4.15 (t, J = 7.2 Hz, 2 H), 3.33 (t, J =
7.2 Hz, 2 H).
Silver Triflate Catalyzed Rearrangement of Oxaziridines 1 to
Nitrones 2 (Table 3, Conditions A); General Procedure
To a DCE soln (4 mL) containing AgOTf (6.5 mg, 0.025 mmol) in
a Schlenk tube under N2, a 3-aryloxaziridine 1a–j (0.5 mmol) was
added at r.t. The reaction mixture was then heated at 70 °C until the
starting material was completely consumed, as monitored by TLC.
The reaction mixture was purified by flash chromatography to di-
rectly afford the corresponding nitrone 2a–j.
13C NMR (75 MHz, CDCl3): d = 142.7, 137.7, 134.4, 129.2, 129.0,
128.9, 128.8, 128.7, 127.8, 127.2, 127.1, 127.0, 126.9, 68.6, 34.1.
C-(4-Methoxyphenyl)-N-(2-phenylethyl)nitrone (2a)18
Colorless crystals (recrystallized from PE–CH2Cl2); mp 71–72 °C.
IR (KBr): 3076, 1604, 1500, 1466, 1254, 1169, 1157, 1024 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.17 (d, J = 8.4 Hz, 2 H), 7.26–
7.20 (m, 5 H), 7.07 (s, 1 H), 6.90 (d, J = 8.1 Hz, 2 H), 4.07 (t, J = 6.9
Hz, 2 H), 3.81 (s, 3 H), 3.29 (t, J = 6.9 Hz, 2 H).
MS (EI, 70 eV): m/z = 301 [M+].
HRMS (EI): m/z [M+] calcd for C21H19NO: 301.1467; found:
301.1469.
N-[2-(4-Fluorophenyl)ethyl]-C-(4-methoxyphenyl)nitrone (2f)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 98–99 °C.
IR (KBr): 3029, 1604, 1507, 1273, 1178, 1160, 1027 cm–1.
13C NMR (75 MHz, CDCl3): d = 160.8, 137.7, 134.2, 130.4, 128.6,
128.5, 126.6, 123.2, 113.6, 67.9, 55.2, 33.9.
MS (EI, 70 eV): m/z = 255 [M+].
HRMS (EI): m/z [M+] calcd for C16H17NO2: 255.1259; found:
1H NMR (300 MHz, CDCl3): d = 8.16 (d, J = 9.0 Hz, 2 H), 7.27–
7.16 (m, 2 H), 7.05 (s, 1 H), 6.97–6.90 (m, 4 H), 4.05 (t, J = 6.9 Hz,
2 H), 3.84 (s, 3 H), 3.27 (t, J = 6.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 163.3, 161.0, 160.1, 134.5, 133.5,
133.4, 130.5, 130.3, 130.2, 123.1, 115.5, 115.3, 113.8, 67.9, 55.3,
33.0.
255.1264.
N-(2-Phenylethyl)-C-(p-tolyl)nitrone (2b)
Colorless liquid.
IR (KBr): 3205, 1666, 1611, 1453, 1261, 1150, 1031 cm–1.
MS (EI, 70 eV): m/z = 273 [M+].
1H NMR (300 MHz, CDCl3): d = 8.06 (d, J = 8.1 Hz, 2 H), 7.30–
7.19 (m, 7 H), 7.09 (s, 1 H), 4.10 (t, J = 6.9 Hz, 2 H), 3.30 (t, J = 7.2
Hz, 2 H), 2.37 (s, 3 H).
HRMS (EI): m/z [M+] calcd for C16H16NO2F: 273.1165; found:
273.1164.
C-(4-Methoxyphenyl)-N-(3-phenylpropyl)nitrone (2g)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 80–81 °C.
IR (KBr): 3436, 1598, 1503, 1251, 1157, 1031 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.23 (d, J = 9.0 Hz, 2 H), 7.32–
7.13 (m, 6 H), 6.94 (d, J = 8.7 Hz, 2 H), 3.90–3.78 (m, 2 H), 3.82 (s,
3 H), 2.73 (t, J = 7.5 Hz, 2 H), 2.38–2.31 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 140.8, 137.8, 134.7, 129.1, 128.7,
128.6, 128.6, 127.7, 126.8, 68.3, 34.0, 21.6.
MS (EI, 70 eV): m/z = 239 [M+].
HRMS (EI): m/z [M+] calcd for C16H17NO: 239.1310; found:
239.1314.
13C NMR (75 MHz, CDCl3): d = 161.0, 140.6, 134.2, 130.5, 128.5,
128.4, 126.2, 123.4, 113.8, 65.7, 55.3, 32.4, 28.7.
C-(4-Allyloxyphenyl)-N-(2-phenylethyl)nitrone (2c)
Colorless solid; mp 56–57 °C.
MS (EI, 70 eV): m/z = 269 [M+].
HRMS (EI): m/z [M+] calcd for C17H19NO2: 269.1416; found:
IR (KBr): 3067, 1607, 1507, 1434, 1245, 1179, 1157, 1018, 996
cm–1.
1H NMR (300 MHz, CDCl3): d = 8.14 (d, J = 7.5 Hz, 2 H), 7.28–
7.19 (m, 5 H), 7.05 (s, 1 H), 6.91 (d, J = 7.2 Hz, 2 H), 6.04–6.02 (m,
1 H), 5.43–5.26 (m, 2 H), 4.56–4.55 (m, 2 H), 4.07 (t, J = 7.2 Hz, 2
H), 3.29 (t, J = 7.2 Hz, 2 H).
269.1414.
N-sec-Butyl-C-(2-methoxyphenyl)nitrone (2h)
Light yellow liquid.
13C NMR (75 MHz, CDCl3): d = 160.0, 137.8, 134.3, 132.7, 130.5,
IR (KBr): 3083, 1598, 1330, 1289, 1245, 1150, 1021 cm–1.
128.8, 128.6, 126.8, 123.4, 118.0, 114.5, 68.7, 68.1, 34.0.
1H NMR (300 MHz, CDCl3): d = 9.34 (d, J = 7.2 Hz, 1 H), 7.88 (s,
1 H), 7.38–7.32 (m, 1 H), 7.05–6.86 (m, 2 H), 3.94–3.86 (m, 1 H),
3.85 (s, 3 H), 2.09–2.01 (m, 1 H), 1.66–1.60 (m, 1 H), 1.48 (d,
J = 6.9 Hz, 3 H), 0.94 (t, J = 7.2 Hz, 3 H).
MS (EI, 70 eV): m/z = 281 [M+].
HRMS (EI): m/z [M+] calcd for C18H19NO2: 281.1416; found:
281.1413.
Synthesis 2009, No. 20, 3399–3404 © Thieme Stuttgart · New York

PAPER
Chemoselective Rearrangement of 3-Aryloxaziridines
3403
13C NMR (75 MHz, CDCl3): d = 156.7, 131.1, 128.7, 127.4, 120.7,
119.6, 109.6, 74.3, 55.5, 27.4, 19.2, 10.7.
13C NMR (75 MHz, CDCl3): d = 167.4, 141.8, 139.0, 131.8, 129.2,
128.8, 128.7, 126.8, 126.5, 41.0, 35.7, 21.4.
MS (EI, 70 eV): m/z = 207 [M+].
MS (EI, 70 eV): m/z = 239 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
HRMS (EI): m/z [M+] calcd for C16H17NO: 239.1310; found:
207.1254.
239.1316.
N-sec-Butyl-C-(3-methoxyphenyl)nitrone (2i)
Colorless liquid.
IR (KBr): 3429, 1670, 1592, 1387, 1320, 1144, 1056 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.31–8.30 (m, 1 H), 7.45–7.26 (m,
3 H), 6.99–6.95 (m, 1 H), 3.86 (s, 3 H), 1.60–1.40 (m, 1 H), 1.49–
1.25 (m, 2 H), 1.41 (d, J = 6.0 Hz, 3 H), 0.97–0.86 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.6, 133.1, 129.2, 121.6, 117.4,
112.1, 74.3, 55.3, 29.7, 27.5, 19.3, 10.8.
4-Allyloxy-N-(2-phenylethyl)benzamide (3c)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 122–
123 °C.
IR (KBr): 3354, 1638, 1548, 1257, 1002 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.65 (d, J = 6.9 Hz, 2 H), 7.33–
7.22 (m, 5 H), 6.91 (d, J = 6.6 Hz, 2 H), 6.09–5.99 (m, 2 H), 5.44–
5.28 (m, 2 H), 4.58–4.55 (m, 2 H), 3.70 (t, J = 6.9 Hz, 2 H), 2.92 (t,
J = 6.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 166.9, 161.1, 139.0, 132.7, 128.8,
128.7, 128.6, 127.1, 126.6, 118.1, 114.5, 68.8, 41.1, 35.8.
MS (EI, 70 eV): m/z = 281 [M+].
HRMS (EI): m/z [M+] calcd for C18H19NO2: 281.1416; found:
MS (EI, 70 eV): m/z = 207 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
207.1255.
N-tert-Butyl-C-(2-methoxyphenyl)nitrone (2j)9
281.1412.
Colorless solid; mp 68–69 °C.
2-Methoxy-N-(2-phenylethyl)benzamide (3d)
Colorless liquid.
IR (KBr): 3395, 1652, 1538, 1239, 1185, 1018 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.22 (m, 7 H), 7.04 (t,
J = 7.2 Hz, 1 H), 6.91 (d, J = 8.1 Hz, 1 H), 3.80–3.75 (m, 3 H), 3.74
(s, 3 H), 2.93 (t, J = 6.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 165.2, 157.4, 139.4, 132.6, 132.2,
128.9, 128.5, 126.4, 121.5, 121.2, 111.2, 55.6, 40.8, 35.6.
IR (KBr): 3168, 1598, 1472, 1362, 1289, 1245, 1109, 1031 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.36 (d, J = 7.8 Hz, 1 H), 8.05 (s,
1 H), 7.35–7.33 (m, 1 H), 7.04–6.86 (m, 2 H), 3.87 (s, 3 H), 1.61 (s,
9 H).
13C NMR (75 MHz, CDCl3): d = 157.1, 131.1, 128.6, 124.3, 120.7,
120.0, 109.6, 70.9, 55.5, 28.3.
MS (EI, 70 eV): m/z = 207 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
MS (EI, 70 eV): m/z = 255 [M+].
HRMS (EI): m/z [M+] calcd for C16H17NO2: 255.1259; found:
207.1248.
Silver Triflate/Acetic Acid Catalyzed Rearrangement of
Oxaziridines 1 to Amides 3 (Table 3, Conditions B); General
Procedure
To a DCE soln (4 mL) containing AgOTf (6.5 mg, 0.025 mmol) in
a Schlenk tube under N2, a 3-aryloxaziridine 1a–j (0.5 mmol) and
AcOH (15 mL, 0.25 mmol) were added at r.t. The reaction mixture
was then heated at 70 °C until the starting material was completely
consumed, as monitored by TLC. The reaction mixture was purified
by flash chromatography to directly afford the corresponding amide
3a–j.
255.1258.
N-(2-Phenylethyl)-1,1¢-biphenyl-4-carboxamide (3e)20
Colorless crystals (recrystallized from PE–CH2Cl2); mp 181–
182 °C.
IR (KBr): 3351, 1636, 1538, 1317, 1008 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.77–7.57 (m, 6 H), 7.47–7.22 (m,
8 H), 6.22 (br s, 1 H), 3.77–3.71 (m, 2 H), 2.95 (t, J = 7.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 167.1, 144.2, 140.0, 138.9, 133.3,
128.9, 128.8, 128.7, 127.9, 127.3, 127.2, 127.2, 126.6, 41.1, 35.7.
MS (EI, 70 eV): m/z = 301 [M+].
HRMS (EI): m/z [M+] calcd for C21H19NO: 301.1467; found:
4-Methoxy-N-(2-phenylethyl)benzamide (3a)19
Colorless crystals (recrystallized from PE–CH2Cl2); mp 116–
117 °C.
301.1463.
IR (KBr): 3329, 1642, 1551, 1330, 1037 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 6.9 Hz, 2 H), 7.34–
7.22 (m, 5 H), 6.89 (d, J = 9.2 Hz, 2 H), 6.11 (br s, 1 H), 3.83 (s, 3
H), 3.70 (td, J = 6.9, 5.9 Hz, 2 H), 2.92 (t, J = 6.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 166.9, 162.1, 139.0, 128.8, 128.7,
128.6, 126.8, 126.5, 113.7, 55.3, 41.0, 35.8.
MS (EI, 70 eV): m/z = 255 [M+].
HRMS (EI): m/z [M+] calcd for C16H17NO2: 255.1259; found:
N-[2-(4-Fluorophenyl)ethyl]-4-methoxybenzamide (3f)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 138–
139 °C.
IR (KBr): 3351, 1633, 1544, 1507, 1264, 1182, 1024 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.67 (d, J = 6.9 Hz, 2 H), 7.18–
7.14 (m, 2 H), 7.01–6.86 (m, 4 H), 6.27 (br s, 1 H), 3.82 (s, 3 H),
3.68–3.61 (m, 2 H), 2.88 (t, J = 7.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 167.0, 163.2, 162.1, 160.0, 134.7,
134.6, 130.2, 130.1, 128.6, 126.7, 115.5, 115.2, 113.7, 55.3, 41.1,
34.9.
MS (EI, 70 eV): m/z = 273 [M+].
HRMS (EI): m/z [M+] calcd for C16H16NO2F: 273.1165; found:
255.1263.
4-Methyl-N-(2-phenylethyl)benzamide (3b)20
Colorless crystals (recrystallized from PE–CH2Cl2); mp 76–77 °C.
IR (KBr): 3335, 1642, 1544, 1324, 1027 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.59 (d, J = 6.3 Hz, 2 H), 7.35–
7.18 (m, 7 H), 6.17 (br s, 1 H), 3.73–3.67 (m, 2 H), 2.92 (t, J = 6.9
Hz, 2 H), 2.37 (s, 3 H).
273.1164.
Synthesis 2009, No. 20, 3399–3404 © Thieme Stuttgart · New York

3404
D. Xing et al.
PAPER
4-Methoxy-N-(3-phenylpropyl)benzamide (3g)
Colorless crystals (recrystallized from PE–CH2Cl2); mp 88–89 °C.
IR (KBr): 3325, 1629, 1557, 1516, 1305, 1254, 1191, 1034 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.63 (d, J = 9.0 Hz, 2 H), 7.32–
7.17 (m, 5 H), 6.88 (d, J = 9.0 Hz, 2 H), 6.05 (br s, 1 H), 3.83 (s, 3
H), 3.48 (q, J = 6.6 Hz, 2 H), 2.72 (t, J = 7.5 Hz, 2 H), 2.00–1.91 (m,
2 H).
13C NMR (75 MHz, CDCl3): d = 166.9, 162.0, 141.5, 128.6, 128.5,
128.4, 126.9, 126.0, 113.6, 55.4, 39.7, 33.5, 31.2.
References
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MS (EI, 70 eV): m/z = 269 [M+].
HRMS (EI): m/z [M+] calcd for C17H19NO2: 269.1416; found:
(3) For leading references, see: (a) Andreae, S.; Schmitz, E.
Synthesis 1991, 327. (b) Choong, I. C.; Ellman, J. A. J. Org.
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269.1417.
N-sec-Butyl-2-methoxybenzamide (3h)
Colorless liquid.
IR (KBr): 3398, 1664, 1538, 1298, 1239, 1018 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.20 (d, J = 6.9 Hz, 1 H), 7.67 (br
s, 1 H), 7.45–7.40 (m, 1 H), 7.10–6.95 (m, 2 H), 4.19–4.10 (m, 1
H), 3.95 (s, 3 H), 1.63–1.53 (m, 2 H), 1.21 (d, J = 6.6 Hz, 3 H), 0.96
(t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.5, 157.3, 132.4, 132.2, 122.0,
121.3, 111.3, 55.9, 46.6, 29.6, 20.4, 10.2.
MS (EI, 70 eV): m/z = 207 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
207.1261.
N-sec-Butyl-3-methoxybenzamide (3i)
Colorless liquid.
IR (KBr): 3266, 1639, 1535, 1248, 1034 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.25 (m, 3 H), 7.05–7.01 (m,
1 H), 5.87 (br s, 1 H), 4.15–4.10 (m, 1 H), 3.86 (s, 3 H), 1.63–1.53
(m, 2 H), 1.24 (m, 3 H), 0.97 (t, J = 7.5 Hz, 3 H).
(9) Christensen, D.; Jørgensen, K. A.; Hazell, R. G. J. Chem.
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(12) Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J. Am. Chem.
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13C NMR (75 MHz, CDCl3): d = 166.7, 159.8, 136.6, 129.5, 118.4,
117.4, 112.3, 55.4, 47.1, 29.8, 20.5, 10.4.
MS (EI, 70 eV): m/z = 207 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
207.1255.
N-tert-Butyl-2-methoxybenzamide (3j)
(13) (a) Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron Lett.
1988, 29, 2817. (b) Akhatou, A.; Rahimi, M.; Cheboub, K.;
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Chem. 2001, 9, 1233.
Colorless liquid.
IR (KBr): 3407, 1661, 1532, 1236, 1018 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.17 (d, J = 7.8 Hz, 1 H), 7.83 (br
s, 1 H), 7.44–7.38 (m, 1 H), 7.09–6.93 (m, 2 H), 3.94 (s, 3 H), 1.46
(s, 9 H).
(15) Smith, H. E.; Cook, S. L.; Warren, M. E. J. Org. Chem.
13C NMR (75 MHz, CDCl3): d = 164.1, 157.2, 132.3, 131.9, 122.8,
1964, 29, 2265.
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3353.
121.3, 111.3, 55.9, 51.0, 28.9.
MS (EI, 70 eV): m/z = 207 [M+].
HRMS (EI): m/z [M+] calcd for C12H17NO2: 207.1259; found:
207.1254.
(19) Kunishima, M.; Kawachi, C.; Hioki, K.; Terao, K.; Tani, S.
Tetrahedron 2001, 57, 1551.
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Acknowledgment
Financial support from The Science and Technology Commission
of Shanghai Municipality is gratefully acknowledged.
Synthesis 2009, No. 20, 3399–3404 © Thieme Stuttgart · New York