Skeletal Rearrangement in the ZnII-Catalyzed [4+2]-Annulation of Disubstituted N-Hydroxy Allenylamines with Nitrosoarenes to Yield Substituted 1,2-Oxazinan-3-one Derivatives

Article abstract of DOI:10.1002/chem.201602579

This work reports zinc-catalyzed [4+2]-annulation reactions of disubstituted N-hydroxy allenylamines with nitrosoarenes to afford substituted 1,2-oxazinan-3-ones with a skeletal rearrangement. This annulation is applicable to a reasonable scope of allenylamines and nitrosoarenes. Our control experiments indicate that nitrosobenzene can also implement this annulation through a radical annulation path, but with poor efficiency. Zn(OTf)₂or AgOTf greatly improves the efficiency of this [4+2]-annulation; the effect of these metal species is discussed in detail.

Full text of DOI:10.1002/chem.201602579

DOI: 10.1002/chem.201602579
Full Paper
&
Annulation Reactions
Skeletal Rearrangement in the ZnII-Catalyzed [4+2]-Annulation of
Disubstituted N-Hydroxy Allenylamines with Nitrosoarenes to
Yield Substituted 1,2-Oxazinan-3-one Derivatives
Pankaj Sharma and Rai-Shung Liu*[a]
Abstract: This work reports zinc-catalyzed [4+2]-annulation
reactions of disubstituted N-hydroxy allenylamines with ni-
trosoarenes to afford substituted 1,2-oxazinan-3-ones with
a skeletal rearrangement. This annulation is applicable to
a reasonable scope of allenylamines and nitrosoarenes. Our
control experiments indicate that nitrosobenzene can also
implement this annulation through a radical annulation
path, but with poor efficiency. Zn(OTf)2 or AgOTf greatly im-
proves the efficiency of this [4+2]-annulation; the effect of
these metal species is discussed in detail.
Introduction
cal and Lewis acid catalysis. In contrast with our previous work
[Eq. (2)],[9a] these [4+2]-annulation reactions are catalyzed by
Zn(OTf)2 or AgOTf to afford substituted 1,2-oxazinan-3-ones
derivatives through a distinct mechanism [Eq. (3)]. Notably, this
[4+2]-annulation affords skeletally rearranged 6-amino-1,2-oxa-
zinan-3-ones with O- and N-difunctionalizations on their C(3)
and C(6) carbons.
Nitroso compounds are highly versatile for introducing N- and
O-containing functionalities through various chemical reac-
tions,[1] including electrophilic additions,[2] nitroso-ene reac-
tions,[1a,b,3] [n+2]-cycloadditions (n=2–4),[4] and redox reac-
tions.[1c,5] Among these reactions, catalytic [4+2]-cycloadditions
of nitroso compounds with 1,3-dienes is of immense interest
as their resulting 3,6-dihydro-1,2-oxazines can be generated
with high enantio- and stereoselectivity [Eq. (1)]. These [4+2]-
cycloadducts undergo facile reductive cleavage to yield 1-
amino-4-hydroxy-2-ene derivatives, which are important build-
ing blocks for the syntheses of natural products and biological-
ly active molecules.[1h,6]
Radical annulation reactions are powerful tools to access
carbo- or heterocyclic compounds.[7] Nitrosoarenes possess low
LUMOs[5] that are readily attacked by radicals at the nitrogen
centers to give nitroxyl radicals.[8] Nitroso compounds should
be useful blocks for radical annulations, but examples are very
few.[9] We reported radical [3+2]-annulations of N-hydroxy alle-
nylamines with nitrosoarenes to form valuable isoxazolidin-5-ol
products [Eq. (2)];[9a] these reactions were assisted with a small
amount (2–10%) of additives such as O2, IPrCuCl/O2, or TEMPO.
In the absence of additives, unsubstituted allenylamines afford-
ed annulation products in approximately 55–60% yield, sug-
gesting that nitrosoarenes can also generate nitroxyl radi-
cals.[9a] Lewis acid catalysts were generally ineffective promot-
ers for these [3+2]-annulation reactions. In view of the contin-
ued interest in the development of nitroso annulations, we in-
vestigate the annulations of nitrosoarenes with 4,4-
disubstituted N-hydroxy allenylamines through combined radi-
Results and Discussion
Table 1 shows the optimization of the [4+2]-annulations be-
tween disubstituted N-hydroxy allenylamine 1a with nitroso-
benzene 2a (1.2 equiv). Although these two reactants alone in
toluene gave the desired [4+2]-annulation product, 6-amino-
1,2-oxazinan-3-one 3a, in 21% yield, byproducts including di-
azene oxide 4 (10%) and (Z)-4-methyl-1-(phenylamino)penta-
1,4-dien-3-one 5 were also produced in significant proportions
[a] P. Sharma, Prof. Dr. R.-S. Liu
Department of Chemistry, National Tsing-Hua University, 101, Sec. 2
Kuang-Fu Rd. Hsinchu, 3003, Taiwan (Republic of China)
E-mail: rsliu@mx.nthu.edu.tw
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201602579.
Chem. Eur. J. 2016, 22, 1 – 8
1
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
(26–28%, entry 1). The molecular structure of compound 3a
was unambiguously confirmed by X-ray diffraction.[10] The cis
Table 1. Optimization of [4+2]-annulation reactions.
1
configuration of compound 5 was indicated from H NMR nu-
clear Overhauser effect (NOE) experiments; this specific geom-
etry enables formation of a hydrogen bond between the
ketone and amino groups. We tested various metal catalysts
(5 mol%) to increase the efficiency of the annulations. To our
pleasure, the use of IPrCuCl/O2 (IPr=1,3-bis(diisopropylphe-
nyl)imidazol-2-ylidene) in toluene at 258C afforded desired 3a
in 60% yield, whereas byproducts 4 and 5 were suppressed to
only 8–10% (entry 2). An enhanced yield (65%) of compound
3a was obtained for IPrCuCl under N2 (entry 3). We tested the
reactions with CuOTf and Cu(OTf)2 catalysts (entries 2 and 3),
which showed no annulation activity; instead, the two cata-
lysts tended to react with nitrosobenzene to form diazene
oxide 4 in significant proportions (30–35%, entries 4 and 5).
CuCl showed an effective activity to yield compound 3 in 60%
yield (entry 6). We employed Zn(OTf)2 (5 mol%) to improve the
yield of compound 3a up to 80% (entry 7). Other Lewis acids
including PPh3AuCl/AgNTf2, Sc(OTf)3, and In(OTf)3, also im-
proved the annulation efficiency, rendering 1,2-oxazinan-3-one
3a in moderate yields (55–62%, entries 8–10). AgOTf (5 mol%)
was as effective as Zn(OTf)2, yielding 1,2-oxazinan-3-one 3a in
82% yield (entry 11), whereas, HOTf and radical initiator
TEMPO were inefficient for this annulation (entries 12 and 13).
Highly acidic catalysts such as Sc(OTf)3 and In(OTf)3 were less
efficient than weakly acidic AgOTf and Zn(OTf)2; we envisage
that the former tends to coordinate with N-hydroxy allenyl-
amines strongly whereas weakly acidic catalysts preferably
complex with nitrosobenzene to become a potent radical ac-
ceptor (see above).
Entry
Catalysts
Time [min]
Yield [%][b]
3a
4
5
1
2
3
4
5
6
7
8
–
15
20
15
15
10
15
15
15
15
15
15
20
15
21
60
65
8
26
10
10
30
35
10
5
15
13
11
5
28
8
IPrCuCl/O2
IPrCuCl
Cu(OTf)2
CuOTf·C6H6
CuCl
Zn(OTf)2
PPh3AuCl/AgNTf2
Sc(OTf)3
In(OTf)3
AgOTf
10
30
20
11
6
15
8
11
6
9
60
82
55
60
62
82
18
–
9
10
11
12
13
TEMPO
HOTf
26
36
28
8
IPr=1,3-Bis(diisopropylphenyl)imidazol-2-ylidene. [a] 1a=0.20m, 2a=
1.2 equiv. [b] Product yields are reported after purification from a silica
gel column.
Table 2. Reaction with 4,4-disubstituted allenylamines.
The scope of these catalytic [4+2]-annulations was assessed
with various 4,4-disubstituted N-hydroxy allenylamines under
the optimum conditions. Entries 1 and 2 of Table 2 show the
suitability of the annulations for substrates 1b and 1c bearing
cyclic alkyl moieties (R1, R2 =cyclohexyl or cyclopentyl); their
resulting products 3b and 3c were produced in satisfactory
yields (73–76%). The reaction scope was extendible to addi-
tional substrates 1d and 1e bearing different alkyl R1 and R2
substituents (R1 =Me, R2 =n-propyl; R1 =R2 =n-propyl), yielding
desired products 3d and 3e in 74–76% (entries 3 and 4);
herein, compound 1d was present as a mixture of two diaste-
reomers (d.r.=3:2). We tested the reactions on substrates 1 f–
1i bearing alterable aniline moieties (R=Me, CO2Et, Cl, Br);
their resulting products 3 f–3i were produced in satisfactory
yields (65–85%, entries 5–8). For meta-bromoaniline analog 3i,
its corresponding product was obtained in 82% yield (entry 9).
These annulations were also compatible with various nitro-
soarenes 2b–2j; the results are provided in Table 3. For nitro-
sobenzene substrates 2b–2d bearing electron-withdrawing
groups (R=Cl, Br, CO2Et) at the para-phenyl positions, their re-
actions with N-hydroxy allenylamine 1a yielded desired prod-
ucts 3k–3m in 35–72% yields (entries 1–3); ester derivative 2d
gave a low yield (35%), probably owing to its competitive co-
ordination with Zn(OTf)2 (entries 1–3). Allenylamines 2e and 2 f
bearing electron-donating groups (R=OCH3, CH3) were effi-
cient for this annulation reaction, giving desired 1,2-oxazinan
[a] 1a=0.20m, 2a=1.2 equiv. [b] Product yields are reported after purifi-
cation from a silica gel column.
&
&
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
derivatives 3n and 3o in 82% and 85% yields, respectively
(entries 4 and 5). We tested the reactions with meta-phenyl
substituted allenylamines 2g–2j; again, electron-rich nitroso-
benzenes 2g and 2h (R=Me, OMe) were more catalytically ef-
ficient than their electron-deficient analogs 2i and 2j (R=Cl,
Br), according to the respective yields, 65–70% versus 40–56%
(entries 6–9). We postulate that highly electron-rich 4-methoxy-
phenylnitroso 2e can increase its affinity for ZnII to attain an
O-bound co-ordination.
ed period (20 h, entry 1, Table 4). In contrast, Zn(OTf)2
(10 mol%) failed to induce any reaction (entry 2). We tested
the feasibility of PhNO (0.2 equiv) to generate nitroxyl radicals,
which gave compound 5 (70%) efficiently together with annu-
lation product 3a (0.17 equiv) and diazene oxide 4 in 3% yield.
The protracted period for entry 3 is due to the complete con-
sumption of PhNO. Accordingly, nitrosobenzene can imple-
ment the formation of cis-1,4-dien-3-one 5 as effectively as
TEMPO, but the key intermediates in the 1a!5 transformation
can be partly trapped by PhNO to afford the annulation prod-
uct 3a.
Table 3. Scope of catalytic [4+2]-annulations with nitrosobenzenes.
Table 4. Control experiments.
Entry
Activator ([mol%])
Time [h]
Yield [%][b]
1a
3a
5
1
2
3
TEMPO (20)
Zn(OTf)2 (10)
PhNO (20)
20
18
20
18
98
5
–
–
17
82
–
70
[a] 1a=0.18m. [b] Product yields are reported after purification from
a silica gel column.
Equation (5) shows important results for elucidating the re-
action mechanism. When N-hydroxy allenylamine 1a was treat-
ed with 2-methylphenylnitroso 2k and Zn(OTf)2 (5 mol%) in
[a] 1a=0.20m, 2a=1.2 equiv. [b] Product yields are reported after purifi-
cation from a silica gel column.
We performed a gram-scale reaction with N-hydroxy allenyl-
amine 1a (0.90 g) and nitrosobenzene 2a (0.60 g) under stan-
dard conditions (toluene, 258C, 20 min); this large-scale pro-
duction proceeded smoothly to afford desired product 3a in
78% yield.
Nitrosobenzene reacts facilely with carbon-based radicals to
quench the radical chain reactions in many instances.[8]
Connell previously reported that a mixture of nitrosoben-
zene and styrene could generate nitroxyl radicals.[11] As nitroso-
benzene itself implemented a cyclization of unsubstituted N-
hydroxy allenylamines owing to the generation of reactive ni-
troxyl radicals,[9a] as described in Equation (2); we examined
the effects of TEMPO on our reaction. Treatment of substrate
1a with TEMPO (20 mol%) effected an oxidation in toluene,
even under nitrogen, yielding (Z)-4-methyl-1-(phenylamino)-
penta-1,4-dien-3-one 5 efficiently in 82% yield, over a protract-
toluene, (Z)-penta-1,4-dien-3-one 6 was isolated in 82% yield;
its molecular structure was determined by X-ray diffraction.[10]
The formation of species 6 suggests the intermediacy of 2,3-di-
hydroisoxalole I; its presence helps to clarify the reaction
mechanism. To confirm the participation of N-hydroxyaniline
2a, an equimolar proportion of C6D5NHOH and PhNO was
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
3
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
tested in this reaction, giving compound 3a containing appre-
ciable amounts (40%) of C6D5 [Eq. (6)]. This annulation process
likely involves N-hydroxyaniline as a nucleophile, but its reac-
tion with (Z)-penta-1,4-dien-3-one 5 with Zn(OTf)2 catalyst
failed to give the desired product 3a.
Scheme 2. A postulate mechanism for radical [4+2]-annulation.
1,4-dien-3-one 5 is not an applicable substrate. In the presence
of Zn(OTf)2, a NꢀO bond cleavage of cyclic nitroxy species H
might give the observed product 3a. In this brief mechanism,
the details of the transformations 1a!I and J!3a will be elu-
cidated in the Supporting Information.
Conclusions
Scheme 1 shows a proposed mechanism to rationalize the
formation of (Z)-penta-1,4-dien-3-one 5 with PhNO or TEMPO,
which may generate nitroxide radicals in small proportions to
furnish the reaction. Herein, we envisage a radical cyclization
of initial 1a to 2,3-dihydroisoxalole species A,[12] which under-
goes slow auto-oxidation to form an aromatic isoxazol-2-iums
B.[9,13] The isopropyl proton of this cation species is highly
acidic as indicated by resonance form B’; such a proton dissoci-
ation is expected to yield species C, which becomes activated
by this released proton to undergo a ring opening, ultimately
yielding the (Z)-penta-1,4-dien-3-one 5.
We have reported Zn(OTf)2-catalyzed [4+2]-annulations of di-
substituted N-hydroxy allenylamines with nitrosoarenes to
yield substituted 1,2-oxazinan-3-ones derivatives with a skeletal
rearrangement. Such annulation reactions are applicable to
a good range of substrates including allenylamines and nitro-
soarenes. Our control experiments indicate that PhNO and
TEMPO can generate nitroxyl radicals to implement the annula-
tions, but the efficiency is greatly enhanced with Zn(OTf)2 or
AgOTf. This work provides one successful example showing
that nitrosoarenes can serve as [N,O]-building units for radical
annulation reactions.
Experimental Section
General
Unless otherwise noted, all reactions were carried out under a nitro-
gen atmosphere in oven-dried glassware by using standard sy-
ringe, cannula, and septa apparatus. Toluene was dried over CaH2
and distilled before use. Reagents were purchased from commer-
cial sources and used without purification, unless otherwise stated.
Reactions were magnetically stirred and monitored by thin layer
chromatography carried out on 0.25 mm E. Merck silica gel plates
(60f–254) using UV light as a visualizing agent and alkaline KMnO4
Scheme 1. TEMPO-mediated oxidative rearrangement of species 1a.
1
and heat as developing agents. H NMR and 13C NMR spectra were
The transformation of N-hydroxy allenylamine 1a into annu-
lation product 3a involves considerable structural rearrange-
ment. A reaction pathway is shown in Scheme 2 based on our
observations [Eqs. (5)–(7)]. Intermediate I was inferred from the
isolation of compound 6 in a control experiment [Eq. (5)]. We
envisage that species I likely forms an alkenylidene species G
through a retro-nitroso ene reaction. A subsequent redox reac-
tion between species G and nitrosobenzene 2a yields a cyclic
iminium H and ZnII–nitroxide anion. Nucleophilic attack of this
nitroxide anion at the iminium H produces an addition product
J; this G!H conversion rationalizes the participation of N-hy-
droxyaniline to deliver the final 3a [Eq. (6)] because (Z)-penta-
recorded with a Varian 400 MHz, Bruker 400, or a Bruker 600 MHz
spectrometers using chloroform-d (CDCl3) and [D6]acetone as the
internal standard.
Standard procedure for synthesis of 3a
A two-necked flask was charged with Zn(OTf)2 (0.09 g, 0.24 mmol)
and dry toluene (4 mL). A dry toluene solution (10 mL) of com-
pound 1a (0.9 g, 4.8 mmol) and nitrosobenzene 2a (0.6 g,
5.7 mmol) was added to this suspension. After stirring at 258C for
15 min, the reaction mixture was filtered over a short Celite bed.
The filtrate was concentrated under reduced pressure and purified
&
&
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
on silica gel (100–200 mesh size) by using column chromatography
with 15% ethyl acetate/n-hexane (Rf =0.5) as eluent to give the de-
sired 4,4-dimethyl-2-phenyl-6-(phenylamino)-1,2-oxazinan-3-one 3a
(1.1 g, 3.7 mmol, 78%) as a white solid. Compound 3a was recrys-
tallized from n-pentane for X-ray diffraction studies.
7.8 Hz, 3H), 5.67–5.63 (m, 1H), 4.54 (bs, 1H), 2.60 (dd, J=14.4,
7.2 Hz, 1H), 2.01–1.89 (m, 2H), 1.71–1.64 (m, 2H), 1.53–1.36 (m,
1H), 1.41 (s, 3H), 0.97–0.94 ppm (m, 3H); 13C NMR (100 MHz,
CDCl3): d=174.5, 144.1, 140.3, 129.4, 128.4, 124.7, 120.2, 119.3,
114.5, 84.8, 42.9, 42.2, 38.6, 23.9, 18.1, 14.6 ppm; Minor; 1H NMR
(600 MHz, CDCl3); d=7.64 (d, J=7.8 Hz, 1H), 7.06 (t, J=7.2 Hz,
1H), 5.63–5.59 (m, 1H), 2.37 ppm (dd, J=13.8, 6.6 Hz, 1H), other
protons merge with others or are not clearly visible; 13C NMR
(100 MHz, CDCl3); d=174.2, 143.9, 140.0, 128.4, 124.6, 120.1, 114.4,
85.4, 43.2, 42.0, 23.1, 17.7 ppm, other carbons merge with others;
ESI-MS calcd for C20H24N2O2: 324.1838; found: 324.1838.
Experimental procedure for the synthesis of compounds 4
and 5
A solution of nitrosobenzene 2a (0.07 g, 0.63 mmol) in toluene
(2 mL) was added slowly to a solution of compound 1a (0.1 g,
0.53 mmol) in dry toluene (2 mL) under N2. After stirring at 258C
for 15 min, the reaction mixture was concentrated under reduced
pressure and purified on silica gel (100–200 mesh) by using
column chromatography with 2% ethyl acetate/hexane (Rf =0.8) as
eluent to give the 1,2-diphenyldiazene oxide 4 (27 mg, 0.14 mmol,
26%) and 4% ethyl acetate/hexane (Rf =0.5) as eluent to give com-
pound (Z)-4-methyl-1-(phenylamino)penta-1,4-dien-3-one 5 (27 mg,
0.16 mmol, 28%) as a light-yellow liquid.
Compound 3e: Yellow solid (15% ethyl acetate/hexane, Rf =0.7,
0.10 g, 0.30 mmol, 74%); m.p.: 151–1528C; 1H NMR (600 MHz,
CDCl3): d=7.64 (d, J=8.0 Hz, 2H), 7.24–7.20 (m, 4H), 7.06 (t, J=
7.2 Hz, 1H), 6.86 (t, J=7.2 Hz, 1H), 6.78 (d, J=8.0 Hz, 2H), 5.56 (q,
J=8.6 Hz, 1H), 4.61 (d, J=9.2 Hz, 1H), 2.44 (dd, J=14.0, 6.1 Hz,
1H), 1.88–1.64 (m, 5H), 1.46–1.35 (m, 4H), 0.97–0.93 ppm (m, 6H);
13C NMR (150 MHz, CDCl3): d=173.4, 144.0, 140.1, 129.4, 128.4,
124.7, 120.1, 119.5, 114.4, 85.5, 46.2, 39.9, 38.2, 17.8, 17.5, 14.6 ppm,
other carbons merge with others; ESI-MS [M+H] calcd for
C22H29N2O2: 353.2229; found: 353.2227.
Experimental procedure for the synthesis of compound 6
Compound 3 f: White solid (20% ethyl acetate/hexane, Rf =0.5,
0.12 g, 0.32 mmol, 85%); m.p.: 177–1788C; 1H NMR (400 MHz,
CDCl3): d=7.91 (d, J=8.4 Hz, 2H), 7.56 (d, J=8.0 Hz, 2H), 7.18 (t,
J=7.6 Hz, 2H), 7.03 (t, J=7.6 Hz, 1H), 6.78 (d, J=8.4 Hz, 2H), 5.69
(q, J=7.6 Hz, 1H), 4.97 (d, J=8.8 Hz, 1H), 4.32 (q, J=6.8 Hz, 2H),
2.54 (dd, J=14.0, 7.6 Hz, 1H), 1.79 (dd, J=14.4, 7.6 Hz, 1H), 1.46 (s,
3H), 1.38–1.35 ppm (m, 6H); 13C NMR (150 MHz, CDCl3): d=174.9,
166.5, 148.0, 140.1, 131.5, 128.5, 124.9, 122.1, 119.1, 113.5, 83.8,
60.6, 43.7, 39.7, 26.4, 24.0, 14.4 ppm; EI-MS calcd for C21H24N2O4:
368.1736; found: 368.1738.
A dry toluene solution (3 mL) of compound 1a (0.1 g, 0.53 mmol)
and 2-methylnitrosobenzene 2k (0.08 g, 0.64 mmol) was added to
a suspension of Zn(OTf)2 (10 mg, 0.03 mmol) in dry toluene (1 mL).
After stirring at 158C for 3 min, the reaction mixture was filtered
over a short Celite bed. The filtrate was concentrated under re-
duced pressure and purified on silica gel (100–200 mesh) by using
column chromatography with 10% ethyl acetate/hexane (Rf =0.5)
as eluent to give the desired (Z)-4-methyl-1-(phenylamino)penta-
1,4-dien-3-one 6 (0.13 g, 0.43 mmol, 82%) as a white solid.
Compound 3a: White solid (0.13 g, 0.43 mmol, 82%); m.p.: 177–
Compound 3g: White solid; (15% ethyl acetate/hexane, Rf =0.5,
0.13 g, 0.42 mmol, 85%); m.p.: 179–1808C; 1H NMR (600 MHz,
CDCl3): d=7.63 (dd, J=8.9, 1.8 Hz, 2H), 7.20 (dt, J=7.4, 1.8 Hz,
2H), 7.05–7.02 (m, 3H), 6.70 (dd, J=8.9, 1.8 Hz, 2H), 5.61 (q, J=
7.6 Hz, 1H), 4.53 (d, J=9.4 Hz, 1H), 2.47 (dd, J=14.4, 7.4 Hz, 1H),
2.27 (s, 3H), 1.76 (dd, J=14.3, 7.7 Hz, 1H), 1.44 (s, 3H), 1.35 ppm (s,
3H); 13C NMR (150 MHz, CDCl3): d=175.0, 141.6, 140.3, 129.9,
129.4, 128.4, 124.6, 119.2, 114.5 (ꢁ2), 85.4, 44.0, 26.5, 24.0,
20.5 ppm; EI-MS calcd for C19H22N2O2: 310.1681; found: 310.1681.
1
1788C; H NMR (600 MHz, CDCl3): d=7.61 (d, J=7.9 Hz, 2H), 7.24–
7.18 (m, 4H), 7.03 (t, J=7.4 Hz, 1H), 6.86 (t, J=7.4 Hz, 1H), 6.79 (d,
J=7.9 Hz, 2H), 5.67–5.63 (m, 1H), 4.58 (d, J=9.4 Hz, 1H), 2.51 (dd,
J=14.3, 7.4 Hz, 1H), 1.79 (dd, J=14.3, 7.6 Hz, 1H), 1.45 (s, 3H),
1.37 ppm (s, 3H); 13C NMR (150 MHz, CDCl3): d=175.0, 144.0, 140.2,
129.4, 128.4, 124.6, 120.2, 119.1, 114.5, 84.9, 43.9, 39.7, 26.5,
24.1 ppm; ESI-MS calcd for C18H20N2O2: 296.1525; found: 296.1525.
Compound 3b: Light-yellow solid (15% ethyl acetate/hexane, Rf =
1
0.6, 0.11 g, 0.33 mmol, 73%); m.p.: 144–1458C; H NMR (600 MHz,
Compound 3h: Yellow solid; (15% ethyl acetate/hexane, Rf =0.4,
0.12 g, 0.36 mmol, 82%); m.p.: 187–1888C; 1H NMR (600 MHz,
CDCl3): d=7.57 (d, J=8.8 Hz, 2H), 7.20 (t, J=7.5 Hz, 2H), 7.16 (d,
J=8.7 Hz, 2H), 7.04 (t, J=7.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 5.58
(q, J=7.6 Hz, 1H), 4.65 (d, J=9.3 Hz, 1H), 2.50 (dd, J=14.4, 7.5 Hz,
1H), 1.76 (dd, J=14.4, 7.5 Hz, 1H), 1.44 (s, 3H), 1.34 ppm (s, 3H);
13C NMR (150 MHz, CDCl3): d=174.9, 142.7, 140.1, 129.3, 128.5,
125.0, 124.8, 119.2, 115.7, 84.8, 43.7, 39.7, 26.4, 24.0 ppm; ESI-MS
calcd for C18H19ClN2O2: 330.1135; found: 330.1133.
CDCl3): d=7.62 (d, J=8.4 Hz, 2H), 7.20–7.18 (m, 4H), 7.03 (t, J=
7.4 Hz, 1H), 6.85 (t, J=7.4 Hz, 1H), 6.78 (d, J=8.4 Hz, 2H), 5.61 (q,
J=9.5 Hz, 1H), 4.61 (bs, 1H), 2.63 (dd, J=14.4, 7.2 Hz, 1H), 2.07–
2.03 (m, 2H), 1.83–1.66 (m, 4H), 1.57–1.43 ppm (m, 5H); 13C NMR
(150 MHz, CDCl3): d=174.7, 144.1, 140.3, 129.4, 128.4, 124.6, 120.1,
119.3, 114.5, 85.2, 43.1, 39.9, 34.4, 31.7, 25.8, 22.1 ppm, one carbon
merges with the others; ESI-MS calcd for C21H24N2O2: 336.1838;
found: 336.1836.
Compound 3c: White solid (15% ethyl acetate/hexane, Rf =0.6,
0.11 g, 0.35 mmol, 76%); m.p.: 178–1798C; 1H NMR (600 MHz,
CDCl3): d=7.60 (d, J=8.0 Hz, 2H), 7.21 (t, J=7.8 Hz, 2H), 7.17 (t,
J=7.8 Hz, 2H), 7.01 (t, J=7.4 Hz, 1H), 6.86 (t, J=7.4 Hz, 1H), 6.78
(d, J=8.0 Hz, 2H), 5.66 (q, J=8.9 Hz, 1H), 4.57 (d, J=9.2 Hz, 1H),
2.61 (dd, J=7.7, 14.3 Hz, 1H), 2.50–2.46 (m, 1H), 2.28–2.24 (m, 1H),
1.86–1.66 (m, 6H), 1.54–1.48 ppm (m, 1H); 13C NMR (150 MHz,
CDCl3): d=175.4, 144.2, 140.5, 129.4, 128.4, 124.5, 120.2, 119.0,
114.6, 85.3, 49.9, 43.0, 35.9, 35.3, 25.6, 25.3 ppm; ESI-MS calcd for
C20H22N2O2: 322.1681; found: 322.1682.
Compound 3i: Light-brown solid; (20% ethyl acetate/hexane, Rf =
1
0.5, 0.09 g, 0.24 mmol, 65%); m.p.: 174–1758C; H NMR (400 MHz,
CDCl3): d=7.57 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.8 Hz, 2H), 7.25–7.18
(m, 2H), 7.04 (t, J=7.2 Hz, 1H), 6.66 (d, J=8.4 Hz, 2H), 5.58 (q, J=
7.6 Hz, 1H), 4.66 (d, J=8.0 Hz, 1H), 2.53–2.47 (m, 1H), 1.78–1.73
(m, 1H), 1.44 (s, 3H), 1.34 ppm (s, 3H); 13C NMR (100 MHz, CDCl3):
d=174.9, 143.2, 140.1, 132.2, 128.5, 124.8, 119.2, 116.1, 112.2, 84.6,
43.7, 39.7, 26.4, 24.0 ppm; ESI-MS [M+H] calcd for C18H20BrN2O2:
375.0708; found: 375.0706.
Compound 3d: Light-yellow solid (20% ethyl acetate/hexane, Rf =
0.6, 0.11 g, 0.35 mmol, 76%); m.p.: 131–1328C; H NMR (600 MHz,
CDCl3), d.r. (3:2): Major; d=7.59 (d, J=7.8 Hz, 1H), 7.24–7.16 (m,
4H), 7.01 (t, J=7.2 Hz, 1H), 6.86 (t, J=7.2 Hz, 1H), 6.78 (d, J=
Compound 3j: Brown solid (20% ethyl acetate/hexane, Rf =0.5,
0.11 g, 0.31 mmol, 82%); m.p.: 167–1688C; 1H NMR (600 MHz,
[D6]acetone): d=7.63 (d, J=9.0 Hz, 2H), 7.20 (t, J=7.8 Hz, 2H),
7.12 (t, J=8.4 Hz, 1H), 7.07 (s, 1H), 7.03 (dt, J=7.2, 1.0 Hz, 1H),
1
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
6.93 (dd, J=7.4, 1.0 Hz, 1H), 6.87 (dd, J=7.4, 1.0 Hz, 1H), 5.85 (t,
J=7.8 Hz, 1H), 2.58 (dd, J=13.8, 7.2 Hz, 1H), 2.01 (dd, J=14.4,
7.8 Hz, 1H), 1.41 (s, 3H), 1.29 ppm (s, 3H); 13C NMR (150 MHz,
[D6]acetone): d=175.5, 147.9, 141.7, 131.6, 129.0, 125.0, 123.4,
122.5, 119.6, 117.5, 113.9, 85.3, 42.8, 40.2, 26.8, 24.3 ppm; ESI-MS
[M+H] calcd for C18H20BrN2O2: 375.0708; found: 375.0704.
21.3 ppm; ESI-MS [M+H] calcd for C19H23N2O2: 311.17595; found:
311.17567.
Compound 3q: White solid (20% ethyl acetate/hexane, Rf =0.4,
0.12 g, 0.37 mmol, 70%); m.p.: 142–1438C; 1H NMR (600 MHz,
CDCl3): d=7.45–7.44 (m, 1H), 7.20 (t, J=8.4 Hz, 2H), 7.11 (t, J=
2.3 Hz, 1H), 7.06 (dt, J=8.3, 2.6 Hz, 1H), 6.92 (d, J=8.4 Hz, 2H),
6.77 (t, J=7.4 Hz, 1H), 6.55–6.53 (m, 1H), 6.40 (d, J=9.1 Hz, 1H),
5.89–5.85 (m, 1H), 3.35 (s, 3H), 2.60–2.56 (m, 1H), 1.99 (dd, J=14.3,
7.4 Hz, 1H), 1.43 (s, 3H), 1.27 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=174.7, 159.8, 145.3, 142.4, 129.2, 128.8, 119.0, 114.0,
110.9, 110.7, 103.2, 84.6, 54.2, 42.1, 39.5, 25.8, 23.0 ppm; ESI-MS
[M+H] calcd for C19H23N2O3: 327.1708; found: 327.17031.
Compound 3k: Light-yellow solid; (20% ethyl acetate/hexane, Rf =
1
0.5, 0.12 g, 0.38 mmol, 72%); m.p.: 178–1798C; H NMR (600 MHz,
CDCl3): d=7.56 (d, J=8.9 Hz, 2H), 7.22 (t, J=7.8 Hz, 2H), 7.13 (d,
J=8.9 Hz, 2H), 6.87 (t, J=7.3 Hz, 1H), 6.77 (d, J=8.0 Hz, 2H), 5.65
(q, J=7.6 Hz, 1H), 4.63 (d, J=9.2 Hz, 1H), 2.50 (dd, J=14.4, 7.4 Hz,
1H), 1.76 (dd, J=14.4, 7.4 Hz, 1H), 1.44 (s, 3H), 1.34 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=175.0, 143.9, 138.9, 129.6, 129.5,
128.4, 120.3, 120.1, 114.4, 85.0, 43.6, 39.7, 26.4, 23.9 ppm; ESI-MS
calcd for C18H19ClN2O2: 330.1135; found: 330.1135.
Compound 3r: Brown solid (20% ethyl acetate/hexane, Rf =0.5,
0.08 g, 0.21 mmol, 40%); m.p.: 169–1708C; 1H NMR (600 MHz,
[D6]acetone): d=7.87–7.86 (m, 1H), 7.64–7.62 (m, 1H), 7.18 (t, J=
7.8 Hz, 2H), 7.14–7.13 (m, 1H), 7.08 (t, J=8.2 Hz, 1H), 6.86 (d, J=
7.9 Hz, 2H), 6.77 (dt, J=7.4, 1.0 Hz, 1H), 6.37 (d, J=9.5 Hz, 1H),
5.92–5.88 (m, 1H), 2.57 (dd, J=14.3, 7.6 Hz, 1H), 1.99 (dd, J=14.3,
7.3 Hz, 1H), 1.40 (s, 3H), 1.27 ppm (s, 3H); 13C NMR (150 MHz,
[D6]acetone): d=175.9, 146.0, 143.2, 130.7, 130.0, 127.3, 122.3,
121.7, 120.1, 117.5, 115.0, 86.2, 42.8, 40.6, 26.7, 24.2 ppm; ESI-MS
[M+H] calcd for C18H20BrN2O2: 375.0709; found: 375.0705.
Compound 3l: Light-brown solid; (20% ethyl acetate/hexane, Rf =
1
0.5, 0.10 g, 0.27 mmol, 51%); m.p.: 187–1888C; H NMR (400 MHz,
CDCl3): d=7.54 (d, J=8.8 Hz, 2H), 7.30 (d, J=8.8 Hz, 2H), 7.26 (t,
J=7.6 Hz, 2H), 6.91 (t, J=7.2 Hz, 1H), 6.80 (d, J=8.0 Hz, 2H), 5.70
(q, J=7.6 Hz, 1H), 4.60 (d, J=9.2 Hz, 1H), 2.55 (dd, J=14.4, 7.2 Hz,
1H), 1.80 (dd, J=14.4, 6.8 Hz, 1H), 1.47 (s, 3H), 1.38 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=175.0, 143.8, 139.4, 131.3, 129.5,
120.4, 117.3, 114.4, 85.0, 43.7, 39.8, 26.4, 24.0 ppm, one carbon
merges with the others; ESI-MS [M+H] calcd for C18H20BrN2O2:
375.0708; found: 375.0706.
Compound 3s: White solid (20% ethyl acetate/hexane, Rf =0.5,
0.10 g, 0.30 mmol, 56%); m.p.: 163–1648C; 1H NMR (600 MHz,
[D6]acetone): d=7.74 (t, J=2.4 Hz, 1H), 7.61–7.60 (m, 1H), 7.20 (t,
J=8.4 Hz, 2H), 7.16 (t, J=8.4 Hz, 1H), 7.01–7.00 (m, 1H), 6.89 (d,
J=9.0 Hz, 2H), 6.79 (dt, J=7.8, 1.2 Hz, 1H), 6.37 (d, J=9.0 Hz, 1H),
5.94–5.90 (m, 1H), 2.60 (dd, J=14.4, 7.8 Hz, 1H), 2.02 (dd, J=14.4,
7.2 Hz, 1H), 1.43 (s, 3H), 1.30 ppm (s, 3H); 13C NMR (150 MHz,
[D6]acetone): d=175.9, 146.0, 143.1, 134.3, 130.4, 130.0, 124.3,
120.1, 118.8, 117.1, 115.0, 86.2, 42.9, 40.5, 26.7, 24.2 ppm; ESI-MS
[M+H] calcd for C18H20ClN2O2: 331.1213; found: 331.1214.
Compound 4: Light-yellow liquid; 1H NMR (400 MHz, CDCl3): d=
8.31–8.28 (m, 2H), 8.15 (d, J=8.7 Hz, 2H), 7.57–7.36 ppm (m, 6H);
13C NMR (100 MHz, CDCl3) : d=148.3, 143.9, 131.5, 129.6, 128.7,
128.6, 125.5, 122.3 ppm; ESI-MS [M+H] calcd for C12H11N2O:
199.0871; found: 199.0867.
Compound 5: Light-yellow liquid; 1H NMR (600 MHz, CDCl3): d=
11.9 (bs, 1H), 7.37 (dd, J=12.3, 7.9 Hz, 1H), 7.30 (t, J=7.9 Hz, 2H),
7.05–7.02 (m, 3H), 5.83 (s, 1H), 5.71 (d, J=7.92 Hz, 1H), 5.46 (s,
1H), 1.94 ppm (s, 3H); 13C NMR (150 MHz, CDCl3): d=193.0, 145.2,
144.0, 140.3, 129.7, 123.4, 120.5, 116.1, 93.3, 18.2 ppm; ESI-MS [M+
H] calcd for C12H14NO: 188.1075; found: 188.1071.
Compound 6: White solid; m.p.: 137–1388C; 1H NMR (600 MHz,
[D6]acetone): d=11.5 (d, J=11.5 Hz, 1H), 7.70 (s, 1H), 7.66 (dd, J=
12.3, 8.14 Hz, 1H), 7.57 (d, J=7.9 Hz, 1H), 7.35 (t, J=8.3 Hz, 2H),
7.22 (d, J=7.9, 2H), 7.20–7.17 (m, 2H), 7.09 (t, J=7.6 Hz, 1H), 7.03
(t, J=7.4 Hz, 1H), 6.34 (d, J=8.1 Hz, 1H), 2.42 (s, 3H), 1.18 ppm (s,
6H); 13C NMR (100 MHz, [D6]acetone): d=202.8, 146.7, 142.5, 139.9,
133.7, 128.8, 128.6, 125.7, 124.7, 124.5, 121.6, 114.5, 92.6, 70.5, 18.4,
17.5 ppm; ESI-MS [M+H] calcd for C19H23N2O2: 311.1759; found:
311.1755.
Compound 3m: White solid (15% ethyl acetate/hexane, Rf =0.5,
0.07 g, 0.18 mmol, 35%); m.p.: 173–1748C; 1H NMR (600 MHz,
CDCl3): d=7.87 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.26–7.24
(m, 2H), 6.91 (t, J=6.6 Hz, 1H), 6.81 (d, J=7.5 Hz, 2H), 5.73 (q, J=
7.7 Hz, 1H), 4.57 (d, J=9.6 Hz, 1H), 4.32 (q, J=6.7 Hz, 2H), 2.56
(dd, J=14.1, 6.9 Hz, 1H), 1.81 (dd, J=14.3, 7.7 Hz, 1H), 1.49 (s, 3H),
1.40 (s, 3H), 1.36 ppm (t, J=6.9 Hz, 3H); 13C NMR (150 MHz, CDCl3):
d=175.4, 166.1, 144.1, 143.8, 130.1, 129.5, 125.9, 120.5, 117.5,
114.5, 85.2, 60.8, 43.6, 40.1, 26.5, 24.0, 14.3 ppm; ESI-MS [M+H]
calcd for C21H25N2O4: 369.1814; found: 369.1809.
Compound 3n: White solid (20% ethyl acetate/hexane, Rf =0.5,
0.14 g, 0.43 mmol, 82%); m.p.: 189–1908C; 1H NMR (600 MHz,
CDCl3): d=7.47 (dd, J=7.0, 2.2 Hz, 2H), 7.20 (t, J=7.5 Hz, 2H), 6.85
(t, J=7.4 Hz, 1H), 6.78 (d, J=7.7 Hz, 2H), 6.72 (dd, J=7.0, 2.2 Hz,
2H), 5.61–5.60 (m, 1H), 4.63 (d, J=9.2 Hz, 1H), 3.72 (s, 3H), 2.49
(dd, J=14.3, 7.4 Hz, 1H), 1.78 (dd, J=14.3, 7.5 Hz, 1H), 1.43 (s, 3H),
1.35 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=174.7, 156.8, 144.1,
133.3, 129.4, 122.0, 120.0, 114.4, 113.6, 84.8, 55.4, 44.0, 39.3, 26.4,
24.1 ppm; ESI-MS calcd for C19H22N2O3: 326.1630; found: 326.1631.
Compound 3o: Light-yellow solid (20% ethyl acetate/hexane, Rf =
1
0.5, 0.14 g, 0.45 mmol, 85%); m.p.: 177–1788C; H NMR (400 MHz,
CDCl3): d=7.49 (d, J=8.5 Hz, 2H), 7.22 (t, J=7.8 Hz, 2H), 7.00 (d,
J=8.5 Hz, 2H), 6.87 (t, J=7.3 Hz, 1H), 6.80 (d, J=7.8 Hz, 2H), 5.62
(q, J=7.6 Hz, 1H), 4.75 (d, J=9.2 Hz, 1H), 2.46 (dd, J=14.2, 7.4 Hz,
1H), 2.25 (s, 3H), 1.77 (dd, J=14.3, 7.6 Hz, 1H), 1.44 (s, 3H),
1.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=174.8, 144.1, 137.7,
134.4, 129.3, 128.9, 119.9, 119.5, 114.4, 84.8, 43.6, 39.4, 26.4, 24.0,
20.7 ppm; ESI-MS calcd for C19H22N2O2: 310.1681; found: 310.1680.
Acknowledgments
Compound 3p: Light-yellow solid (20% ethyl acetate/hexane, Rf =
1
0.5, 0.11 g, 0.34 mmol, 65%); m.p.: 157–1588C; H NMR (400 MHz,
The authors thank the National Science Council, Taiwan for
supporting this work.
CDCl3): d=7.49 (d, J=8.0 Hz, 1H), 7.38 (s, 1H), 7.22 (t, J=6.8 Hz,
2H), 7.08 (t, J=8.0 Hz, 1H), 6.87–6.80 (m, 4H), 5.66 (q, J=8.0 Hz,
1H), 4.64 (d, J=9.2 Hz, 1H), 2.49 (dd, J=14.0, 7.2 Hz, 1H), 2.13 (s,
3H), 1.76 (dd, J=14.0, 7.6 Hz, 1H), 1.45 (s, 3H), 1.34 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=174.9, 144.1, 140.2, 138.3, 129.4,
128.2, 125.4, 120.1, 119.7, 116.2, 114.6, 84.7, 43.8, 39.7, 26.4, 24.0,
Keywords: [4+2]-annulation
·
1,2-oxazinan-3-ones
·
nitrosoarenes · radical annulation · zinc catalysis
&
&
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
[1] a) W. Adam, O. Krebs, Chem. Rev. 2003, 103, 4131–4146; b) K. Mikami,
M. Shimizu, Chem. Rev. 1992, 92, 1021–1050; c) P. Zuman, B. Shah,
Chem. Rev. 1994, 94, 1621–1641; d) H. Yamamoto, N. Momiyama, Chem.
Commun. 2005, 3514–3525; e) P. F. Vogt, M. J. Miller, Tetrahedron 1998,
54, 1317–1348; f) Y. Yamamoto, H. Yamamoto, Eur. J. Org. Chem. 2006,
2031–2043; g) J. Streith, A. Defoin, Synthesis 1994, 1994, 1107–1117;
h) B. S. Bodnar, M. J. Miller, Angew. Chem. Int. Ed. 2011, 50, 5630–5647;
Angew. Chem. 2011, 123, 5746–5764.
[2] a) P. Selig, Angew. Chem. Int. Ed. 2013, 52, 7080–7082; Angew. Chem.
2013, 125, 7218–7220; b) K. Shen, X. Liu, G. Wang, L. Lin, X. Feng,
Angew. Chem. Int. Ed. 2011, 50, 4684–4688; Angew. Chem. 2011, 123,
4780–4784; c) N. Momiyama, H. Yamamoto, Org. Lett. 2002, 4, 3579–
3582; d) A. Yanagisawa, S. Takeshita, Y. Izumi, K. Yoshida, J. Am. Chem.
Soc. 2010, 132, 5328–5329; e) J. M. Janey, Angew. Chem. Int. Ed. 2005,
44, 4292–4300; Angew. Chem. 2005, 117, 4364–4372; f) H.-M. Guo, L.
Cheng, L.-F. Cun, L.-Z. Gong, A.-Q. Miac, Y.-Z. Jiang, Chem. Commun.
2006, 429–431; g) X. Ding, W. Tang, C. Zhu, Y. Chenga, Adv. Synth. Catal.
2010, 352, 108–112.
Chem. 2003, 68, 6591–6596; e) S. Aoyagi, R. Tanaka, M. Naruse, C. Ki-
bayashi, J. Org. Chem. 1998, 63, 8397–8406; f) C. Kibayashi, S. Aoyagi,
Synlett 1995, 1995, 873–879; g) W. Lin, A. Gupta, K. H. Kim, D. Mendel,
M. J. Miller, Org. Lett. 2009, 11, 449–452; h) W. Lin, K. G. Virga, K.-H. Kim,
J. Zajicek, D. Mendel, M. J. Miller, J. Org. Chem. 2009, 74, 5941–5946.
[7] Reviews on radical annulations: a) P. Dowd, W. Zhang, Chem. Rev. 1993,
93, 2091–2115; b) A. J. McCarroll, J. C. Walton, J. Chem. Soc. Perkin
Trans. 1 2001, 3215–3229; c) C. H. Schiesser, U. Wille, H. Matsubara, I.
Ryu, Acc. Chem. Res. 2007, 40, 303–313; d) M. Malacria, Chem. Rev.
1996, 96, 289–306.
[8] a) D. J. Fisher, L. G. Burnett, R. Velasco, J. R. d. Alaniz, J. Am. Chem. Soc.
2015, 137, 11614–11617; b) Y. Miura, T. Tomimura, N. Matsuba, R.
Tanaka, M. Nakatsuji, J. Org. Chem. 2001, 66, 7456–7463; c) W. Adam,
S. E. Bottle, K. Paters, Tetrahedron Lett. 1991, 32, 4283–4286.
[9] a) P. Sharma, R.-S. Liu, Org. Lett. 2016, 18, 412–415; b) S. Ghorpade, P. D.
Jadhav, R.-S. Liu, Chem. Eur. J. 2016, 22, 2915–2919.
[10] CCDC 1480611 (3a) and 1480610 (6) contain the supplementary crystal-
lographic data for this paper. These data are provided free of charge by
The Cambridge Crystallographic Data Centre.
[11] J. Y. Kang, A. Bugarin, B. T. Connell, Chem. Commun. 2008, 3522–3524.
[12] Only N-alkyl or N-ester substituted 2,3-dihydroisoxazoles were reported
in the literature, and their N-phenyl derivatives are unstable owing to
facile oxidation at the aniline center. See: a) J. E. Baldwin, R. G. Puduss-
ery, A. K. Qureshi, B. Sklarz, J. Am. Chem. Soc. 1968, 90, 5325–5326; b) J.
Sims, K. N. Houk, J. Am. Chem. Soc. 1973, 95, 5798–5800.
[13] For isoxazol-2-ium species, see selected examples: a) H. Bae Jeon, K.
Kim, Tetrahedron Lett. 1993, 34, 1939–1940; b) P. DeShong, J. A. Cipolli-
na, N. K. Lowmasted, J. Org. Chem. 1988, 53, 1356–1364; c) R. B. Wood-
ward, R. A. Olafson, H. Mayer, Tetrahedron Suppl. 1966, 22, 321–340;
d) P. DeShong, N. E. Lowmaster, O. Baralt, J. Org. Chem. 1983, 48, 1149–
1150; e) B. D. Wilson, D. M. Burness, J. Org. Chem. 1966, 31, 1565–1569;
f) S. Chimichi, M. Boccalini, M. M. M. Hassan, G. Viola, F. D. Acquab, M.
Curinic, Tetrahedron 2006, 62, 90–96; g) R. B. Woodward, D. J. Wood-
man, Y. Kobayashi, J. Org. Chem. 1967, 32, 388–391.
[3] a) W. Adam, N. Bottke, J. Am. Chem. Soc. 2000, 122, 9846–9847; b) A. G.
Leach, K. N. Houk, J. Am. Chem. Soc. 2002, 124, 14820–14821; c) J. L.
Jeffrey, S. P. McClintock, M. M. Haley, J. Org. Chem. 2008, 73, 3288–3291;
d) D. Atkinson, M. A. Kabeshov, M. Edgar, A. V. Malkov, Adv. Synth. Catal.
2011, 353, 3347–3351.
[4] a) C.-H. Chen, Y.-C. Tsai, R.-S. Liu, Angew. Chem. Int. Ed. 2013, 52, 4599–
4603; Angew. Chem. 2013, 125, 4697–4701; b) S. Chakrabarty, I. Chatter-
jee, B. Wibbeling, C. G. Daniliuc, A. Studer, Angew. Chem. Int. Ed. 2014,
53, 5964–5968; Angew. Chem. 2014, 126, 6074–6078; c) A. Lemos, J. P.
LourenÅo, Tetrahedron Lett. 2009, 50, 1311–1313; d) T. L. Gilchrist, T. G.
Roberts, J. Chem. Soc. Perkin Trans. 1 1983, 1283–1292; e) G. Calvet, M.
Dussaussois, N. Blanchard, C. Kouklovsky, Org. Lett. 2004, 6, 2449–2451.
[5] a) R. E. Kyne, M. C. Ryan, L. T. Kliman, J. P. Morken, Org. Lett. 2010, 12,
3796–3799; b) J. Hutton, W. A. Waters, J. Chem. Soc. B 1968, 191–195;
c) S. Montanari, C. Paradisi, G. Scorrano, J. Org. Chem. 1999, 64, 3422–
3428; d) A. R. Becker, L. A. Sternson, Bioorg. Chem. 1980, 9, 305–312.
[6] a) V. Eschenbrenner-Lux, K. Kumar, H. Waldmann, Angew. Chem. Int. Ed.
2014, 53, 11146–11157; Angew. Chem. 2014, 126, 11326–11337; b) S.
Carosso, M. J. Miller, Org. Biomol. Chem. 2014, 12, 7445–7468; c) F. Li, B.
Yang, M. J. Miller, J. Zajicek, B. C. Noll, U. Mçllmann, H.-M. Dahse, P. A.
Miller, Org. Lett. 2007, 9, 2923–2926; d) T. Mineno, M. J. Miller, J. Org.
Received: May 31, 2016
Published online on && &&, 0000
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
7
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
FULL PAPER
&
Annulation Reactions
P. Sharma, R.-S. Liu*
&& – &&
Skeletal Rearrangement in the ZnII-
Catalyzed [4+2]-Annulation of
Disubstituted N-Hydroxy
Allenylamines with Nitrosoarenes to
Yield Substituted 1,2-Oxazinan-3-one
Derivatives
Skeletons in the closet: Zinc-catalyzed
[4+2]-annulation reactions of disubsti-
tuted N-hydroxy allenylamines with ni-
trosoarenes is reported, affording substi-
tuted 1,2-oxazinan-3-ones with a skeletal
rearrangement.
&
&
Chem. Eur. J. 2016, 22, 1 – 8
www.chemeurj.org
8
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!