Selective intramolecular palladium(II)-catalyzed aminooxygenation vs. diamination of alkenylureas: Efficient microwave-assisted reactions to bicyclic piperazinones

Article abstract of DOI:10.1002/adsc.201300104

Alkenylureas arising from glycine allylamides were proven to be suitable substrates for the synthesis of bicyclic five-membered ring-fused piperazinones. The reported intramolecular domino processes, performed under oxidative conditions with bis(acetonitrile)palladium dichloride as catalyst and copper(II) chloride in a stoichiometric amount by microwave activation, were completely selective, involving either diamination or aminooxygenation. While the latter process is determined by the direct intervention of the urea oxygen on the σ-alkylpalladium intermediate, the diamination reaction can in principle derive from a direct attack of the second nitrogen atom on the palladium complex or on the first formed chloromethylpiperazinone. Indeed, this latter species was isolated and proved to be capable of conversion solely into the imidazopiperazinone. Copyright

Full text of DOI:10.1002/adsc.201300104

UPDATES
DOI: 10.1002/adsc.201300104
Selective Intramolecular Palladium(II)-Catalyzed
Aminooxygenation vs. Diamination of Alkenylureas: Efficient
Microwave-Assisted Reactions to Bicyclic Piperazinones
Gianluigi Broggini,a,* Vincenzina Barbera,b Egle M. Beccalli,c Ugo Chiacchio,b
Andrea Fasana,a Simona Galli,a and Silvia Gazzolaa
a
Dipartimento di Scienza e Alta Tecnologia, Universitꢀ dell’Insubria, via Valleggio 11, 22100 Como, Italy
Fax : (+39)-(0)31-238-6449; phone: (+39)-(0)31-238-6444; e-mail: gianluigi.broggini@uninsubria.it
Dipartimento di Scienze del Farmaco, Universitꢀ di Catania, viale Andrea Doria 6, 95125 Catania, Italy
DISFARM, Sezione di Chimica Organica “A. Marchesini”, Universitꢀ di Milano, via Venezian 21, 20133 Milano, Italy
b
c
Received: February 2, 2013; Revised: April 18, 2013; Published online: May 15, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300104.
Abstract: Alkenylureas arising from glycine allyl-
ACHTUNGTRENNUNGamides were proven to be suitable substrates for
Alkenylureas have been extensively explored in
double intramolecular domino processes providing
the formation of oxazole and imidazole bicyclic prod-
ucts either by transition metal-catalyzed reactions,[7,8]
or by using iodonium reagents[8a] (Figure 1). These
transformations involve an initial carbon-nitrogen
bond formation, followed by the intervention of the
oxygen or the second nitrogen atom of the urea group
on the intermediate to generate the final structure.
Among the cyclizations of alkenylureas promoted by
transition metals, MuÇiz and co-workers have recently
reported a palladium-catalyzed reaction which gives
selectively the diamination products working with
the synthesis of bicyclic five-membered ring-fused
piperazinones. The reported intramolecular domino
processes, performed under oxidative conditions
with bis(acetonitrile)palladium dichloride as cata-
lyst and copper(II) chloride in a stoichiometric
amount by microwave activation, were completely
selective, involving either diamination or aminooxy-
genation. While the latter process is determined by
the direct intervention of the urea oxygen on the
s-alkylpalladium intermediate, the diamination re-
action can in principle derive from a direct attack
of the second nitrogen atom on the palladium com-
plex or on the first formed chloromethylpiperazi-
none. Indeed, this latter species was isolated and
proved to be capable of conversion solely into the
imidazopiperazinone.
PhIACHTNUTGRNEUNG
(OAc)2[7] or a Cu(II) salt[8] as oxidants. Conversely,
the aminooxygenation process was only occasionally
operative when terminally substituted allyl substrates
were used.[8a] A totally selective aminooxygenation
was obtained in the presence of a catalytic system
based on platinum chloride.[9] N-Iodosuccinimide-
Keywords: domino reactions; heterocycles; homo-
geneous catalysis; microwave chemistry; palladium
Introduction
The difunctionalization of alkenes under oxidative
conditions is a fruitful strategy for the synthesis of
various organic compounds.[1] Recent investigations of
palladium-catalyzed oxidative reactions have evi-
denced that domino processes such as aminooxygena-
tions,[2] diaminations,[3] dioxygenations,[4] carboamina-
tions,[5] and aminohalogenations[6] of alkenes can be
efficiently used to achieve (poly)functionalized com-
pounds or bicyclic systems.
Figure 1. State of the art for the cyclization of alkenylureas.
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Selective Intramolecular Palladium(II)-Catalyzed Aminooxygenation vs. Diamination of Alkenylureas
actions of alkenylureas 1 arising from glycine allyl-
AHCTUNGTRENGNaUN mides.
Results and Discussion
Initially, we examined the double intramolecular
domino reaction on the N-phenylurea 1a, deriving
from N-allyl-N-cyclohexylglycine amide which was
chosen as the model. The conditions that successfully
promoted the aminocarboxylation process of N-Boc-
protected allylic amides of a-amino acids, i.e., PdCl2
AHCTUNTGERG(NNUN MeCN)2 5 mol% and CuCl2 in a stoichiometric
amount in DMF at 1008C,[2f] resulted in a scarcely se-
lective process, giving a mixture of three products in
39%, 32% and 11% yields, respectively, following the
order of chromatographic elution (Table 1, entry 1).
Analytical and spectroscopic data allowed us to iden-
Scheme 1. Palladium-catalyzed double intramolecular di-
functionalization of alkenylureas.
mediated reactions were proven to be effective to per- tify the aminochlorination product 4a and the bicyclic
form diaminations and aminoalkoxylations of N-sul- ring-fused compounds 2a and 3a. The distinction be-
A
tween the isomeric oxazolo- and imidazo-piperazine
As a part of our ongoing interest in constructing structures 2a and 3a was achieved on the basis of the
hetero-polycyclic compounds by palladium cataly- 13C NMR chemical shifts of the methylene group of
sis,[11] we have recently reported the intramolecular the five-membered ring, which resulted to be less
aminocarboxylation of tert-butoxycarbonyl-protected shielded for the oxazole ring compared with the imi-
aminoalkenes catalyzed by palladium in the presence dazole one (67.9 ppm vs. 44.4 ppm), in agreement
of copper chloride to produce piperazinone deriva- with the literature data.[12]
tives fused to an oxazolidinone ring (Scheme 1).[2f]
The outcome of the reaction, although occurring
Herein we describe a selective synthesis of oxazolo- with low selectivity, gave these clues: (i) the PdCl2
and imidazo-piperazinones (2 and 3, respectively) by (MeCN)2/CuCl2 catalytic system was proven to be
AHCTUNGTRENNUNG
selective and straightforward Pd(II)-catalyzed micro- suitable for the cyclization of alkenylureas, furnishing
wave-activated aminooxygenation and diamination re- piperazinone products by domino processes; (ii) both
Table 1. Optimization of selective reaction conditions.
Entry
Base
Solvent
Temperature [8C]
Time
2a [%]
3a [%]
4a [%]
1
2
3
4
5
6
7
8
–
–
DMF
THF
100
60
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
15 min
30 min
30 min
24 h
32
83
65
42
27
–
–
–
–
11
–
17
9
13
–
–
–
78
–
–
–
39
–
–
–
–
–
–
–
–
–
–
–
K2CO3
K2CO3
AcONa
DBU
DIPEA
DIPEA
K2CO3
K2CO3
–
DMF
MeCN
DMF
DMF
DMF
CH2Cl2
DMF
DMF
DMF
DMF
100
reflux
100
100
100
40
9
150[a]
60[a]
60[a]
60
10
11
12
85
85
76
–
[a]
MW activation.
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Gianluigi Broggini et al.
UPDATES
oxygen and nitrogen atoms of the urea group can pro- of Table 1) to shorten the reaction times. Ureas 1b–j,
mote the second step of the process giving the diver- easily prepared by removal of the tert-butoxycarbonyl
gent formation of a five-membered ring fused to the group from Boc-glycine allylic amides and subsequent
piperazine moiety; (iii) besides aminooxygenation re- reaction with the appropriate isocyanate, were envis-
actions analogous to those observed with carbamate aged as substrates suitable to warrant a satisfactory
derivatives, alkenylureas can undergo aminochlorina- survey of substituents on the aryl moiety. Aminooxy-
tion and diamination processes.
genation and diamination processes evidenced similar
Both PdCl2A(MeCN)2 and CuCl2 were proven to be outcomes for all alkenylureas, leading to the bicylic
CHTUNGTRENNUNG
essential for the conversion of 1a to bicyclic pro- products 2 and 3 with the yields described in Table 2.
ducts.[2f] In order to obtain more selective processes, It is worth noting that both domino reactions are in-
different parameters including base, solvent and tem- hibited by the presence of a substituent such as
perature were screened in combination with the es- methyl, phenyl or methoxycarbonyl group on the ter-
tablished PdCl2ACHTUNGTRENNUNG(MeCN)2/CuCl2 catalytic system. The minal position of the allylic moiety. The domino pro-
most significant results are collected in Table 1. The cesses performed on optically active substrates, such
use of THF at 608C gave the aminooxygenation prod- as the N,N-allylcyclohexylamide of l-valine and l-
uct 2a in 83% yield (entry 2). Due to the satisfactory phenylalanine, gave in both cases inseparable mix-
behaviour of these conditions to involve the oxygen tures of diastereoisomeric bicyclic products.
atom in the domino process, we tested new conditions
It should be remarked that the molecular structure
in the presence of a base to favour the diamination of the oxazolo-piperazinone 2d, obtained from the 2-
reaction. Although in a few cases the formation of the
imidazoACHTUNGTRENNUNG[1,5-a]pyrazine product 3a was observed, the
use of various bases such as K2CO3, AcONa, DIPEA
and DBU in different solvents did not provide a satis-
factory outcome of the diamination process (Table 1,
entries 3–8). Conversely, the activation by microwave
irradiation highlighted the determinant role of tem-
perature to improve the selectivity in the aminooxy-
genation and diamination pathways. Firstly, the expo-
sure to the microwaves of a DMF solution of 1a in
the presence of K2CO3 at 1508C for 15 min led to the
diamination product 3a as the sole product, isolated
in 78% yield (Table 1, entry 9). Working under the
same conditions at lower temperature (60 vs. 1508C)
for 30 min, only the aminooxygenation compound 2a
was observed (Table 1, entry 10). Further investiga-
tions revealed that the selectivity in this process is
preserved on working in the absence of the base at
608C, also by conventional heating (Table 1, en-
tries 11 and 12).
Table 2. Scope of aminooxygenation and diamination reac-
tions.
Substrate
R
Ar
Conditions[a] 2 [%] 3 [%]
1b
1b
1c
1c
1d
1d
1e
1e
1f
1f
1g
1g
1h
1h
1i
Cy 4-Cl-C6H4
Cy 4-Cl-C6H4
Cy 4-NO2-C6H4
Cy 4-NO2-C6H4
Cy 2-NO2-C6H4
Cy 2-NO2-C6H4
Cy 4-MeO-C6H4
Cy 4-MeO-C6H4
Bn C6H5
A
B
A
B
A
B
A
B
C
B
A
B
A
B
A
B
A
B
75
71
77
78
79
76
72
74
77
73
78
80
79
74
72
76
78
73
Comparing the outcomes of the cyclizations report-
ed in Table 1, in particular the conditions of entries 9
and 10, temperature seems to be determinant for the
formation of oxazolyl and imidazolyl compounds.
This feature can justify the total selectivity of the di-
Bn C6H5
Bn 4-Cl-C6H4
Bn 4-Cl-C6H4
Bn 4-NO2-C6H4
Bn 4-NO2-C6H4
Bn 2-NO2-C6H4
Bn 2-NO2-C6H4
Bn 4-MeO-C6H4
Bn 4-MeO-C6H4
ACHTUNGTRENNUNGamination product obtained by microwave irradiation
working at 1508C (entry 10), plausibly due to the
rapid heating achieved by this activation technique
that avoids the alternative product. On the other
hand, the possibility that the oxazolo-piperazine 2a
may convert into 3a by a progressive heating was ex-
cluded by the treatment of the former at 1508C in
DMF, either in the absence or in the presence of the
catalytic system.
Based on these results, we verified the scope of the
reaction on a wide range of alkenylureas, in all cases
by microwave irradiation and preferring the presence
of K2CO3 in the aminooxygenation reactions (entry 10
1i
1j
1j
[a]
Conditions A: PdCl
(3 mmol) and urea (1 mmol), DMF, 608C, MW irradia-
tion, 30 min; conditions B: PdCl2A(MeCN)2 (10 mol%),
2ACHTUNGTREN(NUNG MeCN)2 (10 mol%), CuCl2
CTHUNGTRENNUNG
CuCl2 (3 mmol), K2CO3 (3 mmol), and urea (1 mmol),
DMF, 1508C, MW irradiation, 15 min; conditions C:
PdCl
2ACHTUNGTERN(NUNG MeCN)2 (10 mol%), CuCl2 (3 mmol) and urea
(1 mmol), THF, 608C, 24 h.
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Selective Intramolecular Palladium(II)-Catalyzed Aminooxygenation vs. Diamination of Alkenylureas
conversion of compound 4a was unsuccessful also on
heating in THF or by treatment under microwave ir-
radiation in DMF in the absence of the couple
PdCl2ACHTNUGTRNEUNG(MeCN)2/CuCl2. Conversely, on performing the
reaction with the catalytic system in DMF at 1508C
under microwave activation, the chloro derivative 4a
was quantitatively converted into the imidazo-pipera-
zinone product 3a. The transformation into the diami-
nation product was achievable also without Pd cata-
lyst and CuCl2, even if the presence of K2CO3 was re-
quired to have a quantitative yield.
Figure 2. Ortep drawing, at 30% probability level, of the
molecular structure of species 2d.
This behaviour was confirmed by submitting differ-
ent chloromethylpiperazinones to aminooxygenation
nitrophenyl-substituted urea 1d by performing the re- and diamination reactions, as described in Table 3.
action at 608C under microwave activation, was con- Compounds 4f, h, j were converted solely into the
firmed by a single crystal X-ray diffraction study imidazo-fused products 3f, h, j, isolated in all cases in
(Figure 2).[13]
high yields.
Having in hand the aminochlorination product 4a,
This investigation on the reactivity of the chlorome-
we planned some experiments to find indications on thylpiperazinones furnished new insights on the mech-
its possible role as the precursor for the oxazole and anism of the double intramolecular domino processes.
imidazole bicyclic products 2 and 3.[14] Firstly, chloro- Even if the conversion of the compound 1 into the
methylpiperazinone 4a was treated under the condi- imidazole bicyclic product 3 can involve the chloro in-
tions which were successful in the aminooxygenation termediate 4 or a direct intervention of the nitrogen
process [i.e., PdCl2ACHTNUGTRNEUNG(MeCN)2/CuCl2 as the catalytic atom on the s-alkyl-complex A, the aminooxygena-
system in THF at 608C with conventional heating, or tion process can only arise from an intramolecular nu-
in DMF at 608C for 30 min under microwave activa- cleophilic attack by the oxygen atom of the urea on
tion], but no reaction was observed (Scheme 2). The the s-alkyl-complex Aꢀ (Figure 3). In both pathways,
CuCl2 would inhibit the common palladium b-hydride
elimination favouring the loss of the Pd species
through a transient palladium oxidation[15] or by for-
mation of a heterobimetallic s-Pd/Cu complex.[16] The
Table 3. Control experiments proving the role of chloro-
methyl derivatives as possible intermediates toward deriva-
tives 3.
Substrate
R
Ar
Conditions[a] 2 [%] 3 [%]
4f
4f
4h
4h
4j
Bn C6H5
Bn C6H5
Bn 4-NO2-C6H4
Bn 4-NO2-C6H4 C, D
Bn 4-MeO-C6H4
Bn 4-MeO-C6H4 C, D
E
C, D
E
–
–
–
–
–
–
92
–
97
–
89
–
E
4j
[a]
Conditions C: PdCl2ACHTNUGTRNEUNG(MeCN)2 (10 mol%), CuCl2
(3 mmol) and urea (1 mmol), THF, 608C, 24 h; conditions
D: PdCl2A(MeCN)2 (10 mol%), CuCl2 (3 mmol), and urea
CTHUNGTRENNUNG
(1 mmol), DMF, 608C, MW irradiation, 1 h; conditions
E: K2CO3 (3 mmol) and urea (1 mmol), DMF, 1508C,
MW irradiation, 15 min.
Scheme 2. Attempts to promote oxygenation and amination
reactions from the chloromethyl derivative 4a.
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Gianluigi Broggini et al.
UPDATES
Figure 3. Proposed mechanism for the Pd(II)/CuCl2-mediated aminooxygenation and diamination reactions.
aminooxygenation process generates the intermediate ment as intermediates in the aminooxygenation path-
B and the elimination of H+ furnishes the product 2. way.
The domino processes plausibly occur by a selective
trans-amino-palladation, as proven by studies con-
ducted on deuterated unfunctionalized aminoalkene- Experimental Section
s.[7a]
In the attempt to convert the chloro derivatives General Remarks
into the bicyclic products, the results observed
Reagents and solvents were used as received from commer-
matched the hypothesis proposed about the cycliza-
cial sources. Flash column chromatography was performed
tion of the analogous alkenyl carbamates,[2f] where
employing 230–400 mesh silica gel. Analytical thin layer
chloromethyl-substituted products were never detect-
ed, making plausible a direct attack of the oxygen
atom of the tert-butoxycarbonyl group on the palladi-
um intermediate.
chromatography was performed on silica gel 60 F254. Melt-
ing points were measured with a Bꢂchi B-540 apparatus and
are uncorrected. IR spectra were recorded on a 550 Nicolet
FT-IR spectrophotometer. Nuclear magnetic resonance
spectra were acquired on an AVANCE 400 Bruker spec-
1
trometer operating at 400 MHz for H NMR and 100 MHz
1
for 13C NMR. 13C spectra were H decoupled and multiplici-
Conclusions
ties were determined by the APT pulse sequence. Mass
spectra were determined on an HPLC-MS LCQ-Advantage
Thermo Finnigan instrument. Elemental analyses were exe-
cuted on a PerkinElmer CHN Analyzer Series II 2400.
Detailed procedures for the preparation of alkenylureas
and details on the X-ray diffraction measurement and analy-
sis are available as Supporting Information.
In conclusion, we have developed selective double in-
tramolecular aminooxygenation and diamination reac-
tions of alkenylureas to yield bicyclic products con-
taining a piperazinone ring. These Pd(II)-catalyzed
transformations under microwave irradiation provide
efficient and selective synthetic protocols for the con-
struction of 3-arylimino-oxazolo
ACHTUNGERTN[NUNG 3,4-a]pyrazin-6-one
General Procedure for the Aminooxygenation
Reactions
and 2-aryl-imidazo[1,5-a]pyrazin-3,6-dione derivatives
AHCTUNGTRENNUNG
in few steps from readily available precursors. The
aminooxygenation process can also be carried out in
satisfactory yield by conventional heating, even if the
reaction times are longer. From the mechanistic point
of view, the reactions performed on the chloromethyl-
A mixture of PdCl2ACHTNUTGRNEUNG(MeCN)2 (0.1 mmol), CuCl2 (3 mmol)
and urea 1 (1 mmol) in DMF (10 mL) was heated at 608C
for 30 min under microwave irradiation. Brine (15 mL) was
added and the mixture was extracted with CH2Cl2 (3ꢃ
15 mL). The organic phase was dried over Na2SO4 and the
piperazinones allowed us to exclude their involve- solvent removed under reduced pressure. The crude mixture
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Selective Intramolecular Palladium(II)-Catalyzed Aminooxygenation vs. Diamination of Alkenylureas
was purified by silica gel column chromatography (petrole-
um ether/AcOEt 3:7).
C18H22N4O4: C 60.32, H 6.19, N 15.63; found: C 60.09, H
6.41, N 15.70.
7-Cyclohexyl-3-(phenylimino)-1,7,8,8a-tetrahydro-3H-
7-Cyclohexyl-3-(4-methoxyphenylimino)-1,7,8,8a-tetrahy-
oxazolo
G
dro-3H-oxazoloACHTGUNTERNNU[G 3,4-a]pyrazine-6(5H)-one (2e): Yield: 78%;
solid; mp 1568C. IR: n=1757, 1585 cmÀ1
;
white solid; mp 1298C. IR: n=1749, 1589, 1260 cmÀ1
;
(400 MHz, CDCl3): d=1.25–1.82 [m, 10H, (CH2)5], 3.15 (dd,
1H, J=11.1, 9.8 Hz, NCHH), 3.28 (dd, 1H, J=11.1, 3.8 Hz,
NCHH), 3.82–3.87 (m, 1H, NCH), 3.88 (d, J=17.8 Hz, 1H,
CHH), 4.02 (dd, 1H, J=8.6, 4.4 Hz, OCHH), 4.43 (dd, 1H,
1H NMR (400 MHz, CDCl3): d=1.25–1.83 [m, 10H,
(CH2)5], 3.22 (dd, 1H, J=11.1, 9.3 Hz, NCHH), 3.34 (dd,
1H, J=11.1, 3.8 Hz, NCHH), 3.76 (s, 3H, OCH3), 3.89–3.93
(m, 1H, NCH), 3.91 (d, 1H, J=18.2 Hz, CHH), 4.06 (dd,
1H, J=8.6, 4.5 Hz, OCHH), 4.47 (dd, 1H, J=8.6, 7.3 Hz,
J=8.6, 7.4 Hz, OCHH), 4.46–4.52 [m, 1H, NCHACHTNUGTRNEG(UN CH2)5],
4.53 (d, 1H, J=17.8 Hz, CHH) 6.89–6.98 (m, 1H, ArH),
7.05 (d, 2H, J=7.6 Hz, ArH), 7.20–7.24 (m, 2H, ArH);
13C NMR (100 MHz, CDCl3): d=25.3 (t), 25.4 (t), 25.6 (t),
29.3 (t), 29.6 (t), 43.6 (t), 46.4 (t), 51.6 (d), 52.6 (d), 67.9 (t),
122.5 (d), 124.4 (d), 128.5 (d), 146.6 (s), 150.9 (s), 164.3 (s);
MS: m/z=313 (M+); anal. calcd. for C18H23N3O2: C 68.98, H
7.40, N 13.41; found: C 69.17, H 7.14, N 13.50.
OCHH), 4.49–4.51 (m, 1H, NCHACHTNGUTERNNU(G CH2)5), 4.54 (d, 1H, J=
18.2 Hz, CHH), 6.80 (d, 2H, J=8.9 Hz, ArH), 7.02 (d, 2H,
J=8.9 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=25.3 (t),
25.5 (t), 25.5 (t), 29.3 (t), 29.7 (t), 43.6 (t), 46.5 (t), 51.7 (d),
52.5 (d), 55.4 (q), 67.8 (t), 113.9 (d), 124.1 (d), 139.6 (s),
150.7 (s), 155.2 (s), 164.4 (s); MS: m/z=343 (M+); anal.
calcd. for C19H25N3O3: C 66.45, H 7.34, N 12.24; found: C
66.38, H 7.62, N 12.47.
7-Cyclohexyl-3-(4-chlorophenylimino),1,7,8,8a-tetrahydro-
3H-oxazolo
G
7-Benzyl-3-(phenylimino)-1,7,8,8a-tetrahydro-3H-oxazolo-
white solid; mp 1038C. IR: n=1755, 1588, 1089 cmÀ1
ACHTUNGTRENNUNG
1H NMR (400 MHz, CDCl3): d=1.33–1.84 [m, 10H,
(CH2)5], 3.23 (dd, 1H, J=11.1, 9.2 Hz, NCHH), 3.35 (dd,
1H, J=11.1, 3.8 Hz, NCHH), 3.95 (d, 1H, J=18.2 Hz,
CHH), 3.95–4.02 (m, 1H, NCH), 4.11 (dd, 1H, J=8.4,
;
3.26 (dd, 1H, J=10.9, 4.0 Hz, NCHH), 3.36 (dd, 1H, J=
10.9, 9.4 Hz, NCHH), 3.95–4.03 (m, 3H, OCHH, CHH,
NCH), 4.41–4.46 (m, 1H, OCHH), 4.46 (d, 1H, J=14.2 Hz,
CHHPh), 4.67 (d, 1H, J=18.3 Hz, CHH), 4.88 (d, 1H, J=
14.2 Hz, CHHPh), 7.00–7.07 (m, 2H, ArH) 7.50–7.23 (m,
8H, ArH); 13C NMR (100 MHz, CDCl3): d=46.1 (t), 48.4
(t), 50.4 (t), 51.3 (d), 67.7 (t), 122.7 (d), 124.0 (d), 128.0 (d),
128.2 (d),128.6 (d), 128.9 (d), 139.7 (s), 146.4(s), 150.7 (s),
165.1 (s); MS: m/z=321 (M+); anal. calcd. for C19H19N3O2:
C 71.01, H 5.96, N 13.08; found: C 70.83, H 6.25, N 13.21.
7-Benzyl-3-(4-chlorophenylimino)-1,7,8,8a-tetrahydro-3H-
4.3 Hz, OCHH), 4.51–5.56 (m, 3H, OCHH, NCHACHTNUGTRNEG(UN CH2)5,
CHH), 7.01 (d, 2H, J=8.6 Hz, ArH), 7.19 (d, 2H, J=
8.7 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=25.3 (t), 25.4
(t), 25.5 (t), 29.3 (t), 29.7 (t), 43.7 (t), 46.3 (t), 51.7 (d), 52.6
(d), 68.0 (t), 124.7 (d),128.7 (d), 145.0 (s), 147.2 (s), 151.1
(s), 164.2 (s); MS: m/z=347 (M+); anal. calcd. for
C18H22ClN3O2: C 62.15, H 6.37, N 12.08; found: C 61.91, H
6.61, N 12.31.
7-Cyclohexyl-3-(4-nitrophenylimino)-1,7,8,8a-tetrahydro-
oxazolo
ACHTUNGTRENNUNG
3H-oxazolo
[3,4-a]pyrazine-6(5H)-one (2c): Yield: 71%;
solid; mp 1078C. IR: n=1748, 1584, 1098 cmÀ1
;
yellow solid; mp 1188C. IR: n=1750, 1581, 1522, 1349 cmÀ1
;
(400 MHz, CDCl3): d=3.26 (dd, 1H, J=11.3, 3.8 Hz,
NCHH), 3.48 (dd, 1H, J=11.3, 9.1 Hz, NCHH), 4.00 (d,
1H, J=18.6 Hz, CHH), 4.01–4.02 (m, 2H, OCHH, NCH),
4.44–4.48 (m, 1H, OCHH), 4.47 (d, 1H, J=14.4 Hz,
CHHPh), 4.64 (d, 1H, J=18.2 Hz, CHH), 4.88 (d, 1H, J=
14.4 Hz, CHHPh), 7.00 (d, 2H, J=8.7 Hz, ArH), 7.19 (d,
2H, J=8.6 Hz, ArH) 7.27–7.32 (m, 6H, ArH); 13C NMR
(100 MHz, CDCl3): d=44.5 (t), 48.4 (t), 50.4 (t), 51.2 (d),
67.8 (t),118.5 (s),124.7 (d), 127.7 (d), 128.0 (d), 128.3
(d),128.5 (d), 128.9 (d), 135.8 (s), 144.9 (s), 150.9 (s), 164.9
(s); MS: m/z=335 (M+); anal. calcd. for C19H18ClN3O2: C
64.13, H 5.10, N 11.81; found: C 64.20, H 4.85, N 11.51.
7-Benzyl-3-(4-nitrophenylimino)-1,7,8,8a-tetrahydro-3H-
1H NMR (400 MHz, CDCl3): d=1.17–1.83 [m, 10H,
(CH2)5], 3.26 (dd, 1H, J=11.0, 9.2 Hz, NCHH), 3.43 (dd,
1H, J=11.0, 3.8 Hz, NCHH), 3.97 (d, 1H, J=18.3 Hz,
CHH), 3.98–4.11 (m, 1H, NCH), 4.20 (dd, 1H, J=8.6,
4.5 Hz, OCHH), 4.57 (d, 1H, J=18.3 Hz, CHH), 4.61–4.65
(m, 2H, OCHH, NCHACHTNUGTRNEUGN(CH2)5), 7.16 (d, 2H, J=9.0 Hz,
ArH), 8.11 (d, 2H, J=8.9 Hz, ArH); 13C NMR (100 MHz,
CDCl3): d=25.3 (t), 25.4 (t), 25.5 (t), 29.3 (t), 29.7 (t), 43.8
(t), 46.1 (t), 51.7 (d), 52.6 (d), 68.4 (t), 123.8 (d), 125.0 (d),
142.6 (s), 151.9 (s), 153.4 (s), 164.2 (s); MS: m/z=358 (M+);
anal. calcd. for C18H22N4O4: C 60.32, H 6.19, N 15.63; found:
C 60.39, H 6.32, N 15.49.
7-Cyclohexyl-3-(2-nitrophenylimino)-1,7,8,8a-tetrahydro-
oxazolo
ACHTUNGTREN[NGNU 3,4-a]pyrazine-6(5H)-one (2h): Yield: 72%; pale
3H-oxazolo
[3,4-a]pyrazine-6(5H)-one (2d): Yield: 77%;
yellow solid; mp 1248C. IR: n=1760, 1588, 1519, 1340 cmÀ1
;
yellow solid; mp 1268C. IR: n=1754, 1579, 1492, 1333 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=3.32 (dd, 1H, J=11.2,
4.0 Hz, NCHH), 3.39 (dd, 1H, J=11.2, 9.2 Hz, NCHH), 4.00
(d, 1H, J=18.4 Hz, CHH), 4.06–4.13 (m, 2H, OCHH,
NCH), 4.47 (d, 1H, J=14.6 Hz, CHHPh), 4.54 (dd, 1H, J=
8.4, 2.2 Hz, OCHH), 4.67 (d, 1H, J=18.4 Hz, CHH), 4.88
(d, 1H, J=14.6 Hz, CHHPh), 7.14–7.26 (m, 2H, ArH),
7.27–7.37 (m, 5H, ArH), 8.01–8.12 (m, 2H, ArH); 13C NMR
(100 MHz, CDCl3): d=45.9 (t), 48.5 (t), 50.5 (t), 51.2 (d),
68.3 (t), 123.8 (d), 124.6 (d), 128.1 (d), 128.3 (d),128.4 (d),
128.9 (d), 135.7 (s), 142.7 (s), 151.8 (s), 155.3 (s), 164.5 (s);
MS: m/z=366 (M+); anal. calcd. for C19H18N4O4: C 62.29, H
4.95, N 15.29; found: C 62.51, H 5.22, N 15.37.
1H NMR (400 MHz, CDCl3): d=1.18–1.84 [m, 10H,
(CH2)5], 3.35–3.38 (m, 2H, NCHH, NCHH), 3.98 (d, 1H,
J=18.2 Hz, CHH), 4.01–4.05 (m, 1H, NCH), 4.08 (dd, 1H,
J=8.6, 3.8 Hz, OCHH), 4.46 (dd, 1H, J=8.6, 7.2 Hz,
OCHH), 4.53–4.55 (m, 1H, NCHACTHNUTRGNEUNG(CH2)5), 4,56 (d, 1H, J=
18.2 Hz, CHH) 7.04–7.12 (m, 2H, ArH), 7.42–7.46 (m, 1H,
ArH), 7.87(dd, 1H, J=8.4, 1.4 Hz, ArH); 13C NMR
(100 MHz, CDCl3): d=25.3 (t), 25.4 (t), 25.5 (t), 29.3 (t),
29.7 (t), 43.9 (t), 46.3 (t), 52.4 (d), 52.6 (d), 67.8 (t), 122.4
(d),124.9 (d), 126.6 (d),133.3 (d), 142.4 (s), 142.8 (s), 152.5
(s), 163.8 (s); MS: m/z=358 (M+); anal. calcd. for
Adv. Synth. Catal. 2013, 355, 1640 – 1648
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1645

Gianluigi Broggini et al.
UPDATES
7-Benzyl-3-(2-nitrophenylimino)-1,7,8,8a-tetrahydro-3H-
3.2 Hz, NCHH), 3.54 (dd, 1H, J=9.4, 2.6 Hz, NCHH), 3.85
(d, 1H, J=18.6 Hz, CHH), 3.97–4.03 (m, 2H, NCHH,
NCH), 4.50 (d, 1H, J=18.6 Hz, CHH), 4.50–4.56 [m, 1H,
oxazoloACHTUNGTRENNUNG[3,4-a]pyrazine-6(5H)-one (2i): Yield: 74%; pale
yellow solid; mp 1328C. IR: n=1757, 1585, 1511, 1356 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=3.26 (dd, 1H, J=11.5,
4.0 Hz, NCHH), 3.48 (dd, 1H, J=11.5, 9.4 Hz, NCHH), 3.98
(dd, 1H, J=8.7, 3.8 Hz, OCHH), 4.06 (d, 1H, J=18.4 Hz,
CHH), 4.01–4.08 (m, 1H, NCH), 4.39 (dd, 1H, J=8.7,
7.1 Hz, OCHH), 4.43 (d, 1H, J=14.1 Hz, CHHPh), 4.66 (d,
1H, J=18.3 Hz, CHH), 4.96 (d, 1H, J=14.5 Hz, CHHPh),
7.07–7.12 (m, 2H, ArH), 7.27–7.45 (m, 6H, ArH), 7.87 (d,
1H, J=7.5 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=46.0
(t), 48.5 (t), 50.4 (t), 51.9 (d), 67.7 (t), 122.5 (d), 124.9 (d),
126.6 (d), 128.0 (d), 128.2 (d), 128.9 (d), 133.3 (d), 135.7 (s),
142.3 (s), 143.6 (s), 152.3 (s), 164.6 (s); MS: m/z=366 (M+);
anal. calcd. for C19H18N4O4: C 62.29, H 4.95, N 15.29; found:
C 62.16, H 5.09, N 15.51.
NCHACTHNUTGRNEGNU(CH2)5], 7.24 (d, 2H, J=8.4 Hz, ArH), 7.34 (d, 2H, J=
8.6 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=25.3 (t), 25.4
(t), 25.5 (t), 29.3 (t), 29.7 (t), 44.5 (t), 44.7 (t), 46.1 (t), 47.7
(d), 52.5 (d), 121.1 (d), 127.9 (s), 128.9 (d), 137.7 (s), 155.5
(s), 164.3 (s); MS: m/z=347 (M+); anal. calcd. for
C18H22ClN3O2: C 62.15, H 6.37, N 12.08; found: C 61.99, H
6.61, N 12.29.
7-Cyclohexyl-2-(4-nitrophenyl)-1,7,8,8a-tetrahydro-
imidazoACHTNUTRGENNUG[1,5-a]pyrazine-3,6HCATUNGTRENN(UGN 2H,5H)-dione (3c): Yield: 78%;
brown solid; mp 1628C. IR: n=1757, 1726, 1536, 1361 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.12–1.81 [m, 10H,
(CH2)5], 3.26 (dd, 1H, J=11.5, 9.6 Hz, NCHH), 3.44 (dd,
1H, J=11.5, 3.1 Hz, NCHH), 3.64 (dd, 1H, J=9.2, 2.6 Hz,
NCHH), 3.87 (d, 1H, J=18.3 Hz, CHH), 4.04–4.10 (m, 2H,
NCHH, NCH), 4.50 (d, 1H, J=18.3 Hz, CHH), 4.48–4.54
7-Benzyl-3-(4-methoxyphenylimino)-1,7,8,8a-tetrahydro-
3H-oxazolo
ACHTUNGTRENNUNG[3,4-a]pyrazine-6(5H)-one (2j): Yield: 77%;
white solid; mp 1368C. IR: n=1761, 1586, 1253 cmÀ1
;
[m, 1H, NCHACHTUNTRGNEUNG(CH2)5], 7.71 (d, 2H, J=9.0 Hz, ArH), 7.20 (d,
1H NMR (400 MHz, CDCl3): d=3.26 (dd, 1H, J=11.7,
3.6 Hz, NCHH), 3.36 (dd, 1H, J=11.1, 10.4 Hz, NCHH),
3.75–3.80 (m, 4H, OCHH, OCH3), 3.95–4.03 (m, 2H, CHH,
NCH), 4.26–4.46 (m, 1H, OCHH), 4.47 (d, 1H, J=14.7 Hz,
CHHPh), 4.67 (d, 1H, J=18.4 Hz, CHH), 4.87 (d, 1H, J=
14.6 Hz, CHHPh), 6.80 (d, 2H, J=8.8 Hz, ArH), 7.03 (d,
2H, J=8.7 Hz, ArH) 7.27–7.36 (m, 6H, ArH); 13C NMR
(100 MHz, CDCl3): d=46.2 (t), 48.4 (t), 50.3 (t), 51.2 (d),
55.4 (q), 67.7 (t), 113.9 (d), 122.7 (d), 127.9 (d), 128.5 (d),
129.4 (d), 135.6 (s), 139.5 (s), 150.5 (s), 155.3 (s), 165.2 (s);
MS: m/z=351 (M+); anal. calcd. for C20H21N3O3: C 68.36, H
6.02, N 11.96; found: C 68.07, H 6.12, N 12.11.
2H, J=9.0 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=25.3
( t), 25.4 (t), 25.5 (t), 29.3 (t), 29.7 (t), 44.6 (t), 44.8 (t), 46.0
(t), 47.5 (d), 52.6 (d), 116.2 (d),125.0 (d), 142.3 (s), 145.4 (s),
154.8 (s), 163.8 (s); MS: m/z=358 (M+); anal. calcd. for
C18H22N4O4: C 60.32, H 6.19, N 15.63; found: C 60.06, H
6.37, N 15.70.
7-Cyclohexyl-2-(2-nitrophenyl)-1,7,8,8a-tetrahydro-
imidazoACHTNUTRGENNUG[1,5-a]pyrazine-3,6HCATUNGTRENN(UGN 2H,5H)-dione (3d): Yield: 80%;
white solid; mp 1418C. IR: n=1751, 1729, 1513, 1356 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.11–1.80 [m, 10H,
(CH2)5], 3.37 (dd, 1H, J=12.1, 3.8 Hz, NCHH), 3.46–3.49
(m, 1H, NCHH), 3.63 (dd, 1H, J=9.1, 2.3 Hz, NCHH), 3.64
(dd, 1H, J=9.1, 2.6 Hz, NCHH), 3.83 (d, 1H, J=18.3 Hz,
CHH), 3.95–3.05 (m, 1H, NCH), 4.07–4.11 (m, 1H, NCHH),
4.43 (d, 1H, J=18.4 Hz, CHH), 4.48–4.59 [m, 1H, NCH-
General Procedure for the Diamination Reactions
AHCTUNGTREN(GNUN CH2)5], 7.34–7.39 (m, 2H, ArH), 7.61–7.66 (m, 1H, ArH),
A mixture of PdCl2ACHTUNRGTNEUNG(MeCN)2 (0.1 mmol), CuCl2 (3 mmol),
7.93 (dd, 1H, J=8.1, 1.4 Hz, ArH); 13C NMR (100 MHz,
CDCl3): d=25.3 (t), 25.4 (t), 25.6 (t), 29.3 (t), 29.7 (t), 43.9
(t), 44.9 (t), 48.2 (t), 48.9 (d), 52.6 (d), 125.7 (d),126.9 (d),
127.0 (d), 132.4 (s), 133.7 (d), 145.6 (s), 156.1 (s), 164.2 (s);
MS: m/z=358 (M+); anal. calcd. for C18H22N4O4: C 60.32, H
6.19, N 15.63; found: C 60.45, H 5.90, N 15.44.
K2CO3 (3 mmol), and urea 1 (1 mmol) in DMF (10 mL) was
heated at 1508C for 15 min under microwave irradiation.
Brine (15 mL) was added and the mixture was extracted
with CH2Cl2 (3ꢃ15 mL). The organic phase was dried over
Na2SO4 and the solvent removed under reduced pressure.
The crude mixture was purified by silica gel column chroma-
tography (petroleum ether/AcOEt 3:7).
7-Cyclohexyl-2-(4-methoxyphenyl)-1,7,8,8a-tetrahydro-
imidazoACHTNUTRGENNUG[1,5-a]pyrazine-3,6HCATUNGTRENN(UGN 2H,5H)-dione (3e): Yield: 79%;
7-Cyclohexyl-2-(phenyl)-1,7,8,8a-tetrahydroimidazo
a]pyrazine-3,6(2H,5H)-dione (3a): Yield: 78%; beige solid;
mp 1478C. IR: n=1753, 1722 cmÀ1 1H NMR (400 MHz,
ACHTUNGTNER[NUNG 1,5-
pale yellow solid; mp 1968C. IR: n=1755, 1728, 1253 cmÀ1
;
ACHTUNGTRENNUNG
1H NMR (400 MHz, CDCl3): d=1.09–1.80 [m, 10H,
(CH2)5], 3.24–3.30 (m, 1H, NCHH), 3.33 (dd, 1H, J=10.9,
4.0 Hz, NCHH), 3.52 (dd, 1H, J=10.9, 2.5 Hz, NCHH), 3.80
(s, 3H, OCH3), 3.83 (d, 1H, J=18.5 Hz, CHH), 3.90–4.02
(m, 2H, NCHH, NCH), 4.50 (d, 1H, J=18.5 Hz, CHH),
;
CDCl3): d=1.25–1.82 [m, 10H, (CH2)5], 3.23 (dd, 1H, J=
11.2, 9.4 Hz, NCHH), 3.34 (dd, 1H, J=11.2, 3.8 Hz,
NCHH), 3.55 (dd, 1H, J=9.1, 2.6 Hz, NCHH), 3.82 (d, J=
18.3 Hz, 1H, CHH), 3.91–3.98 (m, 1H, NCH), 4.01 (dd, 1H,
J=9.1, 7.6 Hz, NCHH), 4.49 (d, 1H, J=18.4 Hz, CHH),
4.51–4.56 [m, 1H, NCHACHTNUGTRNEUGN(CH2)5], 6.89 (d, 2H, J=9.1 Hz,
ArH), 7.43 (d, 2H, J=9.1 Hz, ArH); 13C NMR (100 MHz,
CDCl3): d=25.3 (t), 25.4 (t), 25.5 (t), 29.3 (t), 29.7 (t), 44.2
(t), 44.8 (t), 46.7 (t), 47.8 (d), 52.4 (d), 55.5 (q), 114.2
(d),119.6 (d), 133.0 (s), 155.7 (s), 156.2 (s), 164.6 (s); MS: m/
z=343 (M+); anal. calcd. for C19H25N3O3: C 66.45, H 7.34,
N 12.24; found: C 66.46, H 7.04, N 12.02.
4.50–4.56 [m, 1H, NCHACHTNUGTRNEGNU(CH2)5], 7.04–7.09(m, 1H, ArH),
7.27–7.35 (m, 2H, ArH), 7.53 (d, 2H, J=8.8 Hz, ArH);
13C NMR (100 MHz, CDCl3): d=25.3 (t), 25.4 (t), 25.5 (t),
29.3 (t), 29.6 (t), 44.3 (t), 44.7 (t), 46.2 (t), 47.3 (d), 52.4 (d),
117.43 (d), 123.1 (d), 128.9 (d), 139.7 (s), 155.8 (s), 164.5 (s);
MS: m/z=313 (M+); anal. calcd. for C18H23N3O2: C 68.98, H
7.40, N 13.41; found: C 69.27, H 7.17, N 13.60.
7-Benzyl-2-(phenyl)-1,7,8,8a-tetrahydroimidazo
azine-3,6(2H,5H)-dione (3f): Yield: 74%; white solid; mp
1588C. IR: n=1759, 1720 cmÀ1 1H NMR (400 MHz,
ACHTUNGTRENUN[NG 1,5-a]pyr-
AHCTUNGTRENNUNG
7-Cyclohexyl-2-(4-chlorophenyl)-1,7,8,8a-tetrahydro-
;
imidazoACHTUNGTRENNUNG[1,5-a]pyrazine-3,6CAHTUNGTRENN(UGN 2H,5H)-dione (3b): Yield: 73%;
beige solid; mp 1618C. IR: n=1750, 1724, 1085 cmÀ1
;
CDCl3): d=3.25 (dd, 1H, J=11.8, 3.8 Hz, NCHH), 3.35–
3.45 (m, 1H, NCHH), 3.47 (dd, 1H, J=8.6, 2.4 Hz, NCHH),
3.93 (d, J=18.5 Hz, 1H, CHH), 3.96–4.03 (m, 2H, NCHH,
1H NMR (400 MHz, CDCl3): d=1.26–1.83 [m, 10H,
(CH2)5], 3.19–3.25 (m, 1H, NCHH), 3.37 (d, 1H, J=9.4,
1646
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1640 – 1648

Selective Intramolecular Palladium(II)-Catalyzed Aminooxygenation vs. Diamination of Alkenylureas
NCH), 4.49 (d, J=14.6 Hz, 1H, CHHPh), 4.62 (d, 1H, J=
18.5 Hz, CHH), 4.82 (d, 1H, J=14.6 Hz, CHHPh), 7.07–7.09
(m, 1H, ArH), 7.26–7.36 (m, 7H, ArH), 7.51 (dd, 2H, J=
8.8, 1.1 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=44.5 (t),
46.0 (t), 47.3 (d), 49.3 (t), 50.4 (t), 117.5 (d), 123.1 (d), 123.1
(d), 128.0 (d), 128.2 (d), 128.5 (d), 128.6 (d), 128.9 (d), 129.0
(d), 135.8 (s), 139.6 (s), 155.8 (s), 165.3 (s); MS: m/z=321
(M+); anal. calcd. for C19H19N3O2: C 71.01m, H 5.96, N
13.08; found: C 70.88, H 6.19, N, 12.76.
13C NMR (100 MHz, CDCl3): d=44.6 (t), 46.6 (t), 47.5 (d),
49.2 (t), 50.4 (t), 55.5 (q), 114.2 (d), 119.6 (d), 127.9 (d),
128.3 (d), 129.9 (d), 132.9 (s), 138.7 (s), 155.8 (s), 147.1 (s),
165.4(s); MS: m/z=351 (M+); anal. calcd. for C20H21N3O3: C
68.36, H 6.02, N 11.96; found: C 68.11, H 5.76, N 12.25.
Acknowledgements
7-Benzyl-2-(4-chlorophenyl)-1,7,8,8a-tetrahydroimidazo-
A
ACHTUNGTRENNUNG(2H,5H)-dione (3g): Yield: 72%; pale
Thanks are due to the Ministero dell’Universitꢀ e della Ricer-
ca as well as to Insubria University, Milano University and
Catania University for financial support.
;
1H NMR (400 MHz, CDCl3): d=3.27 (dd, 1H, J=11.9,
4.1 Hz, NCHH), 3.34–3.40 (m, 1H, NCHH), 3.44 (dd, 1H,
J=8.9, 2.8 Hz, NCHH), 3.93 (d, J=18.5 Hz, 1H, CHH),
3.95–3.99 (m, 2H, NCHH, NCH), 4.49 (d, J=14.6 Hz, 1H,
CHHPh), 4.62 (d, 1H, J=18.5 Hz, CHH), 4.82 (d, 1H, J=
14.6 Hz, CHHPh), 7.25–7.36 (m, 7H, ArH), 7.46 (dd, 2H,
J=7.0, 2.0 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=44.5
(t), 46.0 (t), 47.3 (d), 49.3 (t), 50.4 (t), 118.5 (d), 128.0 (d),
128.3 (d), 128.8 (d), 128.9 (d), 133.8 (s), 135.8 (s), 138.2 (s),
155.5 (s), 165.1 (s); MS: m/z=335 (M+); anal. calcd. for
C19H18ClN3O2: C 64.13, H 5.10, N 11.81; found: C 64.08, H
4.82, N 12.09.
References
[1] a) D. M. Schultz, J. P. Wolfe, Synthesis 2012, 44, 351–
361; b) R. I. McDonald, G. Liu, S. S. Stahl, Chem. Rev.
2011, 111, 2981–3019; c) E. M. Beccalli, G. Broggini, M.
Martinelli, S. Sottocornola, Chem. Rev. 2007, 107,
5318–5365; d) S. R. Chemler, Org. Biomol. Chem. 2009,
7, 3009–3019; e) K. H. Jensen, M. S. Sigman, Org.
Biomol. Chem. 2008, 6, 4083–4088; f) V. Kotov, C. C.
Scarborough, S. S. Stahl, Inorg. Chem. 2007, 46, 1910–
1923.
7-Benzyl-2-(4-nitrophenyl)-1,7,8,8a-tetrahydroimidazo-
E
ACHTUNGTRENNUNG(2H,5H)-dione (3h): Yield: 76%; pale
;
[2] For aminooxygenation reactions, see: a) E. J. Alexani-
an, C. Lee, E. J. Sorensen, J. Am. Chem. Soc. 2005, 127,
7690–7691; b) G. Liu, S. S. Stahl, J. Am. Chem. Soc.
2006, 128, 7179–7181; c) L. V. Desai, M. S. Sanford,
Angew. Chem. 2007, 119, 5839–5842; Angew. Chem.
Int. Ed. 2007, 46, 5737–5740; d) P. Szolcsꢄnyi, T.
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1H NMR (400 MHz, CDCl3): d=3.27- 3.28 (m, 2H, NCHH),
3.56 (dd, 1H, J=11.8, 3.8 Hz, NCHH), 3.96 (d, J=18.5 Hz,
1H, CHH), 4.02–4.10 (m, 2H, NCHH, NCH), 4.53 (d, J=
14.5 Hz, 1H, CHHPh), 4.62 (d, 1H, J=18.5 Hz, CHH), 4.81
(d, 1H, J=14.5 Hz, CHHPh), 7.27–7.37 (m, 5H, ArH), 7.68
(d, 2H, J=9.3 Hz, ArH), 8.21 (d, 2H, J=9.4 Hz, ArH);
13C NMR (100 MHz, CDCl3): d=44.4 (t), 45.8 (t), 47.0 (d),
49.6 (t), 50.5 (t), 116.3 (d), 125.0 (d), 128.1 (d), 128.3 (d),
129.1 (d), 135.6 (s), 145.2 (s), 152.7 (s), 154.7 (s), 164.6 (s);
MS: m/z=366 (M+); anal. calcd. for C19H18N4O4: C 62.29, H
4.95, N 15.29; found: C 62.44, H 4.72, N 15.42.
7-Benzyl-2-(2-nitrophenyl)-1,7,8,8a-tetrahydroimidazo-
A
ACHTUNGTRENNUNG(2H,5H)-dione (3i): Yield: 78%; white
;
1H NMR (400 MHz, CDCl3): d=3.26 (dd, 1H, J=9.3,
3.6 Hz, NCHH), 3.53–3.63 (m, 2H, NCHH, NCHH), 3.93
(d, J=18.5 Hz, 1H, CHH), 4.00–4.10 (m, 2H, NCHH,
NCH), 4.41 (d, J=14.7 Hz, 1H, CHHPh), 4.56 (d, 1H, J=
18.5 Hz, CHH), 4.96 (d, 1H, J=14.7 Hz, CHHPh), 7.28–7.38
(m, 7H, ArH), 7.61–7.66 (m, 1H, ArH), 7.93 (dd, 1H, J=
8.1, 1.4 Hz, ArH); 13C NMR (100 MHz, CDCl3): d=44.7 (t),
48.0 (t), 48.5 (d), 48.8 (t), 50.3 (t), 122.5 (d), 126.9 (d), 127.0
(d), 127.9 (d), 128.2 (d), 128.9 (d), 132.4 (s), 133.3 (d), 133.6
(d), 135.9 (s), 145.6 (s), 156.0 (s), 164.9 (s); MS: m/z=366
(M+); anal. calcd. for C19H18N4O4: C 62.29, H 4.95, N 15.29;
found: C 62.07, H 5.12, N 15.22.
7-Benzyl-2-(4-methoxyphenyl)-1,7,8,8a-tetrahydroimidazo-
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A
ACHTUNGTRENNUNG
;
(400 MHz, CDCl3): d=3.24 (dd, 1H, J=11.8, 4.0 Hz,
NCHH), 3.37–3.44 (m, 2H, NCHH, NCHH), 3.79 (s, 3H,
OCH3), 3.91 (d, J=18.5 Hz, 1H, CHH), 3.92–3.98 (m, 2H,
NCHH, NCH), 4.50 (d, J=14.6 Hz, 1H, CHHPh), 4.61 (d,
1H, J=18.5 Hz, CHH), 4.82 (d, 1H, J=14.6 Hz, CHHPh),
6.88 (d, 1H, J=9.1 Hz, ArH), 7.28–7.41 (m, 7H, ArH);
Adv. Synth. Catal. 2013, 355, 1640 – 1648
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1647

Gianluigi Broggini et al.
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0.067 and 0.155 for 1914 observed reflections;=0.119
and 0.185 for 3213 reflections. Goodness of fit, highest
peak and deepest hole=1.038, 0.4 eꢇÀ3 and À0.2 eꢇÀ3.
CCDC 922353 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
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ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1640 – 1648