Reactions of mono- and bicyclic enol ethers with the I2- hydroperoxide system

Article abstract of DOI:10.1039/c3ra46462h

Reactions of mono- and bicyclic enol ethers with I₂-H ₂O₂, I₂-Bu^tOOH, and I ₂-tetrahydropyranyl hydroperoxide systems have been studied. It was shown that the reaction pathway depends on th

Full text of DOI:10.1039/c3ra46462h

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Reactions of mono- and bicyclic enol ethers with
the I2–hydroperoxide system†
Cite this: RSC Adv., 2014, 4, 7579
*
Alexander O. Terent'ev, Alexander T. Zdvizhkov, Alena N. Kulakova,
Roman A. Novikov, Ashot V. Arzumanyan and Gennady I. Nikishin
Reactions of mono- and bicyclic enol ethers with I2–H2O2, I2–ButOOH, and I2–tetrahydropyranyl
hydroperoxide systems have been studied. It was shown that the reaction pathway depends on the
nature of peroxide and the ring size. The reaction of 2,3-dihydrofuran and 3,4-dihydro-2H-pyran with
the I2–hydroperoxide system affords iodoperoxides, a-iodolactones, and a-iodohemiacetals. Bicyclic
enol ethers are transformed into vicinal iodoperoxides only in the reaction with the I2–H2O2 system,
whereas the reaction with I2–ButOOH gives the hydroperoxidation product.
Received 7th November 2013
Accepted 7th January 2014
DOI: 10.1039/c3ra46462h
www.rsc.org/advances
easily undergo decomposition by a homolytic or heterolytic
mechanism.
Introduction
The present study is in the line with the current trends of
using the I2–H2O2 system for the peroxidation and halogenation
of organic compounds. This system shows unique and unpre-
dictable reactivity, which is manifested in the fact that the
reactions with this system afford a great variety of products. An
idea of the combination of iodine or its compounds with
peroxides was successfully implemented for the introduction of
the peroxide moiety into carbonyl compounds21 and alkenes,22
in the synthesis of monoperoxyacetal-containing compounds23
and cyclic triperoxides,24 for the activation and introduction of
iodine in the iodoalkoxylation of alkenes,25 the iodination of
arenes,26 ketones,27 and alkynes.28 Besides, this system was used
for the Baeyer–Villiger oxidation of ketones to lactones,29 the
ring contraction of 1,2-quinones to form cyclopentenones,30 the
oxidative C–N31 and C–O32 coupling, and the oxidative cycliza-
tion to form heterocyclic compounds.33
The results of investigations covering the iodination of
organic compounds or iodine-catalyzed transformations,
including peroxides, are summarized in reviews.34–36
In our previous study we showed that the reaction of enol
ethers 1 (containing an exocyclic oxygen atom) with the I2–H2O2
system in Et2O produces 2-iodo-1-methoxyhydroperoxides 2 and
2-iodoketones 3. Depending on the reaction conditions, either
compounds 2 or 3 can be synthesized in preparative yield
(Scheme 1).37
In the last few decades an extensive development of methods for
the synthesis of organic peroxides has been observed, for
example, catalysts in combination with hydroperoxides are used
such as H2WO4,1 phosphomolybdic and phosphotungstic
acids,2 methyltrioxorhenium (MeReO3) in triuoroethanol,3
triuroacetic acid with cinchona alkaloids,4 Re2O7,5 BF3$Et2O,6
CAN,7 silicon-supported sodium hydrogen sulfate,8 cam-
phorsulfonic acid,9 SrCl2$6H2O,10 and also salts of ruthenium,11
copper,12 cobalt,13 and iron,14 including Gif15 and metal-
loporphyrin16 systems. This development is associated with the
fact that many compounds of this class exhibit pronounced
antimalarial and anthelmintic activities.17 Some synthesized
compounds show antiparasitic activity comparable to or higher
than that of the natural peroxide artemisinin commonly used in
medical practice.18 The search for natural substances and the
synthesis of new compounds with antitumor activity is a rela-
tively new and fast-developing eld of application of this class of
compounds.19 Peroxides are widely used in the polymer chem-
istry as radical polymerization initiators and cross-linking
reagents.20 These aspects of the application of compounds
containing the –O–O– moiety stimulated the development of
new approaches to their synthesis.
However, despite the more than a hundred year history of the
development of this eld of chemistry, the selective synthesis
and the controlled transformation of peroxides, as well as their
analysis, still present difficulties due to low stability of these
compounds (compared to other classes) and the fact that they
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991
Leninsky Prospect 47, Moscow, Russian Federation. E-mail: terentev@ioc.ac.ru
† Electronic supplementary information (ESI) available: Copies of 1H, 13C NMR, IR
and HRMS spectra. See DOI: 10.1039/c3ra46462h
Scheme
2-iodo ketones 3.
1 Synthesis of 2-iodo-1-methoxyhydroperoxides 2 and
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In the present study, we focused our attention on another iodine. An increase in the reaction time to 2 h had no
type of enol ethers, featuring an endocyclic oxygen atom (4a,b substantial effect of the yield of 5b (Table 1, entry 9). The use of
and 10a–c). Contrary to expectations, cyclic enol ethers 4a,b and a twofold excess of iodine led to a decrease in the yield of 5a to
10a–c show substantially different behaviour in the reaction 56% (Table 1, entry 3). A decrease in the amount of TBHP (Table
with the iodine–hydroperoxide system compared to their acyclic 1, entry 4) compared to entry 2 had no effect on the yield of the
analogues 1 (Scheme 2).
product. The replacement of Et2O (the reaction medium) by
We studied two groups of enol ethers–monocyclic enol more polar solvent CH3CN or a CH3CN–Et2O mixture led to a
ethers, such as 2,3-dihydrofuran 4a and 3,4-dihydro-2H-pyran sharp decrease in the yield of 5a,b and 6a,b (entries 5, 7, 10, and
4b, and more complex compounds, such as bicyclic enol ethers, 14). The reaction with the use of THPHP requires 2 h for the
in which a ve-membered 10a, six-membered 10b, or seven- synthesis of 6a,b to be efficient (Table 1, entries 6 and 12). On
membered 10c carbocycle is fused with the dihydropyran ring. the whole, the yields of dihydrofuran derivatives 5a and 6a
(Table 1, entries 1–7) are lower compared to their dihydropyran
homologs 5b and 6b (Table 1, entries 8–14). At room tempera-
ture, dihydropyran polymerizes under the action of the reaction
system used, which leads to a decrease in the yield of 5b
(Table 1, entry 11).
Reactions of 2,3-dihydrofuran 4a and 3,4-dihydro-2H-pyran 4b
with the iodine–H2O2 system
The reaction of dihydrofuran 4a with the iodine–H2O2 system at
ꢀ
0 C affords a complex mixture of products consisting of iodo-
hydroperoxide 7a (yield 65%), a-iodolactone 9a (yield 15%), and
hemiacetal 8a (yield 15%). The reaction of dihydropyran 4b with
the iodine–H2O2 system produced a mixture of iodohydroper-
oxide 7b (yield 74%) and hemiacetal 8b (yield 12%), the expec-
ted iodovalerolactone was not detected. Apparently, this is
associated with the fact that d-valerolactone, unlike g-butyro-
lactone, easily polymerizes.38
Reaction of bicyclic enol ethers 10b,c with the I2–H2O2 system
One important feature to consider when comparing mono- and
bicyclic enol ethers is the absence of hydrogen atoms near
double bond in the later systems. Usually peroxides containing
R2(R0O)COOH fragment are more stable than R2HCOOH
peroxides, since they have no easily oxidizable CH fragment.
This difference in stability is observed in acid-catalyzed peroxi-
Reactions of 2,3-dihydrofuran 4a and 3,4-dihydro-2H-pyran 4b
with the iodine–tert-butyl (TBHP) and iodine–
tetrahydropyranyl hydroperoxide (THPHP) systems
dation of aldehydes and ketones or their acetals6 with hydrogen
peroxide. It is common knowledge that aldehydes can be easily
oxidated by H2O2 in carboxylic acids, in contrast more rigid
The iodoperoxidation of 2,3-dihydrofuran (Table 1, entries 1–7) conditions are needed for oxidation of ketones by H2O2 with the
4a and 3,4-dihydropyran 4b (Table 1, entries 8–14) was per- same result.39 In the case of base-catalyzed processes,
formed in Et2O, CH3CN, or CH3CN–Et2O using a two- or four- R2HCOOH peroxides can be rearranged in ketones by means of
fold molar excess of TBHP (Table 1, entries 1–5 and 8–11) or a Kornblun–DeLaMare reaction.40
fourfold molar excess of THPHP (Table 1, entries 6–7 and 12–14)
Apparently, this is the reason why iodohydroperoxides of
and iodine (0.5–2 mole per mole of 4). To suppress the oxidative bicyclic enol ethers 10b,c are formed more selectively than
ꢀ
side reactions, the synthesis was performed at 0 C (Scheme 3 analogous peroxides of monocyclic enol ethers 4a,b, which
and Table 1).
undergo further transformations (Scheme 4).
The highest yield of products 5a (76%) and 5b (91%) was
The conditions of the peroxidation of bicyclic ethers 10b,c
achieved when the reaction was performed for 30 min (Table 1, (Table 2, entries 15–20) were optimized taking into account the
entries 2 and 8) in the presence of an equivalent amount of conditions of entry 2 (Table 1). The most signicant parameters,
Scheme 2 Reactions of cyclic enol ethers 4a,b, and 10a–c with the iodine–hydroperoxide system.
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Table 1 Reactions of 2,3-dihydrofuran 4a and 3,4-dihydro-2H-pyran 4b with the I2–TBHP and I2–THPHP systems; synthesis of peroxides 5a,b
and 6a,b
Yield of 5a,b
and 6a,b, %
Entrya
Solvent
ROOH
Molar ratio: I2/4a,b
Reaction time, min
1
2
3
4
5
6
7
8
Et2O
Et2O
Et2O
Et2O
CH3CN–Et2O
Et2O
CH3CN
Et2O
Et2O
CH3CN–Et2O
Et2O
TBHP
TBHP
TBHP
TBHP
0.5 (4a)
1 (4a)
2 (4a)
2 (4a)
2 (4a)
1 (4a)
1 (4a)
1 (4b)
1 (4b)
1 (4b)
1 (4b)
1 (4b)
1 (4b)
1 (4b)
30
30
30
30
30
120
120
30
120
30
30
120
30
28 (5a)
76 (5a)
56 (5a)
77 (5a)
52 (5a)
78 (6a)
35 (6a)
91 (5b)
88 (5b)
56 (5b)
17 (5b)
86 (6b)
42 (6b)
46 (6b)
TBHP
THPHP
THPHP
TBHP
TBHP
TBHP
9
10
11b
12
13
14
TBHP
Et2O
Et2O
CH3CN
THPHP
THPHP
THPHP
120
a
b
Molar ratio: ROOH/4a,b ¼ 4 (entries 1–3, 5–14) and 2 (entry 4). At 20–25 ꢀC.
viz., the temperature and the reaction medium, were varied. As
the temperature was lowered from room temperature to ꢁ40 ꢀC,
the yield of target product 11b increased from trace amounts to
82% (Table 2, entries 15–17) due, apparently, to the reduction of
the effect of polymerization with the participation of enol ether.
The reaction in CH3CN (Table 2, entries 18 and 19) produces
virtually no iodohydroperoxide 11b.
Iodohydroperoxides 11b,c are unstable compounds and they
decompose during isolation and storage.
Reaction of bicyclic enol ethers 10a–c with the I2–ButOOH
system
Scheme 3 Reactions of 2,3-dihydrofuran 4a and 3,4-dihydro-2H-
pyran 4b with the I2–TBHP and I2–THPHP systems.
TBHP is much more bulky than hydrogen peroxide, which has a
decisive effect on the structure of the reaction products. Thus,
tert-butyl hydroperoxide adds at the double bond, whereas
iodine is not involved in the nal product.
The reactions of bicyclic ethers 10a–c with the I2–ButOOH
system were performed using a fourfold molar excess of TBHP
and an equimolar amount of iodine, with the resulting forma-
tion of peroxidated oxabicycloalkanes 12a–c (Scheme 5 and
Table 3).
In the reaction with the I2–ButOOH system, like in the
reaction with I2–H2O2, the temperature and the nature of the
solvent (Table 3, entries 21–27) play a key role in the synthesis of
target peroxide 12. In entries 22–25 (Table 3), the yield of the
target peroxide increased from 43 to 75% as the reaction
temperature was lowered from 20 to ꢁ70 ꢀC. Acetonitrile (Table
3, entry 26) proved to be unsuitable as a solvent for the synthesis
Scheme 4 Reaction of bicyclic enol ethers 10b,c with the I2–H2O2
system.
Table 2 Reaction of bicyclic enol ethers 10b,c with the I2–H2O2
system; synthesis of iodohydroperoxides 11b,c
Bicyclic enol
Onset temperature
Entry ethers 10b,c Solvent of the reaction, ꢀ
C
Yield of 11b,c, %
15
16
17
18
19
20
10b
10b
10b
10b
10b
10c
Et2O
Et2O
Et2O
CH3CN
20
0
11b, 10
11b, 43
11b, 82
11b, traces
11b, traces
11c, 40
ꢁ40
20
CH3CN ꢁ40
Scheme 5 Reaction of bicyclic enol ethers 10a–c with the I2–ButOOH
system.
Et2O
ꢁ40
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Table 3 Reaction of bicyclic ethers 10a–c with the I2–ButOOH
system; synthesis of peroxides 12a–c
In the 13C NMR spectra, the signal of the monoperoxyacetal
moiety is observed at d 103–113, which is consistent with the
known data.45 The spectra of peroxides 5 show the signal of the
tertiary carbon atom of the tert-butylperoxide group at d 79–81.
The spectra of peroxides 6 display several signals of the per-
oxiacetal moiety due to the formation of different steter-
oisomers. The 13C NMR spectra show signals of the
CH2O group at d 60–67 ppm and signals of other CH2 groups at
d 24–36. The chemical shis of the CHI group in the 13C NMR
spectra substantially depend on the environment of the
carbon atom. In the spectra of products 5 and 6, the signals of
this group are observed at d 19–23, whereas the signals for
products 11 containing the tertiary carbon atom are shied
downeld (to d 65–76).
The structures of compounds 7a, 8a, 9a, and 7b, 8b, which
were not isolated in the individual state, were unambiguously
established by 1H and 13C NMR spectroscopy using 2D
correlation spectroscopic techniques (COSY, NOESY, editing-
HSQC, HSQC-TOCSY, and HMBC). The molecular skeleton
was established based on heteronuclear correlations. The
O–CH–OOH and O–CH–OH groups in cyclic compounds 7a,
8a, and 7b, 8b differ by the chemical shis in the 13C NMR
spectra. It is known46 that the replacement of one alkoxy
group in acetal by the peroxide group leads to a shi of the
signal of the carbon atom in the O–C–O group to lower eld.
The same dependence was observed in the present study.
Based on the HSQC NMR data, the chemical shis for
hydroperoxides are 105 ppm (7a) and 98 ppm (7b), whereas
the chemical shis for hemiacetals are observed at lower eld
(98 ppm for 8a and 93 ppm for 8b). The similar dependence is
observed in the 1H NMR spectra; for hydroperoxides, the
chemical shis are 5.6 ppm (7a) and 4.9 ppm (7b); for
hemiacetal, the corresponding values are lower (4.8 ppm for
8a and 4.1 ppm for 8b).
Bicyclic enol
Onset temperature
Entry ethers 10b,c Solvent of the reaction, ꢀ
C
Yield of 12a–c, %
21
22
23
24
25
26
27
10a
10b
10b
10b
10b
10b
10c
Et2O
Et2O
Et2O
Et2O
Et2O
ꢁ70
20
12a, 89
12b, 43
12b, 51
12b, 70
12b, 75
12b, traces
12c, 66
0
ꢁ40
ꢁ70
CH3CN ꢁ70
Et2O
ꢁ70
of 12b. Products 12a–c are more stable compared to 11a–c;
however, these cꢀompounds substantially decompose during
storage even at 0 C for one week.
Summary from the Tables 1–3 about inuence of type of
mono- and bicyclic enol ether, hydroperoxide, and solvent on
the structure of the products
It is known that particles with positively charged iodine and
protons are formed in the iodine–hydroperoxide system.28a,41
Both these positively charged particles, as well as iodine add at
the double bond of enol ether thus initiating the peroxidation.
The reactions with dihydrofuran and dihydropyran are accom-
panied by the iodoperoxidation. In the case of bicylic
compounds, the iodoperoxidation is observed only in the
reactions with hydrogen peroxide. The reactions with more
bulky TBHP involve the addition of only this compound,
whereas iodine is not involved in the resulting peroxide. In the
reactions with THPHP, no peroxidation of bicyclic compounds
is observed.
In addition to the formation of iodohydroperoxide 7a, the
reaction of dihydrofuran with the I2–H2O2 system involves the
reduction of the hydroperoxide group with HI giving iodo
alcohol 8a (ref. 42) and the oxidation of 8a with iodine or
particles containing positively charged iodine producing iodo-
lactone 9a.43
The IR spectra of peroxides 5, 6, and 11 show characteristic
CH–I stretching bands in the region of 500–800 cmꢁ1 and CH–O
stretching bands of the peroxyketal moiety in the region of
1020–1300 cmꢁ1
.
The compositions of the synthesized compounds were
established also using HRMS data. The mass spectra of 5, 6, and
12 have peaks corresponding to the molecular ions. According
to the mass-spectrometric data, the ES ionization of 11 leads to
the elimination of the peroxide moiety 11b or iodine atom and
peroxide moiety 11c.
Diethyl ether proved to be a much more efficient solvent
compared to acetonitrile, because it is a good base, an acceptor
of a proton or positively charged iodine, due to which the
synthesis can be performed in a relatively milder acidic
medium. The reaction in acetonitrile yields mainly resin-
ication products due, apparently, to the acid-catalyzed poly-
merization characteristic of enol ethers.44
Conclusions
The reactions of mono- and bicyclic enol ethers with the I2–
H2O2, I2–ButOOH, and I2–tetrahydropyranyl hydroperoxide
systems were studied. We succeeded in synthesizing and char-
Establishment of the structures of the synthesized
compounds
The structures of products 5, 6, 11, and 12 were established by acterizing difficult-to-synthesize unstable oxacyclic peroxides
1H and 13C NMR spectroscopy. The 1H NMR spectra of products and iodoperoxides. It was shown that the reaction pathway
5 and 6 show characteristic signals of the CHI group and the depends on the nature of peroxide and the ring size. The reac-
peroxyacetal moiety at d 3.7–4.15 and 4.9–5.7, respectively. The tion of monocyclic enol ethers with the I2–H2O2 system
signal of the CH2O group is observed at d 3.5–4.0. Signals of produces iodoperoxides, a-iodohemiacetals, and a-iodo-
other CH2 groups are present in the characteristic region at d lactones, whereas the reaction with I2–ButOOH gives only
1.2–2.5.
iodoperoxidation products. Bicylic enol ethers are transformed
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3,4,5,6,7,8-Hexahydro-2H-chromene (10b)50
into vicinal iodoperoxides in 40–82% yields only in the reac-
tions with the I2–H2O2 system, whereas the reaction with I2–
ButOOH affords hydroperoxidation products in 66–89% yields,
iodine being not involved in the target product.
Colorless oil. dH (300 MHz, CDCl3): 1.45–2.34 (12H, m, C(CH2)4C,
(CH2)2CH2O), 3.91 (2H, m, CH2O).
dC (50 MHz, CDCl3): 22.9 (OCH2CH2), 23.1 (CH2CCH2CH2),
23.26
(C(CH2)2CH2CH2C),
25.2
(OCH2CH2CH2),
27.2
(CCH2(CH2)3C), 28.9 (OCCH2), 65.5 (OCH2), 104.3 (CH2CCH2),
146.7 (OCCH2).
Experimental
Calculated (%): C, 78.21; H, 10.21; found (%): C, 78.25; H,
10.18. C9H14O%.
1H and 13C NMR spectra were recorded on Bruker AMX-III 400
(400.1 and 100.6 MHz, respectively) and Bruker AVANCE II 300
(300.1 and 75.5 MHz, respectively) spectrometers in CDCl3.
1
Assignments of H and 13C signals were made and the struc-
2,3,4,5,6,7,8,9-Octahydrocyclohepta[b]pyran (10c)
tures of the compounds were determined with the aid of 2D
COSY, NOESY, editing-HSQC, HSQC-TOCSY, and HMBC spectra
in the case of studying mixtures 7a, 8a, 9a and 7b, 8b.
MeCN (HPLC grade) for ESI-HRMS experiments was ordered
from Merck and used as supplied. All samples for ESI-HRMS
experiments were prepared in 1.5 mL Eppendorf tubes. All
plastic disposables (Eppendorf tubes and tips) used in sample
preparation were washed with MeCN before use.
Colorless oil. dH (300 MHz, CDCl3): 1.33–2.45 (14H, m, (CH2)5,
(CH2)2CH2O), 3.83 (2H, m, CH2O).
dC (75 MHz, CDCl3): 23.4 (CH2CH2O), 25.8 ((CH2)2CH2-
(CH2)2), 27.0 (CH2CH2(CH2)3), 27.2 (O(CH2)2CH2), 31.0
(CH2CCH2), 32.5 (OCCH2CH2), 33.2 (OCCH2), 65.4 (OCH2),
108.3 (CH2CCH2), 152.2 (OCCH2).
Calculated (%): C, 78.90; H, 10.59; found (%): C, 78.96; H,
10.52; C10H16O%.
High resolution mass spectra were recorded on a Bruker
maXis instrument equipped with electrospray ionization (ESI)
ion source.47,48 The all measurements were performed in a
positive (+MS) ion mode (interface capillary voltage: 4500 V)
with scan range m/z: 50–3000. External calibration of the mass
spectrometer was performed with Electrospray Calibrant Solu-
tion (Fluka). A direct syringe injection was used for the all
analyzed solutions in MeCN (ow rate: 3 mL minꢁ1). Nitrogen
was used as nebulizer gas (0.4 bar) and dry gas (4.0 L minꢁ1);
interface temperature was set at 180 ꢀC. The all spectra were
processed by using Bruker DataAnalysis 4.0 soware package.
The TLC analysis was carried out on standard silica gel
chromatography plates. The melting points were determined on
a Koer hot-stage apparatus. Chromatography was performed
on silica gel (0.060–0.200 mm, 60 A, CAS 7631-86-9).
Petroleum ether 40–70 (PE), Et2O, CH3CN, CH2Cl2, and ethyl
acetate (EA) were distilled before use over the corresponding
drying agents. The reagents I2, Na2S2O3$5H2O, and Na2SO4 were
of chemical purity grade. tert-Butyl hydroperoxide (70% solu-
tion in water), 3,4-dihydro-2H-pyran and 2,3-dihydrofuran were
purchased from Acros. Bicyclic enol ethers 10a–c were synthe-
sized according to known procedures.49,50
Reaction of monocyclic enol ethers 4a,b with the I2–H2O2
system. Synthesis of 7a, 8a, 9a and 7b, 8b
Iodine (0.256–1.024 g, 1–4 mmol) was dissolved in Et2O or
CH3CN (10 mL), a 2.53 M ethereal solution of H2O2 (3.16 mL, 8
mmol) was added, and then a solution of 4a or 4b (0.140 or
0.160 g, 2 mmol) in Et2O (2 mL) was added dropwise with stir-
ꢀ
ꢀ
ring at 0 C. The mixture was stirred for 30 min at 0 C. Petro-
leum ether (20 mL) and nely dispersed Na2S2O3$5H2O (1.5 g)
were added, and the mixture was stirred until the it became
colorless. The solid residue and possible polymeric resins were
separated using a silica gel layer. The solvents were rotary
evaporated at 10–15 mmHg and 15–20 ꢀC. The resulting oil
(0.420 g for 7–9a or 0.462 g for 7–8b) was studied by NMR
spectroscopy, including homo- and heteronuclear correlation
spectroscopic techniques (COSY, NOESY, editing-HSQC, HSQC-
TOCSY and HMBC); the structures of the compounds and their
yields were determined from the NMR data.
Experiment to Table 1. Reactions of 3,4-dihydro-2H-pyran 4a
and 2,3-dihydrofuran 4b with the I2–tert-butyl hydroperoxide
and I2–tetrahydropyranyl hydroperoxide systems; synthesis of
peroxides 5a,b and 6a,b
A solution of H2O2 was prepared by the extraction with
diethyl ether from a 37% aqueous H2O2 solution followed by
drying over MgSO4.22 A 51% ethereal solution of tert-butyl
hydroperoxide was prepared by a similar procedure using tert-
butyl hydroperoxide (70% solution in water).
Iodine (0.256–1.024 g, 1–4 mmol) was dissolved in Et2O or
CH3CN (10 mL), a 51% ethereal solution of tert-butyl hydro-
peroxide (0.693 g, 4 mmol or 1.386 g, 8 mmol) or tetrahy-
dropyranyl hydroperoxide (0.945 g, 8 mmol) was added, and
then a solution of 4a or 4b (0.14 or 0.16 g, 2 mmol) in Et2O (2
mL) was added dropwise with stirring at 0 ꢀC. The mixture was
2,3,4,5,6,7-Hexahydrocyclopenta[b]pyran (10a)49
Colorless oil. dH (300 MHz, CDCl3): 1.52–2.29 (10H, m, C(CH2)3C, stirred for 30 or 120 min at 0 ꢀC (in entry 11, at 20–25 ꢀC). Then
C(CH2)2CH2O), 3.96 (2H, m, CH2O). petroleum ether (20 mL) and nely dispersed Na2S2O3$5H2O
dC (50 MHz, CDCl3): 19.3, 21.8 (CCH2CH2CH2C), 22.7 (1.5 g) were added, and the mixture was stirred until it became
(OCH2CH2CH2C), 30.9 (CCH2(CH2)2C), 32.3 (OCCH2(CH2)2C), colorless. The solid residue was ltered off. The solvents were
69.8 (OCH2), 106.8 (CH2CCH2), 151.0 (OCCH2).
Calculated (%): C 77.38; H, 9.74%; found (%): C, 77.45; H, and 6a,b were isolated from the residue by column chroma-
rotary evaporated at 10–15 mmHg and 15–20 ꢀC. Peroxides 5a,b
9.73. C8H12O%.
tography on silica gel. Eluent EA–PE ¼ 1 : 30.
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Experiment to Table 2. Reaction of bicyclic enol ethers 10b,c
2-[(3-Iodotetrahydrofuran-2-yl)peroxy]tetrahydro-2H-pyran
with the I2–H2O2 system to form iodohydroperoxides 11b,c
(6a)
Colorless oil. Rf ¼ 0.6 (EA : PE ¼ 1 : 5). dH (300 MHz, CDCl3):
1.45–2.59 (8H, m, CHICH2, (CH2)3CH(O)OO), 3.50–3.65, 3.96–
4.25, 5.1–5.25, 5.84–5.91 (7H, m, 2CH2O, CHI, 2CH).
dC (75 MHz, CDCl3): 19.0, 19.2, 19.3, 19.9 (CHI, CH2(CH2)2O),
25.0 (CH2CH2O), 27.5, 27.7, 27.8 (CH2CH(O)OO), 36.1, 36.3
(CHICH2), 62.0, 62.3, 62.4, (CH2)3CH2O, 67.8, 68.1
(CHICH2CH2), 100.2, 100.9, 101.8 (CH2CH(O)OO), 113.2, 113.9
(CHICH(O)OO).
Iodine (0.508 g, 2 mmol) was dissolved in Et2O or CH3CN (10 mL),
a 2.53 M ethereal solution of H2O2 (3.16 mL, 8 mmol) was added,
and then a solution of enol ether 10 (10b, 0.280 g, 2 mmol; 10c,
0.304 g, 2 mmol) in Et2O (2 mL) was added dropwise with stirring
at 20, 0, or ꢁ40 ꢀC. The mixture was stirred for 1 h; in the
experiments using cooling, the temperature was gradually raised
to 20–25 ꢀC. Then petroleum ether (20 mL) and nely dispersed
Na2S2O3$5H2O (1.5 g) were added, and the mixture was stirred
until it became colorless. The solid residue was ltered off. The
IR (KBr): 2944 (vs), 2895 (s), 2872 (s), 2852 (s), 1469 (m),
1454 (m), 1441 (m), 1352 (m), 1260 (m), 1204 (s), 1186 (m),
1107 (vs), 1085 (s), 1040 (vs), 1017 (s), 983 (s), 955 (vs), 903 (vs),
ꢀ
solvents were rotary evaporated at 10–15 mmHg and 15–20 C.
Iodohydroperoxides 11b,c were isolated from the residue by
column chromatography on silica gel. Eluent EA–PE ¼ 1 : 5.
874 (s), 817 (m), 430 (m) cmꢁ1
.
HRMS (ESI) m/z [M + Na]+: calculated for [C9H15IO4Na]+:
336.9907. Found: 336.9905.
Experiment to Table 3. Reaction of bicyclic enol ethers 10a–c
with the I2–ButOOH system to form peroxides 12a–c
3-Iodo-2-(tetrahydro-2H-pyran-2-ylperoxy)tetrahydro-2H-
pyran (6b)
Colorless oil. Rf ¼ 0.6 (EA : PE ¼ 1 : 5). dH (300 MHz, CDCl3):
1.52–2.29 (10H, m, CHICH2, (CH2)3CH(O)OO), 3.50–3.65, 3.88–
4.18, 5.19–5.33 (7H, m, 2CH2O, CHI, 2CH).
Iodine (0.508 g, 2 mmol) was dissolved in Et2O or CH3CN (10
mL), a 51% ethereal solution of tert-butyl hydroperoxide (1.386
g, 8 mmol) was added, and then a solution of enol ether 10 (10a,
0.248 g, 2 mmol; 10b, 0.280 g, 2 mmol; 10c, 0.304 g, 2 mmol) in
Et2O (2 mL) was added dropwise with stirring at 20, 0, ꢁ40, or
dC (75 MHz, CDCl3): 19.1, 19.3, 19.5 (CHI, CH2CH2(CH2)2O),
24.8, 25.0, 25.1 (CHICH2CH2CH2O, CHOO(CH2)2CH2), 27.5,
27.6, 27.8 (CH2CH(O)OO), 32.5, 32.7 (CHOOCH2, CHICH2), 62.0,
62.3, 63.5 ((CH2)3CH2O, CHI(CH2)2CH2O, (CH2)3CH2O), 100.1,
100.3, 101.9 (CH2CH(O)OO), 101.7, 102.0 (CHICH(O)OO).
IR (KBr): 2942 (vs), 2872 (vs), 2852 (vs), 2740 (m), 1737 (m),
1468 (s), 1454 (s), 1441 (vs), 1388 (s), 1352 (vs), 1310 (s), 1283 (s),
1261 (s), 1204 (vs), 1186 (vs), 1106 (vs), 1078 (vs), 1040 (vs), 1017
(vs), 953 (vs), 903 (vs), 874 (vs), 817 (s), 697 (m), 589 (m), 567 (m),
ꢀ
ꢁ70 C. The mixture was stirred for 1 h with the temperature
ꢀ
being gradually raised to 20–25 C. Then petroleum ether (20
mL) and nely dispersed Na2S2O3$5H2O (1.5 g) were added, and
the mixture was stirred until it became colorless. The solid
residue was ltered off. The solvents were rotary evaporated at
10–15 mmHg and 15–20 ꢀC. Iodohydroperoxides 12a–c were
isolated from the residue by column chromatography on silica
gel. Eluent EA–PE ¼ 1 : 30.
532 (m), 505 (w), 430 (s) cmꢁ1
.
HRMS (ESI) m/z [M + Na]+: calculated for [C10H17IO4Na]+:
351.0064. Found: 351.0062.
2-(tert-Butylperoxy)-3-iodotetrahydrofuran (5a)
Yellow oil. Rf ¼ 0.84 (EA : PE ¼ 1 : 10). dH (200 MHz, CDCl3):
1.21 (9H, s, (CH3)3C), 2.15–2.19 (1H, m, HCHCHI), 2.47–2.54 (1H,
m, HCHCHI), 4.02–4.22 (3H, m, CH2O, CHI), 5.74 (1H, m, CHO).
dC (75 MHz, CDCl3): 19.6 (CHI), 26.3 (CH3), 36.5 (CH2CH2O),
67.9 (CH2O), 81.3 (C(CH3)3), 113.4 (CHO).
4a-Iodooctahydro-8aH-chromen-8a-yl hydroperoxide (11b)
White crystals; mp 79–81 ꢀC. Rf ¼ 0.55 (EA : PE ¼ 1 : 5). dH (300
MHz, CDCl3): 1.15–2.70 (12H, m, (CH2)4, (CH2)2CH2O), 3.61–
4.05 (2H, m, CH2O), 7.60 (1H, br. s, OOH).
dC (50 MHz, CDCl3): 22.0, 24.0, 24.6, 30.8, 36.6, 41.1 ((CH2)4,
(CH2)2CH2O), 61.5 (CH2O), 65.1 (C–I), 103.8 (COOH).
IR (KBr): 3459 (vs), 3264 (vs), 2955 (vs), 2938 (vs), 2887 (s),
2863 (s), 1712 (m), 1460 (s), 1367 (s), 1289 (s), 1217 (vs), 1190
(vs), 1165 (s), 1094 (s), 1054 (vs), 987 (vs), 902 (s), 869 (s), 842 (m),
IR (KBr): 2979 (vs), 2933 (s), 2897 (s), 1475 (m), 1455 (m), 1439
(m), 1387 (m), 1364 (vs), 1309 (m), 1286 (m), 1245 (s), 1194 (vs),
1151 (m), 1123 (s), 1087 (vs), 1069 (vs), 1036 (s), 996 (vs), 953 9
(s), 920 (s), 860 (s), 773 (m), 754 (m) cmꢁ1
.
HRMS (ESI) m/z [M + Na]+: calculated for [C8H15IO3Na]+:
308.9958. Found: 308.9948.
799 (m), 727 (m), 604 (m), 550 (s), 476 (m) cmꢁ1
.
HRMS (ESI) m/z [M ꢁ OOH]+: calculated for [C9H14IO]+:
2-(tert-Butylperoxy)-3-iodotetrahydro-2H-pyran (5b)
265.0084. Found: 265.0093.
Yellow oil. Rf ¼ 0.15 (EA : PE ¼ 1 : 20). dH (300 MHz, CDCl3):
1.28 (9H, s, (CH3)3C), 1.60–1.66 (2H, m, (CH2CHI)), 2.04–2.07
(1H, m, HCHCH2O), 2.31–2.33 (1H, m, HCHCH2O), 3.62 (1H, m,
HCHO), 3.99–4.2 (2H, m, HCHO, CHI), 5.02 (1H, m, CHO).
dC (75 MHz, CDCl3): 23.4 (CHI), 26.4 (CH2CH2O), 26.5 (CH3),
34.6 (CH2CHI), 64.5 (CH2O), 81.7 (C(CH3)3), 104.6 (CHO).
IR (KBr): 2977 (vs), (vs), 2865 (s), 1467 (m), 1439 (m), 1387
(m), 1364 (vs), 1259 (m), 1244 (m), 1196 (vs), 1170 (m), 1120 (vs),
1097 (s), 1076 (vs), 1038 (s), 1026 (s), 965 (s), 902 (m), 867 (m),
4a-Iodooctahydrocyclohepta[b]pyran-9a(2H)-yl
oxide (11c)
hydroper-
Yellow oil. Rf ¼ 0.39 (EA : PE ¼ 1 : 5). dH (300 MHz, CDCl3):
1.15–2.50 (14H, m, (CH2)5, (CH2)2CH2O), 3.50–3.80 (2H, m,
CH2O).
dC (75 MHz, CDCl3): 20.7, 21.0, 25.8, 27.6, 33.8, 36.4, 44.9
((CH2)5, (CH2)2CH2O), 61.1 (CH2O), 61.5 (CI), 106.3 (COOH).
IR (KBr): 3355 (m), 2930 (vs), 2860 (s), 1705 (m), 1450 (m),
1359 (m), 1212 (m), 1074 (s), 996 (m), 892 (m), 732 (m) cmꢁ1
.
696 (m), 466 (m) cmꢁ1
.
HRMS (ESI) m/z [M + Na ꢁ HI]+: calculated for [C10H16O3]+:
HRMS (ESI) m/z [M + Na]+: calculated for: [C9H17IO3Na]+:
207.0992. Found: 207.1009.
323.0115. Found: 323.0120.
7584 | RSC Adv., 2014, 4, 7579–7587
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7a-(tert-Butylperoxy)octahydrocyclopenta[b]pyran (12a)
Yellow oil. Rf ¼ 0.12 (EA : PE ¼ 1 : 10). dH (300 MHz, CDCl3):
1.23–2.14 (20H, m, (CH2)3COO, (CH2)2CH(CH2)3, CH), 3.66–3.87
(2H, m, CH2O).
dC (50 MHz, CDCl3): 21.0 (CHCH2CH2CH2C), 22.8
(CH2CH2O), 26.7 (C(CH3)3), 28.5, 31.2 (CHCH2CH2,
CH2CH2CH), 36.0 (CCH2), 39.5 (CH), 61.0 (CH2O), 79.0
(OOC(CH3)3), 110.1 (OCOO).
RSC Advances
2 (a) Y. Li, H.-D. Hao and Y. Wu, Org. Lett., 2009, 11, 2691–
2694; (b) H.-D. Hao, Y. Li, W.-B. Han and Y. Wu, Org. Lett.,
2011, 13, 4212–4215; (c) Y. Li, H.-D. Hao, Q. Zhang and
Y. Wu, Org. Lett., 2009, 11, 1615–1618; (d) X. Yan, J. Chen,
Y.-T. Zhu and C. Qiao, Synlett, 2011, 19, 282–2830; (e)
A. O. Terent'ev, I. A. Yaremenko, V. A. Vil', I. K. Moiseev,
S. A. Kon'kov, V. M. Dembitsky, D. O. Levitsky and
G. I. Nikishin, Org. Biomol. Chem., 2013, 11, 2613–2623.
3 (a) J. Iskra, D. Bonnet-Delpon and J. P. Begue, Tetrahedron
Lett., 2003, 44, 6309–6312; (b) K. Zmitek, S. Stavber,
M. Zupan, D. Bonnet-Delpon, S. Charneau, P. Grellier and
J. Iskra, Bioorg. Med. Chem., 2006, 14, 7790–7795.
4 X. Lu, Y. Liu, B. Sun, B. Cindric and L. Deng, J. Am. Chem.
Soc., 2008, 130, 8134–8135.
IR (KBr): 3424 (m), 2944 (vs), 2878 (s), 1738 (s), 1464 (m), 1446
(m), 1067 (s), 993 (s), 915 (m), 900 (m) cmꢁ1
.
HRMS (ESI) m/z [M]+: calculated for [C12H21O3]+: 213.1485.
Found: 213.1492.
8a-(tert-Butylperoxy)octahydro-2H-chromene (12b)
Yellow oil. Rf ¼ 0.11 (EA : PE ¼ 1 : 10). dH (300 MHz, CDCl3):
1.21–1.54 (22H, m, C(CH2)4C, (CH3)3C, OCH2(CH2)2CH, CH),
3.64–3.98 (2H, m, CH2O).
5 (a) P. Ghorai and P. H. Dussault, Org. Lett., 2008, 10, 4577–
4579; (b) P. Ghorai and P. H. Dussault, Org. Lett., 2009, 11,
213–216.
dC (50 MHz, CDCl3): 22.5, 25.9 (CCH2CH2(CH2)2CH,
6 (a) H.-J. Hamann, M. Hecht, A. Bunge, M. Gogol and
J. Liebscher, Tetrahedron Lett., 2011, 52, 107–111; (b)
A. O. Terent'ev, A. V. Kutkin, M. M. Platonov, Y. N. Ogibin
and G. I. Nikishin, Tetrahedron Lett., 2003, 44, 7359–7363;
(c) A. O. Terent'ev, A. V. Kutkin, N. A. Troizky, Y. N. Ogibin
and G. I. Nikishin, Synthesis, 2005, 2215–2219; (d)
A. O. Terent'ev, I. A. Yaremenko, V. A. Vil', V. M. Dembitsky
and G. I. Nikishin, Synthesis, 2013, 45, 246–250.
OCH2CH2),
26.3,
26.6
(CHCH2CH2(CH2)2C,
CH(CH2)2CH2CH2CH), 26.8 (C(CH3)3) 29.8 (CHCH2), 32.3
(OOCCH2) 44.6 (CH), 60.9 (CH2O), 78.8 (OOC(CH3)3), 101.3
(OCOO).
IR (KBr): 2977 (vs), 2936 (vs), 2883 (s), 2860 (s), 1447 (m), 1362
(s), 1254 (m), 1243 (m), 1214 (m), 1200 (s), 1107 (m), 1091 (vs),
1025 (m), 994 (m), 969 (m), 957 (m), 931 (s), 892 (m), 867 (m),
cmꢁ1
.
HRMS (ESI) m/z [M + Na]+: calculated for [C13H24O3Na]+:
251.1618. Found: 251.1619.
7 B. Das, M. Krishnaiah, B. Veeranjaneyulu and B. Ravikanth,
Tetrahedron Lett., 2007, 48, 6286–6289.
8 B. Das, B. Veeranjaneyulu, M. Krishnaiah and
P. Balasubramanyam, J. Mol. Catal. A: Chem., 2008, 284,
116–119.
9 A. Bunge, H. J. Hamann and J. Liebscher, Tetrahedron Lett.,
2009, 50, 524–526.
9a-(tert-Butylperoxy)decahydrocyclohepta[b]pyran (12c)
Yellow oil. Rf ¼ 0.14 (EA : PE ¼ 1 : 10). dH (300 MHz, CDCl3):
1.20–2.01 (24H, m, C(CH2)5C, (CH3)3C, OCH2(CH2)2C, CH), 3.59–
4.10 (2H, m, CH2O).
dC (50 MHz, CDCl3): 20.7, 21.5, 23.4, 26.1
(C(CH2)2CH2(CH2)2C, CH2CH2(CH2)3, OCCH2CH2(CH2)3C,
OCH2CH2), 26.7 (C(CH3)3) 29.8 (CHCH2), 31.4 (O(CH2)2CH2CH),
34.4 (OCCH2), 38.3 (CH), 62.4 (CH2O), 78.7 (OOC(CH3)3), 105.7
(OCOO).
10 D. Azarifar, K. Khosravi and F. Soleimanei, Molecules, 2010,
15, 1433–1441.
11 (a) S.-I. Murahashi and D. Zhang, Chem. Soc. Rev., 2008, 37,
1490–1501; (b) S.-I. Murahashi, T. Naota, T. Kuwabara,
T. Saito, H. Kumobayashi and S. Akutagawa, J. Am. Chem.
Soc., 1990, 112, 7820–7822; (c) S.-I. Murahashi, T. Naota
and K. Yonemura, J. Am. Chem.Soc., 1988, 110, 8256–8258.
12 (a) G. B. Shul'pin, J. Gradinaru and Y. N. Kozlov, Org. Biomol.
Chem., 2003, 1, 3611–3617; (b) S. Araneo, F. Fontana,
F. Minisci, F. Recupero and A. Serri, J. Chem. Soc., Chem.
Commun., 1995, 1399–1400; (c) A. Bravo, H.-R. Bjørsvik,
F. Fontana, L. Liguori and F. Minisci, J. Org. Chem., 1997,
62, 3849–3857; (d) M. B. Meder and L. H. Gade, Eur. J.
Inorg. Chem., 2004, 2716–2722; (e) J. A. Vida, C. M. Samour,
M. H. O'Dea, T. S. T. Wang and J. F. Reinhard, J. Med.
Chem., 1974, 17, 1194–1197; (f) Z. Li and C.-J. Li, J. Am.
Chem. Soc., 2005, 127, 6968–6969; (g) T. Punniyamurthy
and L. Rout, Coord. Chem. Rev., 2008, 252, 134–154.
13 (a) W. Treibs and G. Pellmann, Chem. Ber., 1954, 87, 1201–
1205; (b) L. Saussine, E. Brazi, A. Robine, H. Mimoun,
J. Fischer and R. Weiss, J. Am. Chem. Soc., 1985, 107, 3534–
3540.
IR (KBr): 3400 (m), 2974 (vs), 2934 (vs), 2864 (s), 1735 (s), 1704
(vs), 1456 (m), 1363 (s), 1243 (s), 1197 (s), 1170 (m), 1154 (m),
1052 (m), 910 (m) cmꢁ1
.
HRMS (ESI) m/z [M + Na]+: calculated for [C14H26O3Na]+:
265.1774. Found: 265.1773.
Acknowledgements
This work was supported by the Russian Foundation for Basic
Research (Grant 14-03-00237-a), the Program for Basic Research
of the Presidium of the Russian Academy of Sciences, and the
Ministry of Education and Science of the Russian Federation.
High resolution mass spectra were recorded in the Department
of Structural Studies of Zelinsky Institute of Organic Chemistry,
Moscow.
References
1 (a) C. W. Jefford, W. Li, A. Jaber and J. Boukouvalas, Synth. 14 (a) R. A. Leising, R. E. Norman and L. Que Jr, Inorg. Chem.,
Commun., 1990, 20, 2589–2596; (b) A. Ramirez and
K. A. Woerpel, Org. Lett., 2005, 7, 4617–4620.
1990, 29, 2553–2555; (b) R. A. Leising, Y. Zang and L. Que
Jr, J. Am. Chem. Soc., 1991, 113, 8555–8557; (c) T. Kojima,
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 7579–7587 | 7585

View Article Online
RSC Advances
Paper
´
´
R. A. Leising, S. Yan and L. Que Jr, J. Am. Chem. Soc., 1993,
115, 11328–11335; (d) R. A. Leising, J. Kim, M. A. Perez and
L. Que Jr, J. Am. Chem. Soc., 1993, 115, 9524–9530; (e)
I. W. C. E. Arends, K. U. Ingold and D. D. M. Wayner, J.
Am. Chem. Soc., 1995, 117, 4710–4711.
N. Terzic, D. Opsenica, D. Milic, B. Tinant, K. S. Smith,
ˇ
W. K. Milhous and B. A. Solaja, J. Med. Chem., 2007, 50,
5118–5127; (e) D. M. Rubush, M. A. Morges, B. J. Rose,
D. H. Thamm and T. Rovis, J. Am. Chem. Soc., 2012, 134,
ˇ
ˇ
´
´
ˇ
13554–13557; (f) I. N. Cvijetic, Z. P. Zizak, T. P. Stanojkovic,
´ ´
Z. D. Juranic, N. Terzic, I. M. Opsenica, D. M. Opsenica,
15 F. Minisci, F. Fontana, S. Araneo and F. Recupero, J. Chem.
Soc., Chem. Commun., 1994, 1823–1824.
´
´
I. O. Juranic and B. J. Drakulic, Eur. J. Med. Chem., 2010,
16 F. Minisci, F. Fontana, S. Araneo, F. Recupero, S. Ban and
S. Quici, J. Am. Chem. Soc., 1995, 117, 226–232.
17 (a) B. T. Mott, A. Tripathi, M. A. Siegler, C. D. Moore,
D. J. Sullivan and G. H. Posner, J. Med. Chem., 2013, 56,
2630–2641; (b) X. Wang, Y. Dong, S. Wittlin,
45, 4570–4577.
20 (a) G. Odian, Principles of Polymerization, John Wiley & Sons,
Inc., New Jersey, 4th edn, 2004; (b) E. T. Denisov,
T. G. Denisova and T. S. Pokidova, Handbook of free radical
initiators, John Wiley and Sons, 2003.
ˇ
S. A. Charman, F. C. K. Chiu, J. Chollet, K. Katneni, 21 (a) K. Zmitek, M. Zupan and J. Iskra, Org. Biomol. Chem.,
ˇ
J. Mannila, J. Morizzi, E. Ryan, C. Scheurer, J. Steuten,
J. S. Tomas, C. Snyder and J. L. Vennerstrom, J. Med.
Chem., 2013, 56, 2547–2555; (c) P. H. Dussault, I. Q. Lee,
H. J. Lee, R. J. Lee, Q. J. Niu, J. A. Schultz and U. R. Zope, J.
2007, 5, 3895–3908; (b) K. Zmitek, M. Zupan, S. Stavber
and J. Iskra, J. Org. Chem., 2007, 72, 6534–6540; (c)
N. Kumar, S. I. Khan, M. Sharma, H. Atheaya and
D. S. Rawat, Bioorg. Med. Chem. Lett., 2009, 19, 1675–1677.
Org. Chem., 2000, 65, 8407–8414; (d) H.-X. Jin, H.-H. Liu, 22 A. O. Terent'ev, I. B. Krylov, D. A. Borisov and G. I. Nikishin,
Q. Zhang and Y. Wu, Tetrahedron Lett., 2005, 46, 5767– Synthesis, 2007, 2979–2986.
5769; (e) K. J. McCullough, J. K. Wood, A. K. Bhattacharjee, 23 A. O. Terent'ev, M. M. Platonov, I. B. Krylov,
Y. Dong, D. E. Kyle, W. K. Milhous and J. L. Vennerstrom,
J. Med. Chem., 2000, 43, 1246–1249; (f) K. Ingram,
V. V. Chernyshev and G. I. Nikishin, Org. Biomol. Chem.,
2008, 6, 4435–4441.
I. A. Yaremenko, I. Krylov, L. Hofer, A. O. Terent'ev and 24 A. O. Terent'ev, M. M. Platonov, I. B. Krylov and
J. Keiser, J. Med. Chem., 2012, 55, 8700–8711; (g) H.-X. Jin,
Q. Zhang, H.-S. Kim, Y. Wataya, H.-H. Liu and Y. Wu,
G. I. Nikishin, Russ. Chem. Bull., 2009, 58, 335–338; Izv.
Akad. Nauk, Ser. Khim., 2009, 333–336.
ˇ
Tetrahedron, 2006, 62, 7699–7711; (h) B. A. Solaja, 25 M. Jereb, M. Zupan and S. Stavber, Green Chem., 2005, 7,
´
N. Terzic, G. Pocsfalvi, L. Genena, B. Tinant, D. Opsenica
100–104.
and W. K. Milhous, J. Med. Chem., 2002, 45, 3331–3336; (i) 26 (a) J. Iskra, S. Stavber and M. Zupan, Synthesis, 2004, 1869–
H. Atheaya, S. I. Khan, R. Mamgain and D. S. Rawat,
Bioorg. Med. Chem. Lett., 2008, 18, 1446–1449; (j) C. Singh,
R. Kanchan, S. Chaudhary and S. K. Puri, J. Med. Chem.,
2012, 55, 1117–1126; (k) R. Maurya, A. Soni, D. Anand,
1873; (b) M. M. Kim, R. T. Ruck, D. Zhao and
M. A. Huffman, Tetrahedron Lett., 2008, 49, 4026–4028; (c)
J. Pavlinac, M. Zupan and S. Stavber, Synthesis, 2006, 15,
2603–2607.
M. Ravi, K. S. R. Raju, I. Taneja, N. K. Naikade, S. K. Puri, 27 (a) M. Jereb, M. Zupan and S. Stavber, Chem. Commun., 2004,
´
2614–2615; (b) J. Barluenga, M. Marco-Arias, F. Gonzalez-
Wahajuddin, S. Kanojiya and P. P. Yadav, ACS Med. Chem.
Lett., 2013, 4, 165–169; (l) T. T. Cloete, H. J. Krebs,
J. A. Clark, M. C. Connelly, A. Orcutt, M. S. Sigal, R. K. Guy
and D. D. N'Da, Bioorg. Chem., 2013, 46, 10–16; (m) J. Ruiz,
´
Bobes, A. Ballesteros and J. M. Gonzalez, Chem. Commun.,
2004, 2616–2617; (c) M. Jereb, J. Iskra, M. Zupan and
S. Stavber, Lett. Org. Chem., 2005, 2, 465–468.
B. Tuccio, R. Lauricella, M. Maynadier, H. Vial and 28 (a) A. O. Terent'ev, D. A. Borisov, I. B. Krylov and
C. Andre-Barres, Tetrahedron, 2013, 69, 6709–6720; (n)
D. Chaturvedi, A. Goswami, P. P. Saikia, N. C. Barua and
P. G. Rao, Chem. Soc. Rev., 2010, 39, 435–454; (o)
R. D. Slack, A. M. Jacobine and G. H. Posner, Med. Chem.
Commun., 2012, 3, 281–297.
G. I. Nikishin, Synth. Commun., 2007, 37, 3151–3164; (b)
W. J. Morgan, J. Trossarello, A. Egunjobi, R. Ahamed and
K. S. Aiken, Curr. Org. Synth., 2013, 10, DOI: 10.2174/
15701794113106660069.
29 D. D. Gaikwad, S. A. Dake, R. S. Kulkarni, W. N. Jadhav,
S. B. Kakde and R. P. Pawar, Synth. Commun., 2007, 4093–
4097.
18 (a) R. Amewu, A. V. Stachulski, S. A. Ward, N. G. Berry,
P. G. Bray, J. Davies, G. Labat, L. Vivas and P. M. O'Neill,
Org. Biomol. Chem., 2006, 4, 4431–4436; (b) Y. Dong, 30 S. B. Ferreira, C. R. Kaiser and V. F. Ferreira, Synlett, 2008,
Y. Tang, J. Chollet, H. Matile, S. Wittlin, S. A. Charman, 2625–2628.
W. N. Charman, J. S. Tomas, C. Scheurer, C. Snyder, 31 T. Froehr, C. P. Sindlinger, U. Kloeckner, P. Finkbeiner and
B. Scorneaux, S. Bajpai, S. A. Alexander, X. Wang, B. J. Nachtsheim, Org. Lett., 2011, 13, 3754–3757.
M. Padmanilayam, S. R. Cheruku, R. Brun and 32 (a) M. Uyanik, H. Okamoto, T. Yasui and K. Ishihara, Science,
J. L. Vennerstrom, Bioorg. Med. Chem., 2006, 14, 6368–
6382; (c) C. Singh, H. Malik and S. K. Puri, Bioorg. Med.
Chem. Lett., 2004, 14, 459–462.
2010, 328, 1365–1366; (b) M. Uyanik, D. Suzuki, T. Yasui and
K. Ishihara, Angew. Chem., Int. Ed., 2011, 50, 5331–5334.
33 (a) H. Jiang, H. Huang, H. Cao and C. Qi, Org. Lett., 2010, 12,
5561–5563; (b) Y. Yan, Y. Zhang, Z. Zha and Z. Wang, Org.
Lett., 2013, 15, 2274–2277.
19 (a) M. Jung, H. Kim, K. Lee and M. Park, Mini-Rev. Med.
Chem., 2003, 3, 159–165; (b) J. Kim and E. J. Park, Curr.
Med. Chem.: Anti-Cancer Agents, 2002, 2, 485–537; (c) 34 S. Stavber, M. Jereb and M. Zupan, Synthesis, 2008, 1487–
V. M. Dembitsky, Eur. J. Med. Chem., 2008, 43, 223–251; (d)
1513.
7586 | RSC Adv., 2014, 4, 7579–7587
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View Article Online
Paper
RSC Advances
35 A. Podgorsek, M. Zupan and J. Iskra, Angew. Chem., Int. Ed.,
2009, 48, 8424–8450.
36 M. Jereb, D. Vrazic and M. Zupan, Tetrahedron, 2011, 67,
1355–1387.
37 A. O. Terent'ev, A. M. Borisov, M. M. Platonov,
Z. A. Starikova, V. V. Chernyshev and G. I. Nikishin,
Synthesis, 2009, 24, 4159–4166.
T. Nobuta, N. Tada, A. Fujiya, A. Kariya, T. Miura and
A. Itoh, Org. Lett., 2013, 15, 574–577; (c) M. Eigen and
K. Kustin, J. Am. Chem. Soc., 1962, 84, 1355–1361; (d)
W. C. Bray and H. A. Liebhafsky, J. Am. Chem. Soc., 1931,
53, 38–44; (e) B. J. A. Agreda, R. J. Field and N. J. Lyons, J.
Phys. Chem. A, 2000, 104, 5269–5274.
42 P. Feit, Chem. Ber., 1953, 86, 1252.
´
38 (a) K. N. Houk, A. Jabbari, H. K. Hall Jr and C. Aleman, J. Org. 43 (a) V. V. Zhdankin and P. J. Stang, Chem. Rev., 2002, 102,
Chem., 2008, 73, 2674–2678; (b) W. H. Carothers, Chem. Rev.,
1931, 8, 353–426; (c) H. K. Hall Jr and A. K. Schneider, J. Am.
Chem. Soc., 1958, 80, 6409–6412; (d) T. Biela, A. Kowalski,
J. Libiszowski, A. Duda and S. Penczek, Macromol. Symp.,
2523; (b) P. Gogoi and D. Konwar, Org. Biomol. Chem.,
2005, 3, 3473–3475; (c) N. Mori and H. Togo, Tetrahedron,
2005, 61, 5915–5925; (d) X.-F. Zhao and C. Zhang,
Synthesis, 2007, 551–557.
2006, 240, 47–55; (e) O. Coulembier, P. Degu, 44 (a) J. V. Crivello and T. Yoo, J. Macromol. Sci., Part A: Pure
J. L. Hendrick and P. Dubois, Prog. Polym. Sci., 2006, 31,
723–747; (f) A. C. Albertssohn and I. K. Varma,
Biomacromolecules, 2003, 4, 1466–1486.
Appl.Chem., 1996, 33, 717–733; (b) F. Sanda and
M. Matsumoto, Macromolecules, 1995, 28, 6911–6914; (c)
M. Yonezumi, S. Kanaoka and S. Aoshima, J. Polym. Sci.,
Part A: Polym. Chem., 2008, 46, 4495–4504.
39 (a) K. Sato, M. Aoki and R. Noyori, Science, 1998, 281, 1646–
1647; (b) A. O. Terent'ev, M. M. Platonov, A. S. Kashin and 45 T. J. Fisher and P. H. Dussault, Tetrahedron Lett., 2010, 51,
G. I. Nikishin, Tetrahedron, 2008, 64, 7944–7948; (c) 5615–5617.
V. N. Belov; L. A. Heytz and S. I. Virezub, Reaczii I Metodi 46 A. O. Terent'ev, I. A. Yaremenko, V. A. Vil', V. M. Dembitsky
issledovaniya organicheskich soedineniy, Goshimizdat, and G. I. Nikishin, Synthesis, 2013, 45, 246–250.
Moscow, 1961, 10, pp. 207–208; (d) A. O. Terent'ev, 47 P. A. Belyakov, V. I. Kadentsev, A. O. Chizhov,
M. M. Platonov and A. V. Kutkin, Cent. Eur. J. Chem., 2006,
4, 207–215.
N. G. Kolotyrkina, A. S. Shashkov and V. P. Ananikov,
Mendeleev Commun., 2010, 20, 125–131.
¨
40 (a) M. E. Sengul, Z. Ceylan and M. Balci, Tetrahedron, 1997, 48 V. V. Kachala, L. L. Khemchyan, A. S. Kashin, N. V. Orlov,
53, 10401–10408; (b) M. Oda and Y. Kitahara, Tetrahedron
Lett., 1969, 10, 3295–3296; (c) A. Dastan and M. Balci,
A. A. Grachev, S. S. Zalesskiy and V. P. Ananikov, Russ.
Chem. Rev., 2013, 82, 648–685.
¨
Tetrahedron, 2006, 62, 4003–4010; (d) A. Coskun, M. Guney, 49 Y. N. Ogibin, A. O. Terent'ev, A. V. Kutkin and G. I. Nikishin,
A. Dastan and M. Balci, Tetrahedron, 2007, 63, 4944–4950. Tetrahedron Lett., 2002, 43, 1321–1324.
41 (a) H. A. Liebhafsky, W. C. McGavock, R. J. Reyes, G. M. Roe 50 Y. N. Ogibin, A. O. Terent'ev, V. P. Ananikov and
and L. S. Wu, J. Am. Chem. Soc., 1978, 100, 87–91; (b)
G. I. Nikishin, Russ. Chem. Bull., 2001, 50, 2149–2155.
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