Sequential Ugi four-component reaction (4-CR)/C-H activation using (diacetoxyiodo)benzene for the synthesis of 3-(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones

Article abstract of DOI:10.1002/hlca.201400056

A sequential Ugi four-component reaction (4-CR)/C-H activation using (diacetoxyiodo)benzene is reported. This process is a five-component reaction of aromatic aldehydes, aniline derivatives, isocyanides, phenylpropiolic acid (3-phenylprop-2-ynoic acid), a

Full text of DOI:10.1002/hlca.201400056

Helvetica Chimica Acta – Vol. 97 (2014)
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Sequential Ugi Four-Component Reaction (4-CR)/CꢀH Activation Using
(Diacetoxyiodo)benzene for the Synthesis of 3-(Diphenylmethylidene)-2,3-
dihydro-1H-indol-2-ones
by Elmira Ghabraiea) and Saeed Balalaie*a)b)
a) Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416
Tehran, Iran (fax: þ 98-21-22853650; e-mail: balalaie@kntu.ac.ir)
b) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Dedicated to Prof. Thomas J. J. Mꢀller on the occasion of his 50th birthday
A sequential Ugi four-component reaction (4-CR)/CꢀH activation using (diacetoxyiodo)benzene is
reported. This process is a five-component reaction of aromatic aldehydes, aniline derivatives,
isocyanides, phenylpropiolic acid (3-phenylprop-2-ynoic acid), and (diacetoxyiodo)benzene for the
synthesis of 3-(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones. This procedure offers several
advantages such as good yields, high bond-forming efficiency, selectivity, and short reaction times.
Introduction. – Transition metal-catalyzed cross-coupling has revolutionized the
way chemists form CꢀC bonds. It has a high potential for the construction of
biologically active compounds, polycyclic compounds, and complex molecules [1]. The
most recently reported reactions based on metal-catalyzed cross-coupling were
performed in the presence of Pd catalysts [2]. Palladium-catalyzed cross-coupling of
aryl halides with organometallic reagents is now recognized to be one of the most useful
methods for the construction of CꢀC bond. Most of the reactions using Pd catalysts
need the functionalized substrate, and such starting materials require additional steps
to prepare. In this way, the use of CꢀH bonds in the cross-coupling and its activation has
more advantages, including efficiency of reactions and reducing the synthesis steps [3 –
6]. Most of the CꢀH activation reactions involve an oxidative reagent. During the
recent years, hypervalent iodine compounds have been widely used as mild, environ-
mentally benign, and inexpensive reagents in organic synthesis [7]. These types of
reagents have been used not only in oxidative reaction [8 – 12], but also in CꢀC [13 – 15]
and carbonꢀheteroatom [16][17] bond formation, and rearrangement reactions
[18][19]. The most common hypervalent iodine compound is (diacetoxyiodo)benzene
(PhI(OAc)2; DIB) [20]. The excellent oxidation characteristic of DIB is related to
transformation of IIII to II [21]. As a result of the transmutation of IIII to II, ArI is
obtained as a product. The transition metal catalyst, especially Pd, can cause these
reagents to work efficiently in oxidation reactions [22] such as activation and
functionalization of CꢀH bonds [23][24]. The most important step in this trans-
formation is the oxidation of PdII to PdIV species, which was isolated, and its structure
was established by X-ray crystallography [25].
According to the importance of CꢀH activation reaction and on the other hand the
biological activities of 2-oxindole (¼2,3-dihydro-1H-indol-2-one) compounds [26], we
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

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had used a sequential Ugi four-component reaction (4-CR)/CꢀH activation using Pd
catalyst in the presence of PhI as source of Ph groups for the synthesis of 3-
(diphenyl)methylidene)-2,3-dihydro-1H-indol-2-ones [27]. However, the desired 3-
(phenylmethylidene)-2,3-dihydro-1H-indol-2-ones as products were formed by use of
benzaldehydes bearing electron-donating groups (EDGs) and with benzaldehydes
which contained electron-withdrawing groups (EWGs; Scheme 1).
Searching for novel reaction condition to construct the 3-(diphenylmethylidene)-
2,3-dihydro-1H-indol-2-ones is an interesting subject in this area. Herein, we report the
use of DIB in a sequential Ugi 4-CR/CꢀH activation for the aimed synthesis of 3-
(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones without 3-(phenylmethylidene)-
2,3-dihydro-1H-indol-2-ones as by-products (Scheme 2).
Scheme 1. Synthesis of 3-(Diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones and 3-(Phenylmethyl-
idene)-2,3-dihydro-1H-indol-2-ones through CꢀH Activation According to [27]
Scheme 2. Using of DIB in Sequential Ugi 4-CR/CꢀH Activation for the Synthesis of 3-(Diphenyl-
methylidene)-2,3-dihydro-1H-indol-2-ones 6a – 6p
Results and Discussion. – In our initial study, the four-component reaction (4-CR) of
benzaldehyde (Ar¼ Ph; 1), aniline (2), phenylpropiolic acid (3), and tert-butyl iso-
cyanide (4) was selected as model reaction. After formation of the desired N-substituted
alk-2-yneamide 5 as an intermediate, the cyclization was performed under different
reaction conditions using catalytic amounts of Pd(OAc)2 (5%) and DIB (Scheme 3).

Helvetica Chimica Acta – Vol. 97 (2014)
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Scheme 3. The Model Reaction for the Synthesis of 6a Using Sequential Ugi 4-CR/CꢀH Activation
The effects of Pd catalyst, base, and solvent on the cyclization reaction is compiled
in Table 1. The reaction could not be realized using CsCO3 and K2CO3 as base. Then, we
checked the reaction using amines such as morpholine, Et3N, EtN(iPr)2, and DBU in
different solvents such as MeOH, DMSO, CH2Cl2, and toluene. The best result was
obtained with Pd(OAc)2 (5 mol-%), DIB (2 equiv.), EtN(iPr)2 (2 equiv.) in toluene
under reflux. Encouraged by these results, we tried to optimize the type of catalyst
(Entries 11 and 12). The suitable Pd catalyst turned out to be Pd(OAc)2.
Having established the optimum reaction conditions and in order to extend the
chemical library, we proceeded to screen various benzaldehyde derivatives with EWGs
and EDGs, aniline derivatives, two isocyanides, and by using of DIB to construct 3-
(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones 6a – 6p. In all cases, the reactions
were complete within 5 h. The results are collected in Table 2.
Table 1. Optimization of the Reaction Conditions for the Synthesis of Compound 6a (see Scheme 3)
Entry
Base
Catalyst (5 mol-%)
Solvent
Yield [%]a)
1
2
3
4
5
6
7
8
9
Cs2CO3
K2CO3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(Cl2)2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
DMSO
ClCH2CH2Cl
Toluene
Toluene
Toluene
N.R.
N.R.
20
11
26
46
10
36
41
Morpholine
Et3N
Piperidine
EtN(iPr)2
DBUb)
EtN(iPr)2
EtN(iPr)2
EtN(iPr)2
EtN(iPr)2
EtN(iPr)2
10
11
12
88
63
42
Pd(Cl2)2(PPh3)2
a) Yield of isolated 6a. b) 1,8-Diazabicyclo[5.4.0]undec-7-ene.

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Table 2. Sequential Ugi 4-CR/CꢀH Activation for the Synthesis of Diverse 3-(Diphenylmethylidene)-2,3-
dihydro-1H-indol-2-ones 6a – 6p (see Scheme 2)
Product
Ar
R2
R3
Yield [%]a)
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
Ph
H
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
iPr
tBu
88
76
68
61
78
66
74
65
75
88
71
72
70
85
75
76
4-ClꢀC6H4
3-NO2ꢀC6H4
4-Me2NꢀC6H4
3,4,5-(MeO)3ꢀC6H2
4-Me2NꢀC6H4
4-PhꢀC6H4
4-MeꢀC6H4
4-iPrꢀC6H4
Ph
tBu
tBu
tBu
tBu
cHexb)
tBu
tBu
tBu
cHex
Ph
tBu
4-CNꢀC6H4
4-CF3ꢀC6H4
4-CF3ꢀC6H4
Pyridin-3-yl
Ph
tBu
tBu
cHex
tBu
tBu
a) Yield of isolated products 6a – 6p. b) Cyclohexyl.
The reported method with (diacetoxyiodo)benzene [28] has two disadvantages,
namely, in some cases, low yields as well as long reaction times. Meanwhile, simple N-
substituted alkynamides were used as starting materials.
The structures of the products 6a – 6p were deduced from their IR, 1H- and
1
13C-NMR, and high-resolution mass-spectrometry data. For example, the H-NMR
spectrum of 6h consisted of a singlet for tBu at d(H) 1.37, a singlet for NH at d(H) 5.87,
and a singlet for C(sp3)ꢀH at d(H) 6.11, and also signals of aromatic H-atoms. The
absence of alkyne signals in the 13C-NMR spectra confirmed the formation of the
desired products.
After formation of Ugi 4-CR product 5 (Path a, Scheme 4), insertion of PdII to 5
(Path b), oxidation of PdII to PdIV, and complexation of PdIV with the N-atom of the
aniline moiety leads to intermediate 8 (Scheme 4). The key step for the formation of 8
is related to the conversion of DIB to PhI through reduction of IIII to II (Path c). Then,
C(sp2)ꢀH activation leads to the formation of CꢀPd bond (Path d). Carbopalladation
of 9 results in intermediate 10 (Path e). Insertion of PhI (Path f) and, finally, reductive
elimination affords the desired 3-(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones
6a – 6p.
Conclusions. – We have developed a facile method for the synthesis of 3-
(diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones without any 3-(benzylidene)-2,3-
dihydro-1H-indol-2-ones by-products and introduced DIB as a source of PhI through
sequential Ugi 4-CR/CꢀH activation reaction. Good yields, short reaction times
(compared to other reported methods), diversity-oriented synthesis, and high bond-
forming efficiencies are advantages of this method.

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Scheme 4. Proposed Mechanism for the Formation of 3-(Diphenylmethylidene)-2,3-dihydro-1H-indol-2-
ones 6a – 6p
S. B. gratefully acknowledges Alexander von Humboldt Foundation for research fellowship. We also
thank center of excellence in development of chemical methods (CEDCM), Bu-Ali Sina University of
Hamedan, for kind cooperation and financial support.
Experimental Part
General. Commercially available materials were used without further purification. M.p.: Electro-
thermal 9100 apparatus; uncorrected. IR Spectra: ABB FT-IR FTLA 2000 spectrometer. 1H- and
13C-NMR spectra: Bruker DRX-300 AVANCE spectrometer, at 300 and 75 MHz, resp., as well as on

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Bruker DRX-500 AVANCE spectrometer, at 500 and 125 MHz, resp.; CDCl3 used as solvent. HR-ESI-
MS: Mass-ESI-POS (Apex Qe-FT-ICR instrument) spectrometer; in m/z.
General Procedure for the Synthesis of 3-(Diphenylmethylidene)-2,3-dihydro-1H-indol-2-ones, 6a –
6p, through Sequential Ugi 4-CR/CꢀH Activation. To a soln. of aldehyde 1 (1 mmol) in MeOH (5 ml) was
added aniline as a primary amine 2 (1 mmol), and the mixture was stirred at r.t. (258) for 1 h. Then,
phenylacetylenecarboxylic acid (3; 1 mmol) was added, and stirring was continued for 15 min, followed
by addition of isocyanide 4 (1 mmol). The mixture was stirred for 24 h. The progress of the reaction was
monitored by TLC (petroleum ether/AcOEt 3 :1). After completion of reaction, the solvent was
removed under vacuum, then toluene (20 ml), Pd(OAc)2 (11 mg, 5 mol-%), EtN(iPr)2 (258 mg, 2 mmol),
and PhI(OAc)2 (644 mg, 2 mmol) were simultaneously added to the mixture. The mixture was heated
under reflux for 5 h. Reaction progress was monitored by TLC (hexane/AcOEt 4 :1). After cooling to
r.t., the mixture was diluted with brine. The aq. phase was extracted with AcOEt (2 ꢁ 30 ml). The
combined org. phase was separated, dried (Na2SO4), filtered, concentrated in vacuo, and finally
purified by CC (SiO2; hexane/AcOEt 4 :1) to afford the desired products with good-to-high yields (61 –
88%).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-phenylacetamide
(6a). Yield: 428 mg (88%). Orange solid. M.p. 226 – 2278. IR (KBr): 3316, 1749, 1672. 1H-NMR
(300 MHz, CDCl3): 1.39 (s, tBu); 5.90 (s, NH); 6.16 (s, CH); 6.43 (d, J ¼ 7.7, 1 arom. H); 6.63 (t, J ¼ 7.7, 1
arom. H); 6.79 (d, J ¼ 8.0, 1 arom. H); 6.96 (t, J ¼ 7.7, 1 arom. H); 7.26 – 7.47 (m, 15 arom. H). 13C-NMR
(75 MHz, CDCl3): 28.6; 52.0; 58.6; 111.7; 121.5; 123.0; 123.2; 123.6; 127.8; 128.0; 128.1; 128.5; 128.7;
128.9; 129.2; 129.3; 130.2; 134.7; 140.0; 141.2; 141.3; 155.3; 167.1; 167.2. HR-ESI-MS: 487.2380 ([M þ 1]þ,
C33H31N2Oþ2 ; calc. 487.2386), 509.2200 ([M þ Na]þ, C33H30N2NaOþ2 ; calc. 509.2205).
N-(tert-Butyl)-2-(4-chlorophenyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-
1
acetamide (6b). Yield: 395 mg (76%). Orange solid. M.p. 243 – 2458. IR (KBr): 3315, 1672. H-NMR
(300 MHz, CDCl3): 1.37 (s, tBu); 5.90 (s, NH); 6.11 (s, CH); 6.45 (d, J ¼ 7.7, 1 arom. H); 6.66 (t, J ¼ 7.7, 1
arom. H); 6.79 (d, J ¼ 7.7, 1 arom. H); 7.01 (t, J ¼ 7.7, 1 arom. H); 7.26 – 7.47 (m, 14 arom. H). 13C-NMR
(75 MHz, CDCl3): 28.6; 52.1; 58.0; 111.5; 121.8; 123.1; 123.2; 123.3; 127.9; 128.5; 128.8; 129.0; 129.2;
129.3; 129.4; 129.5; 130.2; 133.1; 134.0; 139.9; 140.8; 141.1; 155.9; 166.8; 167.1. HR-ESI-MS: 521.2007
([M þ 1]þ, C33H30ClN2O2þ ; calc. 521.1996), 543.1822 ([M þ Na]þ, C33H29ClN2NaOþ2 ; calc. 543.1815).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-(3-nitrophenyl)acet-
amide (6c). Yield: 361 mg (68%). Orange solid. M.p. 210 – 2128. IR (KBr): 3314, 1675, 1532, 1353.
1H-NMR (300 MHz, CDCl3): 1.37 (s, tBu); 6.10 (s, NH); 6.21 (s, CH); 6.51 (d, J ¼ 7.8, 1 arom. H); 6.71 (t,
J ¼ 7.8, 1 arom. H); 6.80 (d, J ¼ 7.8, 1 arom. H); 7.05 (t, J ¼ 7.8, 1 arom. H); 7.36 – 7.71 (m, 11 arom. H);
7.68 (dd, J ¼ 7.4, 0.8, 1 arom. H); 8.15 (dd, J ¼ 8.1, 1.2, 1 arom. H); 8.24 (s, 1 arom. H). 13C-NMR
(75 MHz, CDCl3): 28.6; 52.3; 57.7; 111.1; 122.3; 122.9; 123.0; 123.1; 123.4; 127.9; 128.7; 129.0; 129.3; 129.4;
129.5; 129.6; 130.2; 134.2; 136.7; 139.8; 140.1; 140.9; 148.3; 156.7; 166.1; 167.2. HR-ESI-MS: 532.2243
([M þ 1]þ, C33H30N3O4þ ; calc. 532.2236), 570.1798 ([M þ K]þ, C33H29KN3Oþ4 ; calc. 570.1795).
N-(tert-Butyl)-2-[4-(dimethylamino)phenyl]-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-in-
dol-1-yl]acetamide (6d). Yield: 323 mg (61%). Orange solid. M.p. 272 – 2748. IR (KBr): 1670, 3318.
1H-NMR (300 MHz, CDCl3): 1.36 (s, tBu); 5.07 (s, NH); 5.82 (s, CH); 6.38 (d, J ¼ 8.3, 1 arom. H); 6.59 (t,
J ¼ 7.7, 1 arom. H); 6.67 (d, J ¼ 7.1, 2 arom. H); 7.26 – 7.45 (m, 10 arom. H). 13C-NMR (75 MHz, CDCl3):
28.7; 40.3; 51.8; 58.5; 111.7; 112.4; 121.2; 122.0; 122.1; 123.2; 124.0; 127.8; 128.4; 128.9; 129.0; 129.1; 129.3;
130.1; 140.2; 141.5; 141.8; 150.2; 154.5; 167.0; 167.9. HR-ESI-MS: 530.2802 ([M þ 1]þ, C35H36N3O2þ ; calc.
530.2808), 552.2622 ([M þ Na]þ, C35H35N3NaO2þ ; calc. 552.2627).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-(3,4,5-trimethoxy-
phenyl)acetamide (6e). Yield: 449 mg (78%). Orange solid. M.p. 218 – 2208. IR (KBr): 1673, 1755.
1H-NMR (500 MHz, CDCl3): 1.39 (s, tBu); 3.79 – 3.83 (m, 3 MeO); 5.92 (s, NH); 6.08 (s, CH); 6.43 (d, J ¼
8.8, 1 arom. H); 6.63 – 6.65 (m, 3 arom. H); 6.86 (d, J ¼ 7.9, 2 arom. H); 7.01 (t, J ¼ 7.9, 1 arom. H); 7.26 –
7.45 (m, 10 arom. H). 13C-NMR (125 MHz, CDCl3): 28.6; 52.0; 56.3; 59.0; 60.8; 105.7; 111.6; 121.6; 123.0;
123.2; 123.5; 127.8; 128.5; 129.0; 129.2; 129.3; 130.1; 130.2; 138.0; 140.0; 141.2; 141.4; 153.4; 155.3; 167.2.
HR-ESI-MS: 577.2697 ([M þ 1]þ, C36H37N2Oþ5 ; calc. 577.2702), 599.2518 ([M þ Na]þ, C36H36N2NaOþ5 ;
calc. 599.2522), 615.2256 ([M þ K]þ, C36H36KN2O5þ ; calc. 615.2261).

Helvetica Chimica Acta – Vol. 97 (2014)
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N-Cyclohexyl-2-[4-(dimethylamino)phenyl]-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-in-
dol-1-yl]acetamide (6f). Yield: 366 mg (66%). Orange solid. M.p. 204 – 2068. IR (KBr): 1675, 1742, 3328.
1H-NMR (500 MHz, CDCl3): 1.09 – 2.00 (m, 5 CH2); 2.92 (s, Me2N); 3.87 (m, CH(cHex)); 5.89 (d, J ¼ 7.8,
NH); 6.14 (s, CH); 6.40 (d, J ¼ 7.7, 1 arom. H); 6.60 (t, J ¼ 7.6, 1 arom. H); 6.67 (d, J ¼ 8.7, 2 arom. H);
6.84 (d, J ¼ 7.9, 1 arom. H); 6.99 (t, J ¼ 7.8, 1 arom. H); 7.27 (d, J ¼ 8.8, 2 arom. H); 7.26 – 7.45 (m, 7 arom.
H). 13C-NMR (125 MHz, CDCl3): 24.8; 25.5; 32.8; 33.0; 40.4; 48.7; 58.0; 111.6; 112.4; 121.3; 121.8; 122.9;
123.3; 123.9; 127.8; 128.4; 128.9; 129.1; 129.2; 129.3; 129.4; 130.2; 140.1; 141.4; 141.7; 150.2; 154.7; 167.0;
167.5. HR-ESI-MS: 556.2956 ([M þ 1]þ, C37H38N3O2þ ; calc. 556.2964), 578.2778 ([M þ Na]þ,
C37H37N3NaOþ2 ; calc. 578.2783), 594.2517 ([M þ K]þ, C37H37KN3Oþ2 ; calc. 594.2517).
2-(1,1’-Biphenyl-4-yl)-N-(tert-butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-
yl]acetamide (6g). Yield: 416 mg (74%). Red solid. M.p. 173 – 1758. IR (KBr): 1667, 3317. 1H-NMR
(500 MHz, CDCl3): 1.40 (s, tBu); 5.97 (s, NH); 6.20 (s, CH); 6.46 (d, J ¼ 7.7, 1 arom. H); 6.63 (t, J ¼ 7.6, 1
arom. H); 6.80 (d, J ¼ 7.9, 1 arom. H); 6.99 (t, J ¼ 7.5, 1 arom. H); 7.26 – 7.59 (m, 22 arom. H). 13C-NMR
(125 MHz, CDCl3): 28.7; 52.0; 58.5; 111.7; 121.6; 123.0; 123.3; 123.6; 127.1; 127.4; 127.5; 127.9; 128.6;
128.8; 129.3; 129.3; 130.2; 133.7; 140.0; 140.4; 140.9; 141.3; 155.4; 167.2. HR-ESI-MS: 563.2693 ([M þ 1]þ,
C39H35N2Oþ2 ; calc. 563.2693), 585.2513 ([M þ Na]þ, C39H34N2NaOþ2 ; calc. 585.2518).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-(4-methylphenyl)-
1
acetamide (6h). Yield: 325 mg (65%). Orange solid. M.p. 259 – 2618. IR (KBr): 1673, 3414. H-NMR
(500 MHz, CDCl3): 1.37 (s, Me3C); 2.33 (s, Me); 5.87 (s, NH); 6.11 (s, CH); 6.42 (d, J ¼ 9.9, 1 arom. H);
6.62 (t, J ¼ 8.2, 1 arom. H); 6.81 (d, J ¼ 8.3, 1 arom. H); 6.99 (t, J ¼ 8.3, 1 arom. H); 7.14 (d, J ¼ 8.0, 2
arom. H); 7.28 (d, J ¼ 8.0, 2 arom. H); 7.26 – 7.45 (m, 10 arom. H). 13C-NMR (125 MHz, CDCl3): 21.1;
28.6; 51.9; 58.6; 111.7; 121.5; 122.9; 123.2; 123.7; 127.8; 28.1; 128.4; 128.9; 129.1; 129.2; 129.3; 129.4; 130.1;
131.7; 137.8; 140.0; 141.3; 141.4; 155.1; 167.1; 167.3. HR-ESI-MS: 501.2537 ([M þ 1]þ, C34H33N2O2þ ; calc.
501.2542), 523.2356 ([M þ Na]þ, C34H32N2NaOþ2 ; calc. 523.2361), 539.2095 ([M þ K]þ, C34H32KN2Oþ2 ;
calc. 539.2101).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-[4-(propan-2-yl)-
phenyl]acetamide (6i). Yield: 396 mg (75%). Orange solid. M.p. 262 – 2648. IR (KBr):1675, 3328.
1H-NMR (500 MHz, CDCl3): 1.24 (dd, J ¼ 6.9, 1.2, 2 Me); 1.38 (s, tBu); 2.89 (m, Me2CH); 5.89 (s, NH);
6.14 (s, CH); 6.42 (d, J ¼ 7.7, 1 arom. H); 6.63 (t, J ¼ 7.6, 1 arom. H); 6.83 (d, J ¼ 7.9, 1 arom. H); 7.00 (t,
J ¼ 8.1, 1 arom. H); 7.20 (d, J ¼ 8.2, 2 arom. H); 7.32 (d, J ¼ 8.2, 2 arom. H); 7.35 – 7.45 (m, 10 arom. H).
13C-NMR (125 MHz, CDCl3): 21.8; 23.8; 23.9; 28.6; 33.8; 51.9; 58.7; 111.7; 121.4; 122.9; 123.2; 123.7;
126.8; 127.8; 128.2; 128.4; 128.9; 129.2; 129.2; 129.3; 130.2; 132.0; 140.0; 141.3; 141.5; 148.7; 155.1; 167.1;
167.4. HR-ESI-MS: 529.2850 ([M þ 1]þ, C36H37N2O2þ ; calc. 529.2855), 551.2669 ([M þ Na]þ,
C36H36N2NaOþ2 ; calc. 551.2674), 567.2408 ([M þ K]þ, C36H36KN2Oþ2 ; calc. 567.2414).
N-Cyclohexyl-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-phenylacetamide
(6j). Yield: 450 mg (88%). Orange solid. M.p. 202 – 2048. IR (KBr): 3308, 1700, 1655. 1H-NMR
(300 MHz, CDCl3): 1.09 – 2.06 (m, 5 CH2); 3.87 – 3.89 (m, CH(cHex)); 6.08 (d, J ¼ 7.7, NH); 6.25 (s, CH);
6.45 (d, J ¼ 7.7, 1 arom. H); 6.65 (t, J ¼ 7.7, 1 arom. H); 6.82 (d, J ¼ 7.7, 1 arom. H); 7.00 (t, J ¼ 7.7, 1 arom.
H); 7.27 – 7.47 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 24.7; 24.8; 25.5; 32.7; 32.8; 48.8; 58.2; 111.7;
121.6; 123.0; 123.3; 123.5; 127.9; 128.1; 128.5; 128.7; 129.0; 129.3; 129.4; 130.2; 134.5; 139.9; 141.2; 141.3;
155.4; 166.9; 167.1. HR-ESI-MS: 513.2537 ([M þ 1]þ, C35H33N2O2þ ; calc. 513.2542), 535.2356 ([M þ Na]þ,
C35H32N2NaOþ2 ; calc. 535.2361).
2-[5-Bromo-3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-N-(tert-butyl)-2-phenylacet-
1
amide (6k). Yield: 401 mg (71%). Orange solid. M.p. 304 – 3068. IR (KBr): 3324, 1679, 1596. H-NMR
(300 MHz, CDCl3): 1.40 (s, tBu); 6.00 (s, NH); 6.20 (s, CH); 6.48 (d, J ¼ 1.8, 1 arom. H); 6.68 (d, J ¼ 8.5, 1
arom. H); 7.07 (dd, J ¼ 8.5, 1.8, 1 arom. H); 7.35 – 7.50 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3):
28.6; 52.1; 58.5; 113.5; 114.4; 122.6; 125.2; 125.8; 127.9; 128.0; 128.3; 128.5; 128.9; 129.1; 129.3; 129.7;
129.8; 130.4; 130.8; 134.4; 139.5; 140.1; 140.7; 157.1; 166.6; 167.1. HR-ESI-MS: 565.1506 ([M þ 1]þ,
C33H3079BrN2Oþ2 ; calc. 565.1491), 587.1328 ([M þ Na]þ, C33H2979BrN2NaOþ2 ; calc. 587.1310).
N-(tert-Butyl)-2-(4-cyanophenyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-
acetamide (6l). Yield: 368 mg (72%). Orange solid. M.p. 334 – 3368. IR (KBr): 3313, 1671, 1600. 1H-NMR
(300 MHz, CDCl3): 1.36 (s, tBu); 6.04 (s, NH); 6.18 (s, CH); 6.50 (d, J ¼ 7.8, 1 arom. H); 6.71 (t, J ¼ 7.8, 1
arom. H); 6.77 (d, J ¼ 7.8, 1 arom. H); 7.04 (t, J ¼ 7.8, 1 arom. H); 7.36 – 7.40 (m, 6 arom. H); 7.45 – 7.48

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Helvetica Chimica Acta – Vol. 97 (2014)
(m, 6 arom. H); 7.61 (d, J ¼ 8.2, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 28.6; 52.2; 58.0; 111.2; 111.8;
118.5; 122.2; 122.9; 123.3; 127.9; 128.7; 128.8; 129.0; 129.3; 129.5; 129.6; 130.1; 132.2; 139.7; 139.9; 140.2;
140.9; 156.6; 166.1; 167.1. HR-ESI-MS: 512.2346 ([M þ 1]þ, C34H30N3O2þ ; calc. 512.2338), 550.1906
([M þ K]þ, C34H29KN3Oþ2 ; calc. 550.1897).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-[4-(trifluoromethyl)-
phenyl]acetamide (6m). Yield: 381 mg (70%). Orange solid. M.p. 302 – 3048. IR (KBr): 3314, 1668, 1596.
1H-NMR (300 MHz, CDCl3): 1.37 (s, tBu); 6.10 (s, NH); 6.21 (s, CH); 6.49 (d, J ¼ 7.6, 1 arom. H); 6.69 (t,
J ¼ 7.3, 1 arom. H); 6.83 (d, J ¼ 7.5, 1 arom. H); 7.04 (t, J ¼ 7.3, 1 arom. H); 7.38 – 7.51 (m, 12 arom. H);
7.59 (d, J ¼ 7.5, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 28.6; 52.2; 58.2; 111.4; 122.0; 123.1; 123.2; 123.3;
125.3; 125.4; 125.5; 125.6 (CF3); 127.9; 128.4; 128.6; 129.0; 129.3; 129.5; 129.6; 129.9; 130.2; 138.6; 139.8;
140.6; 141.0; 156.3. HR-MS-ESI: 555.2275 ([M þ 1]þ, C34H30F3N2O2þ ; calc. 555.2259), 593.1832 ([M þ
K]þ, C34H29F3KN2Oþ2 ; calc. 593.1818).
N-Cyclohexyl-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-[4-(trifluoromethyl)-
phenyl]acetamide (6n). Yield: 493 mg (85%). Orange solid. M.p. 291 – 2938. IR (KBr): 3313, 1666, 1601.
1H-NMR (300 MHz, CDCl3): 1.08 – 1.37 (m, 5 CH2); 3.82 – 3.91 (m, CH(cHex)); 6.24 (d, NH); 6.28 (s,
CH); 6.49 (d, J ¼ 7.7, 1 arom. H); 6.70 (t, J ¼ 7.7, 1 arom. H); 6.82 (d, J ¼ 7.7, 1 arom. H); 7.04 (t, J ¼ 7.7, 1
arom. H); 7.35 – 7.39 (m, 7 arom. H); 7.43 – 7.51 (m, 6 arom. H); 7.59 (d, J ¼ 8.2, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 24.6; 24.7; 25.4; 32.7; 32.6; 32.8; 48.9; 57.7; 76.6; 111.4; 122.1; 123.1; 123.2; 123.3; 125.4;
125.5 (CF3); 127.9; 128.3; 128.7; 129.0; 129.3; 129.5; 129.6; 129.9; 130.2; 138.4; 139.8; 140.5; 141.0; 156.4;
166.4; 167.2. HR-ESI-MS: 581.2422 ([M þ 1]þ, C36H32F3N2Oþ2 ; calc. 581.2416), 603.2239 ([M þ Na]þ,
C36H31F3N2NaOþ2 ; calc. 603.2235).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-1H-indol-1-yl]-2-(pyridin-3-yl)acet-
1
amide (6o). Yield: 422 mg (75%). Orange solid. M.p. 210 – 2128. IR (KBr): 3316, 1673, 1597. H-NMR
(300 MHz, CDCl3): 1.36 (s, tBu); 6.10 (s, NH); 6.20 (s, CH); 6.47 (d, J ¼ 7.7, 1 arom. H); 6.67 (t, J ¼ 7.7, 1
arom. H); 6.82 (d, J ¼ 7.8, 1 arom. H); 7.03 (t, J ¼ 7.7, 1 arom. H); 7.20 – 7.46 (m, 10 arom. H, 1 pyridine
H); 7.73 (d, J ¼ 7.1, 1 pyridine H); 8.52 (d, J ¼ 4.2, 1 pyridine H); 8.54 (s, 1 pyridine H). 13C-NMR
(75 MHz, CDCl3): 28.6; 52.1; 56.4; 111.3; 113.9; 122.1; 123.1; 123.2; 123.3; 127.9; 128.4; 128.7; 129.0;
129.3; 129.4; 129.5; 130.1; 130.5; 136.1; 139.8; 140.3; 141.0; 149.1; 156.3; 166.2; 167.1. HR-ESI-MS:
488.2320 ([M þ 1]þ, C32H30N3Oþ2 ; calc. 488.2338).
N-(tert-Butyl)-2-[3-(diphenylmethylidene)-2,3-dihydro-2-oxo-5-(propan-2-yl)-1H-indol-1-yl]-2-
phenylacetamide (6p). Yield: 401 mg (76%). Red solid. M.p. 244 – 2468. IR (KBr): 3328, 1677, 1607.
1H-NMR (300 MHz, CDCl3): 0.93 (d, J ¼ 6.9, Me); 0.95 (d, J ¼ 6.9, Me); 1.39 (s, tBu); 2.54 (m, CH); 5.98
(s, NH); 6.15 (s, CH); 6.25 (d, J ¼ 1.5, 1 arom. H); 6.70 (d, J ¼ 8.2, 1 arom. H); 6.85 (dd, J ¼ 8.2, 1.6, 1
arom. H); 7.24 – 7.48 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 23.7; 28.6; 33.4; 51.9; 58.7; 111.3;
121.1; 123.1; 124.0; 127.0; 127.8; 128.0; 128.2; 128.6; 128.9; 129.0; 129.1; 129.3; 130.2; 134.9; 139.3; 139.8;
141.4; 141.8; 154.7; 167.2; 167.3. HR-ESI-MS: 529.2851 ([M þ 1]þ, C36H37N2O2þ ; calc. 529.2855), 551.2671
([M þ Na]þ, C36H36N2NaOþ2 ; calc. 551.2674).
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Received February 20, 2014