Protecting-Group-Free Synthesis of 3-Amino-3-α-prenyl-oxindoles through the Direct Prenylation of Isatin-Derived Imines

Article abstract of DOI:10.1002/ejoc.201800881

A zinc-mediated α-selective prenylation of isatin-derived imine using prenyl bromide as the prenyl source in a sealed tube has been developed. The protocol enables an efficient access to various 3-amino-3-α-prenyl-oxindoles from cheap and readily available chemicals in good to excellent yields. The obtained prenylated adduct can be further manipulated to other more complicated derivatives through cyclization or oxidation, which demonstrated the synthetic usefulness of this methodology. Additionally, we demonstrated that this zinc-mediated methodology is also applicable to cinnamylation and geranylation.

Full text of DOI:10.1002/ejoc.201800881

A Journal of
Accepted Article
Title: Protecting-Group-Free Synthesis of 3-Amino-3-α-prenyl-
oxindoles through the Direct Prenylation of Isatin-derived Imines
Authors: De-Feng Li, Hai-Shan Jin, Jing-Ru Zhang, Yi-Xuan Jiang, and
Li-Ming Zhao
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800881
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800881
Supported by

10.1002/ejoc.201800881
European Journal of Organic Chemistry
Protecting-Group-Free Synthesis of 3-Amino-3-α-prenyl-oxindoles
through the Direct Prenylation of Isatin-derived Imines
,
,
De-Feng Li,† # Hai-Shan Jin,† # Jing-Ru Zhang,† Yi-Xuan Jiang,† and Li-Ming Zhao*,†,‡
†School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116,
Jiangsu, China
‡State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources,
Guangxi Normal University, Guilin 541004, Guangxi, China
lmzhao@jsnu.edu.cn
#These authors contributed equally to this work
Abstract A zinc-mediated α-selective prenylation of isatin-derived imine using prenyl
bromide as the prenyl source in a sealed tube has been developed. The protocol enables an
efficient access to various 3-amino-3-α-prenyl-oxindoles from cheap and readily available
chemicals in good to excellent yields. The obtained prenylated adduct can be further
manipulated to other more complicated derivatives through cyclization or oxidation, which
demonstrated the synthetic usefulness of this methodology. Additionally, we demonstrated
that this zinc-mediated methodology is also applicable to cinnamylation and geranylation.
Keywords: Allylation; 3-Amino-2-oxindoles; Imines; Prenyl bromide; Zinc
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
INTRODUCTION
Nitrogen-containing compounds are of great importance in the drug discovery process and
more than 80% of small-molecule drugs contain at least one nitrogen atom.1 3-Substituted
3-amino-2-oxindoles are important structural motif in biologically active compounds.2 In
particular, 3-amino-3-allyl-2-oxindoles represent highly intriguing scaffolds, which are
important precursors for the synthesis of a wide variety of bioactive compounds.3 As a result,
syntheses of this class of compounds have become an important research area and there are
many reports available to synthesize them via the reactions of imines derived from isatins
with allyl metal reagents.4 However, compared to the extensive works on allylation of
isatin-derived imines, the study of analogous prenylation of isatin imines for the synthesis of
3-amino-3-prenyl-2-oxindoles is far less explored because of the regioselective issue (Scheme
1).4b,4e,5 It is well known that the prenyl fragment is a very important structural motif, which is
featured in a wide variety of natural products.6 Moreover, prenylation is critically important in
the regulation of protein function7 and the addition of a prenyl chain to an aromatic secondary
metabolite often affects its pharmacological activity due to the increase in hydrophobicity of
the molecule.8 These indicate that the incorporation of a prenyl residue into a molecule may
contribute to the enhancement of the biological activity, thus benefiting the drug discovery
and development process.9
NR2

R2HN
R2HN

X
R1
O
R1
O
R1
O
+
Metal
Solvent
N
R3
N
N
R3
adduct
(major procuct)
R3
adduct
(minor product)
Scheme 1. Regioselectivity in Prenylation of Isatin-derived Imines
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
In 2016, Yanagisawa’s group reported an α-selective prenylation of isatin imines using
prenylbarium reagent.10 To the best of our knowledge, this is the only one example in the
literature of a direct α-regioselective allylation of isatin imines. Despite the success, this
synthesis involved the use of metallic barium, which is of high cost and give rise to the
soluble barium salts that are highly toxic to humans.11 Meanwhile, the metallic barium also
has to be carefully used because of its high reactivity, which is dangerous and may cause
ignition when contact with air. On the other hand, a protecting group (such as benzyl or
methyl group) at the N-1 position is necessary for oxindoles in this protocol, which limits the
scope of products accessible through this reaction. In view of the significance of the prenyl
moiety in the metabolism of living organisms and nitrogenous compounds in drug discovery,
we envisaged that the development of a more convenient and general protocol for
3-amino-3-prenyl-2-oxindoles using N-unprotected oxindoles and cheaper and safer reagents
would be of particular value.
Following our interest in the regioselective prenylation and its application12 and the
synthesis of oxindole derivatives,13 herein we report a facile and general zinc-mediated
method for the α-prenylation of isatin-derived imines in a sealed tube to afford
3-amino-3-prenyl-2-oxindoles in good to excellent yields. This protocol uses cheap and safe
zinc as the mediator and readily available prenyl bromide as the prenyl source; it features high
regioselectiviy, efficiency, and high yield. Moreover, a protecting group is unnecessary for
isatin imines in this protocol. In addition, we have been able to expand this α-prenylation
reaction of isatin-derived imine to other α-allylation reactions such as cinnamylation and
geranylation, generating structurally more diverse synthetically useful α-allylated products.
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
RESULTS AND DISCUSSION
We choose N-unprotected isatin imine 1a as the model substrate for reaction condition
screening. The representative results are summarized in Table 1. Taking in account that in
previous works the use of polar aprotic solvents such as hexamethylphosphoramide (HMPA)
or 1,3-dimethyl-2-imidazolidinone (DMI) has proven to be crucial to conduct α-regioselective
prenylation,12a,b the reaction was performed with prenylzinc at 120 °C for 12 h in DMI
initially. As expected, α-product 2a was formed as a major product in 64% yield (entry 1).
Then, other solvents such as N,N-dimethylformamide (DMF) (entry 2), dimethyl sulfoxide
(DMSO) (entry 3), and N,N-dimethylacetamide (DMA) (entry 4) were investigated in order to
improve the reaction yield of 2a, and a good result was observed with DMA as solvent,
affording 2a in 77% yield. Although the above investigation and research provided a good
solution for the regioselective prenylation, the problem here is that these polar aprotic
solvents have significant solubility in organic solvents as well as water, and that they also act
as phase-transfer agents to draw the desired products back into the aqueous layer.
Consequently, the workup procedure can become very time-consuming with multiple washes
and back-extractions. Thus, we investigated other conditions to overcome the limitation and
eventually found that heating a THF solution of imine 1a and prenylzinc at 120 °C in a sealed
tube generated 2a in high yield with excellent regioselectivity (entry 5). The advantage of the
sealed reflux system is that it avoids the use of polar aprotic solvents commonly used in the
α-prenylation process, thereby making the workup procedure and purification very simple and
time-saving. To our delight, shortening the reaction time to 8 h afforded a higher yield of
product 2a at 120 °C (entry 6). Decreasing the reaction temperature to 110 °C still led to a
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
high level of α-product (85%) (entry 7). An attempt to conduct the reaction for a lower
temperature resulted in the yield of 2a dropping to 75% as well as 12% of γ-isomer 3a (entry
8), which underlined the crucial need of the high reaction temperature for the success of the
reaction.
Table 1. Optimization of the Reaction Conditionsa
NPh
PhHN
BrZn
conditions
O
O
N
N
H
H
1a
2a
+
PhHN
O
N
H
3a
entry solvent
T (°C) t (h)
2a (%)b 3a (%)b
1
2
3
4
5
6
7
8
DMIc
120
120
12
12
12
12
12
8
64
63
55
77
86
88
85
75
0
DMFc
0
DMSOc 120
trace
0
DMAc
THFd
THFd
THFd
THFd
120
120
120
110
100
0
0
8
0
12
12
aReactions were carried out with 1a (0.5 mmol), prenyl bromide (1.0 mmol), and zinc (1.5
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
b
c
d
mmol). Isolated yield. Reactions were carried out in a round-bottom flask. Reactions were
carried out in a sealed tube.
With the optimized reaction conditions in hand, various isatin-derived imines 1b-y were
investigated, and the results are summarized in Table 2. The initial investigation of the
reaction was centered on altering the substituents R1 linked to the oxindoles with a free N-H
group. Generally, the avoidance of protecting groups in synthesis is preferred because a
protection/deprotection event lengthens the synthetic sequence, incurring costs from
additional reagents, and leads to a loss of material.14 Also, nonprotected free N-H on the
oxindole allows for facile potential N-substitutions on demand. As expected, this protocol
was applicable to a wide range of N-free isatin imines 1, affording the corresponding products
2 in high yields. For example, substitution at the C5-position on the phenyl ring of imines,
whether electron-donating (entries 1 and 2) or -withdrawing (entries 3 and 4) substituted,
resulted in the formation of the corresponding products 2b-e in good yields ranging from 72
to 86%. The imines containing a bromine group at the C6- or C7-position also provided the
corresponding products 2f and 2g in 86 and 75% yields, respectively (entries 5 and 6).
Subsequently, various anilines with different R2 groups were used in the reaction to examine
the effect of this group on the reaction. Satisfyingly, good substituent tolerance was also
observed as various substitution patterns consistently gave the expected products 2h-r in good
to excellent yields (entries 7-17). It is worth noting that both strong electron-donating group
(-OCH3, entry 9) and strong electron-withdrawing group (-CF3, entry 11) were also well
tolerated, affording the corresponding products 2j and 2l in 80 and 71% yields, respectively.
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
Disubstituted aniline-derived isatin imine 1s also delivered the desired product 2s in
satisfactory yield (entry 18). These results showed that the electronic nature and the position
of the R2 group have little influence on the reactivity. Finally, different protecting groups R3
for the oxindole nitrogen were also screened. Small alkyl protecting groups such as methyl
groups on the N-atom of oxindoles 1t-w reacted well to give desired products 2t-w in
excellent yields (88-91%) (entries 19-22). Meanwhile, the use of a bulky protecting group
such as prenyl and benzyl was also found to be compatible under the optimal conditions,
affording desired product 2x and 2y in 82 and 89% yields, respectively (entries 23 and 24).
Table 2. Substrate Scopea
R2
R2
N
NH
N
BrZn
sealed tube
R1
O
R1
O
N
R3
120 °C, 8 h
R3
2 (α/γ > 95:5)
1
entry
R1，R2，R3
5-CH3, H, H
5-OCH3, H, H
5-F, H, H
yield(%)b
1
2
1
2
3
4
5
6
7
83
82
72
86
86
75
88
1b
1c
1d
1e
1f
2b
2c
2d
2e
2f
5-Br, H, H
6-Br, H, H
7-Br, 4-Br, H
H, 4-CH3, H
1g
1h
2g
2h
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
8
H, 3-CH3, H
H, 4-OCH3, H
H, 4-Br, H
82
80
90
71
85
83
79
81
73
77
72
89
91
90
88
82
89
1i
1j
2i
2j
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1k
1l
2k
2l
H, 4-CF3, H
5-CH3, 4-CH3, H
5-CH3, 2-CH3, H
5-CH3, 4-Cl, H
5-CH3, 4-Br, H
5-F, 2-CH3, H
5-Cl, 4-Br, H
5-Cl, 3,4-Cl2, H
5-Br, H, CH3
H, H, CH3
1m
1n
1o
1p
1q
1r
1s
2m
2n
2o
2p
2q
2r
2s
1t
2t
1u
1v
1w
1x
1y
2u
2v
2w
2x
2y
H, 4-F, CH3
H, 4-Br, CH3
H, 4-OCH3, prenyl
H, H, Bn
aUnless otherwise noted, reaction conditions as for entry 6 in Table 1. bIsolated yield.
To exemplify the practical applicability of this protocol, a scale-up synthesis of 2a was
carried out (Scheme 2). To our delight, the reaction on the gram scale still worked very
efficiently and could be scaled easily to 5 mmol and likely even larger without significantly
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
compromising the yield (80%) [0.5 mmol scale, 88% (entry 6 in Table 1)]. This demonstrated
the applicability of this simple, protecting-group-free protocol as a useful tool in practical
synthetic contexts.
NPh
PhHN
BrZn
sealed tube
120 °C, 8 h
O
O
N
N
H
H
2a
1a
1.11 g (5 mmol)
1.17 g, 80%
Scheme 2. Gram-Scale α-Prenylation of Isatin-derived Imine 1a
Since spirooxindoles bearing a nitrogen heterocycle at the C3-position form the basic
skeleton of many natural products and therapeutic agents,15 and they are generally more
effective at inhibiting cancer cell proliferation than oxygen- or sulfur-containing heterocyclic
C3-substituted molecules,16 we believe that the preparation of their analogs would be useful
for structure-activity relationship studies. Therefore, we randomly chose several
N-unprotected and N-protected 3-amino-3-prenyl-2-oxindoles 2 for the synthesis of
spirooxindoles containing a five-membered nitrogen heterocycle to further investigate the
synthetic utility of this protocol. It was found that compounds 2k and 2u cyclized smoothly to
the spiro pyrrolidine oxindoles 4k and 4u in yields of 90 and 92%, respectively, and an
additional iodine atom was incorporated which could be a synthetic handle for further
diversification of the spirooxindole scaffold (Scheme 3a). Then, other transformations of this
3-amino-3-prenyl-2-oxindole were also explored (Scheme 3b). For instance, the reaction of
2a with selenium dioxide in the presence of pivalic acid (PA) in dichloromethane underwent
the oxidation to afford 4-(indolin-3-yl)-2-methylbut-2-en-1-ol (a commonly found structural
9
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
motif in several bioactive natural products17) 5 in 75% yield. All of these applications
demonstrated the usefulness of compound 2, although they are very elementary.
I
R2PhHN
R2PhN
I2
(a)
R1
O
NaHCO3
MeCN
R1
O
N
N
R3
R3
2
4
4k: R1 = H, R2 = 4-Br, R3 = H, 90%
4u: R1 = H, R2 = H, R3 = CH3, 92%
OH
PhHN
PhHN
SeO2
O
(b)
O
PA/DCM
N
N
H
H
2a
5, 75%
Scheme 3. Synthetic Applications
Encouraged by the above success, we further evaluated other 3-substituted allylmetal
reagents, such as cinnamylzinc bromide, in the reaction with isatin-derived imines (Table 3).
The results showed that cinnamyl-type compound also worked well for various isatin imines
bearing different R1 and R2 groups with a free N-H group (entries 1-6 and 9), as well as
different N-protecting groups R3 such as methyl (entry 7) and benzyl (entry 8) groups under
the
reaction
conditions. The
previous
study
clearly
demonstrated
that
3-amino-3-α-cinnamyl-2-oxindoles are important build blocks for the synthesis of
psychotrimine, a trimeric indole alkaloid.3b Therefore, the direct formation of α-cinnamylated
products has great potential in quick construction of complex skeletons in indole alkaloids
because it overcomes the regioselectivity problem with the previous cinnamylation of isatin
imines,18 which provides the incentive for the development of a new and simple entry into
10
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
psychotrimine.3b
Table 3. α-Selective Allylation of Imines 1 with Cinnamyl Bromide
NPhR2
O
N
R3
R2PhHN
Ph
BrZn
sealed tube
Ph
R1
R1
O
N
120 °C, 8 h
R3
1
6 (α/γ > 95:5)
entry
R1，R2，R3
H, H, H
yield (%)a
1
6
1
2
3
4
5
6
7
8
9
90
88
72
86
87
88
81
82
80
1a
1e
1j
6a
6e
6j
5-Br, H, H
H, 4-OCH3, H
H, 4-Br, H
1k
1l
6k
6l
H, 4-CF3, H
5-F, 2-CH3, H
H, 4-F, CH3
H, H, Bn
1q
1v
1y
1z
6q
6v
6y
6z
5-Br, 4-CH3, H
aIsolated yields of reactions performed on 0.5 mmol scale.
Finally, we extended our methodology toward geranylation of isatin imines, which also
generally leads to the formation of γ-regioselective product.5 Under the similar conditions
with the above prenylation and cinnamylation, the corresponding α-geranylation product 7
was obtained in 78% yield by simple treating compound 1t with geranylzinc bromide in a
11
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
sealed tube at 120 °C for 8 h (Scheme 4).
NPh
Br
BrZn
O
N
sealed tube
120 °C, 8 h
1t
PhHN
Br
O
N
7, 78%
Scheme 4. Reaction of Isatin Imine 1t and Geranylzinc Bromide
CONCLUSIONS
In summary, we have developed a general and efficient method for zinc-mediated
regioselective prenylation of isatin imines, which enables the simple and direct synthesis of
various 3-amino-3-α-prenyl-oxindoles. Furthermore, we have demonstrated that this protocol
is also applicable to other allylation reactions of isatin imines such as cinnamylation and
geranylation. As a related application, several 3-amino-3-α-prenyl-oxindoles have been neatly
transformed into spiro pyrrolidine oxindole and 4-(indolin-3-yl)-2-methylbut-2-en-1-ol,
which further demonstrated the synthetic utility of this methodology.
EXPERIMENTAL SECTION
1
General Methods. IR spectra were recorded with a FTIR spectrophotometer. H NMR and
13C NMR spectra were recorded at 400 and 100 MHz in CDCl3 or DMSO-d6 with chemical
shifts (δ) given in parts per million relative to TMS as an internal standard. Multiplicities are
indicated as follows: s, singlet; d, doublet; t, triplet; m, multiplet; dd, doublet of doublets; etc.
12
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
Coupling constants (J) are given in hertz. High-resolution mass spectra (HRMS) were
recorded using electrospray ionization (ESI) and time-of-flight (TOF) mass analysis.
General Procedure for the Synthesis of α-Adduct 2. Prenyl bromide (1.0 mmol) was added
to a suspension of activated zinc powder (1.5 mmol) in dry THF (5 mL); the reaction mixture
was stirred for 1 h at room temperature. The solution was filtered through a Schlenk filter and
kept under N2 for the following reaction. Isatin-derived Imines 1 (0.5 mmol) and prenylzinc
bromide prepared above were added to a 15 mL sealed tube. The resulting mixture was sealed
and submerged into a 120 °C silicon oil bath. After 8 h, the solution was cooled to room
temperature and the product was purified by column chromatography (3/1 petroleum
ether/ethyl acetate) to afford α-product 2.
3-(3-Methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2a). White solid (128 mg, 88%
yield); mp 186-188 ºC. IR (KBr, ν, cm-1) 3317, 1708. 1H NMR (400 MHz, DMSO-d6) δ 10.58
(s, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 7.2 Hz, 1H), 6.94-6.86 (m, 4H), 6.45 (t, J = 7.3
Hz, 1H), 6.26 (s, 1H), 6.18 (d, J = 8.0 Hz, 2H), 4.84 (t, J = 7.2 Hz, 1H), 2.62-2.54 (m, 2H),
1.53 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 179.3, 147.0, 141.7, 135.7,
130.8, 129.0, 129.0, 123.9, 122.1, 117.0, 116.8, 113.6, 110.1, 64.4, 38.6, 26.2, 18.2. HRMS
(ESI) m/z calcd for C19H19N2O [M － H]－ 291.1497; found 291.1512.
5-Methyl-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2b). White solid (127
1
mg, 83% yield); mp 193-195 ºC. IR (KBr, ν, cm-1) 3330, 1713. H NMR (400 MHz,
DMSO-d6) δ 10.49 (s, 1H), 7.01 (d, J = 7.9 Hz, 1H), 6.94 (s, 1H), 6.88 (t, J = 7.5 Hz, 2H),
6.76 (d, J = 7.8 Hz, 1H), 6.45 (t, J = 7.2 Hz, 1H), 6.25 (s, 1H), 6.19 (d, J = 8.1 Hz, 2H), 4.81
(t, J = 6.9 Hz, 1H), 2.56 (d, J = 7.3 Hz, 2H), 2.20 (s, 3H), 1.54 (s, 3H), 1.37 (s, 3H). 13C NMR
13
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
(100 MHz, DMSO-d6) δ 183.9, 151.7, 144.0, 140.4, 135.6, 135.6, 134.0, 133.8, 129.2, 121.6,
118.3, 114.6, 69.1, 43.4, 30.9, 25.9, 22.9. HRMS (ESI) m/z calcd for C20H21N2O [M － H]－
305.1654; found 305.1650.
5-Methoxy-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2c). White solid
1
(132 mg, 82% yield); mp 188-190 ºC. IR (KBr, ν, cm-1) 3390, 1707. H NMR (400 MHz,
DMSO-d6) δ 10.42 (s, 1H), 6.89 (t, J = 7.4 Hz, 2H), 6.79 (s, 2H), 6.73 (s, 1H), 6.46 (t, J = 7.3
Hz, 1H), 6.25 (s, 1H), 6.20 (d, J = 8.1 Hz, 2H), 4.85 (t, J = 6.9 Hz, 1H), 3.65 (s, 3H),
2.61-2.55 (m, 2H), 1.55 (s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 183.8, 160.1,
151.7, 140.4, 139.6, 137.0, 133.8, 121.8, 121.7, 118.4, 115.4, 115.3, 69.5, 60.5, 43.3, 31.0,
23.0. HRMS (ESI) m/z calcd for C20H21N2O2 [M － H]－ 321.1603; found 321.1588.
5-Fluoro-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2d). White solid (112
1
mg, 72% yield); mp 197-199 ºC. IR (KBr, ν, cm-1) 3350, 1715. H NMR (400 MHz,
DMSO-d6) δ 10.62 (s, 1H), 7.04 (t, J = 9.0 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.91 (t, J = 7.8
Hz, 2H), 6.90-6.85 (m, 1H), 6.48 (t, J = 7.2 Hz, 1H), 6.30 (s, 1H), 6.19 (d, J = 8.4 Hz, 2H),
13
4.84 (t, J = 7.0 Hz, 1H), 2.65-2.24 (m, 2H), 1.55 (s, 3H), 1.37 (s, 3H). C NMR (100 MHz,
DMSO-d6) δ 179.2, 158.6 (J = 236.0 Hz), 146.8, 137.9 (J = 2.2 Hz), 136.1, 133.0 (J = 8.0 Hz),
129.1, 116.5, 115.3 (J = 23.3 Hz), 113.6, 111.6 (J = 24.3 Hz), 111.0, 110.9, 64.9, 64.9 (J =
2.2 Hz), 38.4, 26.1, 18.1. HRMS (ESI) m/z calcd for C19H18FN2O [M － H]－ 309.1403;
found 309.1432.
5-Bromo-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2e). White solid (159
1
mg, 86% yield); mp 221-224 ºC. IR (KBr, ν, cm-1) 3341, 1710. H NMR (400 MHz,
DMSO-d6) δ 10.77 (s, 1H), 7.40 (dd, J = 8.2, 2.0 Hz, 1H), 7.26 (d, J = 1.9 Hz, 1H), 6.93 (t, J
14
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
= 7.9 Hz, 2H), 6.86 (d, J = 8.2 Hz, 1H), 6.50 (t, J = 7.3 Hz, 1H), 6.35 (s, 1H), 6.20 (d, J = 7.9
Hz, 2H), 4.86 (t, J = 7.3 Hz, 1H), 2.66-2.57 (m, 2H), 1.55 (s, 3H), 1.35 (s, 3H). 13C NMR
(100 MHz, DMSO-d6) δ 178.8, 146.7, 141.0, 136.3, 133.4, 131.7, 129.2, 126.7, 117.3, 116.4,
114.1, 113.5, 112.1, 64.7, 38.4, 26.1, 18.1. HRMS (ESI) m/z calcd for C19H19BrN2NaO [M +
Na]+ 393.0578; found 393.0569.
6-Bromo-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2f). White solid (159
1
mg, 86% yield); mp 251-253 ºC. IR (KBr, ν, cm-1) 3322, 1711. H NMR (400 MHz,
DMSO-d6) δ 10.74 (s, 1H), 7.12-7.05 (m, 2H), 7.09 (s, 1H), 6.91 (t, J = 7.8 Hz, 2H), 6.48 (t, J
= 7.2 Hz, 1H), 6.31 (s, 1H), 6.17 (d, J = 8.1 Hz, 2H), 4.85 (t, J = 7.2 Hz, 1H), 2.64-2.52 (m,
2H), 1.56 (s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 178.5, 146.1, 142.8, 135.6,
129.6, 125.2, 124.2, 120.9, 116.7, 115.9, 113.0, 112.4, 63.7, 37.7, 25.6, 17.6. HRMS (ESI)
m/z calcd for C19H19BrN2NaO [M + Na]+ 393.0578; found 393.0572.
7-Bromo-3-((4-bromophenyl)amino)-3-(3-methylbut-2-en-1-yl)indolin-2-one (2g). White
solid (179 mg, 75% yield); mp 184-186 ºC. IR (KBr, ν, cm-1) 3350, 1726. 1H NMR (400 MHz,
DMSO-d6) δ 10.94 (s, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.13-7.18 (m, 3H), 6.90 (t, J = 7.7 Hz,
1H), 6.62 (s, 1H), 6.12 (d, J = 8.8 Hz, 2H), 4.84 (t, J = 7.2 Hz, 1H), 2.63-2.57 (m, 2H), 1.55 (s,
3H), 1.33 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 178.2, 145.4, 140.4, 135.9, 131.7, 131.5,
131.2, 123.4, 122.4, 115.6, 115.0, 107.7, 102.3, 65.0, 38.0, 25.6, 17.6. HRMS (ESI) m/z calcd
for C19H17Br2N2O [M － H]－ 448.9687; found 448.9693.
3-(3-Methylbut-2-en-1-yl)-3-(p-tolylamino)indolin-2-one (2h). White solid (135 mg, 88%
yield); mp 172-174 ºC. IR (KBr, ν, cm-1) 3344, 1712. 1H NMR (400 MHz, DMSO-d6) δ 10.56
(s, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 7.2 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.87 (d, J =
15
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
7.7 Hz, 1H), 6.73 (t, J = 7.8 Hz, 1H), 6.28 (d, J = 7.4 Hz, 1H), 6.14 (s, 1H), 6.12 (s, 1H), 5.88
(d, J = 8.0 Hz, 1H), 4.83 (t, J = 7.3 Hz, 1H), 2.59-2.53 (m, 2H), 2.01 (s, 3H), 1.53 (s, 3H),
1.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 179.3, 146.9, 141.7, 137.8, 135.6, 130.9,
129.0, 128.9, 123.9, 122.1, 117.9, 116.9, 114.8, 110.5, 110.0, 64.4, 38.6, 26.2, 21.7, 18.2.
HRMS (ESI) m/z calcd for C20H21N2O [M － H]－ 305.1654; found 305.1659.
3-(3-Methylbut-2-en-1-yl)-3-(m-tolylamino)indolin-2-one (2i). White solid (126 mg, 82%
yield); mp 190-192 ºC. IR (KBr, ν, cm-1) 3316, 1710. 1H NMR (400 MHz, DMSO-d6) δ 10.58
(s, 1H), 7.20 (t, J = 7.5 Hz, 1H), 7.11 (d, J = 7.1 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.88 (d, J =
7.7 Hz, 1H), 6.74 (t, J = 7.8 Hz, 1H), 6.29 (d, J = 7.4 Hz, 1H), 6.16 (s, 1H), 6.12 (s, 1H), 5.89
(dd, J = 8.1, 1.9 Hz, 1H), 4.84 (t, J = 7.3 Hz, 1H), 2.64-2.52 (m, 2H), 2.02 (s, 3H), 1.54 (s,
3H), 1.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 179.3, 146.9, 141.7, 137.8, 135.7, 130.9,
129.0, 128.9, 123.9, 122.1, 117.9, 116.9, 114.8, 110.5, 110.0, 64.4, 38.6, 26.2, 21.7, 18.2.
HRMS (ESI) m/z calcd for C20H21N2O [M － H]－ 305.1654; found 305.1661.
3-((4-Methoxyphenyl)amino)-3-(3-methylbut-2-en-1-yl)indolin-2-one (2j). White solid
1
(129 mg, 80% yield); mp 146-148 ºC. IR (KBr, ν, cm-1) 3312, 1708. H NMR (400 MHz,
DMSO-d6) δ 10.50 (s, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 7.3 Hz, 1H), 6.92 (t, J = 7.4
Hz, 1H), 6.84 (d, J = 7.7 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 6.17 (d, J = 8.8 Hz, 2H), 5.82 (s,
1H), 4.83 (t, J = 7.2 Hz, 1H), 3.54 (s, 3H), 2.59-2.52 (m, 2H), 1.53 (s, 3H), 1.37 (s, 3H). 13C
NMR (100 MHz, DMSO-d6) δ 179.0, 151.2, 141.2, 140.4, 134.9, 130.5,128.4, 123.4, 121.5,
116.5, 114.7, 114.0, 109.5, 64.5, 55.0, 38.0, 25.6, 17.6. HRMS (ESI) m/z calcd for
C20H21N2O2 [M － H]－ 321.1603; found 321.1625.
3-((4-Bromophenyl)amino)-3-(3-methylbut-2-en-1-yl)indolin-2-one (2k). White solid (167
16
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
1
mg, 90% yield); mp 204-206 ºC. IR (KBr, ν, cm-1) 3305, 1709. H NMR (400 MHz,
DMSO-d6) δ 10.64 (s, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 7.3 Hz, 1H), 7.05 (d, J = 8.8
Hz, 2H), 6.93 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.53 (s, 1H), 6.14 (d, J = 8.8 Hz,
2H), 4.83 (t, J = 7.1 Hz, 1H), 2.63-2.56 (m, 2H), 1.53 (s, 3H), 1.35 (s, 3H). 13C NMR (100
MHz, DMSO-d6) δ 178.9, 146.2, 141.6, 135.9, 131.6, 130.1, 129.2, 123.9, 122.2, 116.6, 115.5,
110.3, 108.0, 64.4, 38.5, 26.2, 18.2. HRMS (ESI) m/z calcd for C19H18BrN2O [M － H]－
369.0603; found 369.0614.
3-(3-Methylbut-2-en-1-yl)-3-((4-(trifluoromethyl)phenyl)amino)indolin-2-one (2l). White
solid (128 mg, 71% yield); mp 162-164 ºC. IR (KBr, ν, cm-1) 3324, 1716. 1H NMR (400 MHz,
DMSO-d6) δ 10.72 (s, 1H), 7.26-7.22 (m, 3H), 7.13 (d, J = 7.2 Hz, 1H), 7.04 (s, 1H),
6.96-6.90 (m, 2H), 6.29 (d, J = 8.6 Hz, 2H), 4.84 (t, J = 7.3 Hz, 1H), 2.66-2.56 (m, 2H), 1.54
(s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 178.5, 150.0, 141.7, 136.1, 129.8,
129.4, 126.4 (J = 3.7 Hz), 125.5 (J = 268.4 Hz), 123.9, 122.3, 116.9 (J = 31.8 Hz), 116.7,
116.4, 113.0, 110.4, 64.3, 38.4, 26.2, 18.2. HRMS (ESI) m/z calcd for C20H18F3N2O [M －
H]－ 359.1371; found 359.1361.
5-Methyl-3-(3-methylbut-2-en-1-yl)-3-(p-tolylamino)indolin-2-one (2m). White solid (136
1
mg, 85% yield); mp 173-175 ºC. IR (KBr, ν, cm-1) 3371, 1706. H NMR (400 MHz,
DMSO-d6) δ 10.42 (s, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.93 (s, 1H), 6.75 (d, J = 7.8 Hz, 1H),
6.69 (d, J = 8.2 Hz, 2H), 6.11 (d, J = 8.2 Hz, 2H), 6.01 (s, 1H), 4.81 (t, J = 6.9 Hz, 1H), 2.54
(d, J = 7.3 Hz, 2H), 2.20 (s, 3H), 2.04 (s, 3H), 1.53 (s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 178.8, 144.1, 138.7, 134.9, 130.5, 130.2, 128.9, 128.6, 124.8, 123.9, 116.4,
113.3, 109.2, 64.0, 38.8, 25.6, 20.6, 19.8, 17.6. HRMS(ESI) m/z calcd for C21H25N2O [M +
17
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
H]+ 321.1967; found 321.1971.
5-Methyl-3-(3-methylbut-2-en-1-yl)-3-(o-tolylamino)indolin-2-one (2n). White solid (133
mg, 83% yield); mp 158-160 ºC. IR (KBr, ν, cm-1) 3371, 1705. 1H NMR (400 MHz, CDCl3) δ
8.72 (s, 1H), 7.02-6.97 (m, 3H), 6.77 (d, J = 7.8 Hz, 1H), 6.72 (t, J = 7.7 Hz, 1H), 6.55 (t, J =
7.3 Hz, 1H), 5.78 (d, J = 8.0 Hz, 1H), 5.30 (t, J = 7.7 Hz, 1H), 4.38 (s, 1H), 2.70-2.57(m, 2H),
13
2.26 (s, 3H), 2.23 (s, 3H), 1.78 (s, 3H), 1.72 (s, 3H). C NMR (100 MHz, CDCl3) δ 180.6,
143.3, 138.5, 137.1, 132.2, 130.9, 130.2, 129.1, 127.0, 124.4, 122.6, 118.0, 116.0, 111.4,
110.3, 64.0, 39.3, 26.2, 21.2, 18.1, 17.6. HRMS(ESI) m/z calcd for C21H23N2O [M － H]－
319.1810; found 319.1813.
3-((4-Chlorophenyl)amino)-5-methyl-3-(3-methylbut-2-en-1-yl)indolin-2-one (2o). White
solid (134 mg, 79% yield); mp 190-192 ºC. IR (KBr, ν, cm-1) 3319, 1713. 1H NMR (400 MHz,
DMSO-d6) δ 10.54 (s, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.95 (s, 2H), 6.93 (s, 1H), 6.77 (d, J =
7.8 Hz, 1H), 6.50 (s, 1H), 6.18 (d, J = 8.0 Hz, 2H), 4.79 (t, J = 6.9 Hz, 1H), 2.56 (d, J = 7.2
Hz, 2H), 2.21 (s, 3H), 1.54 (s, 3H), 1.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 183.5,
150.7, 144.0, 140.5, 135.8, 135.0, 134.2, 133.5, 129.2, 125.2, 121.5, 119.7, 114.8, 69.2, 43.3,
30.9, 25.9, 22.9. HRMS (ESI) m/z calcd for C20H21ClN2NaO [M + Na]+ 363.1240; found
363.1230.
3-((4-Bromophenyl)amino)-5-methyl-3-(3-methylbut-2-en-1-yl)indolin-2-one (2p). White
solid (156 mg, 81% yield); mp 202-204 ºC. IR (KBr, ν, cm-1) 3322, 1715. 1H NMR (400 MHz,
DMSO-d6) δ 10.50 (s, 1H), 7.03-6.98 (t, 3H), 6.90 (s, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.48 (s,
1H), 6.10 (d, J = 8.9 Hz, 2H), 4.76 (t, J = 7.4 Hz, 1H), 2.52 (d, J = 7.3 Hz, 2H), 2.17 (s, 3H),
1.50 (s, 3H), 1.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 178.7, 146.3, 139.2, 135.8,
18
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
131.6, 131.1, 130.2, 129.5, 124.4, 116.7, 115.5, 110.0, 107.9, 64.4, 38.5, 26.2, 21.1, 18.2.
HRMS (ESI) m/z calcd for C20H20BrN2O [M － H]－ 383.0759; found 383.0766.
5-Fluoro-3-(3-methylbut-2-en-1-yl)-3-(o-tolylamino)indolin-2-one (2q). White solid (118
1
mg, 73% yield); mp 190-192 ºC. IR (KBr, ν, cm-1) 3352, 1713. H NMR (400 MHz,
DMSO-d6) δ 10.62 (s, 1H), 7.00-6.94 (m, 2H), 6.89 (d, J = 7.2 Hz, 1H), 6.83-6.80 (m, 1H),
6.62 (t, J = 7.5 Hz, 1H), 6.40 (t, J = 7.3 Hz, 1H), 5.57 (d, J = 8.1 Hz, 1H), 4.89 (t, J = 7.3 Hz,
1H), 4.82 (s, 1H), 2.66-2.57 (m, 2H), 2.13 (s, 3H), 1.54 (s, 3H), 1.43 (s, 3H). 13C NMR (100
MHz, DMSO-d6) δ 179.1, 158.7 (J = 235.9 Hz), 144.0, 137.7 (J = 1.6 Hz), 136.9, 133.0 (J =
7.6 Hz), 130.5, 126.9, 123.4, 117.8, 116.5, 115.4 (J = 23.3 Hz), 113.6, 111.6 (J = 24.3 Hz),
111.1, 111.0 (J = 7.9 Hz), 64.5 (J = 1.4 Hz), 38.7, 26.2, 18.2, 18.0. HRMS (ESI) m/z calcd for
C20H20FN2O [M － H]－ 323.1560; found 323.1571.
5-Chloro-3-((4-bromophenyl)amino)-3-(3-methylbut-2-en-1-yl)indolin-2-one (2r). White
solid (156 mg, 77% yield); mp 197-199 ºC. IR (KBr, ν, cm-1) 3324, 1716. 1H NMR (400 MHz,
DMSO-d6) δ 10.76 (s, 1H), 7.24 (dd, J = 8.3, 2.1 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 7.05 (d, J
= 8.8 Hz, 2H), 6.86 (d, J = 8.3 Hz, 1H), 6.56 (s, 1H), 6.10 (d, J = 8.8 Hz, 2H), 4.79 (t, J = 7.2
Hz, 1H), 2.62-2.52 (m, 2H), 1.51 (s, 3H), 1.31 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ
178.5, 146.0, 140.6, 136.5, 132.4, 131.8, 129.1, 126.4, 124.0, 116.2, 115.5, 111.8, 108.3, 64.7,
38.2, 26.1, 18.1. HRMS (ESI) m/z calcd for C19H17BrClN2O [M － H]－ 403.0213; found
403.0194.
3-(3,4-Dichlorophenylamino)-5-chloro-3-(3-methylbut-2-enyl)indolin-2-one (2s). White
solid (142 mg, 72% yield); mp 209-211 ºC. IR (KBr, ν, cm-1) 3362, 1723. 1H NMR (400 MHz,
DMSO-d6) δ 10.89 (s, 1H), 7.31 (dd, J = 8.2, 1.9 Hz, 1H), 7.20 (s, 1H), 7.18 (s, 1H), 6.92 (d,
19
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
J = 8.3 Hz, 1H), 6.88 (s, 1H), 6.34 (d, J = 2.6 Hz, 1H), 6.16 (dd, J = 8.8, 2.6 Hz, 1H), 4.82 (t,
J = 7.1 Hz, 1H), 2.67-2.54 (m, 2H), 1.55 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 182.8, 151.5, 145.3, 141.5, 136.6, 136.1, 135.7, 134.2, 131.3, 128.9, 123.2,
120.7, 119.2, 118.6, 116.6, 69.4, 42.8, 30.9, 22.9. HRMS (ESI) m/z calcd for C19H16Cl3N2O
[M － H]－ 393.0328; found 393.0352.
5-Bromo-1-methyl-3-(3-methylbut-2-enyl)-3-(phenylamino)indolin-2-one (2t). White
solid (170 mg, 89% yield); mp 169-171 ºC. IR (KBr, ν, cm-1) 3342, 1704. 1H NMR (400 MHz,
DMSO-d6) δ 7.52 (d, J = 9.1 Hz, 1H), 7.31 (s, 1H), 7.07 (d, J = 8.3 Hz, 1H), 6.91 (t, J = 7.7
Hz, 2H), 6.49 (t, J = 7.3 Hz, 1H), 6.40 (s, 1H), 6.10 (d, J = 8.0 Hz, 2H), 4.76 (t, J = 7.1 Hz,
13
1H), 3.17 (s, 3H), 2.66-2.56 (m, 2H), 1.53 (s, 3H), 1.32 (s, 3H). C NMR (100 MHz,
DMSO-d6) δ 181.8, 151.3, 147.3, 141.4, 137.4, 136.6, 134.0, 131.0, 122.2, 120.9, 119.6,
118.3, 115.9, 69.2, 43.2, 31.4, 30.8, 22.9. HRMS(ESI) m/z calcd for C20H21BrN2NaO [M +
Na]+ 407.0735; found 407.0717.
1-Methyl-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2u). White solid (139
1
mg, 91% yield); mp 168-170 ºC. IR (KBr, ν, cm-1) 3330, 1713. H NMR (400 MHz,
DMSO-d6) δ 7.52 (d, J = 8.2 Hz, 1H), 7.30 (d, J = 1.7 Hz, 1H), 7.07 (d, J = 8.3 Hz, 1H), 6.90
(t, J = 7.8 Hz, 2H), 6.49 (t, J = 7.3 Hz, 1H), 6.38 (s, 1H), 6.10 (d, J = 8.1 Hz, 2H), 4.76 (t, J =
7.4 Hz, 1H), 3.17 (s, 3H), 2.67-2.55 (m, 2H), 1.53 (s, 3H), 1.32 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 176.4, 145.9, 142.0, 136.0, 132.1, 131.2, 128.6, 125.7, 116.8, 115.6, 114.2,
113.0, 110.5, 63.8, 37.8, 26.0, 25.5, 17.5. HRMS (ESI) m/z calcd for C20H22N2NaO [M +
Na]+ 329.1630; found 329.1626.
3-((4-Fluorophenyl)amino)-1-methyl-3-(3-methylbut-2-en-1-yl)indolin-2-one (2v). White
20
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
solid (146 mg, 90% yield); mp 132-135 ºC. IR (KBr, ν, cm-1) 3329, 1713. 1H NMR (400 MHz,
DMSO-d6) δ 7.32 (t, J = 7.7 Hz, 1H), 7.18 (d, J = 7.3 Hz, 1H), 7.07 (d, J = 7.7 Hz, 1H), 7.01
(t, J = 7.4 Hz, 1H), 6.72 (t, J = 8.9 Hz, 2H), 6.29 (s, 1H), 6.11-6.08 (m, 2H), 4.74 (t, J = 7.0
Hz, 1H), 3.16 (s, 3H), 2.60-2.57 (m, 2H), 1.51 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 177.4, 156.2 (J = 230.9 Hz), 143.4 (J = 1.4 Hz), 143.3, 136.0, 129.9, 129.3,
123.5, 122.9, 116.5, 115.5 (J = 21.9 Hz), 114.7 (J = 7.3 Hz), 109.1, 64.6, 38.6, 26.5, 26.1,
18.1. HRMS (ESI) m/z calcd for C20H21FN2NaO[M + Na]+ 347.1536; found 347.1528.
3-((4-Bromophenyl)amino)-1-methyl-3-(3-methylbut-2-en-1-yl)indolin-2-one (2w). White
solid (169 mg, 88% yield); mp 146-148 ºC. IR (KBr, ν, cm-1) 3337, 1717. 1H NMR (400 MHz,
DMSO-d6) δ 7.33 (t, J = 7.6 Hz, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H),
7.04-7.00 (m, 3H), 6.60 (s, 1H), 6.05 (d, J = 8.8 Hz, 2H), 4.74 (t, J = 7.2 Hz, 1H), 3.17 (s, 3H),
2.64-2.57 (m, 2H), 1.51 (s, 3H), 1.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 177.1, 146.1,
143.2, 136.2, 131.6, 129.5, 129.3, 123.5, 122.9, 116.3, 115.6, 109.2, 108.1, 64.3, 38.5, 26.5,
26.1, 18.1. HRMS (ESI) m/z calcd for C20H20BrN2O [M － H]－ 383.0759; found 383.0753.
3-((4-Methoxyphenyl)amino)-1,3-bis(3-methylbut-2-en-1-yl)indolin-2-one (2x). White
solid (160 mg, 82% yield); mp 99-101 ºC. IR (KBr, ν, cm-1) 3319, 1698. 1H NMR (400 MHz,
CDCl3) δ 7.32 (d, J = 7.3 Hz, 1H), 7.29-7.25 (m, 2H), 7.04 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 7.8
Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 6.23 (d, J = 8.8 Hz, 2H), 5.00 (t, J = 7.5 Hz, 2H), 4.35-4.21
(m, 2H), 4.09 (s, 1H), 3.63 (s, 3H), 2.68-2.56 (m, 2H), 1.79 (s, 3H), 1.70 (s, 3H), 1.64 (s, 3H),
1.54 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 177.6, 153.4, 139.0, 137.2, 136.5, 130.3, 128.7,
123.9, 122.5, 118.4, 117.9, 115.9, 114.3, 108.9, 65.4, 55.5, 38.7, 38.0, 26.0, 25.6, 18.1, 18.0.
HRMS (ESI) m/z calcd for C25H30N2NaO2 [M + Na]+ 413.2205; found 413.2235.
21
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
1-Benzyl-3-(3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (2y). White solid (170
1
mg, 89% yield); mp 96-98 ºC. IR (KBr, ν, cm-1) 3360, 1715. H NMR (400 MHz, CDCl3) δ
7.32-7.23 (m, 6H), 7.19 (t, J = 7.5 Hz, 1H), 7.00 (t, J = 7.5 Hz, 1H), 6.93 (t, J = 7.2 Hz, 2H),
6.76 (d, J = 7.8 Hz, 1H), 6.65 (t, J = 7.3 Hz, 1H), 6.20 (d, J = 7.7 Hz, 2H), 5.07 (t, J = 7.6 Hz,
1H), 4.96 (d, J = 15.5 Hz, 1H), 4.89 (d, J = 15.5 Hz, 1H), 4.40 (s, 1H), 2.75-2.64 (m, 2H),
13
1.67 (s, 3H), 1.57 (s, 3H). C NMR (100 MHz, CDCl3) δ 177.9, 145.3, 142.0, 137.8, 135.8,
130.1, 129.0, 128.8, 128.7, 127.6, 123.8, 122.9, 119.1, 115.7, 115.3, 109.5, 64.5, 44.1, 39.2,
26.1, 18.1. HRMS (ESI) m/z calcd for C26H26N2NaO [M + Na]+ 405.1943; found 405.1940.
Procedure for the Synthesis of Compounds 4k and 4u. Sodium bicarbonate (1.5 mmol) and
iodine (1.5 mmol) were added to compounds 2k or 2u (0.5 mmol) in anhydrous acetonitrile
(15 ml). After the mixture was stirred at room temperature for 6 h under nitrogen, the solvent
was removed under reduced pressure. To the residue was added a solution of sodium sulfite.
The mixture was extracted with dichloromethane for three times and dried over anhydrous
magnesium sulfate. The residue was purified by column chromatography (5/1 petroleum
ether/ethyl acetate) to afford the products 4k or 4u.
1'-(4-Bromophenyl)-4'-iodo-5',5'-dimethylspiro[indoline-3,2'-pyrrolidin]-2-one
(4k).
White solid (223 mg, 90% yield); mp 223-225 ºC. IR (KBr, ν, cm-1) 1712. 1H NMR (400 MHz,
DMSO-d6) δ 10.77 (s, 1H), 7.22-7.13 (m, 3H), 7.01 (d, J = 7.3 Hz, 1H), 6.89 (dd, J = 17.6,
7.7 Hz, 2H), 6.39 (d, J = 9.0 Hz, 2H), 4.72 (dd, J = 12.7, 6.2 Hz, 1H), 2.68-2.55 (m, 2H), 1.75
(s, 3H), 1.49 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 179.7, 142.4, 141.6, 131.5, 129.6,
129.4, 123.4, 123.0, 119.3, 110.7, 110.3, 71.7, 64.4, 46.8, 33.0, 26.4, 25.2. HRMS (ESI) m/z
calcd for C19H17BrIN2O [M － H]－ 494.9569; found 494.9548.
22
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
4'-Iodo-1,5',5'-trimethyl-1'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one (4u). White solid
1
(199 mg, 92% yield); mp 95-97 ºC. IR (KBr, ν, cm-1) 1715. H NMR (400 MHz, CDCl3) δ
7.29-7.25 (m, 4H), 7.06 (d, J = 6.8 Hz, 1H), 7.00 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H),
6.23 (d, J = 8.8 Hz, 2H), 4.95 (dd, J = 12.9, 6.2 Hz, 1H), 3.27 (s, 3H), 2.69-2.54 (m, 2H), 1.79
(s, 3H), 1.57 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 178.4, 142.7, 142.4, 137.5, 137.3, 129.2,
129.1, 123.5, 122.8, 121.2, 108.5, 82.2, 71.6, 64.6, 47.5, 32.7, 27.3, 26.6, 25.3. HRMS (ESI)
m/z calcd for C20H21IN2NaO [M + Na]+ 455.0596; found 455.0583.
Procedure for the Synthesis of Alcohol 5. Compound 2a (146 mg, 0.5 mmol), selenium
dioxide (28 mg, 0.25 mmol), pivalic acid (102 mg, 1.0 mmol), and dichloromethane (5 mL)
were added to a 25 mL flask. After 12 h of stirring at room temperature, the reaction mixture
was diluted with dichloromethane, washed with sat. sodium bicarbonate and brine, and
purified by column chromatography (1/1 petroleum ether/ethyl acetate) to afford alcohol 5.
3-(4-Hydroxy-3-methylbut-2-en-1-yl)-3-(phenylamino)indolin-2-one (5). White solid (116
1
mg, 75% yield); mp 101-103 ºC. IR (KBr, ν, cm-1) 3335, 1716. H NMR (400 MHz,
DMSO-d6) δ 10.63 (s, 1H), 7.22 (t, J = 7.3 Hz, 1H), 7.11 (d, J = 7.3 Hz, 1H), 6.96-6.87 (m,
4H), 6.46 (t, J = 7.2 Hz, 1H), 6.28 (s, 1H), 6.16 (d, J = 8.0 Hz, 2H), 4.97 (t, J = 7.4 Hz, 1H),
4.61 (t, J = 5.3 Hz, 1H), 3.69 (d, J = 5.1 Hz, 2H), 2.68-2.53 (m, 2H), 1.62 (s, 3H). 13C NMR
(100 MHz, DMSO-d6) δ 179.3, 146.9, 141.6, 140.4, 130.6, 129.1, 129.0, 123.9, 122.2, 118.3,
117.0, 113.5, 110.3, 64.3, 59.7, 37.9, 22.1. HRMS (ESI) m/z calcd for C19H19N2O2 [M － H]
－
307.1447; found 307.1467.
General Procedure for the Synthesis of α-Adduct 6. Cinnamyl bromide (1.0 mmol) was
added to a suspension of activated zinc powder (1.5 mmol) in dry THF (5 mL); the reaction
23
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
mixture was refluxed for 1 h. The solution was filtered through a Schlenk filter and kept
under N2 for the following reaction. Isatin-derived Imines 1 (0.5 mmol) and cinnamylzinc
bromide prepared above were added to a 15 mL sealed tube. The resulting mixture was sealed
and submerged into a 120 °C silicon oil bath. After 8 h, the solution was cooled to room
temperature and the product was purified by column chromatography (3/1 petroleum
ether/ethyl acetate) to afford α-product 6.
3-Cinnamyl-3-(phenylamino)indolin-2-one (6a). White solid (153 mg, 90% yield); mp
1
194-196 ºC. IR (KBr, ν, cm-1) 3360, 1717. H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H),
7.22-7.18 (m, 2H), 7.17-7.12 (m, 4H), 7.09 (d, J = 7.4 Hz, 1H), 6.88 (t, J = 7.5 Hz, 1H),
6.84-6.79 (m, 3H), 6.40 (t, J = 7.2 Hz, 1H), 6.27 (s, 1H), 6.25 (d, J = 16.6 Hz, 1H), 6.14 (d, J
= 8.2 Hz, 2H), 5.86 (dt, J = 15.3, 7.4 Hz, 1H), 2.77 (dd, J = 13.1, 6.5 Hz, 1H), 2.58 (dd, J =
13.1, 8.4 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ 179.0, 146.9, 141.5, 137.2, 134.3, 130.6,
129.2, 129.1, 127.9, 126.4, 124.0, 123.0, 122.3, 117.2, 113.7, 110.4, 64.7, 43.2. HRMS (ESI)
m/z calcd for C23H20N2NaO [M + Na]+ 363.1473; found 363.1491.
5-Bromo-3-cinnamyl-3-(phenylamino)indolin-2-one (6e). White solid (184 mg, 88% yield);
mp 201-203 ºC. IR (KBr, ν, cm-1) 3137, 1722. 1H NMR (400 MHz, DMSO-d6) δ 10.76 (s, 1H),
7.36 (dd, J = 8.2, 2.1 Hz, 1H), 7.26-7.21 (m, 3H), 7.20-7.15 (m, 3H), 6.89 (t, J = 7.2 Hz, 2H),
6.80 (d, J = 8.2 Hz, 1H), 6.46 (t, J = 7.3 Hz, 1H), 6.39 (s, 1H), 6.29 (d, J = 15.8 Hz, 1H), 6.16
(d, J = 7.7 Hz, 2H), 5.89-5.82 (m, 1H), 2.83 (dd, J = 13.1, 6.5 Hz, 1H), 2.64 (dd, J = 13.3, 8.5
13
Hz, 1H). C NMR (100 MHz, DMSO-d6) δ 178.5, 146.6, 140.9, 137.1, 134.7, 133.2, 132.0,
129.2, 129.1, 128.0, 126.8, 126.4, 122.5, 117.5, 114.2, 113.6, 112.3, 64.9, 43.0. HRMS (ESI)
m/z calcd for C23H18BrN2O [M － H]－ 417.0603; found 417.0625.
24
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
3-Cinnamyl-3-((4-methoxyphenyl)amino)indolin-2-one (6j). White solid (133 mg, 72%
yield); mp 167-169 ºC. IR (KBr, ν, cm-1) 3304, 1710. 1H NMR (400 MHz, DMSO-d6) δ 10.52
(s, 1H), 7.24-7.19 (m, 2H), 7.17-7.12 (m, 5H), 6.90 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 7.7 Hz,
1H), 6.48 (d, J = 9.2 Hz, 2H), 6.26 (d, J = 15.8 Hz, 1H), 6.14 (d, J = 8.9 Hz, 2H), 5.92-5.84
(m, 1H), 5.89 (s, 1H), 3.48 (s, 3H), 2.77 (dd, J = 13.3, 6.4 Hz, 1H), 2.58 (dd, J = 13.2, 8.3 Hz,
1H). 13C NMR (100 MHz, DMSO-d6) δ 179.3, 151.9, 141.6, 140.9, 137.2, 134.2, 130.9, 129.1,
129.1, 127.8, 126.4, 124.2, 123.2, 122.2, 115.4, 114.6, 110.3, 65.3, 55.6, 43.2. HRMS (ESI)
m/z calcd for C24H21N2O2 [M － H]－ 369.1603; found 369.1588.
3-((4-Bromophenyl)amino)-3-cinnamylindolin-2-one (6k). White solid (180 mg, 86%
yield); mp 191-194 ºC. IR (KBr, ν, cm-1) 3308, 1713. 1H NMR (400 MHz, DMSO-d6) δ 10.71
(s, 1H), 7.31-7.20 (m, 6H), 7.17 (d, J = 7.2 Hz, 1H), 7.07 (d, J = 8.9 Hz, 2H), 6.97 (t, J = 8.1
Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.64 (s, 1H), 6.33 (d, J = 15.8 Hz, 1H), 6.18 (d, J = 8.9 Hz,
13
2H), 5.97-5.86 (m, 1H), 2.86 (dd, J = 13.3, 6.0 Hz, 1H), 2.67 (dd, J = 13.3, 8.4 Hz, 1H). C
NMR (100 MHz, DMSO-d6) δ 178.6, 146.2, 141.5, 137.1, 134.5, 131.6, 130.0, 129.4, 129.1,
127.9, 126.4, 124.1, 122.8, 122.4, 115.6, 110.5, 108.2, 64.7, 43.1. HRMS (ESI) m/z calcd for
C23H18BrN2O [M － H]－ 417.0603; found 417.0626.
3-Cinnamyl-3-((4-(trifluoromethyl)phenyl)amino)indolin-2-one (6l). White solid (177 mg,
87% yield); mp 164-166 ºC. IR (KBr, ν, cm-1) 3313, 1715. 1H NMR (400 MHz, DMSO-d6) δ
10.78 (s, 1H), 7.30-7.17 (m, 9H), 7.13 (s, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 7.7 Hz,
1H), 6.39-6.26 (m, 3H), 5.92 (dt, J = 15.1, 7.2 Hz, 1H), 2.90 (dd, J = 13.0, 6.4 Hz, 1H), 2.71
(dd, J = 12.7, 8.6 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ 178.2, 149.9, 141.5, 137.1,
134.6, 129.6, 129.5, 129.1, 127.9, 126.5, 126.4, 125.6 (J = 268.5 Hz), 124.1, 124.0, 122.5,
25
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
122.5, 117.0 (J = 31.8 Hz), 113.0, 110.6, 64.5. HRMS (ESI) m/z calcd for C24H18F3N2O [M
－ H]－ 407.1371; found 407.1381.
3-Cinnamyl-5-fluoro-3-(o-tolylamino)indolin-2-one (6q). White solid (164 mg, 88% yield);
mp 187-189 ºC. IR (KBr, ν, cm-1) 3368, 1724. 1H NMR (400 MHz, DMSO-d6) δ 10.68 (s, 1H),
7.26-7.21 (m, 4H), 7.19-7.15 (m, 1H), 7.02-7.00 (m, 2H), 6.91 (d, J = 7.0 Hz, 1H), 6.84 (dd, J
= 9.2, 4.3 Hz, 1H), 6.64 (t, J = 7.7 Hz, 1H), 6.46-6.39 (m, 2H), 5.97 (dt, J = 15.5, 7.5 Hz, 1H),
5.60 (d, J = 7.9 Hz, 1H), 4.96 (s, 1H), 2.86 (dd, J = 13.5, 6.5 Hz, 1H), 2.73 (dd, J = 13.3, 8.2
Hz, 1H), 2.14 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 178.8, 159.7 (J = 236.3 Hz), 143.9,
137.6, 137.6, 137.1, 135.0, 132.8 (J = 7.6 Hz), 130.5, 129.1, 128.0, 126.8, 123.6, 122.8, 117.9,
115.6 (J = 23.3 Hz), 111.7 (J = 24.4 Hz), 111.5, 111.3, 111.2, 64.7 (J = 1.5 Hz), 43.3, 18.1.
HRMS (ESI) m/z calcd for C24H20FN2O[M － H]－ 371.1560; found 371.1566.
3-Cinnamyl-3-((4-fluorophenyl)amino)-1-methylindolin-2-one (6v). White solid (151 mg,
81% yield); mp 133-135 ºC. IR (KBr, ν, cm-1) 3321, 1701. 1H NMR (400 MHz, DMSO-d6) δ
7.28 (t, J = 7.6 Hz, 1H), 7.25-7.19 (m, 2H), 7.18-7.12 (m, 4H), 7.06 (d, J = 7.6 Hz, 1H), 7.00
(t, J = 7.6 Hz, 1H), 6.69 (t, J = 8.9 Hz, 2H), 6.35 (s, 1H), 6.24 (d, J = 15.8 Hz, 1H), 6.09-6.60
(m, 2H), 5.86-5.80 (m, 1H), 3.10 (s, 3H), 2.80 (dd, J = 13.5, 7.1 Hz, 1H), 2.61 (dd, J = 13.4,
8.2 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ 177.2, 155.3 (J = 231.2 Hz), 143.4, 143.4 (J =
1.7 Hz), 137.1, 134.4, 129.7, 129.4, 129.1, 127.9, 126.3, 123.8, 123.0, 122.8, 115.5 (J = 21.9
Hz), 114.8 (J = 7.3 Hz), 109.3, 64.8, 43.2, 26.6. HRMS (ESI) m/z calcd for C24H20FN2O [M
－ H]－ 371.1560; found 371.1550.
1-Benzyl-3-cinnamyl-3-(phenylamino)indolin-2-one (6y). White solid (176 mg, 82% yield);
mp 122-124 ºC. IR (KBr, ν, cm-1) 3354, 1712. 1H NMR (400 MHz, DMSO-d6) δ 7.33 (d, J =
26
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
7.1 Hz, 2H), 7.29-7.20 (m, 6H), 7.16-7.12 (m, 4H), 7.03 (t, J = 7.3 Hz, 1H), 6.97 (d, J = 7.8
Hz, 1H), 6.85 (t, J = 7.9 Hz, 2H), 6.51-6.47 (m, 2H), 6.35 (d, J = 15.8 Hz, 1H), 6.17 (d, J =
7.8 Hz, 2H), 5.82 (dt, J = 15.4, 7.4 Hz, 1H), 4.97 (d, J = 15.6 Hz, 1H), 4.89 (d, J = 15.6 Hz,
13
1H), 2.96 (dd, J = 13.3, 6.2 Hz, 1H), 2.82 (dd, J = 13.2, 8.3 Hz, 1H). C NMR (100 MHz,
DMSO-d6) δ 177.5, 146.7, 142.3, 137.0, 136.7, 134.6, 130.0, 129.3, 129.1, 129.0, 128.9,
128.0, 127.9, 127.8, 126.4, 123.9, 123.1, 122.6, 117.5, 114.0, 109.9, 64.5, 43.6, 43.5. HRMS
(ESI) m/z calcd for C30H25N2O [M － H]－ 429.1967; found 429.1987.
5-Bromo-3-cinnamyl-3-(p-tolylamino)indolin-2-one (6z). White solid (173 mg, 80% yield);
mp 196-198 ºC. IR (KBr, ν, cm-1) 3334, 1715. 1H NMR (400 MHz, DMSO-d6) δ 10.80 (s, 1H),
7.41 (dd, J = 8.2, 1.9 Hz, 1H), 7.41 (s, 1H), 7.30 (d, J = 7.2 Hz, 2H), 7.25-7.19 (m, 3H), 6.94
(t, J = 7.8 Hz, 2H), 6.85 (d, J = 8.2 Hz, 1H), 6.51 (t, J = 7.3 Hz, 1H), 6.43 (s, 1H), 6.35 (d, J =
15.8 Hz, 1H), 6.22 (d, J = 8.1 Hz, 2H), 5.91 (dt, J = 15.3, 7.3 Hz, 1H), 3.33 (s, 3H), 2.88 (dd,
J = 13.0, 6.5 Hz, 1H), 2.69 (dd, J = 12.9, 8.5 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ
177.9, 146.0, 140.3, 136.5, 134.1, 132.7, 131.4, 128.6, 128.6, 127.4, 126.2, 125.8, 122.0,
116.9, 113.6, 113.0, 111.8, 64.3, 42.4. HRMS (ESI) m/z calcd for C24H21BrN2NaO [M + Na]+
455.0735; found 455.0717.
Procedure for the Synthesis of α-Adduct 7. Geranyl bromide (1.0 mmol) and lithium
chloride (2.0 mmol) was added to a suspension of activated zinc powder (1.5 mmol) in dry
THF (5 mL); the reaction mixture was stirred for 1 h at room temperature. The solution was
filtered through a Schlenk filter and kept under N2 for the following reaction. Imine 1t (157
mg, 0.5 mmol) and geranylzinc bromide prepared above were added to a 15 mL sealed tube.
The resulting mixture was sealed and submerged into a 120 °C silicon oil bath. After 8 h, the
27
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
solution was cooled to room temperature and the product was purified by column
chromatography (3/1 petroleum ether/ethyl acetate) to afford α-product 7.
(E)-5-Bromo-3-(3,7-dimethylocta-2,6-dien-1-yl)-1-methyl-3-(phenylamino)indolin-2-one
(7). White solid (176 mg, 78% yield); mp 113-115 ºC. IR (KBr, ν, cm-1) 3348, 1704. 1H NMR
(400 MHz, CDCl3) δ 7.45 (dd, J = 8.2, 2.0 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 6.98 (dd, J = 8.5,
7.4 Hz, 2H), 6.78 (d, J = 8.2 Hz, 1H), 6.66 (t, J = 7.4 Hz, 1H), 6.17-6.13 (m, 2H), 5.04 (t, J =
7.4 Hz, 2H), 4.37 (s, 1H), 3.24 (s, 3H), 2.70-2.64 (m, 1H), 2.89-2.53 (m, 1H), 2.02-1.96 (m,
4H), 1.67 (s, 3H), 1.59 (s, 3H), 1.55 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 177.3, 144.9,
142.2, 141.7, 132.3, 131.9, 131.7, 129.1, 126.9, 123.8, 119.1, 119.0, 115.8, 114.9, 114.4,
114.4, 109.7, 64.4, 40.0, 39.0, 26.7, 26.4, 25.7, 17.8, 16.4. HRMS (ESI) m/z calcd for
C25H29BrN2NaO [M + Na]+ 475.1361; found 475.1337.
ACKNOWLEDGMENTS
This work was supported by the Science and Technology Support Program of Jiangsu
Province (BE2017643) and the Open Project Program of the State Key Laboratory for
Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University
(CMEMR2017-B11).
REFERENCES
[1] E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257-10274.
[2] a) M. Ochi, K. Kawasaki, H. Kataoka, Y. Uchio, H. Nishi, Biochem. Bioph. Res. Comm.
2001, 283, 1118-1123; b) R. S. Kumar, S. M. Rajesh, S. Perumal, D. Banerjee, P. Yogeeswari,
28
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800881
European Journal of Organic Chemistry
D. Sriram, Eur. J. Med. Chem. 2010, 45, 411-422; c) M. Schoenberger, C. Leggett, S. W.
Kim, J. M. Hooker, Bioorg. Med. Chem. Lett. 2010, 20, 3103-3106; d) H. Turner, Future Med.
Chem. 2016, 8, 227-238.
[3] a) A. K. Ghosh, G. Schiltz, R.S. Perali, S. Leshchenko, S. Kay, D. E. Walters, Y. Koh, K.
Maeda, H. Mitsuya, Bioorg. Med. Chem. Lett. 2006, 16, 1869-1873; b) N. Takahashi, T. Ito,
Y. Matsuda, N. Kogure, M. Kitajima, H. Takayama, Chem. Commun. 2010, 46, 2501-2503; c)
C. H. Wang, J. Reilly, N. Brand, S. Schwartz, S. Alluri, T. M. Chan, A. V. Buevich, A. K.
Ganguly, Tetrahedron Lett. 2010, 51, 6213-6215; d) C. H. Wang, A. R. White, S. N.
Schwartz, S. Alluri, T. M. Cattabiani, L. K. Zhang, T. M. Chan, A. V. Buevich, A. K.
Ganguly, Tetrahedron 2012, 68, 9750-9762.
[4] a) G. Lesma, N. Landoni, T. Pilati, A. Sacchetti, A. Silvani, J. Org. Chem. 2009, 74,
4537-4541; b) B. Alcaide, P. Almendros, C. Aragoncillo, Eur. J. Org. Chem. 2010, 2010,
2845-2848; c) Z.-Y. Cao, Y. Zhang, C.-B. Ji, J. Zhou, Org. Lett. 2011, 13, 6398-6401; d) S.
Nakamura, K. Hyodo, M. Nakamura, D. Nakane, H. Masuda, Chem. Eur. J. 2013, 19,
7304-7309; e) D. Chen, M.-H. Xu, Chem. Commun. 2013, 49, 1327-1329; f) T. Chen, C. Cai,
Org. Biomol. Chem. 2016, 14, 5019-5022.
[5] Q. Tan, X. Wang, Y. Xiong, Z. Zhao, L. Li, P. Tang, M. Zhang, Angew. Chem., Int. Ed.
2017, 56, 4829-4833.
[6] a) V. P. Papageorgiou, A. N. Assimopoulou, E. A. Couladouros, D. Hepworth, K. C.
Nicolaou, Angew. Chem., Int. Ed. 1999, 38, 271-300; b) M. Wang, X. Feng, L. Cai, Z. Xu, T.
Ye, Chem. Commun. 2012, 48, 4344-4346; c) K. Kitahara, J. Shimokawa, T. Fukuyama,
Chem. Sci. 2014, 5, 904-907; d) Y. Taniguchi, M. Yamada, H. Taniguchi, Y. Matsukura, K.
29
This article is protected by copyright. All rights reserved.