Chemo- and Regioselective Palladium(II)-Catalyzed Aminoarylation of N-Allylureas Providing 4-Arylmethyl Imidazolidinones

Article abstract of DOI:10.1055/s-0037-1611539

The aminoarylation reaction of N -allylureas under oxidative palladium catalysis, in the absence of ligands and by using inexpensive H ₂ O ₂ as the sole oxidant, occurs in a chemo- and regioselective fashion. This intramolecular process takes place via a 5- exo -trig cyclization, and represents an easy approach to 4-arylmethyl imidazolidinones.

Full text of DOI:10.1055/s-0037-1611539

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
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S. Giofrè et al.
Paper
Synthesis
Chemo- and Regioselective Palladium(II)-Catalyzed Aminoarylation
of N-Allylureas Providing 4-Arylmethyl Imidazolidinones
Sabrina Giofrèa
Egle M. Beccalli*a
Francesca Foschib
Concetta La Rosaa
Leonardo Lo Prestib
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Michael S. Christodouloua
a DISFARM, Sezione di Chimica Generale e Organica “A.
Marchesini”, Università degli Studi di Milano, via Venezian
21, 20133 Milano, Italy
egle.beccalli@unimi.it
b Dipartimento di Chimica, Università degli Studi di Milano,
via Golgi 19, 20133 Milano, Italy
Received: 08.03.2019
Accepted after revision: 16.04.2019
Published online: 14.05.2019
Based on literature data, aminoarylation reactions are of
great interest, as intra- or intermolecular processes, provid-
ing heterocyclic systems.7 In particular, 4-arylmethyl imid-
azolidinones have been prepared from N-allylureas and aryl
bromides. The reactions are performed under Pd(0) cataly-
sis in the presence of a ligand and a base in toluene at
110 °C under N2 (Scheme 1).
DOI: 10.1055/s-0037-1611539; Art ID: ss-2019-t0161-op
Abstract The aminoarylation reaction of N-allylureas under oxidative
palladium catalysis, in the absence of ligands and by using inexpensive
H2O2 as the sole oxidant, occurs in a chemo- and regioselective fashion.
This intramolecular process takes place via a 5-exo-trig cyclization, and
represents an easy approach to 4-arylmethyl imidazolidinones.
Previous work7p
Key words palladium catalysis, aminoarylation, hydrogen peroxide,
imidazolidinones, ureas, domino reaction
Pd2(dba)3 (1 mol%)
O
Xantphos (2 mol%)
t-BuONa (1.2 equiv)
ArBr (1.2 equiv)
O
R
R'
R
R'
N
N
N
N
H
toluene, 110 °C
N2
The synthesis of complex molecules through the forma-
tion of more than one bond in a single step represents a
powerful tool for organic chemists.1 Among the transition-
metal-catalyzed reactions, the double functionalization of
unsaturated systems under palladium catalysis represents a
rapid and economical method to obtain functionalized sub-
strates. In particular, when the domino process involved the
formation of an intramolecular C-N bond on alkenes,
alkynes or allenes combined to a new C-C, C-O or C-N bond
formation, the result was the synthesis of functionalized
(poly)heterocyclic systems.2 Synthetic strategies involving
the palladium catalyst under oxidative conditions3 repre-
sent a complementary reactivity to the Pd(0)-catalyzed re-
actions of aryl(alkyl) halides, offering the possibility of al-
ternative regioselectivity during bond formation. In this
context, the use of hydrogen peroxide as the sole oxidant is
quite rare.4
In continuation of our interest in the difunctionalization
reactions of alkenes, we have applied palladium-catalyzed
reactions in arylation/halogenation, arylation/esterifica-
tion, aminohalogenation and diamination processes.5 Re-
cently we focused our attention on oxyarylation studies
and reported the formation of oxazepanes through a selec-
tive 7-endo-cyclization process.6
Ar
Present work
PdCl2(MeCN)2 (10 mol%)
H2O2 (1.3 equiv)
ArSnBu3 (1.1 equiv)
O
O
R
R'
R
R'
N
N
N
N
H
THF, 25 °C
Ar
Scheme 1 Aminoarylation of secondary N-allylureas
In the present work, we were interested in extending
the arylation process combined with the formation of new
bonds, with the purpose of: (a) searching for new condi-
tions for the difunctionalization of alkenes and heterocy-
clization, (b) investigating in-depth the chemo- and regi-
oselectivity of the process, and (c) achieving mild reaction
conditions.
Toward this aim, we envisaged the reactivity of N-ally-
lureas as ambident nucleophiles, showing the possibility of
C–N vs C–O bond formation and allowing the construction
of cyclic ureas or isoureas.8 The presence of a second nucle-
ophile among the reagents paved the way for a difunction-
alization process (Scheme 2, eq. a). Moreover, these sub-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

B
S. Giofrè et al.
Paper
Synthesis
strates offered the possibility of regioselective 5-exo-trig/6-
endo-trig cyclization in the amination step, with the pres-
ence of an aryl nucleophile resulting in the aminoarylation
reaction involving the formation of C–N and C–C bonds
(Scheme 2, eq. b).
never observed in our experiments (see Table 1).4a,b,7q,10a,11
Moreover, palladium-catalyzed oxidative oxyarylation reac-
tions highlighted the preference for the endo-cyclization.6
To improve the yield of the reaction, and to exclude the
formation of the 4-chloromethy-limidazolidinone by-prod-
uct, we tested different reaction conditions by changing the
oxidant and the solvent (Table 1). The use of Cu(OAc)2 as the
oxidant was unfruitful (entry 2), as were a silver salt (entry
3) and 1,4-benzoquinone (BQ) (entry 4). Positive results
were obtained with inexpensive H2O2 as the sole oxidant
(entry 5). The palladium catalyst was essential for the out-
come of the reaction (entry 6), whereas solvents other than
THF did not result in formation of the desired product (en-
tries 7 and 8).
The use of different aryl nucleophiles such as aryl bo-
ronic acids, Grignard reagents and arylzinc bromide didn’t
provide any addition. To exploit the central role of the aryl-
stannane reagent, 4-benzyloxyphenyltributylstannane (2b)
was also tested with various N-allylureas (1b–h). Using the
optimized conditions (see Table 1, entry 5), the reactions
proceeded smoothly providing exclusive formation of the
4-substituted imidazolidinones 3, confirming the selective
5-exo cyclization (Table 2). Only in two cases (the reactions
O
R'
O
N
R'
Pd(II)
oxidant
R
N
N
R
R'
R
H
N
N
N
O
and/or
(eq. a)
Nu
Nu
Nu
ambident
nucleophilic ureas
cyclic ureas
O
cyclic isoureas
O
O
R'
N
R
R'
Ar
R
5-exo-trig
N
R
R'
6-endo-trig
N
N
H
N
N
(eq. b)
Ar
Scheme 2 Chemo- and regioselectivity of secondary N-allylureas
Substrate 1a, prepared in quantitative yield from the
simple one-step reaction between p-tolylisocyanate and
methylallylamine at room temperature in acetonitrile, was
selected for this study. Initially we tested the use of a cata-
lytic amount of PdCl2(MeCN)2 (10 mol%) in the presence of
a slight excess of both CuCl2 as oxidant and phenyltributyl-
stannane (2a) as nucleophile. The complete conversion of
the substrate afforded the aminoarylation product 3aa (39%
yield) along with 4-chloromethyl-imidazolidinone 4 (35%
yield), arising from an aminohalogenation process due to
the double action of the copper salt as an oxidant and a nu-
cleophile (Scheme 3).
Table 1 Optimization of the Reaction Conditions for the Aminoaryla-
tion of N-Allylurea 1aa
O
Me
p-tolyl
N
N
PdCl2(MeCN)2 (10 mol%)
CuCl2 (1.2 equiv)
PhSnBu3 (1.1 equiv)
Ph
O
3aa
(39%)
Me
p-tolyl
O
catalyst (10 mol%)
O
N
N
H
+
oxidant (1.3 equiv)
Me
p-Tol
THF, 25 °C, 24 h
Me
p-Tol
(2a) PhSnBu3 (1.1 equiv)
N
N
O
N
N
1a
H
solvent
Me
p-tolyl
Ph
N
N
25 °C, 24 h
1a
3aa
Cl
Scheme 3 Aminoarylation reaction of the substrate 1a with 2a
4
(35%)
Entry
Catalyst
Oxidant
Solvent
3aa (%)b
The observed cyclization was totally chemoselective
due to the addition of the nitrogen to the double bond, re-
sulting in formation of the cyclic urea. Moreover, the reac-
tion gave exclusive 5-exo-trig cyclization, showing total re-
gioselectivity with the formation of 4-substituted imidazo-
lidinones. The selective formation of the imidazolidinone
scaffold is a valuable goal because of the presence of this
heterocycle in numerous natural products9a and in a wide
range of pharmaceuticals including anti-inflammatory,9b
anti-infective,9c antibacterial9d and antitumor agents.9e–g
It is worth noting the exo-cyclization process. In fact,
when exo-cyclizations on protected aminoalkenes have
been reported,10 generally, palladium-catalyzed difunction-
alization of 4-pentenyl-amides under oxidative conditions
afforded hexatomic six-membered rings, a result which was
1
2
3
4
5
6
7
8
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
–
CuCl2
Cu(OAc)2
AgCO3
BQ
THF
THF
THF
THF
THF
THF
MeCN
DMF
39c
–
traces
traces
59
H2O2
d
H2O2
–
PdCl2(MeCN)2
PdCl2(MeCN)2
H2O2
traces
traces
H2O2
a Reaction conditions: 1a (0.25 mmol), catalyst (10 mol%), oxidant (1.3
equiv), arylating agent (1.1 equiv), solvent (5 mL).
b Yield of isolated product.
c Compound 4 was also isolated in 35% yield.
d Starting material was recovered.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

C
S. Giofrè et al.
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Synthesis
of substrates 1a and 1g with arylstannanes 2b and 2a, re-
spectively) were the corresponding products not isolated
from the reaction mixture.
On the basis of the previous results reported on the
aminoarylation of alkenes under Pd(II) catalysis,7e,i,r,s a plau-
sible mechanism is shown in Scheme 4. Arylpalladium(II)
species (a) was initially formed by transmetalation of the
arylstannane, followed by insertion of the double bond gen-
erating the -alkyl-Pd(II) intermediate (b). Reductive elimi-
nation of Pd(0) and oxidation to Pd(II) by H2O2 completed
the catalytic cycle.
Table 2 Aminoarylation of N-Allylureas 1a–h
PdCl2(MeCN)2 (10 mol%)
H2O2 (1.3 equiv)
O
O
R
R'
2 (1.1 equiv)
R
R'
N
N
N
N
H
THF, 25 °C, 24 h
O
Ar
3aa–hb
1a–h
R
R'
2a = PhSnBu3
2b = 4-BnOC6H4SnBu3
N
N
H
ArSnBu3
ArPdCl(MeCN)2
1
Substrate
R
R′
p-tolyl
ArSnBu3 Product
Yield (%)a
a
Pd(II)
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
Me
Me
Me
Me
Me
Me
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
3aa
3ab
3ba
3bb
3ca
3cb
3da
3db
3ea
3eb
3fa
73
–
O
H2O
p-tolyl
Ts
R
R'
N
N
59
48
66
51
62
71
58
50
38
56
–
H
PdArCl
Ts
H2O2
4-ClC6H4
4-ClC6H4
Ts
Pd(0)
R
O
N
O
R
N
N
cyclohexyl
R'
Cl–
N
R'
cyclohexyl
Ts
Pd Ar
2
cyclohexyl
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ts
Ar
b
cyclohexyl
Scheme 4 Proposed mechanism for the 5-exo-trig cyclization of sub-
strates 1
Ph
Ph
Ph
Ph
Ph
Ph
1f
3fb
1g
1g
1h
1h
3ga
3gb
3ha
3hb
The aminoarylation process was also applied to a non-
terminal alkene. N-2-Butenyl-N-phenyl-N′-tosyl-urea 5 af-
forded 4-(2-phenylethyl)-imidazolidinone 6 as the aminoa-
rylation product (Scheme 5). In this case the process was
improved by using the Pd complex in the presence of (S)-4-
tert-butyl-2-(2-pyridyl)oxazoline as the ligand. The struc-
ture of the obtained product was justified through the iso-
lation of 4-vinyl-imidazolidinone 7, which resulted from
the amination step only. The subsequent aryl insertion step
with reverse regiochemistry afforded the aminoarylation
product 6.
Ts
55
59
54
4-MeC6H4
4-MeC6H4
a Yield of isolated product.
The ring structure was unambiguously confirmed by
single-crystal X-ray diffraction analysis of the product 3ea
(Figure 1).12
O
O
Cl
N
N
Ph
Ts
N
N
H
PdCl2(MeCN)2 (10 mol%)
ligand (12 mol%)
O
6
Ph
3ea
Ph
Ts
H2O2 (1.3 equiv)
PhSnBu3 (1 equiv)
(49%)
N
N
H
+
THF, 25 °C, 24 h
O
5
Ph
Ts
N
N
Figure 1 Left: molecular structure of the S-enantiomer of compound
3ea, as determined by single-crystal X-ray diffraction. Right: ORTEP rep-
resentation showing the corresponding in-crystal molecular conforma-
tion of (S)-3ea at room temperature. Thermal ellipsoids are drawn at
the 25% probability level. C: gray; H: white; O: red; N: blue; Cl: green.
7
(11%)
Scheme 5 Aminoarylation reaction of substrate 5
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

D
S. Giofrè et al.
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Synthesis
We also applied the developed procedure for the amino-
arylation of N-homoallylic substituted urea 8 with phenyl-
tributylstannane under the same reaction conditions. The
corresponding product, 4-phenyl-1,3-diazepan-2-one 9,
was obtained in 57% yield via a 7-endo-trig cyclization pro-
cess (Scheme 6). This result supported a mechanism similar
to that suggested in Scheme 4.6 Initially, the double bond of
the substrate 8 underwent the arylation step (through the
insertion of PhPdCl arising from transmetalation) with the
formation of the -alkyl-Pd(II) intermediate. -Hydride
elimination and a subsequent amination step, with reverse
regiochemistry involving the benzylic position, provided
the 4-phenyl-1,3-diazepane 9.
N-Allyl-N-methyl-N′-tolyl-urea (1a)13
White solid; yield: 620 mg (76%); mp 110 °C (hexane/Et2O).
1H NMR (300 MHz, CDCl3):  = 7.35–7.19 (m, 2 H), 7.09 (d, J = 8.2 Hz, 2
H), 6.73 (br s, 1 H), 6.10–5.66 (m, 1 H), 5.43–5.15 (m, 2 H), 3.96 (d, J =
5.4 Hz, 2 H), 3.00 (s, 3 H), 2.29 (s, 3 H).
N-Allyl-N-methyl-N′-tosyl-urea (1b)14
Colorless oil; yield: 1040 mg (97%).
1H NMR (300 MHz, CDCl3):  = 7.93 (d, J = 8.3 Hz, 2 H), 7.38–7.27 (m, 3
H), 5.72 (ddt, J = 15.8, 10.5, 5.3 Hz, 1 H), 5.17 (dd, J = 20.5, 13.7 Hz, 2
H), 3.83 (d, J = 5.3 Hz, 2 H), 2.86 (s, 3 H), 2.43 (s, 3 H).
N-Allyl-N-methyl-N′-(4-chlorophenyl)urea (1c)13
White solid; yield: 842 mg (94%); mp 115 °C (hexane/Et2O).
1H NMR (400 MHz, CDCl3):  = 7.32 (d, J = 8.8 Hz, 2 H), 7.23 (d, J = 8.8
Hz, 2 H), 6.45 (br s, 1 H), 5.76–5.94 (m, 1 H), 5.25–5.30 (m, 2 H), 3.97
(d, J = 5.2 Hz, 2 H), 3.01 (s, 3 H).
O
O
PdCl2(MeCN)2 (10 mol%)
H2O2 (1.3 equiv)
PhSnBu3 (1 equiv)
Ph
p-Tol
Ph
p-Tol
N
N
H
N
N
Ph
THF, 25 °C, 24 h
8
9
N-Allyl-N-cyclohexyl-N′-tosyl-urea (1d)
(57%)
Yellow oil; yield: 1317 mg (98%).
Scheme 6 Aminoarylation reaction of substrate 8
IR: 1658 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.79 (d, J = 8.1 Hz, 2 H), 7.26 (d, J = 8.5
Hz, 2 H), 5.99–5.84 (m, 1 H), 5.35–5.18 (m, 2 H), 3.52 (d, J = 6.7 Hz, 2
H), 2.91–2.72 (m, 1 H), 2.40 (s, 3 H), 1.98–0.96 (m, 10 H).
13C NMR (101 MHz, CDCl3):  = 155.3 (s), 143.4 (s), 142.5 (s), 139.3 (s),
129.9 (d), 129.6 (d), 126.4 (d), 121.7 (t), 55.7 (d), 47.0 (t), 29.5 (t), 25.9
(t), 25.1 (t), 24.6 (t), 21.5 (q).
In summary, we have developed a process for the ami-
noarylation of N-allylureas in the presence of aryltributyl-
stannanes. The reactions are performed under ligand-free
Pd catalysis using H2O2 as the oxidant. The reaction is che-
mo- and regioselective, affording the corresponding imid-
azolidinones as the exclusive cyclic products.
MS: m/z = 337.26 [M + H]+.
N-Allyl-N-cyclohexyl-N′-(4-chlorophenyl)urea (1e)
White solid; yield: 1113 mg (95%); mp 122 °C (hexane/Et2O).
Thin-layer chromatographic separations were performed on precoat-
ed Merck silica gel 60-F254. Preparative separations were performed
by flash chromatography using Merck silica gel (0.035–0.070 mm).
Melting points were determined by the capillary method with a Büchi
B-540 apparatus and are uncorrected. IR spectra were measured with
a Jasco FT/IR 5300 spectrophotometer. For oil compounds were used
NaCl disks and for solid compounds KBr pellets. 1H NMR and 13C NMR
spectra were recorded with an AVANCE 400 Bruker spectrometer at
400 and 100 MHz, a Varian Oxford 300 MHz spectrometer at 300 and
75 MHz and an AVANCE 500 Bruker spectrometer at 500 and 125
MHz, respectively. Chemical shifts are given as  values in ppm rela-
tive to residual solvent peaks (CHCl3) as the internal reference. 13C
NMR spectra are 1H-decoupled and the determination of the multi-
plicities was achieved from the APT pulse sequence. Mass spectra
were recorded using electrospray ionization (ESI) technique on a LCQ
Advantage Thermo Finningan spectrometer. Elemental analyses were
executed on a Perkin-Elmer CHN Analyzer Series II 2400.
IR: 1663 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.31–7.23 (m, 2 H), 7.23–7.15 (m, 2 H),
6.52 (br s, 1 H), 5.90 (ddt, J = 17.3, 10.1, 5.0 Hz, 1 H), 5.54–5.14 (m, 2
H), 4.23 (tt, J = 11.5, 3.4 Hz, 1 H), 3.83 (dt, J = 4.8, 1.8 Hz, 2 H), 1.95–
0.90 (m, 10 H).
13C NMR (75 MHz, CDCl3):  = 155.4 (s), 138.1 (s), 136.2 (d), 128.7 (d),
127.5 (s), 120.6 (d), 117.2 (s), 54.2 (d), 45.1 (t), 31.0 (t), 25.8 (t), 25.5
(t).
MS: m/z = 293.75 [M + H]+.
Anal. Calcd for C16H21ClN2O: C, 65.63; H, 7.23; N, 9.57. Found: C,
65.55; H, 7.29; N, 9.69.
N-Allyl-N-phenyl-N′-(4-chlorophenyl)urea (1f)
White solid; yield: 1098 mg (96%); mp 75–76 °C (hexane/Et2O).
IR: 1670 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.62–7.07 (m, 9 H), 6.19 (br s, 1 H),
6.08–5.76 (m, 1 H), 5.29–5.05 (m, 2 H), 4.35 (d, J = 6.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 153.8 (s), 141.1 (s), 137.4 (s), 133.9 (d),
130.3 (d), 128.7 (d), 128.5 (d), 128.3 (d), 127.8 (s), 120.4 (d), 117.6 (t),
52.3 (t).
N-Protected Ureas 1, 5 and 8; General Procedure
To a solution of the appropriate amine (4 mmol) in MeCN (40 mL) was
added dropwise the isocyanate (4 mmol) at 0 °C under an inert atmo-
sphere. The reaction mixture was allowed to warm to room tempera-
ture and stirred for 24 h. The solvent was evaporated under reduced
pressure and the crude product was used without any further purifi-
cation.
MS: m/z = 287.54 [M + H]+.
Anal. Calcd for C16H15ClN2O: C, 67.02; H, 5.27; N, 9.77. Found: C,
66.96; H, 5.36; N, 9.81.
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Synthesis
N-Allyl-N-phenyl-N′-tosyl-urea (1g)
Aminoarylation of Ureas; General Procedure
Orange solid; yield: 1293 mg (98%); mp 74–76 °C (hexane/Et2O).
A mixture of urea 1, 5 or 8 (0.25 mmol), PdCl2(MeCN)2 (10 mol%),
H2O2 (0.33 mmol) and arylstannane 2a or 2b (0.25 mmol) in THF (0.2
M) was stirred at room temperature. In the case of substrate 5, the li-
gand (S)-4-tert-butyl-2-(2-pyridyl)oxazoline (12 mol%) was also add-
ed to the reaction mixture. After 24 h, the solvent was evaporated un-
der reduced pressure and H2O (10 mL) was added. The aqueous layer
was extracted with CH2Cl2 (3 × 10 mL) and the combined organic lay-
er dried was over Na2SO4 and concentrated under reduced pressure.
The crude residue was purified by silica gel column chromatography
to afford the corresponding imidazolidinones 3, 4, 6 and 7 or diaze-
pane 9.
IR: 1696 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 8.3 Hz, 2 H), 7.53–7.38 (m, 3
H), 7.38–7.26 (m, 2 H), 7.19 (d, J = 7.2 Hz, 2 H), 7.09 (br s, 1 H), 5.79
(ddt, J = 16.7, 10.2, 6.4 Hz, 1 H), 5.13–4.97 (m, 2 H), 4.18 (d, J = 6.3 Hz,
2 H), 2.46 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 150.1 (s), 144.6 (s), 139.3 (s), 136.1 (s),
132.4 (d), 130.6 (d), 129.5 (d), 129.1 (d), 128.4 (d), 128.3 (d), 118.7 (t),
52.4 (t), 21.7 (q).
MS (ESI): m/z = 353.67 [M + Na]+.
Anal. Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48. Found: C,
61.66; H, 5.67; N, 8.31.
4-Benzyl-1-methyl-3-(p-tolyl)imidazolidin-2-one (3aa)
Yellow oil; yield: 51 mg (73%); Rf = 0.37 (hexane/EtOAc, 3:1).
N-Allyl-N-phenyl-N′-tolyl-urea (1h)
IR: 1680 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.34 (d, J = 8.3 Hz, 2 H), 7.30–7.03 (m, 7
H), 4.40–4.29 (m, 1 H), 3.27 (t, J = 8.7 Hz, 1 H), 3.14–3.00 (m, 2 H), 2.72
(s, 3 H), 2.59 (dd, J = 13.6, 9.7 Hz, 1 H), 2.27 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 136.7 (s), 136.2 (s), 133.4 (s), 129.6 (d),
129.2 (d), 128.7 (d), 126.8 (d), 121.4 (d), 54.8 (d), 49.4 (t), 38.1 (t), 31.1
(q), 20.8 (q).
Pale-yellow solid; yield: 1000 mg (94%); mp 83–84 °C (hexane/Et2O).
IR: 1660 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.69–7.24 (m, 5 H), 7.24–7.16 (m, 2 H),
7.06 (d, J = 8.3 Hz, 2 H), 6.15 (br s, 1 H), 5.97 (ddt, J = 17.4, 9.8, 6.1 Hz,
1 H), 5.27–4.96 (m, 2 H), 4.37 (dt, J = 6.1, 1.2 Hz, 2 H), 2.29 (s, 3 H).
13C NMR (75 MHz, CDCl3):  = 154.1 (s), 141.5 (s), 136.2 (s), 134.2 (d),
132.5 (s), 130.2 (d), 129.3 (d), 128.5 (d), 128.0 (d), 119.4 (d), 117.4 (t),
52.3 (t), 20.7 (q).
MS: m/z = 281.51 [M + H]+.
Anal. Calcd for C18H20N2O: C, 77.11; H, 7.19; N, 9.99. Found: C, 77.22;
H, 7.12; N, 9.91.
MS: m/z = 267.27 [M + H]+, 289.29 [M + Na]+.
Anal. Calcd for C17H18N2O: C, 76.66; H, 6.81; N, 10.52. Found: C, 76.54;
H, 6.90; N, 10.57.
4-(Chloromethyl)-1-methyl-3-(p-tolyl)imidazolidin-2-one (4)
Yellow oil; yield: 54 mg (35%); Rf = 0.39 (hexane/EtOAc, 3:1).
(E)-N-But-2-en-1-yl-N-phenyl-N′-tosyl-urea (5)
IR: 1696 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.32 (d, J = 8.2 Hz, 2 H), 7.17 (d, J = 8.0
Hz, 2 H), 4.60–4.27 (m, 1 H), 3.70–3.59 (m, 2 H), 3.56–3.38 (m, 2 H),
2.90 (s, 3 H), 2.34 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 158.1 (s), 135.5 (s), 134.2 (s), 129.8 (d),
121.7 (d), 54.5 (d), 48.4 (t), 43.8 (t), 31.0 (q), 20.8 (q).
White solid; yield: 1087 mg (79%); mp 104–107 °C (dec.).
IR: 1690 cm–1
.
1H NMR (300 MHz, CDCl3):  = 8.01–7.85 (m, 2 H), 7.50–7.26 (m, 5 H),
7.19–7.11 (m, 2 H), 6.93 (br s, 1 H), 5.46–5.36 (m, 2 H), 4.12–4.01 (m,
2 H), 2.44 (s, 3 H), 1.58 (ddd, J = 4.0, 2.0, 1.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 149.9 (s), 144.5 (s), 139.4 (s), 136.2 (s),
130.4 (d), 130.2 (d), 129.4 (d), 129.0 (d), 128.4 (d), 128.3 (d), 125.1 (d),
51.7 (t), 21.6 (q), 17.6 (q).
MS: m/z = 239.34 [M + H]+.
Anal. Calcd for C12H15ClN2O: C, 60.38; H, 6.33; N, 11.74. Found: C,
60.49; H, 6.30; N, 11.68.
MS: m/z = 345.62 [M + H]+.
4-Benzyl-1-methyl-3-tosylimidazolidin-2-one (3ba)
Anal. Calcd for C18H20N2O3S: C, 62.77; H, 5.85; N, 8.13. Found: C,
62.86; H, 5.79; N, 8.04.
Yellow oil; yield: 52 mg (59%); Rf = 0.43 (hexane/EtOAc, 3:1).
IR: 1690 cm–1
.
1-(But-3-en-1-yl)-1-phenyl-3-(p-tolyl)urea (8)
1H NMR (400 MHz, CDCl3):  = 7.91 (d, J = 8.2 Hz, 2 H), 7.29–7.07 (m, 7
H), 4.54–4.34 (m, 1 H), 3.43 (dd, J = 13.0, 3.6 Hz, 1 H), 3.19 (t, J = 9.0
Hz, 1 H), 2.98 (dd, J = 9.2, 3.4 Hz, 1 H), 2.71 (dd, J = 13.2, 9.9 Hz, 1 H),
2.58 (s, 3 H), 2.35 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 153.9 (s), 144.6 (s), 136.6 (s), 135.7 (s),
129.6 (d), 129.5 (d), 128.8 (d), 128.2 (d), 127.2 (d), 115.2 (d), 54.9 (d),
48.7 (t), 40.8 (t), 30.5 (q), 21.7 (q).
Pale-yellow oil; yield: 1001 mg (89%).
IR: 1678 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.49 (t, J = 7.4 Hz, 2 H), 7.38 (dd, J =
15.1, 7.7 Hz, 1 H), 7.32 (d, J = 7.2 Hz, 2 H), 7.15 (d, J = 8.4 Hz, 2 H), 7.03
(d, J = 8.3 Hz, 2 H), 6.03 (s, 1 H), 5.80 (ddt, J = 17.0, 10.2, 6.8 Hz, 1 H),
5.06 (dd, J = 21.0, 5.3 Hz, 2 H), 3.92–3.73 (m, 2 H), 2.39–2.28 (m, 2 H),
2.26 (s, 3 H).
MS: m/z = 345.32 [M + H]+.
13C NMR (75 MHz, CDCl3):  = 154.2 (s), 141.4 (s), 136.3 (s), 135.4 (d),
132.4 (s), 130.3 (d), 129.2 (d), 128.8 (d), 128.1 (d), 119.4 (d), 116.6 (t),
48.7 (t), 32.9 (t), 20.7 (q).
Anal. Calcd for C18H20N2O3S: C, 62.77; H, 5.85; N, 8.13. Found: C,
62.83; H, 5.80; N, 8.17.
MS: m/z = 281.18 [M + H]+.
4-(4-Benzyloxyphenyl)methyl-1-methyl-3-tosylimidazolidin-2-
one (3bb)
Anal. Calcd for C18H20N2O: C, 77.11; H, 7.19; N, 9.99. Found: C, 77.33;
H, 7.12; N, 9.90.
Yellow oil; yield: 54 mg (48%); Rf = 0.39 (hexane/EtOAc, 3:1).
IR: 1696 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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S. Giofrè et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.89 (dd, J = 18.8, 8.3 Hz, 2 H), 7.43–
7.20 (m, 7 H), 7.04 (d, J = 8.4 Hz, 2 H), 6.85 (d, J = 8.4 Hz, 2 H), 4.97 (s, 2
H), 4.46–4.26 (m, 1 H), 3.34 (dd, J = 13.5, 3.3 Hz, 1 H), 3.19 (t, J = 9.0
Hz, 1 H), 2.97 (dd, J = 9.4, 3.2 Hz, 1 H), 2.66 (dd, J = 13.4, 9.7 Hz, 1 H),
2.57 (s, 3 H), 2.35 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 158.0 (s), 153.9 (s), 144.5 (s), 136.9 (s),
136.6 (s), 130.5 (d), 129.6 (d), 128.6 (d), 128.2 (d), 128.0 (d), 127.9 (s),
127.5 (d), 70.1 (t), 55.0 (d), 48.7 (t), 39.9 (t), 30.5 (q), 21.7 (q).
4-(4-Benzyloxyphenyl)methyl-1-cyclohexyl-3-tosylimidazolidin-
2-one (3db)
Yellow oil; yield: 92 mg (71%); Rf = 0.36 (hexane/EtOAc, 2:1).
IR: 1692 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.01 (d, J = 8.2 Hz, 2 H), 7.47–7.28 (m, 7
H), 7.11 (d, J = 8.4 Hz, 2 H), 6.94 (d, J = 8.4 Hz, 2 H), 5.06 (s, 2 H), 4.61–
4.44 (m, 1 H), 3.69–3.52 (m, 1 H), 3.46–3.23 (m, 2 H), 3.04 (dd, J = 9.2,
2.6 Hz, 1 H), 2.75 (dd, J = 13.5, 9.3 Hz, 1 H), 2.44 (s, 3 H), 1.92–0.87 (m,
10 H).
MS: m/z = 451.39 [M + H]+.
13C NMR (101 MHz, CDCl3):  = 158.0 (s), 152.9 (s), 144.4 (s), 137.0 (s),
136.8 (s), 130.6 (d), 129.5 (d), 128.6 (d), 128.3 (d), 128.1 (d), 128.0 (d),
127.9 (s), 127.4 (d), 115.2 (d), 70.1 (t), 55.1 (d), 51.4 (d), 42.2 (t), 39.5
(t), 30.1 (t), 29.7 (t), 25.3 (t), 25.2 (t), 21.7 (q).
Anal. Calcd for C25H26N2O4S: C, 66.65; H, 5.82; N, 6.22. Found: C,
66.51; H, 5.89; N, 6.20.
4-Benzyl-1-methyl-3-(4-chlorophenyl)imidazolidin-2-one (3ca)
MS: m/z = 519.67 [M + H]+.
White solid; yield: 50 mg (66%); mp 90 °C (hexane/Et2O); Rf = 0.41
(hexane/EtOAc, 3:1).
Anal. Calcd for C30H34N2O4S: C, 69.47; H, 6.61; N, 5.40. Found: C,
69.55; H, 6.69; N, 5.34.
IR: 1651 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.53 (d, J = 8.8 Hz, 2 H), 7.42–7.21 (m, 5
H), 7.16 (d, J = 7.2 Hz, 2 H), 4.45 (ddd, J = 12.9, 8.6, 4.1 Hz, 1 H), 3.40 (t,
J = 8.8 Hz, 1 H), 3.23 (dd, J = 8.9, 4.7 Hz, 1 H), 3.12 (dd, J = 13.8, 3.1 Hz,
1 H), 2.82 (s, 3 H), 2.72 (dd, J = 13.7, 9.4 Hz, 1 H).
4-Benzyl-1-cyclohexyl-3-(4-chlorophenyl)imidazolidin-2-one
(3ea)
White solid; yield: 54 mg (58%); mp 76 °C, Rf = 0.43 (hexane/EtOAc,
13C NMR (101 MHz, CDCl3):  = 137.5 (s), 136.2 (s), 131.3 (s), 129.2 (d),
129.0 (d), 128.8 (d), 128.5 (s), 127.0 (d), 121.7 (d), 54.3 (d), 49.1 (t),
37.9 (t), 31.0 (q).
3:1).
IR: 1698 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.55 (d, J = 8.7 Hz, 2 H), 7.42–7.23 (m, 5
H), 7.13 (d, J = 6.8 Hz, 2 H), 4.51–4.32 (m, 1 H), 3.81–3.62 (m, 1 H),
3.38 (t, J = 8.7 Hz, 1 H), 3.17 (dd, J = 8.8, 3.9 Hz, 1 H), 3.04 (dd, J = 14.0,
2.7 Hz, 1 H), 2.71 (dd, J = 13.8, 8.8 Hz, 1 H), 1.88–0.98 (m, 10 H).
MS: m/z = 301.79 [M + H]+.
Anal. Calcd for C17H17ClN2O: C, 67.88; H, 5.70; N, 9.31. Found: C,
67.97; H, 5.62; N, 9.36.
13C NMR (75 MHz, CDCl3):  = 156.7 (s), 137.7 (s), 136.2 (s), 129.2 (d),
129.0 (d), 128.7 (d), 128.0 (s), 126.9 (d), 121.3 (d), 54.3 (d), 51.2 (d),
42.1 (t), 37.6 (t), 30.2 (t), 29.9 (t), 25.5 (t), 25.5 (t).
4-(4-Benzyloxyphenyl)methyl-1-methyl-3-(4-chlorophenyl)imid-
azolidin-2-one (3cb)
MS: m/z = 369.45 [M + H]+.
Yellow oil; yield: 52 mg (51%); Rf = 0.38 (hexane/EtOAc, 3:1).
IR: 1646 cm–1
.
Anal. Calcd for C22H25ClN2O: C, 71.63; H, 6.83; N, 7.59. Found: C,
71.58; H, 6.80; N, 7.66.
1H NMR (400 MHz, CDCl3):  = 7.59–7.28 (m, 9 H), 7.03 (d, J = 8.3 Hz, 2
H), 6.91 (d, J = 8.3 Hz, 2 H), 5.04 (s, 2 H), 4.43–4.28 (m, 1 H), 3.37 (t, J =
8.7 Hz, 1 H), 3.18 (dd, J = 8.5, 4.4 Hz, 1 H), 3.00 (d, J = 13.9 Hz, 1 H),
2.78 (s, 3 H), 2.65 (dd, J = 13.7, 9.2 Hz, 1 H).
Single-Crystal X-ray Diffraction Analysis
The data collection was carried out on a Bruker AXS Smart APEX 3-
circle diffractometer with graphite-monochromated Mo K radiation
( = 0.71073 Å) at a nominal power of the source of 50 kV × 30 mA. A
100% complete full sphere of reflections was measured up to a resolu-
tion of sinθ/ = 0.45 Å–1 by means of 5  scans of the reciprocal lattice.
The Saint+15 and SADABS16 programs were employed to account for
systematic errors, including absorption and beam anisotropy correc-
tions. The compound crystallizes in a P21/c centric lattice [a =
11.1136(19) Å, b = 12.867(2) Å, c = 29.058(5) Å,  = 94.558(11)°] as a
1:1 racemate, with two molecules with inverse handedness per
asymmetric unit and a total of 8 molecules per cell. The molecular
structure was solved through the charge flipping method17 and least-
squares refined within the Independent Atom Model approximation
implemented in SHELX.18 A total of 23311 individual structure factor
amplitudes, corresponding to 3255 independent observations, en-
tered the fitting, giving a final agreement factor R1(F) of 0.1064 for
1758 Fo > 4(Fo) in conjunction with a goodness-of-fit of 1.040 and
largest Fourier residuals of +0.40/–0.31 e/Å3, both close to the chlo-
rine heavy atom. See the Supporting Information for more details.
13C NMR (101 MHz, CDCl3):  = 158.0 (s), 157.9 (s), 137.5 (s), 136.9 (s),
130.2 (d), 129.1 (d), 129.0 (d), 128.6 (d), 128.4 (s), 128.0 (d), 127.5 (d),
121.8 (d), 115.2 (d), 70.1 (t), 54.4 (d), 49.1 (t), 37.00 (t), 31.0 (q).
MS: m/z = 407.85 [M + H]+.
Anal. Calcd for C24H23ClN2O2: C, 70.84; H, 5.70; N, 6.88. Found: C,
70.95; H, 5.63; N, 6.79.
4-Benzyl-1-cyclohexyl-3-tosylimidazolidin-2-one (3da)
Yellow oil; yield: 64 mg (62%); Rf = 0.44 (hexane/EtOAc, 3:1).
IR: 1658 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 8.1 Hz, 2 H), 7.31–7.16 (m, 5
H), 7.10 (d, J = 7.2 Hz, 2 H), 4.54–4.37 (m, 1 H), 3.58–3.42 (m, 1 H),
3.31 (dd, J = 13.4, 3.4 Hz, 1 H), 3.17 (t, J = 9.0 Hz, 1 H), 2.95 (dd, J = 9.3,
2.6 Hz, 1 H), 2.70 (dd, J = 13.3, 9.4 Hz, 1 H), 2.35 (s, 3 H), 1.79–0.62 (m,
10 H).
13C NMR (101 MHz, CDCl3):  = 152.9 (s), 144.5 (s), 136.7 (s), 135.7 (s),
129.6 (d), 129.5 (d), 128.8 (d), 128.2 (d), 127.1 (d), 55.0 (d), 51.4 (d),
42.1 (t), 40.4 (t), 30.0 (t), 29.7 (t), 25.3 (t), 25.2 (t), 21.7 (q).
4-(4-Benzyloxyphenyl)methyl-1-cyclohexyl-3-(4-chlorophe-
nyl)imidazolidin-2-one (3eb)
MS: m/z = 413.26 [M + H]+.
Pale-yellow oil; yield: 59 mg (50%); Rf = 0.32 (hexane/EtOAc, 3:1).
Anal. Calcd for C23H28N2O3S: C, 66.96; H, 6.84; N, 6.79. Found: C,
66.89; H, 6.92; N, 6.69.
IR: 1698 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

G
S. Giofrè et al.
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Synthesis
1H NMR (300 MHz, CDCl3):  = 7.60–7.51 (m, 2 H), 7.49–7.30 (m, 7 H),
7.10–7.00 (m, 2 H), 6.98–6.89 (m, 2 H), 5.07 (s, 2 H), 4.40 (ddd, J =
12.5, 8.6, 3.9 Hz, 1 H), 3.74 (tt, J = 12.1, 3.9 Hz, 1 H), 3.39 (t, J = 8.8 Hz,
1 H), 3.17 (dd, J = 8.9, 4.3 Hz, 1 H), 2.98 (dd, J = 13.9, 3.3 Hz, 1 H), 2.68
(dd, J = 13.9, 8.7 Hz, 1 H), 1.93–0.95 (m, 10 H).
13C NMR (75 MHz, CDCl3):  = 157.9 (s), 156.7 (s), 137.8 (s), 137.0 (s),
130.3 (d), 129.0 (d), 128.6 (d), 128.5 (s), 128.0 (d), 127.4 (d), 121.3 (d),
115.1 (d), 70.1 (t), 54.4 (d), 51.2 (d), 42.1 (t), 36.8 (t), 30.3 (t), 29.9 (t),
25.5 (t), 25.5 (t).
MS: m/z = 513.43 [M + H]+.
Anal. Calcd for C30H28N2O4S: C, 70.29; H, 5.51; N, 5.46. Found: C,
70.38; H, 5.43; N, 5.43.
4-Benzyl-1-phenyl-3-(p-tolyl)imidazolidin-2-one (3ha)
Colorless oil; yield: 50 mg (59%); Rf = 0.38 (hexane/EtOAc, 4:1).
IR: 2921, 1705, 1404, 1292 cm–1
1H NMR (300 MHz, CDCl3):  = 7.55–7.44 (m, 4 H), 7.37–7.13 (m, 9 H),
7.10–7.01 (m, 1 H), 4.64–4.51 (m, 1 H), 3.85 (t, J = 9.0 Hz, 1 H), 3.65
(dd, J = 9.2, 5.3 Hz, 1 H), 3.20 (dd, J = 13.7, 3.3 Hz, 1 H), 2.74 (dd, J =
13.7, 9.6 Hz, 1 H), 2.36 (d, J = 8.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 155.3 (s), 140.1 (s), 136.1 (s), 135.5 (s),
134.3 (s), 129.7 (d), 129.4 (d), 129.2 (d), 128.8 (d), 128.8 (d), 127.0 (d),
122.8 (d), 122.3 (d), 118.0 (d), 54.3 (d), 47.1 (t), 38.5 (t), 20.9 (q).
.
MS: m/z = 475.56 [M + H]+, 498.03 [M + Na]+.
Anal. Calcd for C29H31ClN2O2: C, 73.33; H, 6.58; N, 5.90. Found: C,
73.46; H, 6.50; N, 5.84.
4-benzyl-3-(4-chlorophenyl)-1-phenylimidazolidin-2-one (3fa)
Colorless oil; yield: 34 mg (38%); Rf = 0.31 (hexane/EtOAc, 4:1).
MS: m/z = 343.60 [M + H]+.
IR: 1690 cm–1
.
Anal. Calcd for C23H22N2O: C, 80.67; H, 6.48; N, 8.18. Found: C, 80.75;
H, 6.54; N, 8.11.
1H NMR (300 MHz, CDCl3):  = 7.61–7.53 (m, 2 H), 7.51–7.44 (m, 2 H),
7.43–7.13 (m, 8 H), 7.11–7.02 (m, 2 H), 4.67–4.51 (m, 1 H), 3.90 (t, J =
9.0 Hz, 1 H), 3.67 (dd, J = 9.3, 4.8 Hz, 1 H), 3.18 (dd, J = 13.8, 3.4 Hz, 1
H), 2.77 (dd, J = 13.8, 9.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3):  = 154.8 (s), 139.7 (s), 136.8 (s), 135.7 (s),
129.4 (s), 129.1 (d), 128.9 (d), 128.8 (d), 127.2 (d), 123.2 (d), 122.7 (d),
118.2 (d), 53.9 (d), 47.0 (t), 38.3 (t).
4-(4-Benzyloxyphenyl)methyl-1-phenyl-3-(p-tolyl)imidazolidin-
2-one (3hb)
Colorless oil; yield: 61 mg (54%); Rf = 0.40 (hexane/EtOAc, 4:1).
IR: 1690 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.57–7.19 (m, 13 H), 7.12–7.04 (m, 3
H), 6.97–6.88 (m, 2 H), 5.04 (s, 2 H), 4.59–4.45 (m, 1 H), 3.86 (t, J = 8.9
Hz, 1 H), 3.64 (dd, J = 9.2, 5.3 Hz, 1 H), 3.12 (dd, J = 13.8, 3.3 Hz, 1 H),
2.69 (dd, J = 13.8, 9.5 Hz, 1 H), 2.37 (s, 3 H).
MS: m/z = 363.17 [M + H]+.
Anal. Calcd for C22H19ClN2O: C, 72.82; H, 5.28; N, 7.72. Found: C,
72.76; H, 5.25; N, 7.79.
13C NMR (75 MHz, CDCl3):  = 157.9 (s), 155.3 (s), 140.1 (s), 136.9 (s),
135.5 (s), 134.2 (s), 130.2 (d), 129.7 (d), 128.7 (d), 128.6 (d), 128.3 (s),
128.0 (d), 127.4 (d), 122.7 (d), 122.2 (d), 118.0 (d), 115.2 (d), 70.1 (t),
54.3 (d), 47.1 (t), 37.5 (t), 20.9 (q).
4-(4-Benzyloxyphenyl)methyl-1-phenyl-3-(4-chlorophenyl)imid-
azolidin-2-one (3fb)
Yellow oil; yield: 66 mg (56%); Rf = 0.34 (hexane/EtOAc, 4:1).
IR: 1688 cm–1
.
MS: m/z = 449.48 [M + H]+, 471.52 [M + Na]+.
1H NMR (300 MHz, CDCl3):  = 7.62–7.28 (m, 13 H), 7.15–7.03 (m, 3
H), 6.97–6.84 (m, 2 H), 5.04 (s, 2 H), 4.62–4.46 (m, 1 H), 3.90 (t, J = 9.0
Hz, 1 H), 3.66 (dd, J = 9.2, 4.9 Hz, 1 H), 3.10 (dd, J = 13.9, 3.4 Hz, 1 H),
2.73 (dd, J = 13.9, 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3):  = 158.0 (s), 154.9 (s), 139.7 (s), 136.9 (s),
130.2 (d), 129.4 (s), 129.1 (d), 128.8 (d), 128.6 (d), 128.0 (d), 127.9 (s),
127.4 (d), 123.1 (d), 122.6 (d), 118.2 (d), 115.3 (d), 70.1 (t), 53.9 (d),
47.0 (t), 37.4 (t).
Anal. Calcd for C30H28N2O2: C, 80.33; H, 6.29; N, 6.25. Found: C, 80.26;
H, 6.28; N, 6.28.
4-Phenethyl-1-phenyl-3-tosylimidazolidin-2-one (6)
Colorless oil; yield: 52 mg (49%); Rf = 0.29 (hexane/EtOAc, 4:1).
IR: 1695 cm–1
.
1H NMR (300 MHz, CDCl3):  = 8.00 (d, J = 8.3 Hz, 2 H), 7.50–7.08 (m,
12 H), 4.57–4.46 (m, 1 H), 4.03 (t, J = 9.1 Hz, 1 H), 3.56 (dd, J = 9.2, 3.4
Hz, 1 H), 2.77–2.64 (m, 2 H), 2.50–2.37 (m, 4 H), 2.28–2.15 (m, 1 H).
13C NMR (75 MHz, CDCl3):  = 144.8 (s), 140.0 (s), 138.3 (s), 136.1 (s),
129.6 (d), 129.0 (d), 128.6 (d), 128.3 (d), 128.3 (d), 126.4 (d), 124.4 (d),
119.5 (s), 118.7 (d), 53.1 (d), 48.1 (t), 36.3 (t), 30.3 (t), 21.7 (q).
MS: m/z = 469.57 [M + H]+.
Anal. Calcd for C29H25ClN2O2: C, 74.27; H, 5.37; N, 5.97. Found: C,
74.36; H, 5.31; N, 5.94.
4-(4-Benzyloxyphenyl)methyl-1-phenyl-3-tosylimidazolidin-2-
one (3gb)
MS: m/z = 420.90 [M + H]+.
Anal. Calcd for C24H24N2O3S: C, 68.55; H, 5.75; N, 6.66. Found: C,
68.63; H, 5.71; N, 6.60.
Yellow oil; yield: 71 mg (55%); Rf = 0.36 (hexane/EtOAc, 3:1).
IR: 1695 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.96 (d, J = 8.2 Hz, 2 H), 7.41–7.15 (m,
11 H), 7.08 (d, J = 8.4 Hz, 2 H), 7.00 (t, J = 7.1 Hz, 1 H), 6.86 (d, J = 8.5
Hz, 2 H), 4.97 (s, 2 H), 4.65–4.41 (m, 1 H), 3.72 (t, J = 9.1 Hz, 1 H),
3.50–3.37 (m, 2 H), 2.76 (dd, J = 13.4, 9.8 Hz, 1 H), 2.36 (s, 3 H).
4-Vinyl-1-phenyl-3-tosylimidazolidin-2-one (7)
Colorless oil; yield: 10 mg (11%); Rf = 0.19 (hexane/EtOAc, 4:1).
IR: 1689 cm–1
.
13C NMR (101 MHz, CDCl3):  = 158.1 (s), 151.4 (s), 144.9 (s), 138.4 (s),
136.9 (s), 136.3 (s), 130.6 (d), 129.6 (d), 128.9 (d), 128.6 (d), 128.4 (d),
128.0 (d), 127.7 (s), 127.5 (d), 124.3 (d), 118.8 (d), 115.3 (d), 70.1 (t),
54.5 (d), 47.2 (t), 40.0 (t), 21.7 (q).
1H NMR (500 MHz, CDCl3):  = 8.02–7.97 (m, 2 H), 7.48–7.43 (m, 2 H),
7.38–7.31 (m, 4 H), 7.14 (d, J = 7.4 Hz, 1 H), 5.95 (ddd, J = 17.0, 10.1,
8.0 Hz, 1 H), 5.53 (dd, J = 17.0 Hz, 1 H), 5.38 (d, J = 10.2 Hz, 1 H), 4.94
(td, J = 8.8, 3.4 Hz, 1 H), 4.15 (t, J = 9.1 Hz, 1 H), 3.58 (dd, J = 9.3, 3.4 Hz,
1 H), 2.45 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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13C NMR (126 MHz, CDCl3):  = 151.3 (s), 144.7 (s), 138.4 (s), 136.2 (s),
135.2 (d), 129.5 (d), 129.0 (d), 128.6 (d), 124.4 (d), 119.4 (t), 118.7 (d),
55.8 (d), 49.2 (t), 21.7 (q).
Almendros, P.; Rodriguez-Acebes, R. J. Org. Chem. 2006, 71,
2346. (k) Beccalli, E. M.; Bernasconi, A.; Borsini, E.; Broggini, G.;
Rigamonti, M.; Zecchi, G. J. Org. Chem. 2010, 75, 6923.
(3) (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318. (b) Chen, X.; Engle, K. M.; Wang, D.-
H.; Yu, J.-Q. Angew. Chem. Int. Ed. 2009, 48, 5094. (c) Beccalli, E.
M.; Broggini, G.; Gazzola, S.; Mazza, A. Org. Biomol. Chem. 2014,
12, 6767.
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Chen, P.; Liu, G. Org. Lett. 2015, 17, 1485. (c) Zhu, H.; Chen, P.;
Liu, G. J. Am. Chem. Soc. 2014, 136, 1766. (d) Yin, G.; Liu, G.
Angew. Chem. Int. Ed. 2008, 47, 5442.
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Fasana, A.; Galli, S.; Gazzola, S. Adv. Synth. Catal. 2013, 355,
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MS: m/z = 365.22 [M + Na]+.
1,4-Diphenyl-3-(p-tolyl)-1,3-diazepan-2-one (9)
Colorless oil; yield: 51 mg (57%); Rf = 0.37 (hexane/EtOAc, 3:1).
IR: 1694 cm–1
.
1H NMR (300 MHz, CDCl3):  = 7.62–7.11 (m, 12 H), 7.05 (d, J = 8.4 Hz,
2 H), 4.93 (dd, J = 8.1, 6.2 Hz, 1 H), 3.82 (td, J = 7.3, 2.0 Hz, 2 H), 2.28 (s,
3 H), 2.24–2.02 (m, 2 H), 1.90–1.49 (m, 2 H).
13C NMR (75 MHz, CDCl3):  = 154.4 (s), 141.7 (s), 141.1 (s), 136.2 (s),
132.5 (s), 130.4 (d), 129.3 (d), 128.7 (d), 128.6 (d), 128.3 (d), 128.2 (d),
126.9 (d), 119.5 (d), 63.4 (d), 48.3 (t), 37.1 (t), 26.0 (t), 20.7 (q).
MS: m/z = 379.81 [M + Na]+.
Anal. Calcd C24H24N2O: C, 80.86; H, 6.79; N, 7.86. Found: C, 81.07; H,
6.70; N, 7.79.
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Funding Information
Università degli Studi di Milano is acknowledged for financial sup-
port. Support from European Cooperation in Science and Technology
through CMST COST Action [CA15106 - C–H Activation in Organic
Synthesis (CHAOS)] is also gratefully acknowledged.
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Supporting information for this article is available online at
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I