Cerium(IV) ammonium nitrate: Reagent for the versatile oxidative functionalization of styrenes using N-hydroxyphthalimide

Article abstract of DOI:10.1016/j.tet.2019.03.030

Cerium(IV) ammonium nitrate was found to be a versatile reagent for the oxidative functionalization of styrenes using N-hydroxyphthalimide and iodine affording three different types of products with oxyphthalimide, nitrate and iodide groups. It was shown

Full text of DOI:10.1016/j.tet.2019.03.030

Accepted Manuscript
Cerium(IV) ammonium nitrate: Reagent for the versatile oxidative functionalization of
styrenes using N-hydroxyphthalimide
Igor B. Krylov, Stanislav A. Paveliev, Olesya K. Matveeva, Alexander O. Terent'ev
PII:
S0040-4020(19)30317-5
https://doi.org/10.1016/j.tet.2019.03.030
TET 30216
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 December 2018
Revised Date: 12 March 2019
Accepted Date: 16 March 2019
Please cite this article as: Krylov IB, Paveliev SA, Matveeva OK, Terent'ev AO, Cerium(IV) ammonium
nitrate: Reagent for the versatile oxidative functionalization of styrenes using N-hydroxyphthalimide,
Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.03.030.
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Cerium(IV) ammonium nitrate: reagent for
the versatile oxidative functionalization of
styrenes using N-hydroxyphthalimide
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Igor B. Krylov, Stanislav A. Paveliev, Olesya K. Matveeva and Alexander O. Terent’ev

1
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Tetrahedron
journal homepage: www.elsevier.com
Cerium(IV) ammonium nitrate: reagent for the versatile oxidative functionalization of
styrenes using N-hydroxyphthalimide
Igor B. Krylov a,b, Stanislav A. Paveliev a, Olesya K. Matveeva a,c and Alexander O. Terent’ev a,b,c
a N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., Moscow 119991, Russian Federation
b All-Russian Research Institute for Phytopathology, B. Vyazyomy, Moscow Region 143050, Russian Federation
c D. I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, Moscow 125047, Russian Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Cerium(IV) ammonium nitrate was found to be a versatile reagent for the oxidative
functionalization of styrenes using N-hydroxyphthalimide and iodine affording three different
types of products with oxyphthalimide, nitrate and iodide groups. It was shown that reaction of
styrenes with N-hydroxyphthalimide and cerium(IV) ammonium nitrate can be selectively
directed to oxynitro-oxyphthalimides and dioxyphthalimides depending on the reaction
conditions, in particular a solvent. Reaction of styrenes with iodine under the action of N-
hydroxyphthalimide and cerium(IV) ammonium nitrate leads to the formation of iodo-
oxyphthalimides.
Available online
Dedicated to Corresponding Member of the Russian
Academy of Sciences G. I. Nikishin on the occasion
of his 90th birthday.
Keywords:
free radicals;
2019 Elsevier Ltd. All rights reserved
.
imide-N-oxyl radicals;
N-hydroxyimides;
oxidative functionalization;
cerium(IV) ammonium nitrate
1. Introduction
Recently, N-hydroxyphthalimide has gained growing interest
in PINO-mediated difunctionalization of styrenes to obtain
oxygenated products.26-39 The use of various oxidants allows to
implement oxyimidation in conjunction with oxynitration,40
iodination,41,42 or double oxyimidation of styrenes43 (Scheme 1).
Cerium(IV) compounds hold a special place among the
variety of oxidants used in organic synthesis. The high redox
potential (+1.61 V vs NHE), low toxicity, ease of handling,
commercial availability and high solubility in organic solvents
favorably distinguishes Ce(IV) and its compounds from other
transition metals. Ce(IV) salts, especially cerium(IV) ammonium
nitrate (CAN, (NH4)2Ce(NO3)6) are widely used as an effective
single-electron oxidant in various oxidation1-3 and oxidative
coupling4-9 reactions. Large number of papers is devoted to CAN-
catalyzed processes.10,11
CAN is known to generate radicals from 1,3-dicarbonyl
compounds,12,13 azide anions,14,15 thiocyano-anions6,15 and
sulfinates.16 Under the action of CAN, N-hydroxyphthalimide
(NHPI) is oxidized to the phthalimide-N-oxyl (PINO) radical,17
which is the effective mediator of aerobic oxygenation and
various processes of C-H functionalization.18-22 The CAN/NHPI
system was employed in the aerobic oxidation of aromatic
alcohols,23 Ritter-type amidation of alkanes and alkylarenes,24
benzylic oxynitration25 and oxyimidation17.
Scheme 1. The present work is in the context of the oxidative
oxynitration-oxyimidation (I), dioxyimidation (II) and iodo-
oxyimidation (III) of styrenes using N-hydroxyphthalimide.
———
Corresponding author. Tel.: +7-916-385-4080; e-mail: terentev@ioc.ac.ru

2
Tetrahedron
ACCEPTED MANUSCRIPT
Table 1. Screening of the conditions of the reaction of styrene 1a with N-hydroxyphthalimide 2 and CAN. a
Entry Molar ratio 1a/2 Molar ratio CAN/2 Solvent
Time, h Yield of 3a b (%) Yield of 4 b (%) Yield of 5a b (%)
1
2
3
3
2
3
2
2
3
3
3
1
1
1.5
3
3
3
3
3
3
3
3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
AcOH
acetone
MeOH
MeOH
MeOH
MeOH
2
26 (14)
40 (29)
41 (31)
30
<5
12
47
15
9
2 c
3 c
4 c
5 c
6 c,d
7
2
2
2
2
16
1
2
13
10
7
1
2
27
20
2
2
55 (45)
10
<5
8
10
46
65
53 (42)
56
53
74 (65)
68
61
68
53
66
32
5
2
2
8
2
2
9
<5
<5
<5
<5
<5
<5
<5
<5
<5
<5
21
9
2
2
5
10
11
12
13
14
15
16
17
18
19 e
20 c,e
0.5
0.5
0.5
2
2
<5
0.5
0.5
<5
<5
EtOAc/H2O (2/1) 0.5
<5
2
PhMe/H2O (2/1)
DCM/H2O (2/1)
0.5
0.5
<5
2
<5
2
AcOH/H2O (2/1) 0.5
MeCN/H2O (2/1) 0.5
14
2
12
2
dioxane
dioxane
MeCN
2
2
2
10
2
<5
32 (20)
2
19
28
8
a General reaction conditions: CAN (1.0-3.0 mmol) was added to a mixture of styrene 1a (0.5-2.0 mmol) and N-hydroxyphthalimide 2 (1.0 mmol) in a solvent
(6.0 mL), and stirred at 20-25 °C for 0.5-2 h under air atmosphere. For entries with a mixture of solvents, v/v ratio is in parentheses.
b Yield was determined by 1H NMR spectroscopy using p-methoxyacetophenone as an internal standard; isolated yields are given in parentheses.
c Solution of N-hydroxyphthalimide 2 in MeCN (15.0 mL) was added dropwise for 30 min to the mixture of styrene 1a and CAN in MeCN (3.0 mL).
d At 0 °C, under argon atmosphere.
e Under O2 atmosphere.
In this work, the combination of CAN and NHPI is proposed
as a versatile system for selective difunctionalization of styrenes,
opening the direct way to three different types of products.
The optimal molar ratio of styrene 1a, N-hydroxyphthalimide 2
and CAN, allowing to obtain the product 3a with the yield of
41%, was 2:1:2 (Table 1, entry 3). In these conditions the yields
of side-products were 16% for 4 and 9% for 5a. Carrying out the
reaction in an inert atmosphere at 0 °C allowed to almost
completely avoid the formation of side-products 4 and 5a, and
thereby the yield of nitrate ester 3a increased to 55% (Table 1,
entry 6).
2. Results and discussion
In the present work, the oxidative difunctionalization of
styrenes under the action of N-hydroxyphthalimide 2 and
cerium(IV) ammonium nitrate was carried out. At the first stage
the model reaction of styrene 1a with N-hydroxyphthalimide 2
and CAN was examined (Table 1). In the experiment (Table 1,
entry 1, in MeCN) with the molar ratio styrene 1a:NHPI 2:CAN
= 2:1:3 dioxyphthalimide 5a was identified as the main product
with the 47% yield along with the high amount of nitrate ester 3a
(26% yield). The goal of our research was to find the optimal
condition for the selective synthesis of the products 3a and 5a.
When using AcOH, acetone or MeOH (Table 1, entries 7-12),
as well as binary single- or two-phase systems (EtOAc, PhMe,
DCM, AcOH and MeCN mixed with H2O, Table 1, entries 13-
17) as a solvent with the ratio of styrene 1a:NHPI 2:CAN = 2:1:3
the main pathway of the reaction was the double addition of N-
hydroxyphthalimide 2 to the C=C bond of styrene 1a with the
formation of dioxyimide 5a. The highest yield (74%) of 5a was
achieved by carrying out the reaction in MeOH with the molar
ratio of styrene 1a, NHPI 2 and CAN 0.5:1:1.5 (Table 1, entry
12). In the reaction of styrene 1a with N-hydroxyphthalimide 2 in
dioxane (Table 1, entries 18 and 19) keto-oxyimide 4 was
observed as one of the major product, and in the reaction under
oxygen atmosphere (Table 1, entry 19) the yield of 4 was 32%.
Comparable yield of the product 4 (28%) was obtained using
MeCN as the solvent (Table 1, entry 20).
The influence of reaction parameters on the yield of nitrate
ester 3a was evaluated in entries 2-6. In order to decrease the
yield of dioxyphthalimide 5a a solution of N-hydroxyphthalimide
2 was added dropwise to the mixture of styrene 1a and CAN in
MeCN. Slow addition of N-hydroxyphthalimide improved the
yield of 3a to 40% (Table 1, entry 2). Molar ratio of styrene 1a,
N-hydroxyphthalimide 2 and CAN was optimized in entries 3-6.

3
Table 2. Scope of the oxynitration-oxyimidation of
Table 3. Dioxyimidation of styrenes 1a,c,d and esters 1j,k
with N-hydroxyphthalimide 2 under the action of CAN. a
ACCEPTED MANUSCRIPT
vinylarenes 1a-h with N-hydroxyphthalimide 2 under the
action of CAN. a
ONO2
O
O
N
Cl
O
5a (65)
5c (50)
5d (36)
3a (45)
3d (55)
3b (60)
3e (51)
3c (62)
3f (43)
5j (66)
a Reaction conditions: vinyl substrate 1a,c,d,j,k (0.5 mmol), N-
5k (64)
hydroxyphthalimide 2 (1.0 mmol), CAN (1.5 mmol), MeOH (6.0 mL), at 20-
25 °C for 30 min under air atmosphere. b Isolated yield.
3g (56)
3h (69)
It was found, that the formation of products containing iodine
atom in the benzylic position occurred. The influence of the
nature of a solvent, as well as oxidant and a source of iodine on
the yield of iodo-oxyimide 6a was studied in the model reaction
of styrene 1a with iodine under the action of N-
hydroxyphthalimide 2 (Table 4).
a Reaction conditions: solution of N-hydroxyphthalimide 2 in MeCN (15.0
mL) was added dropwise for 30 min to a mixture of vinylarene 1a-h (2.0
mmol) and CAN (2.0 mmol) in MeCN (3.0 mL), and then stirred at 0 °C for 2
h under argon atmosphere. b Isolated yield.
In order to study the scope of the developed method
vinylarenes 1b-h were involved in the reaction under optimized
conditions for the synthesis of 3a (Table 1, entry 6) to obtain
nitrate esters 3b-i with yield from 43% to 69% (Table 2).
The direction of the process is highly dependent on the nature
of a solvent. Thus, carrying out the reaction in MeOH, MeCN,
DCM, H2O or MeCN/H2O mixture (Table 4, entries 1-5) resulted
in the formation of product 6a with the yield of 11-42%. Two-
phase DCM/H2O system permitted to increase the yield of
compound 6a to 70% (Table 4, entry 6). With the use of
DCM/H2O system molar ratio of starting reagents and the iodine
source were optimized (Table 4, entries 7-11). The optimal ratio
of CAN to NHPI is 1.5; the reaction with 1.2 equivalents of CAN
(Table 4, entry 7) led to the formation of product 6a with the
decreased yield (64% vs 70% with 1.5 equiv. of CAN).
Employing NaI•2H2O, TBAI or NH4I as the iodine source (Table
4, entries 8-10) product 6a was obtained with the yields
comparable to the reaction with molecular iodine, but in these
cases, it was necessary to use a large amount of oxidizing agent.
The introduction of twofold molar excess of styrene 1a allowed
us to obtain 6a in 86% yield (Table 4, entry 11).
The obtained results show that the reaction has general
character, and successfully proceeds with styrenes bearing both
electron-withdrawing substituents in the aromatic ring – Cl (3c,
62%), F (3d, 55%) and Br (3f, 43%), and electron-donating
methyl group (3b, 3e, 3g, 51-60%). Reaction with indene 1h
gave product 3h with the yield of 69%.
Treatment of terminal olefins – 1-hexene, 1-octene, and
allylbenzene with NHPI/CAN system led to a complex mixture
of products presumably due to the numerous side processes of
oxidation of the allylic methylene fragment.18
Using optimized conditions for the synthesis of 5a (Table 1,
entry 12), dioxyimides 5c,d were obtained from styrenes 1c,d
with the yields of 50% and 36%, respectively (Table 3). It was
found that the reaction scope was not limited to the vinylarenes.
In the reaction of vinyl acetate 1j and methyl acrylate 1k with N-
hydroxyphthalimide 2 and CAN under the optimal conditions for
dioxyimidation (Table 1, entry 12), as well as using the
conditions for oxynitration-oxyimidation (Table 1, entry 6) only
dioxyimides 5j and 5k were isolated with 66% (dioxyimidation
conditions; 78% – oxynitration-oxyimidation conditions) and
Among
the
other
tested
metal-based
oxidants
(NH4)4Ce(SO4)4•2H2O, Ce(SO4)2 and Mn(OAc)3•2H2O showed
good results (Table 4, entries 12, 13 and 16, yield of 6a 60-66%).
Catalytic oxidative system of Ce(IV)/KBrO3 (Table 4, entry 14,
yield of 6a 10%)44 and Ce(IV)/Ag(II)/(NH4)2S2O8 (Table 4, entry
15, yield of 6a 43%)45 exhibited poor efficacy in the iodo-
oxyimidation of styrene 1a. When Fe(ClO4)3•8H2O and
Pb(OAc)4 were used the yield of the desired product 6a did not
exceed 34% (Table 4, entries 17-19).
64% (dioxyimidation conditions; 36%
oxyimidation conditions) yields.
–
oxynitration-
Based on the literature data40,41 we assumed that the reaction
of styrenes with N-hydroxyphthalimide and cerium(IV)
ammonium nitrate proceeds through the formation of stable
benzylic radical. Aiming to expand synthetic applicability of this
process with the radical formation I2 was introduced into the
reaction with styrenes under the action of NHPI and CAN.
With the optimal conditions (Table 4, entry 11) for the
synthesis of 6a in hands, we obtained iodo-oxyimides 6b-i with
the yields from 62% to 72% in the reactions with vinylarenes 1b-
h and vinyl acetate 1i (Table 5). The reaction was successful with
styrenes bearing Cl, F and Br atoms (products 6c, 6d, 6f, yield
70-72%).

4
Tetrahedron
hydroxyphthalimide, cerium(IV) ammonium nitrate and I2 was
Table 4. Optimization of the iodo-oxyimidation of styrene
ACCEPTED MANUSCRIPT
proposed (Scheme 3).
1a under the action of the N-hydroxyphthalimide 2, iodine
and oxidant with the formation of product 6a. a
Table 5. Scope of the iodo-oxyimidation of vinylarenes 1a-i
and vinyl acetate 1j with N-hydroxyphthalimide 2 under the
action of I2 and CAN. a
Oxidant (molar ratio:
mol/mol of 2)
Yield of
Entry
Solvent
6a b (%)
1
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.5)
(NH4)2Ce(NO3)6 (1.2)
(NH4)2Ce(NO3)6 (3.0)
(NH4)2Ce(NO3)6 (3.0)
(NH4)2Ce(NO3)6 (3.0)
(NH4)2Ce(NO3)6 (1.5)
(NH4)4Ce(SO4)4•2H2O (1.5)
Ce(SO4)2 (1.5)
MeOH
14
42
11
27
32
70
64
71
70
48
86
66
60
2
MeCN
3
DCM
4
H2O
5
MeCN/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
DCM/H2O (2/1)
6
6a (86)
6d (70)
6b (64)
6e (66)
7
6c (72)
6f (71)
8 c
9 d
10 e
11 f
12
13
6g (67)
(NH4)2Ce(NO3)6 (0.1)
KBrO3 (1.0)
14 g
DCM/H2O (2/1)
DCM/H2O (2/1)
10
43
6h (62)
6j (65)
(NH4)4Ce(SO4)4•2H2O (0.05)
[Ag(bipy)2]S2O8 (0.1)
(NH4)2S2O8 (3.0)
15 h
16
17
18
19
Mn(OAc)3•2H2O (1.5)
Fe(ClO4)3•8H2O (1.5)
Fe(ClO4)3•8H2O (1.5)
Pb(OAc)4 (0.6)
AcOH
65
MeCN
13
6i (53), dr = 1:1
DCM/H2O (2/1)
DCM
ND
34
a Reaction conditions: vinyl substrate 1a-j (2.0 mmol), N-hydroxyphthalimide
2 (1.0 mmol), I2 (0.5 mmol), CAN (1.5 mmol), DCM/H2O (2:1 v/v, 6.0 mL),
at 20-25 °C for 30 min under air atmosphere. b Isolated yield.
a General reaction conditions: oxidant (0.6-3.0 mmol) was added to a mixture
of styrene 1a (1.0 mmol), N-hydroxyphthalimide 2 (1.0 mmol) and I2 (0.5
mmol) in a solvent (6.0 mL), and stirred at 20-25 °C for 30 min under air
atmosphere. For entries with mixture of solvents, v/v ratio is in the
parentheses. ND = Not detected.
The applicability of the developed method for carrying out
synthesis on a gram scale was demonstrated by the preparation of
compounds 3a and 6a with the yields of 38% and 80%,
respectively (Scheme 2).
b Isolated yield.
ONO2
O
O
c NaI•2H2O (1.0 mmol) was employed.
d TBAI (1.0 mmol) was employed.
e NH4I (1.0 mmol) was employed.
f Styrene 1a (2.0 mmol) was employed.
g Reaction time 1 h.
O
CAN (10 mmol, 5.48 g)
MeCN, 0° C, Ar, 2 h
N
+
N
OH
O
O
1a
2
3a (0.63 g, 38%)
(10 mmol, 1.04 g) (5 mmol, 0.816 g)
I
O
O
I2 (2.5 mmol, 0.635 g)
CAN (7.5 mmol, 4.11 g)
O
N
+
N
OH
DCM/H2O (2:1 v/v)
rt, 30 min
h Reaction time 2 h.
O
O
1a
2
6a (1.57 g, 80%)
The iodo-oxyimidation of styrenes with methyl group in the
aromatic ring proceeds with slightly lower yields, products 6b, 6e
and 6g were isolated with yields from 64% to 67%. When indene
1h was introduced into the reaction, product 6h was obtained
with the yield of 62%; β-methyl styrene 1i gave equimolar
mixture of diastereomeric iodo-oxyimides with the total yield of
53% (Table 5, 6i). Vinyl acetate 1j gave the product of iodo-
oxyimidation 6j in 65% yield.
(10 mmol, 1.04 g) (5 mmol, 0.816 g)
Scheme 2. Gram-scale synthesis of the compounds 3a and 6a.
At the first stage, N-hydroxyphthalimide 2 is oxidized by
CAN to form phthalimide-N-oxyl radical (PINO), which adds to
a terminal carbon atom of the double C=C bond of styrene 1
giving benzylic radical A, which can undergo further
transformations, depending on the solvent and order of addition
of reagents, by radical or ionic routes. In the presence of the large
amount of NHPI in a solution PINO is generated more efficiently
and it traps intermediate A with the formation of product 3.
When I2 is in the reaction medium, it traps radical A to form
product 4.41,42 In the case when NHPI is added dropwise to the
On the basis of our previous experience41 and literature data
describing the reaction of N-hydroxyphthalimide with CAN17 and
the addition of resulting O-centered radical to styrenes,40,41
a
mechanism of the interaction of styrenes with N-

5
mixture of styrene 1 and CAN, concentration of PINO is low and
radical A undergo oxidation by Ce(IV) to form carbocation B,
turnings. Toluene (PhMe) was distilled over sodium metal.
ACCEPTED MANUSCRIPT
which reacts with NO3 anion yielding nitrate ester 5.46
Acetone was distilled over KMnO4. Glacial acetic acid (AcOH)
and dioxane were used as is from commercial sources.
-
Vinylarenes 1a-i, vinyl acetate 1j, methyl acrylate 1k, N-
hydroxyphthalimide (NHPI) 2, cerium(IV) ammonium nitrate
(CAN, (NH4)2Ce(NO3)6), cerium(IV) ammonium sulfate
dihydrate
(Ce(SO4)2),
((NH4)4Ce(SO4)4•2H2O),
potassium bromate
cerium(IV)
(KBrO3),
sulfate
ammonium
peroxydisulfate ((NH4)2S2O8), manganese(III) acetate dihydrate
(Mn(OAc)3•2H2O), iron(III) perchlorate hydrate
(Fe(ClO4)3•nH2O) (anhydrous basis purity ca. 65%), lead(IV)
tetraacetate (Pb(OAc)4), sodium iodide dihydrate (NaI•2H2O),
tetrabutylammonium iodide (TBAI) and ammonium iodide
(NH4I) were commercial reagents (Acros, Sigma, Alfa Aesar).
Tetrakis(bipyridine)silver(II) peroxydisulfate ([Ag(bipy)2]S2O8)
was synthesized according to the literature.47
Scheme 3. Mechanism of oxidative difunctionalization of
styrene 1 under the action of N-hydroxyphthalimide 2,
cerium(IV) ammonium nitrate and I2.
All the new compounds (3d, 5j, 5k and 6j) were characterized
1
using H and 13C NMR spectroscopy, FT-IR spectroscopy, HR-
3. Conclusion
MS and/or elemental analysis. Compounds 3d and 5d were
characterized using 19F spectroscopy. 1H and 13C NMR spectra of
the known compounds (3a-c, 3e-i, 4, 5a,c,d and 6a-i) were in
agreement with the literature data.31,40,41,43
Tunable difunctionalization of styrenes using cerium(IV)
ammonium nitrate/N-hydroxyphthalimide system was developed.
Depending on the reaction conditions, such as nature of a solvent,
molar ratio of starting reagents and temperature, vicinal oxynitro-
oxyphthalimides or dioxyphthalimides were synthesized.
Reaction of styrenes with iodine in the presence of N-
hydroxyphthalimide and cerium(IV) ammonium nitrate affords
iodo-oxyimides. Besides styrenes, electron-deficient and
electron-rich vinyl-containing substrates, such as vinyl acetate
and methyl acrylate were successfully introduced in the reaction
with NHPI/CAN system. The proposed mechanism involves the
generation of phthalimide-N-oxyl radical, its addition to a
terminal carbon atom of the double C=C bond resulting C-
centered benzyl radical, which transformations via ionic or
radical path determine the structure of the reaction product.
4.2. Experimental procedure for Table 1
N-hydroxyphthalimide 2 (163 mg, 1.0 mmol) and CAN (548-
1644 mg, 1.0-3.0 mmol) were added to a stirred solution of
styrene 1a (52-208 mg, 0.5-2.0 mmol) in MeCN, AcOH, acetone,
EtOAc/H2O, PhMe/H2O, DCM/H2O, AcOH/H2O or dioxane (6.0
mL; for the mixture of solvents the ratio was 2:1 v/v) at 20-25 °C
under air atmosphere. In the entries 2-6 solution of N-
hydroxyphthalimide 2 (163 mg, 1.0 mmol) in MeCN (15 mL)
was added dropwise for 30 min to the mixture of styrene 1a (104-
208 mg, 1.0-2.0 mmol) and CAN (1096-1644 mg, 2.0-3.0 mmol)
in MeCN (3 mL). In the entry 6 reaction was carried out at 0 °C
under argon atmosphere. After stirring the reaction mixture at 20-
25 °C for 0.5-2 h, aqueous solution of Na2S2O4 (200 mg in 30 mL
of water) was added and the mixture was extracted with DCM
(3×10 mL), combined extracts were washed with saturated
aqueous NaHCO3 solution (20 mL), then with water (20 mL),
dried over anhydrous Na2SO4 and filtered. DCM was rotary
evaporated at 40-45 °C under reduced pressure (20-30 mmHg).
The yields of products 3a, 4 and 5a were determined by 1H NMR
spectroscopy using p-methoxyacetophenone as the internal
standard. In the selected entries (1, 2, 3, 6, 9, 12 and 19) desired
product was isolated by column chromatography on silica gel
using DCM/EtOAc mixture as eluent (with the volume part of
EtOAc gradually increased from 0% to 3%).
4. Experimental part
4.1. General methods
1H and 13C NMR spectra were recorded on Bruker AVANCE
II 300 spectrometer (300.13 MHz and 75.47 MHz, respectively)
in CDCl3. Chemical shifts were reported in parts per million
(ppm), and the residual solvent peak was used as an internal
1
reference: H (CDCl3 δ=7.26 ppm), 13C (CDCl3 δ=77.16 ppm).
Multiplicity was indicated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), dd (doublet of doublets), dt (doublet of
triplets), td (triplet of doublets), m (multiplet).
High-resolution mass spectra (HR-MS) were measured on a
Bruker maXis instrument using electrospray ionization (ESI).
The measurements were performed in a positive ion mode
(interface capillary voltage – 4500 V); mass range from m/z 50 to
m/z 3000 Da; external calibration with Electrospray Calibrant
Solution (Fluka). A syringe injection was used for all acetonitrile
solutions (flow rate 3 µL/min). Nitrogen was applied as a dry
gas; interface temperature was set at 180 °C.
4.2.1. 2-((1,3-dioxoisoindolin-2-yl)oxy)-1-
phenylethyl nitrate (3a)
1
White solid: 45% yield (148 mg); mp = 112-114 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.90-7.73 (m, 4H), 7.42-7.35 (m, 5H),
6.30 (dd, J1 = 9.4 Hz, J2 = 3.0 Hz, 1H), 4.55 (dd, J1 = 12.6 Hz, J2
= 9.4 Hz, 1H), 4.35 (dd, J1 = 12.6 Hz, J2 = 3.0 Hz, 1H). 13C NMR
(75.47 MHz, CDCl3): δ = 163.5, 134.9, 133.6, 129.9, 129.2,
128.8, 126.9, 123.9, 82.7, 77.3.
The TLC analysis was carried out on standard silica gel
chromatography plates (ALUGRAMR Xtra SIL G/UV254).
Column chromatography was performed using silica gel (0.060-
0.200 mm, 60 A, CAS 7631-86-9, Acros).
4.2.2. 2-(2-oxo-2-phenylethoxy)isoindoline-1,3-
dione (4)
1
White solid: 20% yield (56 mg); mp = 177-178 °C. H NMR
Column chromatography was performed using silica gel
(0.060-0.200 mm, 60 Å, Acros).
(300.13 MHz, CDCl3): δ = 8.03-7.94 (m, 2H), 7.87-7.70 (m, 4H),
7.65-7.56 (m, 1H), 7.54-7.44 (m, 2H), 5.44 (s, 2H). 13C NMR
(75.47 MHz, CDCl3): δ = 192.3, 163.1, 134.8, 134.5, 134.2,
129.0, 128.7, 128.4, 123.8, 78.6.
Dichloromethane (DCM) was distilled over K2CO3.
Acetonitrile (MeCN) and ethyl acetate (EtOAc) were distilled
over P2O5. Methanol (MeOH) was distilled over magnesium

6
Tetrahedron
ACCEPTED MANUSCRIPT
4.2.3. 2,2'-((1-phenylethane-1,2-
diyl)bis(oxy))bis(isoindoline-1,3-dione) (5a)
6.29 (dd, J1 = 9.4 Hz, J2 = 2.9 Hz, 1H), 4.56 (dd, J1 = 12.6 Hz, J2
= 9.4 Hz, 1H), 4.36 (dd, J1 = 12.6 Hz, J2 = 2.9 Hz, 1H), 2.37 (s,
3H). 13C NMR (75.47 MHz, CDCl3): δ = 163.5, 139.2, 134.9,
133.6, 130.6, 129.2, 128.9, 127.5, 124.0, 82.9, 77.5, 21.5.
1
White solid: 65% yield (139 mg); mp = 179-180 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.84-7.65 (m, 8H), 7.61-7.53 (m, 2H),
7.41-7.32 (m, 3H), 5.86 (dd, J1 = 7.4 Hz, J2 = 3.7 Hz, 1H), 4.94
(dd, J1 = 11.5 Hz, J2 = 7.4 Hz, 1H), 4.57 (dd, J1 = 11.5 Hz, J2 =
3.7 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ = 163.6, 163.3,
134.6, 134.4, 134.3, 129.9, 129.1, 129.0, 128.8, 128.3, 123.7,
123.6, 85.9, 79.6.
4.3.5. 1-(3-bromophenyl)-2-((1,3-dioxoisoindolin-2-
yl)oxy)ethyl nitrate (3f)
1
White solid: 43% yield (175 mg); mp = 124-125 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.93-7.74 (m, 4H), 7.60-7.48 (m, 2H),
7.40-7.23 (m, 2H), 6.25 (dd, J1 = 9.1 Hz, J2 = 3.2 Hz, 1H), 4.52
(dd, J1 = 12.6 Hz, J2 = 9.1 Hz, 1H), 4.34 (dd, J1 = 12.6 Hz, J2 =
3.2 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ = 163.5, 136.0,
135.0, 133.1, 130.9, 130.0, 128.8, 125.5, 124.0, 123.3, 81.7.
4.3. General procedure for synthesis of compounds 3a-i
(experimental for Table 2)
Solution of N-hydroxyphthalimide 2 (163 mg, 1.0 mmol) in
MeCN (15.0 mL) was added dropwise for 30 min to a stirred
mixture of vinylarene 1a-h (208-366 mg, 2.0 mmol) and CAN
(1096 mg, 2.0 mmol) in MeCN (3.0 mL) at 0 °C under argon
atmosphere. After stirring at 0 °C under argon atmosphere for 2 h
reaction mixture was concentrated on a rotary evaporator to a
volume of 5 mL at 40-45 °C under reduced pressure (20-30
mmHg) and aqueous solution of Na2S2O4 (200 mg in 20 mL of
water) was added. The mixture was extracted with DCM (3×10
mL), combined extracts were washed with saturated aqueous
NaHCO3 solution (20 mL), then with water (20 mL), dried over
anhydrous Na2SO4 and filtered. DCM was rotary evaporated at
40-45 °C under reduced pressure (20-30 mmHg). Products 3a-h
were isolated by column chromatography on silica gel using
DCM/EtOAc mixture as eluent (with the volume part of EtOAc
gradually increased from 0% to 3%).
4.3.6. 2-((1,3-dioxoisoindolin-2-yl)oxy)-1-(o-
tolyl)ethyl nitrate (3g)
1
White solid: 56% yield (192 mg); mp = 110-111 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.92-7.76 (m, 4H), 7.38-7.18 (m, 4H),
6.58 (dd, J1 = 9.5 Hz, J2 = 2.5 Hz, 1H), 4.53 (dd, J1 = 12.7 Hz, J2
= 9.5 Hz, 1H), 4.28 (dd, J1 = 12.7 Hz, J2 = 2.5 Hz, 1H), 2.48 (s,
3H). 13C NMR (75.47 MHz, CDCl3): δ = 163.5, 135.6, 134.9,
132.1, 131.2, 129.6, 128.9, 127.0, 125.8, 124.0, 80.2, 76.8, 19.1.
HRMS (ESI): m/z [M+NH4]+ calcd for C17H14N2O6: 360.1190;
found 360.1198.
4.3.7. 2-((1,3-dioxoisoindolin-2-yl)oxy)-2,3-
dihydro-1H-inden-1-yl nitrate (3h)
1
White solid: 69% yield (235 mg); mp = 162-163 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.92-7.74 (m, 4H), 7.53-7.28 (m, 4H),
6.65 (m, 1H), 5.18-5.11 (m, 1H), 3.62 (dd, J1 = 17.8 Hz, J2 = 7.1
Hz, 1H), 3.41-3.28 (m, 1H). 13C NMR (75.47 MHz, CDCl3): δ =
163.9, 142.1, 134.9, 134.1, 131.1, 128.8, 128.1, 126.9, 125.4,
124.0, 90.2, 89.5, 36.1.
4.3.1. 2-((1,3-dioxoisoindolin-2-yl)oxy)-1-(p-
tolyl)ethyl nitrate (3b)
1
White solid: 60% yield (205 mg); mp = 128-130 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.92-7.76 (m, 4H), 7.30 (d, J = 9.0
Hz, 2H), 7.22 (d, J = 9.0 Hz, 2H), 6.29 (dd, J1 = 9.5 Hz, J2 = 3.0
Hz, 1H), 4.56 (dd, J1 = 12.6 Hz, J2 = 9.5 Hz, 1H), 4.35 (dd, J1 =
12.6 Hz, J2 = 3.0 Hz, 1H), 2.36 (s, 3H). 13C NMR (75.47 MHz,
CDCl3): δ = 163.5, 140.0, 134.9, 130.6, 129.9, 128.9, 126.9,
123.9, 82.8, 77.3, 21.3.
4.4. General procedure for synthesis of compounds 5a,c,d,i,j
(experimental for Table 3)
CAN (822 mg, 1.5 mmol) was added to a stirred mixture of
vinyl substrate 1a,c,d,i,j (43-70 mg, 0.5 mmol) and N-
hydroxyphthalimide 2 (163 mg, 1.0 mmol) in MeOH (6.0 mL) at
20-25 °C. After stirring the reaction mixture under air
atmosphere at 20-25 °C for 30 min, aqueous solution of Na2S2O4
(200 mg in 30 mL of water) was added and the mixture was
extracted with DCM (3×10 mL), combined extracts were washed
with saturated aqueous NaHCO3 solution (20 mL), then with
water (20 mL), dried over anhydrous Na2SO4 and filtered. DCM
was rotary evaporated at 40-45 °C under reduced pressure (20-30
mmHg). Products 5a,c,d,i,j were isolated by column
chromatography on silica gel using DCM/EtOAc mixture as
eluent (with the volume part of EtOAc gradually increased from
0% to 3%).
4.3.2. 1-(4-chlorophenyl)-2-((1,3-dioxoisoindolin-
2-yl)oxy)ethyl nitrate (3c)
1
White solid: 62% yield (224 mg); mp = 127-128 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.92-7.74 (m, 4H), 7.44-7.32 (m, 4H),
6.28 (dd, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H), 4.54 (dd, J1 = 12.5 Hz, J2
= 9.2 Hz, 1H), 4.35 (dd, J1 = 12.5 Hz, J2 = 3.2 Hz, 1H). 13C NMR
(75.47 MHz, CDCl3): δ = 163.5, 136.0, 135.0, 132.2, 129.5,
128.8, 128.4, 124.0, 81.9, 77.1.
4.3.3. 1-(4-fluorophenyl)-2-((1,3-dioxoisoindolin-2-
yl)oxy)ethyl nitrate (3d)
1
White solid: 55% yield (190 mg); mp = 136-137 °C. H NMR
4.4.1. 2,2'-((1-(4-chlorophenyl)ethane-1,2-
(300.13 MHz, CDCl3): δ = 7.91-7.74 (m, 4H), 7.41 (dd, J1 = 8.5
Hz, J2 = 5.2 Hz, 2H), 7.22 (t, J = 8.5 Hz, 2H), 6.28 (dd, J1 = 9.1
Hz, J2 = 3.2 Hz, 1H), 4.54 (dd, J1 = 12.5 Hz, J2 = 9.1 Hz, 1H),
4.34 (dd, J1 = 12.5 Hz, J2 = 3.2 Hz, 1H). 13C NMR (75.47 MHz,
CDCl3): δ = 163.52 (d, J = 249.5 Hz), 163.46, 135.0, 129.6 (d, J
= 3.3 Hz), 129.1 (d, J = 8.6 Hz), 128.8, 124.0, 116.4 (d, J = 21.9
Hz), 81.9, 77.2. 19F NMR (282.40 MHz, CDCl3): δ = -111.57. IR
(KBr) ν(cm-1): 1792, 1734, 1644, 1607, 1513, 1469, 1377, 1275,
1187, 1128, 1081, 1020, 1020, 1001, 877, 853, 840, 699, 530,
517. Anal. Calcd for C16H11FN2O6: C, 55.50; H, 3.20; N, 8.09.
Found: C, 55.54; H, 3.09; N, 8.03.
diyl)bis(oxy))bis(isoindoline-1,3-dione) (5c)
1
White solid: 50% yield (116 mg); mp = 106-107 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.85-7.67 (m, 8H), 7.55 (d, J = 8.4
Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 5.81 (dd, J1 = 7.0 Hz, J2 = 4.3
Hz, 1H), 4.88 (dd, J1 = 11.3 Hz, J2 = 7.0 Hz, 1H), 4.55 (dd, J1 =
11.3 Hz, J2 = 4.3 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ =
163.6, 163.3, 135.9, 134.7, 134.6, 132.9, 129.8, 129.1, 129.01,
128.96, 123.8, 123.7, 85.1, 79.1.
4.4.2. 2,2'-((1-(4-fluorophenyl)ethane-1,2-
diyl)bis(oxy))bis(isoindoline-1,3-dione) (5d)
1
White solid: 36% yield (80 mg); mp = 108-109 °C. H NMR
4.3.4. 2-((1,3-dioxoisoindolin-2-yl)oxy)-1-(m-
(300.13 MHz, CDCl3): δ = 7.88-7.65 (m, 8H), 7.64-7.54 (m, 2H),
7.12-7.01 (m, 2H), 5.82 (dd, J1 = 7.0 Hz, J2 = 4.3 Hz, 1H), 4.89
(dd, J1 = 11.3 Hz, J2 = 7.0 Hz, 1H), 4.57 (dd, J1 = 11.3 Hz, J2 =
4.3 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ = 163.6, 163.3,
tolyl)ethyl nitrate (3e)
1
White solid: 51% yield (174 mg); mp = 119-120 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.92-7.76 (m, 4H), 7.34-7.18 (m, 4H),

7
134.7, 134.5, 130.5 (d, J = 8.5 Hz), 130.3 (J = 3.2 Hz), 129.01,
128.96, 123.8, 123.7, 115.9 (J = 21.6 Hz), 85.1, 79.2. 19F NMR
(282.40 MHz, CDCl3): δ = -111.96.
then with water (20 mL), dried over anhydrous Na2SO4 and
ACCEPTED MANUSCRIPT
filtered. DCM was rotary evaporated at 20-25 °C under reduced
pressure (20-30 mmHg) Products 6a-i were isolated by column
chromatography on silica gel using DCM/EtOAc as eluent (with
the volume part of EtOAc gradually increased from 0% to 5%).
4.4.3. 1,2-bis((1,3-dioxoisoindolin-2-yl)oxy)ethyl
acetate (5j)
1
4.6.1. 2-(2-iodo-2-(p-tolyl)ethoxy)isoindoline-1,3-
White solid: 66% yield (135 mg); mp = 176-178 °C. H NMR
dione (mixture of regioisomers 4:1) (6b)
(300.13 MHz, CDCl3): δ = 7.87-7.72 (m, 8H), 6.66 (dd, J1 = 7.4
Hz, J2 = 3.5 Hz, 1H), 4.76 (dd, J1 = 12.2, J2 = 3.5 Hz, 1H), 4.44
(dd, J1 = 12.2, J2 = 7.4 Hz, 1H), 2.18 (s, 3H). 13C NMR (75.47
MHz, CDCl3): δ = 169.9, 163.3, 163.1, 134.83, 134.80, 128.83,
128.79, 124.0, 123.9, 96.1, 75.0, 20.9. IR (KBr) ν(cm-1): 1798,
1779, 1740, 1375, 1360, 1207, 1185, 1128, 985, 877, 698. Anal.
Calcd for C20H14N2O8: C, 58.54; H, 3.44; N, 6.83. Found: C,
58.49; H, 3.43; N, 6.81.
1
White solid: 64% yield (260 mg); mp = 135-136 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.84-7.66 (m, 4H), 7.47-7.35 (m, 2H),
7.17 (d, J = 7.8 Hz, 0.4H), 7.09 (d, J = 7.9 Hz, 1.6H), 5.56-5.45
(m, 1H), 4.97-4.87 (m, 0.8H), 4.67 (dd, J1 = 10.7 Hz, J2 = 5.6 Hz,
0.8H), 3.73 (dd, J1 = 10.4 Hz, J2 = 6.2 Hz, 0.2H), 3.57 (dd, J1 =
10.4 Hz, J2 = 8.0 Hz, 0.2H), 2.33 (s, 0.6H), 2.25 (s, 2.4H). 13C
NMR (75.47 MHz, CDCl3): δ = 163.3, 138.7, 136.8, 134.7,
129.7, 128.8, 127.7, 123.7, 81.3, 25.6, 21.3.
4.4.4. Methyl 2,3-bis((1,3-dioxoisoindolin-2-
yl)oxy)propanoate (5k)
4.6.2. 2-(2-(4-chlorophenyl)-2-
iodoethoxy)isoindoline-1,3-dione (6c)
1
White solid: 64% yield (131 mg); mp = 134-136 °C. H NMR
1
(300.13 MHz, CDCl3): δ = 7.89-7.72 (m, 8H), 5.29-5.23 (m, 1H),
4.88-4.72 (m, 2H), 3.89 (s, 3H). 13C NMR (75.47 MHz, CDCl3):
δ = 166.6, 163.3, 163.1, 134.7, 128.9, 123.9, 123.8, 82.7, 53.3. IR
(KBr) ν(cm-1): 1795, 1747, 1466, 1422, 1375, 1310, 1272, 1187,
1131, 1080, 1063, 1016, 984, 875, 780, 696, 517. HRMS (ESI):
m/z [M+NH4]+ calcd for C20H14N2O8: 428.1088; found 428.1074.
White solid: 72% yield (307 mg); mp = 137-138 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.87-7.70 (m, 4H), 7.50 (d, J = 8.5
Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 5.50 (dd, J1 = 10.2 Hz, J2 = 5.3
Hz, 1H), 4.97-4.86 (m, 1H), 4.68 (dd, J1 = 10.7 Hz, J2 = 5.3 Hz,
1H). 13C NMR (75.47 MHz, CDCl3): δ = 163.3, 138.5, 134.8,
134.4, 129.3, 129.2, 128.8, 123.7, 81.2, 23.7.
4.5. Experimental procedure for Table 4
4.6.3. 2-(2-(4-fluorophenyl)-2-
iodoethoxy)isoindoline-1,3-dione (6d)
Iodine (127 mg, 0.5 mmol) was added to a stirred mixture of
styrene 1a (104 mg, 1.0 mmol) and N-hydroxyphthalimide 2 (163
mg, 1.0 mmol) in MeOH, MeCN, DCM, H2O, MeCN/H2O,
DCM/H2O or AcOH (6.0 mL; for the mixture of solvents the
ratio was 2:1 v/v) at 20-25 °C. Then, oxidant ((NH4)2Ce(NO3)6,
1
White solid: 70% yield (288 mg); mp = 153-154 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.87-7.68 (m, 4H), 7.57-7.48 (m, 2H),
7.00 (t, J = 8.5 Hz, 2H), 5.50 (dd, J1 = 10.1 Hz, J2 = 5.4 Hz, 1H),
4.98-4.80 (m, 1H), 4.66 (dd, J1 = 10.7 Hz, J2 = 5.4 Hz, 1H). 13C
NMR (75.47 MHz, CDCl3): δ = 163.3, 162.5 (d, J = 248.6 Hz),
135.8 (d, J = 3.4 Hz), 134.8, 129.8 (d, J = 8.4 Hz), 128.8, 123.7,
115.9 (d, J = 21.8 Hz), 81.5, 24.1.
(NH4)4Ce(SO4)4•2H2O,
Ce(SO4)2,
(NH4)2Ce(NO3)6/KBrO3,
(NH4)4Ce(SO4)4•2H2O/[Ag(bipy)2]S2O8/(NH4)2S2O8, Mn(OAc)3•
2H2O, Fe(ClO4)3•8H2O or Pb(OAc)4, 222-1644 mg, 1.5-3.0
mmol) was added. In the entries 8-10 NaI•2H2O, TBAI or NH4I
(145-369 mg, 1.0 mmol) were employed instead of I2. In the
entry 11 styrene 1a (208 mg, 2.0 mmol) was employed. After
stirring the reaction mixture under air atmosphere at 20-25 °C for
30 min, DCM (30 mL) was added. The mixture was washed with
aqueous solution of Na2S2O3•5H2O (200 mg in 20 mL of water),
saturated aqueous NaHCO3 solution (20 mL), then with water (20
mL), dried over anhydrous Na2SO4 and filtered. DCM was rotary
evaporated at 20-25 °C under reduced pressure (20-30 mmHg).
Product 6a was isolated by column chromatography on silica gel
using DCM/EtOAc mixture as eluent (with the volume part of
EtOAc gradually increased from 0% to 5%).
4.6.4. 2-(2-iodo-2-(m-tolyl)ethoxy)isoindoline-1,3-
dione (6e)
1
White solid: 66% yield (269 mg); mp = 123-124 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.82-7.67 (m, 4H), 7.34-7.27 (m, 2H),
7.20-7.13 (m, 1H), 6.98 (d, J = 7.4 Hz, 1H), 5.48 (dd, J1 = 9.7
Hz, J2 = 5.7 Hz, 1H), 4.97-4.88 (m, 1H), 4.67 (dd, J1 = 10.7 Hz,
J2 = 5.7 Hz, 1H), 2.30 (s, 3H). 13C NMR (75.47 MHz, CDCl3): δ
= 163.2, 139.7, 138.6, 134.7, 129.5, 128.9, 128.8, 128.4, 125.0,
123.6, 81.3, 25.5, 21.45.
4.6.5. 2-(2-(3-bromophenyl)-2-
iodoethoxy)isoindoline-1,3-dione (6f)
1
White solid: 71% yield (334 mg); mp = 134-135 °C. H NMR
4.5.1. 2-(2-iodo-2-phenylethoxy)isoindoline-1,3-
(300.13 MHz, CDCl3): δ = 7.84-7.70 (m, 4H), 7.69-7.64 (m, 1H),
7.50-7.44 (m, 1H), 7.36-7.29 (m, 1H), 7.22-7.14 (m, 1H), 5.42
(dd, J1 = 5.4 Hz, J2 = 10.1 Hz, 1H), 4.93-4.84 (m, 1H), 4.65 (dd,
J1 = 10.8 Hz, J2 = 5.4 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ
= 163.2, 142.1, 134.8, 131.7, 131.0, 130.5, 128.7, 126.7, 123.8,
122.7, 81.2, 23.2.
dione (6a)
1
White solid: 86% yield (338 mg); mp = 135-136 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.85-7.68 (m, 4H), 7.54 (d, J = 7.4
Hz, 2H), 7.36-7.17 (m, 3H), 5.53 (dd, J1 = 9.8 Hz, J2 = 5.7 Hz,
1H), 5.00-4.88 (m, 1H), 4.71 (dd, J1 = 10.7 Hz, J2 = 5.7 Hz, 1H).
13C NMR (75.47 MHz, CDCl3): δ = 163.3, 139.8, 134.7, 128.9,
128.7, 128.6, 127.9, 123.7, 81.4, 25.2.
4.6.6. 2-(2-iodo-2-(o-tolyl)ethoxy)isoindoline-1,3-
dione (6g)
1
4.6. General procedure for synthesis of compounds 6a-j
(experimental for Table 5)
White solid: 67% yield (273 mg); mp = 112-113 °C. H NMR
(300.13 MHz, CDCl3): δ = 7.82-7.69 (m, 4H), 7.59 (d, J = 7.5
Hz, 1H), 7.21-7.09 (m, 3H), 5.69 (dd, J1 = 9.7 Hz, J2 = 5.9 Hz,
1H), 5.11-5.02 (m, 1H), 4.75 (dd, J1 = 10.6 Hz, J2 = 5.9 Hz, 1H),
2.40 (s, 3H). 13C NMR (75.47 MHz, CDCl3): δ = 163.2, 137.5,
136.3, 134.7, 131.3, 128.8 128.6, 126.8, 126.1, 123.7, 80.4, 22.4,
19.3.
Iodine (127 mg, 0.5 mmol) was added to a stirred mixture of
vinyl substrate 1a-i (172-366 mg, 2.0 mmol) and N-
hydroxyphthalimide 2 (163 mg, 1.0 mmol) in DCM/H2O (6.0
mL, 2:1 v/v) at 20-25 °C. Then, CAN (822 mg, 1.5 mmol) was
added. After stirring the reaction mixture under air atmosphere at
20-25 °C for 30 min, DCM (30 mL) was added and the mixture
was washed with aqueous solution of Na2S2O3•5H2O (200 mg in
20 mL of water), saturated aqueous NaHCO3 solution (20 mL),
4.6.7. 2-((1-iodo-2,3-dihydro-1H-inden-2-
yl)oxy)isoindoline-1,3-dione (6h)

8
Tetrahedron
1
ACCEPTED MANUSCRIPT
Acknowledgment
White solid: 62% yield (251 mg); mp = 164-165 °C. H
NMR (300.13 MHz, CDCl3): δ = 7.91-7.76 (m, 4H), 7.52-7.45
(m, 1H), 7.31-7.25 (m, 3H), 5.95 (m, 1H), 5.36 (dt, J1 = 5.6 Hz,
J2 = 1.4 Hz, 1H), 3.55 (dd, J1 = 17.6 Hz, J2 = 5.6 Hz, 1H), 3.33
(d, J = 17.6 Hz, 1H). 13C NMR (75.47 MHz, CDCl3): δ = 164.1,
143.0, 139.6, 134.9, 129.2, 128.9, 128.1, 125.9, 125.2, 123.9,
96.2, 36.0, 29.5.
This work was supported by the Russian Foundation for Basic
Research (grant № 18-33-00613).
Supplementary data
Supplementary data associated with this article can be found
in the online version, at http://dx.doi.org/xxxx.
4.6.8. 2-((1-iodo-1-phenylpropan-2-
yl)oxy)isoindoline-1,3-dione (6i)
References and notes
White solid: 53% yield (215 mg), mixture of diastereomers
1:1; mp = 118-119 °C. 1H NMR (300.13 MHz, CDCl3): δ = 7.92-
7.66 (m, 4H), 7.60-7.48 (m, 2H), 7.37-7.11 (m, 3H), 5.42 (d, J =
7.5 Hz, 0.5H), 5.32 (d, J = 6.8 Hz, 0.5H), 4.84-4.68 (m, 1H), 1.69
(d, J = 6.1 Hz, 1.5H), 1.32 (d, J = 6.3 Hz, 1.5H). 13С NMR (75.47
MHz, CDCl3): δ = 164.1, 163.8, 140.3, 139.9, 134.8, 134.6,
129.13, 129.07, 128.9, 128.74, 128.67, 128.6, 128.50, 128.3,
123.8, 123.6, 87.4, 85.5, 34.3, 32.2, 19.4, 16.8.
1. Nair, V.; Deepthi, A. Chem. Rev. 2007, 107, 1862-91.
2. Nikishin, G. I.; Kapustina, N. I.; Sokova, L. L.; Bityukov, O. V.;
Terent'ev, A. O. Tetrahedron Lett. 2017, 58, 352-354.
3. Deleersnyder, K.; Schaltin, S.; Fransaer, J.; Binnemans, K.; Parac-
Vogt, T. N. Tetrahedron Lett. 2009, 50, 4582-4586.
4. Nair, V.; Panicker, S. B.; Nair, L. G.; George, T. G.; Augustine,
A. Synlett 2003, 0156-0165.
5. Nair, V.; Mathew, J.; Prabhakaran, J. Chem. Soc. Rev. 1997, 26,
127-132.
6. Terent’ev, A. O.; Sharipov, M. Y.; Glinuskin, A. P.; Krylov, I. B.;
Gaidarenko, D. V.; Nikishin, G. I. Mendeleev Commun. 2016, 26,
226-227.
4.6.9. 2-((1,3-dioxoisoindolin-2-yl)oxy)-1-iodoethyl
acetate (6j)
1
White solid: 65% yield (244 mg); mp = 132-133 °C. H NMR
7. Krylov, I. B.; Paveliev, S. A.; Shelimov, B. N.; Lokshin, B. V.;
Garbuzova, I. A.; Tafeenko, V. A.; Chernyshev, V. V.; Budnikov,
A. S.; Nikishin, G. I.; Terent'ev, A. O. Org. Chem. Front. 2017, 4,
1947-1957.
8. Terent'ev, A. O.; Krylov, I. B.; Timofeev, V. P.; Starikova, Z. A.;
Merkulova, V. M.; Ilovaisky, A. I.; Nikishin, G. I. Adv. Synth.
Catal. 2013, 355, 2375-2390.
9. Terent’ev, A. O.; Krylov, I. B.; Lipatnikov, A. D. Russ. J. Gen.
Chem. 2014, 84, 2084-2087.
10. Sridharan, V.; Menendez, J. C. Chem. Rev. 2010, 110, 3805-49.
11. Prajapati, N. P.; Vekariya, R. H.; Patel, H. D. Synth. Commun.
2015, 45, 2399-2425.
12. Szumny, A.; Wawrzenczyk, C. Synlett 2006, 2006, 1523-1526.
13. Nair, V.; Suja, T.; Mohanan, K. Synthesis 2006, 2006, 2335-2338.
14. Trahanovsky, W. S.; Robbins, M. D. J. Am. Chem. Soc. 1971, 93,
5256-5258.
15. Nair, V.; Nair, L. G.; George, T. G.; Augustine, A. Tetrahedron
2000, 56, 7607-7611.
(300.13 MHz, CDCl3): δ = 7.88-7.74 (m, 4H), 7.02 (dd, J1 = 10.3
Hz, J2 = 2.4 Hz, 1H), 4.72 (dd, J1 = 12.7 Hz, J2 = 10.3 Hz, 1H),
4.56 (dd, J1 = 12.7 Hz, J2 = 2.4 Hz, 1H), 2.15 (s, 3H). 13C NMR
(75.47 MHz, CDCl3): δ = 168.7, 163.4, 135.0, 128.8, 123.9, 81.3,
48.8, 21.2. IR (KBr) ν(cm-1): 1792, 1759, 1734, 1466, 1439,
1376, 1209, 1186, 1134, 1111, 1081, 1038, 1013, 986, 940, 901,
877, 842, 785, 702, 669, 517. HRMS (ESI): m/z [M+H]+ calcd for
C12H10INO5: 375.9676; found 375.9668.
4.7. Gram scale synthesis of compound 3a (experiment for
Scheme 2)
Solution of N-hydroxyphthalimide 2 (0.816 g, 5.0 mmol) in
MeCN (75.0 mL) was added dropwise for 30 min to a stirred
mixture of styrene 1a (1.04 g, 10.0 mmol) and CAN (5.48 g, 10.0
mmol) in MeCN (15.0 mL) at 0 °C under argon atmosphere.
After the stirring at 0 °C for 2 h reaction mixture was
concentrated on a rotary evaporator to a volume of 10 mL at 40-
45 °C under reduced pressure (20-30 mmHg) and aqueous
solution of Na2S2O4 (200 mg in 100 mL of water) was added. The
mixture was extracted with DCM (3×30 mL), combined extracts
were washed with saturated aqueous NaHCO3 solution (50 mL),
then with water (50 mL), dried over anhydrous Na2SO4 and
filtered. DCM was rotary evaporated under reduced pressure (20-
30 mmHg). Product 3a was isolated by column chromatography
on silica gel using DCM/EtOAc mixture as eluent (with the
volume part of EtOAc gradually increased from 0% to 5%).
Yield of 3a was 0.63 g (38%).
16. Nair, V.; Augustine, A.; George, T. G.; Nair, L. G. Tetrahedron
Lett. 2001, 42, 6763-6765.
17. Terent'ev, A. O.; Krylov, I. B.; Sharipov, M. Y.; Kazanskaya, Z.
M.; Nikishin, G. I. Tetrahedron 2012, 68, 10263-10271.
18. Recupero, F.; Punta, C. Chem. Rev. 2007, 107, 3800-42.
19. Melone, L.; Punta, C. Beilstein J. Org. Chem. 2013, 9, 1296-310.
20. Coseri, S. Catal. Rev. 2009, 51, 218-292.
21. Ishii, Y.; Sakaguchi, S. Catal. Today 2006, 117, 105-113.
22. Ishii, Y.; Sakaguchi, S.; Iwahama, T. Adv. Synth. Catal. 2001,
343, 393-427.
23. Soo Kim, S.; Rajagopal, G. Synth. Commun. 2004, 34, 2237-2243.
24. Sakaguchi, S.; Hirabayashi, T.; Ishii, Y. Chem. Commun. 2002,
516-517.
25. Kamijo, S.; Amaoka, Y.; Inoue, M. Tetrahedron Lett. 2011, 52,
4654-4657.
26. Bag, R.; De, P. B.; Pradhan, S.; Punniyamurthy, T. Eur. J. Org.
Chem. 2017, 2017, 5424-5438.
27. Xia, X.-F.; Zhu, S.-L.; Hu, Q.-T.; Chen, C. Tetrahedron 2016, 72,
8000-8003.
4.8. Gram scale synthesis of compound 6a (experiment for
Scheme 2)
Iodine (0.635 g, 2.5 mmol) was added to a stirred mixture of
styrene 1a (1.04 g, 10.0 mmol) and N-hydroxyphthalimide 2
(0.816 g, 5.0 mmol) in DCM/H2O (90 mL, 2:1 v/v) at 20-25 °C.
Then, CAN (4.11 g, 7.5 mmol) was added. After stirring the
reaction mixture under air atmosphere at 20-25 °C for 30 min the
mixture was washed with aqueous solution of Na2S2O3•5H2O
(200 mg in 50 mL of water), saturated aqueous NaHCO3 solution
(50 mL), then with water (50 mL), dried over anhydrous Na2SO4
and filtered. DCM was rotary evaporated at 20-25 °C under
reduced pressure (20-30 mmHg). Product 6a was isolated by
column chromatography on silica gel using DCM/EtOAc as
eluent (with the volume part of EtOAc gradually increased from
0% to 5%). Yield of 6a was 1.57 g (80%).
28. Bag, R.; Sar, D.; Punniyamurthy, T. Org. Biomol. Chem. 2016, 14,
3246-55.
29. Yamamoto, D.; Soga, M.; Ansai, H.; Makino, K. Org. Chem.
Front. 2016, 3, 1420-1424.
30. Luo, J.; Zhang, J. J. Org. Chem. 2016, 81, 9131-9137.
31. Samanta, S.; Ravi, C.; Joshi, A.; Pappula, V.; Adimurthy, S.
Tetrahedron Lett. 2017, 58, 721-725.
32. Xia, X. F.; Zhu, S. L.; Gu, Z.; Wang, H.; Li, W.; Liu, X.; Liang,
Y. M. J. Org. Chem. 2015, 80, 5572-80.
33. Andia, A. A.; Miner, M. R.; Woerpel, K. A. Org. Lett. 2015, 17,
2704-7.
34. Zhang, J.-z.; Tang, Y. Adv. Synth. Catal. 2016, 358, 752-764.
35. Samanta, S.; Donthiri, R. R.; Ravi, C.; Adimurthy, S. J. Org.
Chem. 2016, 81, 3457-63.
36. Huang, L.; Zheng, S. C.; Tan, B.; Liu, X. Y. Org. Lett. 2015, 17,
1589-92.

9
37. Li, Y. X.; Wang, Q. Q.; Yang, L. Org. Biomol. Chem. 2017, 15,
42. Xu, X.; Li, X.; Chen, K.; Tang, Y.; Zhu, H.; Chen, F.; Yan, X.
Synlett 2018, 29, 1634-1638.
ACCEPTED MANUSCRIPT
1338-1342.
38. Li, Y.; Zhou, X.; Zheng, G.; Zhang, Q. Beilstein J. Org. Chem.
2015, 11, 2721-6.
43. Xia, X.-F.; Zhu, S.-L.; Zhang, D. Tetrahedron 2015, 71, 8517-
8520.
39. Xia, X. F.; Gu, Z.; Liu, W.; Wang, H.; Xia, Y.; Gao, H.; Liu, X.;
Liang, Y. M. J. Org. Chem. 2015, 80, 290-5.
40. Bag, R.; Sar, D.; Punniyamurthy, T. ACS Omega 2017, 2, 6278-
6290.
44. Ho, T.-L. Synthesis 1978, 936.
45. Skarżewski, J. Tetrahedron 1984, 40, 4997-5000.
46. Yang, B.; Hou, S.-M.; Ding, S.-Y.; Zhao, X.-N.; Gao, Y.; Wang,
X.; Yang, S.-D. Adv. Synth. Catal. 2018.
41. Krylov, I. B.; Paveliev, S. A.; Syroeshkin, M. A.; Korlyukov, A.
A.; Dorovatovskii, P. V.; Zubavichus, Y. V.; Nikishin, G. I.;
Terent'ev, A. O. Beilstein J. Org. Chem. 2018, 14, 2146-2155.
47. Po, H. Coord. Chem. Rev. 1976, 20, 171-195.