In situ generation of nitroso compounds from catalytic hydrogen peroxide oxidation of primary aromatic amines and their one-pot use in hetero-Diels-Alder reactions

Article abstract of DOI:10.1002/ejoc.200700368

A method for in situ generation of nitroso compounds from organoselenium-catalyzed oxidation of anilines by hydrogen peroxide was developed. The generated nitroso compounds were subsequently used in hetero-Diels-Alder reactions. A variety of oxazines were synthesized in reasonable to good yields by this one-pot procedure using primary aromatic amines with different substituents and various conjugated dienes. This strategy might facilitate the current methodologies for nitroso chemistry since no isolation or purification of the nitroso compounds is required. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700368

FULL PAPER
DOI: 10.1002/ejoc.200700368
In Situ Generation of Nitroso Compounds from Catalytic Hydrogen Peroxide
Oxidation of Primary Aromatic Amines and Their One-Pot Use in Hetero-
Diels–Alder Reactions
Dongbo Zhao,[a] Mikael Johansson,[a] and Jan-E. Bäckvall*[a]
Keywords: Tandem reaction / Nitroso compounds / Selenium / Aniline oxidation / Aqueous hydrogen peroxide
A method for in situ generation of nitroso compounds from
organoselenium-catalyzed oxidation of anilines by hydrogen
peroxide was developed. The generated nitroso compounds
were subsequently used in hetero-Diels–Alder reactions. A
variety of oxazines were synthesized in reasonable to good
yields by this one-pot procedure using primary aromatic
amines with different substituents and various conjugated
dienes. This strategy might facilitate the current methodolo-
gies for nitroso chemistry since no isolation or purification of
the nitroso compounds is required.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
synthesis of oxazines (hetero-Diels–Alder adducts) from
primary aromatic amines, H2O2 and conjugated dienes is
also described.
Introduction
Since their emergence over one century ago,[1] nitroso
compounds have been used as powerful synthetic reagents
in a variety of organic transformations, such as nitroso al-
dol reactions,[2] nitroso ene reactions,[3] Diels–Alder cyclo-
additions,[4] additions of Grignard reagents,[5] and coup-
lings with amines to yield azoarenes.[6] Recently, there has
been an increased use of nitroso chemistry in the area of
asymmetric catalysis.[2–4] Methods for the preparation of
these interesting compounds from primary amines include
direct oxidation by peracids (particularly Caro’s acid),[7] po-
tassium permanganate[8] or molybdic peroxo complexes.[9]
Catalytic oxidations with H2O2 as terminal oxidant in the
presence of rhenium,[10] tungsten,[11] molybdenum[9] or sele-
nium oxides[6d] catalysts for the oxidation of amines to ni-
troso compounds have been reported. However, these cata-
lytic oxidation procedures are often slow, which might lead
to the formation of dimeric byproducts such as azo or
azoxy derivatives as well as to over-oxidation to the nitro
compounds (Scheme 1).[12] The ultimate goal with the pres-
ent work is to develop coupled oxidation systems in which
PhNO is the key reagent/catalyst and where the latter is
generated in situ from aniline. Herein we report an efficient
and selective oxidation of primary aromatic amines to ni-
troso compounds with H2O2 catalyzed by diphenyl diselen-
ide (PhSeSePh). Moreover, a one-pot procedure for the
Scheme 1. A series of oxidized products from primary aromatic
amines.
Results and Discussion
Seleninic acid or seleninic anhydride has been reported
to be an extremely efficient oxidant for the transformation
of hydroxylamine to nitroso compounds.[13] Because dis-
elenides can be easily oxidized by hydrogen peroxide to se-
leninic acid or peroxyseleninic acid,[14] we initiated a study
on the direct oxidation of aniline (1a) by aqueous H2O2
(35%) in the presence of some commercially available sele-
nium catalysts (5–10 mol-%).
The results are summarized in Table 1. In most cases, 1a
was completely oxidized to the target nitrosobenzene (2a)
with high selectivity within 1–2 h (Entries 1–4) and only
trace amounts of azobenzene byproduct could be detected,
except when PhSeH was used as catalyst (Entry 5). Phenyl-
tellurium also catalyzed this oxidation, but the reaction was
much slower (Entry 6). According to the reported oxidative
selenium chemistry in the literature[14] and control oxi-
[a] Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University,
10691 Stockholm, Sweden
Fax: +46-8-154908
E-mail: jeb@organ.su.se
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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D. Zhao, M. Johansson, J.-E. Bäckvall
FULL PAPER
dation reaction of aniline using stoichiometric amounts of water. The diene substrate scope was rather broad and both
PhSeO2H,[15] it was supposed that the real active oxidant in cyclic and acyclic dienes were applicable in this system to
this system should be peroxyseleninic acid instead of selen- give moderate to good yields of oxazines for two steps. Both
inic acid.
NMR yield and isolated yield are given in Table 2; in most
cases the isolated yield of the product was 10–20% lower
than the yield determined by H NMR spectroscopy of the
Table 1. Catalytic selective oxidation of aniline by aqueous hydro-
gen peroxide.[a]
1
crude product. Reaction of 2a with 1,3-cyclopentadiene (3a)
afforded 4aa. Due to the instability of HDA adduct 4aa on
the silica gel column,[16] it could not be isolated in pure
form. However, the yield was determined to be 60% on the
1
basis of H NMR spectroscopy of the crude material (En-
try 1). The use of 1,3-cyclohexadiene (3b) and 1,3-cyclohep-
tadiene (3c) both produced the corresponding HDA ad-
ducts in good yields (Entries 2–3). The reaction with (Z,Z)-
1,3-cyclooctadiene (3d) as diene was found to proceed very
slowly, and the HDA adduct 4ad could hardly be detected
(Entry 4).[17] The tandem reaction involving noncyclic
dienes 3e–k and aniline 1a with the present procedure also
worked well and generated the desired 2-phenyl-3,6-dihydro-
2H-[1,2]oxazines 4ae–ak in fair yields. Among them, 3e and
3f were chosen to represent symmetric dienes and examined
under the same reaction conditions (Entries 5, 6). For un-
[a] No side product from oxidation of the benzene ring could be
detected. [b] Determined by H NMR spectroscopy. [c] Azoxy by-
product was found instead of azo compound.
1
Organocatalytic (including proline analogs and Brønsted symmetrical dienes such as 3g–i, usually two diastereoiso-
1
acid catalysts) and Lewis-acid-catalyzed asymmetric reac- mers were observed in the crude H NMR spectroscopy.
tions of nitroso compounds have become a hot topic and Unsuccessful attempts were made to separate both dia-
gained considerable attention in recent years.[2–4] However, stereomers from one another by chromatography in these
in almost all of these reactions, the nitrosobenzene analog cases (Entries 7–9). However, 1H NMR spectroscopy al-
(often commercially available) was used as the added reac- lowed a satisfactory characterization of the products. Inter-
tion component. Due to the toxicity and mutagenicity of estingly, only one isomer could be observed in the case of
nitroso compounds, it is quite attractive to perform further unsymmetrical dienes 3j and 3k, respectively (Entries 10,
transformation in one-pot after in situ generation of the 11). To the best of our knowledge, HDA adducts 4aj–ak
nitroso compound since isolation and purification can be have not been reported previously despite some existing an-
avoided.[4e,4h,4k] Although the impurities from the crude ni- alogs in literature.[4d] It is noteworthy that these HDA ad-
trosobenzene may cause some side reactions in the second ducts can be transformed by different procedures to a vari-
reaction, the potential advantage of this one-pot strategy ety of products, such as mitomycin and other compounds
for organic synthesis is obvious. To realize the proposed with pharmaceutical interest.[18] Jørgensen et al. have devel-
tandem one-pot procedure, some modifications might be oped a one-pot procedure to prepare oxazines (HDA ad-
useful and necessary to minimize the negative effect of the ducts) from primary aromatic amines, hydrogen peroxide
impurities or to increase the tolerance of the second reac- and conjugated dienes in the presence of catalytic amount
tion. For this purpose, hetero-Diels–Alder cycloaddition re- of a (peroxo)molybdenum complex.[4e] Although this mo-
action (HDA) of the generated nitroso compound with con- lybdenum complex was a selective catalyst for the oxidation
jugated dienes was chosen as a test reaction (Scheme 2).[4e] of primary aromatic amines to nitroso compounds and tol-
To our delight, oxazine (4a) formation proceeded erant toward conjugated dienes, the reaction usually took
smoothly within 2–6 h by simple addition of a series of con- 18 h to reach completion. In terms of easy availability of
jugated dienes (3) to the in situ generated solution of ni- catalyst, reaction time and compatible outcome of target
troso compound 2a from selenide-catalyzed oxidation of molecules, our method seems to be a competitive alterna-
aniline by H2O2 (Table 2). The consecutive HDA reaction tive.[19]
was found to be tolerant to the impurities generated from
The synthetic aspects of the new method, shown in
the first oxidation step, unreacted hydrogen peroxide or the Scheme 2, have been clearly demonstrated by the results in
Scheme 2. One-pot procedure for further organic synthesis and catalysis based on in situ generation of nitroso compounds by catalytic
oxidation with aqueous hydrogen peroxide.
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Nitroso Compounds
FULL PAPER
Table 2. Diene substrate scope for aniline oxidation/hetero-Diels–Alder one-pot reaction.[a]
[a] The HDA rection was performed using 1.2 equiv. of diene 3, which was added subsequently after the oxidation reaction, unless
otherwise noted. [b] 2 equiv. of diene was used and HDA reaction was performed for 6 h. [c] Only one isomer was obtained. [d] The
isomer ratio is ca. 2:1. [e] The isomer ratio is ca. 1:1. [f] Contaminated with some azoxy byproducts. [g] Not stable on column. [h] The
isomer ratio is ca. 5:2. [i] Based on the amount of aniline employed.
Table 2. Further investigation of the synthetic utility were adducts, 3-aryl-2-oxa-3-azabicyclo[2.2.2]oct-5-enes 4ab–mb.
undertaken using different aniline substrates 1b–m, 1,3-cy- Primary aromatic amines having electron-donating (En-
clohexadiene (3b) as a standard diene, aqueous H2O2 and tries 2–5, 10, 12–13) and electron-withdrawing substituents
the selenium catalyst PhSeSePh. As shown in Table 3, the (Entries 6–9, 11) were oxidized to the corresponding nitroso
tandem reaction led to a smooth formation of the HDA compounds 2 with good to high selectivities (6:1 Ǟ 30:1)
Table 3. Organoselenium-catalyzed oxidation of aniline analogs followed by hetero-Diels–Alder reaction with 1,3-cyclohexadiene.[a]
[a] For reaction condition see Table 2. [b] 8 h. [c] Azoxy byproduct was observed instead. [d] 24 h. [e] Overlapping. [f] Full conversion
but not stable on column.
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D. Zhao, M. Johansson, J.-E. Bäckvall
FULL PAPER
a MicrOTOF 125 spectrometer. Infrared spectra were recorded
with a Perkin–Elmer Spectrum One B v5.0 FT-IR spectrometer.
Column chromatography was carried out using silica gel (Merck,
60–230 mesh). Thin-layer chromatography was performed on silica
gel 60 F254 (Merck). All the oxazine compounds 4 were prepared
in racemic form.
within a couple of hours. Incidentally, p-nitroaniline could
not be oxidized under current reaction condition maybe be-
cause it is too electron-deficient. All amines, except two (1k
and 1m), examined gave complete conversion with
2.2 equiv. of 35% aq. H2O2 as terminal oxidants and 5 mol-
% of PhSeSePh catalyst.
The major side product observed in the first step (oxi- General Procedure for the One-Pot Tandem Reaction: The PhSe-
SePh catalyst (6.2 mg, 5 mol-%), anilines 1 (0.4 mmol, 1 equiv.) and
35% aqueous H2O2 (77 μL, 0.88 mmol, 2.2 equiv.) were mixed in
0.5 mL of CHCl3 at room temp. After 1–2 h of vigorous stirring,
the anilines were completely converted into the corresponding ni-
troso compounds 2 according to H NMR monitoring. tert-Butyl
methyl ether was used as an internal standard to give the NMR
dation) was dimeric azoarenes generated from the coupling
of nitroso compounds and the corresponding unreacted
aniline analogs with the exception of 1h, where the azoxy
byproduct was detected instead. The HDA reaction of in
situ generated nitroso compounds 2a–m and 1,3-cyclohexa-
diene turned out to be nicely proceeding due to the compat-
ible NMR yield of both 2 and 4 outlined in Table 3. The
isolated yield of the HDA adducts 4 was still 10–20% lower
than the NMR yield of the crude products. The decrease in
1
yields of nitroso compounds. Conjugated dienes
3 (0.48–
0.80 mmol, 1.2–2.0 equiv.) were then added to the reaction mixture
which was stirred for an additional 2–6 h. After evaporation of the
solvent, the NMR yield was determined by 1H NMR analysis of
yield of those HDA adducts by workup was attributed to the crude products. Purification by silca gel column chromatog-
raphy (eluent: AcOEt/pentane) gave the analytically pure HDA ad-
ducts 4. The following known compounds show 1H and 13C NMR
spectroscopic data identical to those in ref.[4e]: 3-Phenyl-2-oxa-3-
azabicyclo[2.2.2]oct-5-ene (4ab), 3-p-tolyl-2-oxa-3-azabicyclo-
[2.2.2]oct-5-ene (4bb), 3-(4-methoxyphenyl)-2-oxa-3-azabicyclo-
the possible chromatographic, photoinduced, or thermal
transformation which previously has been observed for ana-
logs HDA adducts.[20]
[2.2.2]oct-5-ene
(4db),
3-(4-chlorophenyl)-2-oxa-3-azabicyclo-
Conclusions
[2.2.2]oct-5-ene (4fb), 3-[4-(trifluoromethyl)phenyl]-2-oxa-3-azabi-
cyclo[2.2.2]oct-5-ene (4ib). See also in the Supporting Information
for other known compounds. The new compounds are charac-
terized as follows:
A method for in situ generation of nitroso compounds
from organoselenium-catalyzed oxidation of anilines by hy-
drogen peroxide was developed. This was used for a one-
pot synthesis of oxazines (hetero-Diels–Alder adducts) from
primary aromatic amines, H2O2 and conjugated dienes. The
first step, the organoselenium-catalyzed oxidation of ani-
lines by hydrogen peroxide, was highly chemoselective and
efficient for the generation of nitroso compounds within a
couple of hours. The consecutive HDA cycloaddition reac-
tions were tolerant to the impurities of the nitroso com-
pounds from the first oxidation step. A variety of different
oxazines could be synthesized in reasonable yield by this
procedure from primary aromatic amines with different
substituents and various dienes. This new tandem pro-
cedure could serve as a convenient and environmentally
friendly method for the formation of oxazine compounds
since no isolation or purification of nitroso compounds is
required. Moreover, this strategy based on in situ genera-
tion of nitroso compounds might facilitate the current
methodologies of nitroso compounds, especially in both al-
dol-type and hetero-Diels–Alder reactions. We are currently
investigating other procedures for the in situ generation of
nitroso compounds from primary anilines and H2O2 with
the aim of using them in coupled electron-transfer oxi-
dations.
3-Ethyl-2-phenyl-3,6-dihydro-2H-[1,2]oxazine and 6-Ethyl-2-phenyl-
3,6-dihydro-2H-[1,2]oxazine (4ah): 53.5 mg, yield Ͻ 70% generated
from aniline 1a (0.4 mmol) and diene 3h (0.8 mmol). Rf = 0.3 (pen-
tane/EtOAc,20:1). 1H NMR (400 MHz, CDCl3, italics for major
isomer): δ = 0.94 (t, J = 7.7 Hz, 3 H), 1.08 (t, J = 7.7 Hz, 3 H),
1.59–1.81 (m, 2 H), 3.70–3.78 (m, 1 H), 3.84–3.94 (m, 2 H), 4.26–
4.34 (m, 1 H), 4.47–4.55 (m, 2 H), 5.87–6.09 (m, 2 H), 6.93–7.00
(m, 1 H), 7.05–7.15 (m, 2 H), 7.26–7.34 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 10.0, 10.4, 23.5, 26.5, 51.6, 60.1, 67.3, 79.0,
115.3, 116.5, 121.6, 121.8, 122.9, 125.3, 127.1, 128.7, 128.8, 129.9,
148.6, 150.7 ppm. IR (liquid, CH Cl ): ν = 2970, 2875, 1596, 1491,
˜
2
2
1211, 751, 689 cm–1. HRMS (ESI): calcd. for C12H15NNaO+ [M +
Na]+ 212.1046; found 212.1036.
2-Phenyl-3,6-dihydro-2H-[1,2]oxazin-6-yl Acetate (4aj): 39.0 mg,
yield = 45% generated from aniline 1a (0.4 mmol) and diene 3j
(0.8 mmol). Rf = 0.4 (pentane/EtOAc, 5:1). 1H NMR (400 MHz,
CDCl3): δ = 2.15 (s, 3 H), 3.69–3.76 (m, 1 H), 4.02 (ddd, J1 = 16.4,
J2 = 5.6, J3 = 1.8 Hz, 1 H), 5.95–6.00 (m, 1 H), 6.31–6.37 (m, 1
H), 6.50–6.52 (m, 1 H), 7.04 (tt, J1 = 7.3, J2 = 1.1 Hz, 1 H), 7.09–
7.13 (m, 2 H), 7.29–7.34 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.2, 50.9, 90.7, 116.4, 123.1, 123.2, 128.8, 129.1,
149.5, 170.1 ppm. IR (liquid, CH Cl ): ν = 3056, 2815, 1742, 1600,
˜
2
2
1495, 1224, 1116, 957, 760 cm–1. HRMS (ESI): calcd. for
C12H13NNaO3 [M + Na]+ 242.0788; found 242.0789.
+
6-Methoxy-2-phenyl-3,6-dihydro-2H-[1,2]oxazine (4ak): 103.3 mg,
yield = 54% generated from aniline 1a (1.0 mmol) and diene 3k
(1.5 mmol). H NMR (400 MHz, CDCl3): δ = 3.60 (s, 3 H), 3.67
Experimental Section
1
General: All the chemicals, including selenium catalysts, aniline an-
alogs, aqueous H2O2 (35%) and conjugated dienes are commer-
cially available and were used as delivered without further purifica-
tion. NMR spectra were recorded with Bruker AMX-400 and Var-
ian Oxford AS400 instruments. Chemical shifts δ are given in ppm
and coupling constants J in Hz. Mass spectra were recorded with
(ddd, J1 = 16.4, J2 = 4.3, J3 = 1.8 Hz, 1 H), 3.97 (ddd, J1 = 16.4,
J2 = 5.3, J3 = 1.4 Hz, 1 H), 5.13 (m, 1 H), 5.95 (m, 1 H), 6.17 (m,
1 H), 7.01 (t, J = 7.4 Hz, 1 H), 7.17 (d, J = 8.7 Hz, 2 H), 7.32 (dd,
J1 = 8.7, J2 = 7.3 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 51.7, 56.1, 99.0, 116.0, 122.6, 125.0, 127.7, 128.9, 150.5 ppm. IR
(liquid, CH Cl ): ν = 3056, 2931, 2823, 1635, 1600, 1493, 1396,
˜
2
2
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Nitroso Compounds
FULL PAPER
1213, 1192, 1106, 1093, 755, 691 cm–1. HRMS (ESI): calcd. for diene 3b (0.48 mmol). Rf = 0.5 (pentane/EtOAc, 5:1). 1H NMR
C11H13NNaO2 [M + Na]+ 214.0838; found 214.0832.
(400 MHz, CDCl3): δ = 1.32–1.40 (m, 1 H), 1.52–1.61 (m, 1 H),
2.17–2.33 (m, 8 H), 4.39–4.45 (m, 1 H), 4.66–4.71 (m, 1 H), 6.15–
6.20 (m, 1 H), 6.55–6.60 (m, 2 H), 6.61–6.65 (m, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 21.4, 21.5, 24.0, 56.3, 69.0, 115.2,
+
3-(4-tert-Butylphenyl)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4cb):
43.7 mg, yield = 45% generated from aniline 1c (0.4 mmol) and
diene 3b (0.48 mmol). Rf = 0.6 (pentane/EtOAc, 5:1). 1H NMR
(400 MHz, CDCl3): δ = 1.19 (s, 9 H), 1.30–1.40 (m, 2 H), 1.50–
1.61 (m, 2 H), 2.20–2.37 (m, 2 H), 4.35–4.42 (m, 1 H), 4.65–4.75
(m, 1 H), 6.15–6.20 (m, 1 H), 6.55–6.62 (m, 1 H), 6.93 (d, J =
8.6 Hz, 2 H), 7.22 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.4, 23.9, 31.4, 34.0, 56.3, 68.9, 117.1, 125.1, 130.1,
123.8, 130.0, 131.5, 137.8, 152.4 ppm. IR (liquid, CH Cl ): ν =
˜
2
2
2969, 2926, 1596, 1467, 1453, 1250, 1065, 938, 912, 833, 708 cm–1.
HRMS (ESI): calcd. for C14H17NNaO+ [M + Na]+ 238.1202; found
238.1209.
Supporting Information (see footnote on the first page of this
article): General procedure and characterization of some known
oxazine compounds 4.
131.5, 144.6, 149.7 ppm. IR (KBr): ν = 2927, 2965, 1508, 1362,
˜
944, 835, 824 cm–1. HRMS (ESI): calcd. for C16H21NNaO+ [M +
Na]+ 266.1515; found 266.1510.
3-[4-(Trifluoromethoxy)phenyl]-2-oxa-3-azabicyclo[2.2.2]oct-5-ene
(4eb): 35.2 mg, yield Ͼ 65% generated from aniline 1e (0.2 mmol)
and diene 3b (0.24 mmol). Rf = 0.2 (pentane/EtOAc, 10:1). 1H
NMR (400 MHz, CDCl3): δ = 1.31–1.43 (m, 1 H), 1.52–1.64 (m, 1
H), 2.16–2.36 (m, 2 H), 4.36–4.41 (m, 1 H), 4.68–4.73 (m, 1 H),
6.11–6.16 (m, 1 H), 6.55–6.60 (m, 1 H), 6.96–7.00 (m, 2 H), 7.03–
Acknowledgments
This research was supported by the Swedish Research Council
(VR).
7.07 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.2, 23.8, [1] A. Baeyer, Ber. Dtsch. Chem. Ges. 1874, 7, 1638–1640.
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56.6, 69.3, 118.3, 121.1, 129.7, 131.6, 143.8, 150.9 ppm; the signal
for OCF3 as a q is of low intensity to observe. 19F NMR (376 MHz,
CDCl ): δ = –58.2 (s) ppm. IR (KBr): ν = 2974, 2944, 1506, 1269,
˜
3
1215, 1151, 839 cm–1. HRMS (ESI): calcd. for C13H12F3NNaO2
+
[M + Na]+ 294.0712; found 294.0709.
3-o-Tolyl-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4jb): 53.6 mg, yield =
67 % generated from aniline 1j (0.4 mmol) and diene 3b
(0.48 mmol). Rf = 0.3 (pentane/EtOAc, 10:1). 1H NMR (400 MHz,
CDCl3): δ = 1.36–1.46 (m, 1 H), 1.48–1.58 (m, 1 H), 2.22–2.37 (m,
5 H), 3.97–4.02 (m, 1 H), 4.70–4.75 (m, 1 H), 6.02–6.08 (m, 1 H),
6.71–6.77 (m, 1 H), 6.92–6.98 (m, 1 H), 7.02–7.11 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 17.9, 22.0, 23.8, 54.7, 69.2,
120.7, 123.6, 125.5, 128.6, 129.1, 130.3, 132.4, 149.5 ppm. IR (li-
quid, CH Cl ): ν = 2970, 2927, 1602, 1482, 1218, 940, 762 cm–1.
˜
2
2
HRMS (ESI): calcd. for C13H15NNaO+ [M + Na]+ 224.1046; found
224.1053.
3-(2-Bromophenyl)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4kb):
68.3 mg, yield = 64% generated from aniline 1k (0.4 mmol) and
diene 3b (0.48 mmol). Rf = 0.6 (pentane/EtOAc, 10:1). 1H NMR
(400 MHz, CDCl3): δ = 1.34–1.44 (m, 1 H), 1.48–1.58 (m, 1 H),
2.22–2.32 (m, 1 H), 2.33–2.42 (m, 1 H), 4.52–4.57 (m, 1 H), 4.72–
4.77 (m, 1 H), 5.99–6.06 (m, 1 H), 6.68–6.76 (m, 1 H), 6.85–6.92
(m, 1 H), 7.09–7.18 (m, 2 H), 7.45 (dd, J1 = 7.9, J2 = 1.3 Hz, 1 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 21.6, 23.5, 54.8, 69.5,
114.5, 122.8, 125.0, 127.0, 128.9, 132.3, 132.8, 148.9 ppm. IR (li-
quid, CH Cl ): ν = 3056, 2965, 2933, 1581, 1460, 1370, 1028, 938,
˜
2
2
757 cm–1. HRMS (ESI): calcd. for C12H12BrNNaO+ [M + Na]+
287.9994; found 287.9980.
3-m-Tolyl-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4lb): 32.7 mg, yield =
41 % generated from aniline 1l (0.4 mmol) and diene 3b
1
(0.48 mmol). Rf = 0.5 (pentane/EtOAc, 5:1). H NMR (400 MHz,
[5] For selected examples, see F. Kopp, I. Sapountzis, P. Knochel,
Synlett 2003, 885–887.
CDCl3): δ = 1.32–1.42 (m, 1 H), 1.52–1.64 (m, 2 H), 2.20–2.40 (m,
5 H), 4.40–4.47 (m, 1 H), 4.67–4.74 (m, 1 H), 6.16 (t, J = 6.9 Hz,
1 H), 6.58 (t, J = 6.9 Hz, 1 H), 6.75 (d, J = 7.6 Hz, 1 H), 6.79–6.86
(m, 2 H), 7.09 (t, J = 7.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.3, 21.6, 24.0, 56.4, 69.1, 114.5, 118.1, 122.8, 128.1,
[6] a) P. Gölitz, A. de Meijere, Angew. Chem. Int. Ed. Engl. 1977,
16, 854–855; b) R. Behrendt, M. Schenk, H.-J. Musiol, L. Mor-
oder, J. Pept. Sci. 1999, 5, 519–529; c) M. H. Davey, V. Y. Lee,
R. D. Miller, T. J. Marks, J. Org. Chem. 1999, 64, 4976–4979;
d) B. Priewisch, K. Rück-Braun, J. Org. Chem. 2005, 70, 2350–
2352.
[7] a) W. Seidenfaden, Houben–Weyl, Methoden der organischen
Chemie, 4th ed., vol. 10/1 (Ed.: E. Müller), Thieme, Stuttgart,
1971, p. 1053–1058. For perbenzoic acid, see: b) Y. Yost, H. R.
Gutmann, J. Chem. Soc. C 1970, 2497–2499; c) L. Di Nunno,
S. Florio, P. E. Todesco, J. Chem. Soc. C 1970, 1433–1434. For
129.9, 131.5, 138.1, 151.0 ppm. IR (liquid, CH Cl ): ν = 3056,
˜
2
2
2935, 2858, 1604, 1585, 1488, 1370, 1254, 944, 906, 781, 693 cm–1.
HRMS (ESI): calcd. for C13H15NNaO+ [M + Na]+ 224.1046; found
224.1037.
3-(3,5-Dimethylphenyl)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4mb):
34.0 mg, yield = 40% generated from aniline 1m (0.4 mmol) and
Eur. J. Org. Chem. 2007, 4431–4436
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4435

D. Zhao, M. Johansson, J.-E. Bäckvall
FULL PAPER
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[15] Compared with the combination of catalytic PhSeSePh and
stoichiometric H2O2, much lower conversion of aniline was ob-
tained when stoichiometric amounts of PhSeO2H were em-
ployed (2.2 equiv.) in the absence of H2O2. In the latter case
only 25% conversion of aniline was achieved after 2 h to give
azo compound as the main product (no nitroso compound
could be detected.).
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the beginning was also tried in our system, but almost no target
oxazines (Ͻ5%) could be observed despite the full consump-
tion of the aniline substrate after 2 h of reaction. It was sup-
posed that the conjugated dienes react with selenium catalyst
to generate non-active selenium species and thus retard the
catalytic oxidation reaction of aniline under the one-pot reac-
tion conditions.
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Received: April 24, 2007
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Published Online: July 10, 2007
4436
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Eur. J. Org. Chem. 2007, 4431–4436