Iodine Acetate as a Mild Selective Agent for the Wagner–Meerwein Rearrangement in 3a,6-Epoxyisoindoles

Article abstract of DOI:10.1007/s10593-020-02752-y

[Figure not available: see fulltext.] The iodine-initiated cationic skeletal Wagner–Meerwein rearrangement in tetrahydro-3a,6-epoxyisoindol-1-ones has been studied. It was shown that by the action of iodine acetate in acetic anhydride the reaction proceed

Full text of DOI:10.1007/s10593-020-02752-y

DOI 10.1007/s10593-020-02752-y
Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
Iodine acetate as a mild selective agent for the Wagner–Meerwein
rearrangement in 3a,6-epoxyisoindoles
Vladimir P. Zaytsev1*, Dmitriy F. Mertsalov1, Anastasiya M. Trunova1, Anastasiya V. Khanova1,
Eugeniya V. Nikitina1, Anna А. Sinelshchikova2, Mikhail S. Grigoriev2
1 RUDN University,
6 Miklukho-Maklaya St., Moscow 117198, Russia; е-mail: vzaitsev@sci.pfu.edu.ru
2 Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences,
31/4 Leninskiy prosp., Moscow 119071, Russia
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(7), 930–935
Submitted April 9, 2020
Accepted May 4, 2020
The iodine-initiated cationic skeletal Wagner–Meerwein rearrangement in tetrahydro-3a,6-epoxyisoindol-1-ones has been studied. It was
shown that by the action of iodine acetate in acetic anhydride the reaction proceeds regio- and stereoselectively with the formation of
5-iodo-4,6-epoxycyclopenta[c]pyridin-4-yl acetates. The proposed reagent provides better yields of rearrangement products than those
described in the literature.
Keywords: cyclopenta[c]pyridines, iodine acetate, isoindoles, IMDAF reaction, intramolecular Diels–Alder reaction, Wagner–Meerwein
rearrangement.
The Wagner–Meerwein rearrangement was discovered
by Wagner in his study of the dehydration of bicyclic
terpenes1a and was studied in detail in the 1920s by
Meerwein,1b who proposed the cationic mechanism of this
reaction generally accepted today.1c A distinctive feature of
the process is the [1,2]-sigmatropic shift of a hydrogen
atom, an alkyl or aryl substituent; since the bond migrates
to an electron-deficient center, the rearrangement is often
called anionotropic (sextet or nucleophilic).2 This type of
rearrangement plays an important role in the chemical
transformations of nitrogen- and oxygen-containing
bridged heterocycles due to the ability to carry out complex
transformation of the carbon skeleton in one step, which
makes it possible to obtain from relatively simple starting
compounds products that are practically inaccessible in
other ways.3
or by the action of N-bromosuccinimide4a (Scheme 1). It was
shown that, depending on the electrophilic agent used,
rearrangement can lead to both tricyclic compounds 2 and
cyclopentapyridine 3. Subsequently, the conditions found
were used to convert 3a,6-epoxyisoindoles 4 into sigma
receptor antagonists (structures 5).4b In 1989, Keay et al.
studied the iodine-initiated rearrangement of 4а,7-epoxy-
octahydronaphthalen-1-ones (6). Later, it was shown that,
depending on the substituents R3 and R4, either tricyclic
product 7 or hydrogenated azulene 84c is formed (Scheme 1).
When replacing a carbon atom with a nitrogen atom in
carbocycle of 4а,7-epoxyoctahydronaphthalene 9, the main
reaction product turned out to be heterocycle 10.4d Using
Br2 in an alkaline medium, Woodward and Baer carried out
a
rearrangement using the example of tetrahydro-
4,7-epoxybenzofuran-1,3-dione and refuted erroneous
statement by Diels and Alder about the formation of an
endo adduct of furan with maleic anhydride.5
Analysis of the presented data does not allow one to
reliably predict the direction of the rearrangement. All
described examples have been studied on a limited number
of substrates, and the use of molecular halogens and
The halogen-initiated Wagner–Meerwein cationic
rearrangement in oxabicycloheptenes4 coupled with carbon-
or nitrogen-containing rings was first demonstrated in
1985, when Young and Street succeeded in transforming
tetrahydro-3a,6-epoxyisoindol-1-ones 1 under the condi-
tions of the Prévost–Woodward reaction (I2/AcOAg/AcOH)
0009-3122/20/56(7)-0930©2020 Springer Science+Business Media, LLC
930

Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
Scheme 1
expensive transition metal salts significantly limits the
scope of this method. In this work, we proposed and tested
cheap and readily available AcOI as a rearrangement
initiator and a source of a positively charged halogen ion.
The choice of AcOI,6 obtained by one-pot synthesis from
Oxone and iodine,6a is due to its cheapness, simplicity of
synthesis and isolation, and the unambiguous direction of
rearrangement. In addition, AcOI is an excellent reagent for
the functionalization of unsaturated hydrocarbons6a,c–e and
is also used for other molecular rearrangements6d,e in the
synthesis of heterocyclic compounds of the pyrrole series6f
and for modifications of organoelement compounds.6g
The present work is aimed at further accumulating
experimental data and establishing the rules of the iodine-
initiated Wagner–Meerwein rearrangement in bicyclic aza-
heterocycles.7
The starting compounds were 3а,6-epoxyisoindolones
12a–h, synthesized in two steps according to known
methods3h,8 from furfurylamines 11a–f and maleic
anhydride or acryloyl(methacryloyl) chloride (IMDAF
reaction, from the IntraMolecular Diels–Alder Reaction of
Furan). To improve the solubility in Ac2O, the carboxylic
acid synthesized from furfurylamine 11h was converted
into methyl ester 12h. Isoindolones 12a–h obtained in
this way were isolated as individual diastereomers with
the relative configuration of the substituents shown in
Scheme 2 (Table 1).
We used AcOI obtained by one-pot synthesis from
Oxone and iodine6a as an initiator of the Wagner–
Meerwein rearrangement of isoindolones 12a–h, which
favorably distinguishes the proposed method from the
conditions described earlier4a (I2/AcOAg). The reaction of
AcOI with 7-oxabicycloheptenes 12a–h (Scheme 2)
proceeds quickly and under mild conditions (from 0.5 to
5 h at room temperature). In this case, the products of the
skeletal rearrangement, 4,6-epoxycyclopenta[c]pyridines
13a–h, are formed, as a rule, in higher yields (Table 1) as
compared with the reactions carried out under the
conditions of the Prévost–Woodward reaction.4
The halogen-initiated transformations of isoindolones
12a–h can proceed in two ways (Scheme 3). Theoretically,
Table 1. Yields of starting epoxyisoindolones 12a–h
and products of their rearrangement 13a–h
Rearrange-
Epoxy-
isoindolone
Yield,
%
Yield,
%
R1
R2
R3
ment
product
Ph
4-MeC6H4
4-ClC6H4
4-FC6H4
4-F3CC6H4
4-MeOC6H4
Ph
H
H
H
483h
42
87
77
75
77
71
71
67
66
12a
12b
12c
12d
12e
12f
13a
13b
13c
13d
13e
13f
H
H
H
66
H
H
60
H
H
H
49
H
45
Me
H
H
258
833h
12g
12h
13g
13h
Ph
CO2Me
Scheme 2
931

Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
iodonium ion A can transform into two alternative
carbocations B and C, the subsequent migration of
neighboring σ-bonds in which leads to the mesomerically
stabilized D (tertiary) and E (secondary) cations. The
rearrangement is completed by the addition of acetate anion
from the reaction medium to the carbocation sites. Thus, as
a result of skeletal rearrangement, the formation of two
tricyclic products 13 and 14 is possible.
additionally confirmed by X-ray structural analysis using
1
one example (Fig. 1). In the H NMR spectra, the most
characteristic signals of cyclopentapyridines 13a–h include
singlet signals of 5-CH protons of the bridge and 6-CH
protons in the bridgehead at 3.90–4.26 and 4.66–4.86 ppm,
respectively, and also doublets of 4а-CH protons with a
coupling constant J4а,7а = 4.0–4.3 Hz in the 3.38–3.72 ppm
range. In the carbon spectra, the signals of quaternary
carbon atoms C-4 at 103.7–104.7 ppm as well as carbon
atoms C-5 at 83.9–86.5 ppm, located in the vicinity of the
iodine atom, are most clearly identified.
Scheme 3
X-ray structural analysis of a single crystal of compound
13d confirmed the structure of the product of the
sigmatropic rearrangement and the formation of the
4,6-epoxycyclopenta[c]pyridine framework (Fig. 1). The
molecule contains a flattened piperidone ring in the chair
conformation and two five-membered rings, tetrahydro-
furan and cyclopentane, joined with it in the envelope
conformation. Compound 13d crystallizes in the triclinic
system, P1 space group (unit cell parameters are listed in
Table 2 in the Supplementary information file). The
molecule occupies a common position, the number of
formula units per cell is equal to 2. The main bond lengths,
bond and torsion angles are given in Tables 3–5 in the
Supplementary information file. In the crystal packing, the
oxygen atom of the carbonyl group acts as an acceptor of
the hydrogen bond with the CH group of the aromatic ring
of the neighboring molecule, which was previously
observed for molecules with similar structures.7
It was experimentally established that the sigmatropic
rearrangement of isoindolones 12a–h, regardless of
substituents R, proceeds chemoselectively via intermediate
cations B and D, leading exclusively to epoxycyclopenta[c]-
pyridines 13a–h. The absence of alternative products 14
can be explained, first, by a more significant decrease in
the Baeyer and Pitzer strain of the system during the
formation of products 13 (the coupling of two five-
membered and six-membered rings in cyclopentapyridines
13 is preferable to a set of three five-membered rings in
tricyclic compounds 14). Second, in cation C, the
migration of the neighboring σ-bond should be more
difficult than in cation B, since in cation B the migrating
bond is additionally included in the pyrrolidone ring, and,
therefore, is more strained (less strong) compared to the
alternative bond in cation C. Third, the direction of
migration of the σ-bond is associated with the formation of
tertiary carbocation D in the second step, which is more
stable than secondary cation E.
Figure 1. Molecular structure of tricyclic compound 13d, thermal
ellipsoids are at the 50% probability level.
To conclude, in this work it was shown for the first time
that iodine acetate generated in situ from iodine and Oxone
in acetic anhydride medium is a convenient reagent for
initiating the Wagner–Meerwein sigmatropic rearrange-
ment in tetrahydro-3a,6-epoxyisoindol-1-ones. It has been
found that the reaction proceeds stereo- and chemo-
specifically, leading to the formation of 5-iodo-4,6-epoxy-
cyclopenta[c]pyridin-4-yl acetates in good yields.
The structure of the rearrangement products
epoxycyclopenta[c]pyridines 13a–h was established by
analogy with previously published studies3h,3i,7 and
932

Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
Experimental
golden plates, mp 163–164°С. IR spectrum, ν, cm–1: 1694
1
(NCO). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.68
IR spectra were registered on an Infralum FT-801
Fourier spectrometer in KBr pellets. 1H, 13C, and 19F NMR
spectra were acquired on a JEOL JNM-ECA 600
spectrometer (600, 151, and 565 MHz, respectively),
Residual signals of deuterated solvents were used as
internal standards (CDCl3: 7.26 ppm for 1Н nuclei, 77.2 ppm
(1Н, dd, J = 12.1, J = 8.6, 7-СН2); 2.30 (1Н, ddd,
J = 12.1, J = 4.5, J = 3.5, 7-СН2); 2.62 (1Н, dd, J = 8.6,
J = 3.5, 7а-СН); 4.10 (1Н, d, J = 11.3, 3-СН2); 4.42 (1Н, d,
J = 11.3, 3-СН2); 5.10 (1Н, dd, J = 4.5, J = 1.5, 6-СН);
6.45 (1Н, dd, J = 5.6, J = 1.5, 5-СН); 6.46 (1Н, d, J = 5.6,
4-СН); 7.31 (2Н, d, J = 8.8, H Ar); 7.58 (2Н, d, J = 8.8,
Н Ar). 13C NMR spectrum (CDCl3), δ, ppm: 29.0; 48.8;
50.9; 79.4; 88.0; 121.3; 129.0; 129.8; 133.0; 137.6; 138.1;
173.6. Mass spectrum, m/z (Irel, %): 263 [М]+ (10), 261 [М]+
(33), 111 (9), 81 (100), 55 (36), 53 (19). Found, %:
С 64.18; Н 4.56; N 5.44. С14H12ClNO2. Calculated, %: С
64.25; Н 4.62; N 5.35.
1
for 13C nuclei; DMSO-d6: 2.50 ppm for Н nuclei, 39.5 ppm
for 13C nuclei). Mass spectra of compounds 12b–d,f were
recorded on a Thermo DSQ II – Focus GC mass spectro-
meter (EI ionization, 70 eV, 200°C source temperature,
helium carrier gas, RTX-5MS column). ESI mass spectra of
compounds 12e, 13a–h were recorded on an Agilent 6470
mass spectrometer, AJS ESI ionization source (ZORBAX
RRHD Eclipse Plus C18 reversed-phase chromatographic
column, 3×50 mm, 1.8 μ m, mobile phase – MeCN (70%),
H2O (30%), and HCO2H (0.2%), 0.4 ml/min flow, 40°C
temperature). Elemental analysis was performed on a Euro
Vector EA-3000 CHNS-analyzer. Melting points were
determined in open capillaries on SMP 10 or SMP 30
apparatuses and are uncorrected. Sorbfil PTSKh-АF-А-UF-
254 plates were used for TLC, visualization in iodine vapor
or with KMnO4 reagent.
(3aRS,6RS,7aSR)-2-(4-Fluorophenyl)-2,3,7,7a-tetrahydro-
3a,6-epoxyisoindol-1(6H)-one (12d). Yield 8.82 g (60%),
light-yellow powder, mp 117–118°С. IR spectrum, ν, cm–1:
1
1693 (NCO). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
1.67 (1Н, dd, J = 11.6, J = 8.6, 7-СН2); 2.30 (1Н, ddd,
J = 11.6, J = 4.5, J = 3.5, 7-СН2); 2.62 (1Н, dd,
J = 8.6, J = 3.5, 7а-СН); 4.09 (1Н, d, J = 11.6, 7-СН2);
4.43 (1Н, d, J = 11.6, 7-СН2); 5.10 (1Н, dd, J = 4.5,
J = 1.5, 6-СН); 6.44 (1Н, dd, J = 5.8, J = 1.5, 5-СН); 6.47
(1Н, d, J = 5.8, 4-СН); 7.05 (2Н, dd, J = 9.1, J = 8.6,
H Ar); 7.58 (2Н, dd, J = 9.1, J = 4.5, Н Ar). 13C NMR
spectrum (CDCl3), δ, ppm (J, Hz): 29.0; 48.7; 51.3; 79.4;
88.2; 115.7 (d, J = 23.1); 122.2 (d, J = 7.2); 133.0; 135.6
(d, J = 2.9); 137.6; 159.7 (d, J = 244.2); 173.5. Mass
spectrum, m/z (Irel, %): 245 [М]+ (2), 122 (6), 109 (10), 95
(15), 81 (100), 55 (38), 53 (30). Found, %: С 68.49;
Н 4.88; N 5.83. С14H12FNO2. Calculated, %: С 68.56;
Н 4.93; N 5.71.
Reagents were supplied by Acros Organics or Alfa
Aesar and were used without additional purification.
Yields, elemental analysis data, and physicochemical
characteristics of compounds 12a,g have been published
previously.3h,8 The synthesis and physicochemical characte-
ristics of ester 12h have been described earlier.3h
Synthesis of 3a,6-epoxy-2,3,7,7a-tetrahydroisoindol-
1-ones 12b–f (General method). A solution of the
corresponding amine 11a–f (0.06 mol), acryloyl chloride
(7.3 ml, 0.09 mol), and Et3N (16.7 ml, 0.12 mol) in PhMe
(100 ml) was heated under reflux for 6–10 h (TLC control,
for compounds 12b,c,e,f, eluent EtOAc–hexane, 1:1; for
compound 12d, eluent EtOAc–hexane, 2:3). The mixture
was cooled and poured into H2O (100 ml). The organic
layer was separated, the aqueous layer was extracted with
AcOEt (3×50 ml). The organic fractions were combined
and dried over anhydrous MgSO4. The extract was
evaporated under reduced pressure, and the residue was
recrystallized from a hexane–AcOEt mixture.
(3aRS,6RS,7aSR)-2-[4-(Trifluoromethyl)phenyl]-
2,3,7,7a-tetrahydro-3a,6-epoxyisoindol-1(6H)-one (12e).
Yield 8.67 g (49%), light-yellow powder, mp 196–197°С.
1
IR spectrum, ν, cm–1: 1688 (NCO). H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 1.69 (1Н, dd, J = 11.8, J = 8.8,
7-СН2); 2.31 (1Н, ddd, J = 11.8, J = 4.5, J = 3.5, 7-СН2);
2.65 (1Н, dd, J = 8.8, J = 3.5, 7а-СН); 4.17 (1Н, d, J = 11.6,
3-СН2); 4.46 (1Н, d, J = 11.6, 3-СН2); 5.10 (1Н, dd,
J = 4.5, J = 1.5, 6-СН); 6.45 (1Н, dd, J = 6.1, J = 1.5,
5-СН); 6.47 (1Н, d, J = 6.1, 4-СН); 7.60 (2Н, d, J = 8.6,
H Ar); 7.79 (2Н, d, J = 8.6, Н Ar). 13C NMR spectrum
(CDCl3), δ, ppm (J, Hz): 29.2; 49.0; 50.7; 79.4; 87.9;
119.4; 124.2 (q, J = 271.7); 126.1 (q, J = 33.2); 126.2 (q,
J = 4.3); 132.9; 137.8; 142.5; 174.0. Mass spectrum, m/z
296 [M+H]+. Found, %: С 60.96; Н 4.02; N 4.82.
С15H12F3NO2. Calculated, %: С 61.02; Н 4.10; N 4.74.
(3aRS,6RS,7aSR)-2-(4-Methoxyphenyl)-2,3,7,7a-tetra-
hydro-3a,6-epoxyisoindol-1(6H)-one (12f). Yield 6.94 g
(45%), light-yellow powder, mp 123–124°С. IR spectrum,
(3aRS,6RS,7aSR)-2-(4-Methylphenyl)-2,3,7,7a-tetra-
hydro-3a,6-epoxyisoindol-1(6H)-one (12b). Yield 6.07 g
(42%), light-yellow powder, mp 152–154°С. IR spectrum,
1
ν, cm–1: 1682 (NCO). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.66 (1Н, dd, J = 11.9, J = 8.8, 7-СН2); 2.30 (1Н,
ddd, J = 11.9, J = 4.7, J = 3.5, 7-СН2); 2.32 (3H, s, CH3);
2.62 (1Н, dd, J = 8.8, J = 3.5, 7а-СН); 4.10 (1Н, d, J = 11.4,
3-СН2); 4.43 (1Н, d, J = 11.4, 3-СН2); 5.10 (1Н, dd, J = 4.7,
J = 1.5, 6-СН); 6.43 (1Н, dd, J = 5.9, J = 1.5, 5-СН); 6.46
(1Н, d, J = 5.9, 4-СН); 7.16 (2Н, d, J = 8.6, H Ar); 7.48
(2Н, d, J = 8.6, Н Ar). 13C NMR spectrum (CDCl3),
δ, ppm: 21.0; 28.9; 48.8; 51.1; 79.3; 88.3; 120.5; 129.5;
133.2; 134.5; 137.0; 137.5; 173.4. Mass spectrum, m/z
(Irel, %): 241 [М]+ (100), 212 (11), 186 (10), 107 (8), 91 (9),
81 (99), 55 (42), 53 (16). Found, %: С 74.60; Н 6.18;
N 5.92. С15H15NO2. Calculated, %: С 74.67; Н 6.27; N 5.81.
(3aRS,6RS,7aSR)-2-(4-Chlorophenyl)-2,3,7,7a-tetrahydro-
3a,6-epoxyisoindol-1(6H)-one (12c). Yield 10.36 g (66%),
1
ν, cm–1: 1679 (NCO). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.65 (1Н, dd, J = 11.9, J = 8.8, 7-СН2); 2.28 (1Н,
ddd, J = 11.9, J = 4.5, J = 3.5, 7-СН2); 2.60 (1Н, dd, J = 8.8,
J = 3.5, 7а-СН); 3.78 (3H, s, CH3); 4.06 (1Н, d, J = 11.6,
3-СН2); 4.41 (1Н, d, J = 11.6, 3-СН2); 5.09 (1Н, dd,
J = 4.5, J = 1.5, 6-СН); 6.42 (1Н, dd, J = 5.8, J = 1.5,
5-СН); 6.45 (1Н, d, J = 5.8, 4-СН); 6.89 (2Н, d, J = 9.1,
H Ar); 7.49 (2Н, d, J = 9.1, Н Ar). 13C NMR spectrum
(CDCl3), δ, ppm: 28.8; 48.6; 51.5; 55.6; 79.3; 88.3; 114.2;
122.4; 132.6; 133.2; 137.4; 156.9; 173.3. Mass spectrum, m/z
933

Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
(Irel, %): 257 [М]+ (15), 176 (6), 123 (7), 95 (11), 81 (77),
(2H, d, J = 8.8, H Ar); 7.45 (2H, d, J = 8.8, Н Ar).
13C NMR spectrum (DMSO-d6), δ, ppm: 19.8; 22.1; 36.0;
37.2; 46.8; 53.6; 84.0; 103.7; 127.8; 128.8; 130.9; 140.3;
168.4; 169.1. Mass spectrum, m/z: 448 [M+H]+, 450
55 (100), 53 (32). Found, %: С 69.95; Н 5.80; N 5.53.
С15H15NO3. Calculated, %: С 70.02; Н 5.88; N 5.44.
Synthesis of 5-iodo-4,6-epoxycyclopenta[c]pyridin-4-yl
acetates 13a–h (General method). A suspension of iodine
(0.32 g, 1.25 mmol) and Oxone (1.54 g, 2.5 mmol) in a
mixture of Ac2O (7.55 ml, 80 mmol) and AcOH (7.4 ml,
130 mmol) was stirred at 50°С in a flask shielded from
light for 20 h until complete discoloration of the solution.
The mixture was then cooled to room temperature, and the
corresponding isoindolone 12a–h (2 mmol) was added.
The reaction mixture was stirred for 0.5–5 h (TLC control,
eluents: for compound 13а, EtOAc–hexane, 1:2; for
compounds 13b,c,e,f,h, EtOAc–hexane, 1:1; for compound
13d, EtOAc–hexane, 2:3; for compound 13g, EtOAc–
hexane, 1:3), poured into H2O (50 ml), neutralized with
K2CO3, extracted with CH2Cl2 (3×25 ml). The combined
organic fractions were dried over anhydrous Na2SO4, the
solvent was evaporated under reduced pressure, and the
residue was recrystallized from a hexane–AcOEt mixture.
(4SR,4aRS,5SR,6RS,7aSR)-5-Iodo-2-phenyl-1-oxoocta-
[M+H]+. Found, %:
С 42.86; H 3.30; N 3.24.
C16H15ClINO4. Calculated, %: С 42.93; H 3.38; N 3.13.
(4SR,4aRS,5SR,6RS,7aSR)-2-(4-Fluorophenyl)-5-iodo-
1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl-
acetate (13d). Yield 0.67 g (77%), colorless prisms,
mp 168–169°С (decomp.). IR spectrum, ν, cm–1: 1737,
1661 (NCO, OCO), 597 (CI). 1H NMR spectrum (DMSO-d6),
δ, ppm (J, Hz): 1.58 (1H, dd, J = 11.6, J = 4.0, 7-CH2);
2.33 (1Н, t, J = 11.6, 7-CH2); 2.03 (3Н, s, СН3); 2.97 (1Н,
dt, J = 11.6, J = 4.0, 7a-CH); 3.55 (1Н, d, J = 4.0, 4a-CH);
4.12 (2Н, br. s, 3-CH2); 4.22 (1Н, br. s, 5-CH); 4.66 (1H,
br. s, 6-CH); 7.22 (2H, t, J = 8.3, H Ar); 7.32–7.34 (2H, m,
H Ar). 13C NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
19.8; 22.1; 35.9; 37.1; 46.8; 54.2; 83.9; 103.7; 115.6 (d,
J = 23.1); 128.3 (d, J = 8.7); 137.7 (d, J = 2.9); 161.0 (d,
J = 242.7); 168.4; 169.1. 19F NMR spectrum (DMSO-d6),
δ, ppm: –115.1. Mass spectrum, m/z: 432 [M+H]+. Found,
%: С 44.51; H 3.44; N 3.34. C16H15FINO4. Calculated, %:
С 44.57; H 3.51; N 3.25.
hydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl
acetate
(13a). Yield 0.7 g (87%), light-beige powder, mp >157°С.
IR spectrum, ν, cm–1: 1737, 1670 (NCO, OCO), 597 (CI).
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.84 (1H, dd,
J = 13.1, J = 4.3, 7-CH2); 2.13 (3Н, s, СН3); 2.41 (1Н, dd,
J = 13.1, J = 11.3, 7-CH2); 3.08 (1Н, dt, J = 11.3, J = 4.3,
7a-CH); 3.38 (1Н, d, J = 4.3, 4a-CH); 3.91 (1Н, br. s,
5-CH); 4.16 (1H, d, J = 13.1, 3-CH2); 4.16 (1Н, d, J = 13.1,
3-CH2); 4.71 (1H, br. s, 6-CH); 7.24–7.31 (3H, m, Н Ar);
7.41 (2H, t, J = 7.6, Н Ar). 13C NMR spectrum (CDCl3),
δ, ppm: 17.9; 22.3; 36.9; 38.1; 46.6; 54.7; 84.3; 104.1;
126.1; 127.5; 129.4; 140.8; 169.1; 169.2. Mass spectrum,
m/z: 414 [M+H]+. Found, %: С 46.45; H 3.83; N 3.47.
C16H16INO4. Calculated, %: С 46.51; H 3.90; N 3.39.
(4SR,4aRS,5SR,6RS,7aSR)-5-Iodo-2-[4-(trifluoromethyl)-
phenyl]-1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyri-
din-4-yl acetate (13e). Yield 0.68 g (71%), colorless
rhombuses, mp 155–156°С (decomp.). IR spectrum, ν, cm–1:
1
1736, 1661 (NCO, OCO), 601 (CI). H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.61 (1H, d, J = 12.6, 7-CH2);
2.04 (3Н, s, СН3); 2.35 (1Н, t, J = 12.6, 7-CH2); 3.01 (1Н,
dd, J = 12.6, J = 4.0, 7a-CH); 3.58 (1Н, t, J = 4.0, 4a-CH);
4.15 (1H, dd, J = 12.9, J = 3.5, 3-СН2); 4.23 (1Н, dd,
J = 12.9, J = 3.5, 3-СН2); 4.23 (1Н, br. s, 5-CH); 4.68 (1H,
br. s, 6-CH); 7.55 (2H, d, J = 8.7, H Ar); 7.76 (2Н, d,
J = 8.7, H Ar). 13C NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 19.7; 22.1; 36.0; 37.4; 46.9; 53.1; 84.0; 103.7;
124.0 (q, J = 271.6); 125.8 (q, J = 4.3); 126.3; 126.6 (q,
J = 33.2); 145.0; 168.4; 169.4. 19F NMR spectrum (DMSO-d6),
δ, ppm: –60.7. Mass spectrum, m/z: 482 [M+H]+. Found,
%: С 42.35; H 3.07; N 3.03. C17H15F3INO4. Calculated, %:
С 42.43; H 3.14; N 2.91.
(4SR,4aRS,5SR,6RS,7aSR)-5-Iodo-2-(4-methylphenyl)-
1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl
acetate (13b). Yield 0.66 g (77%), colorless powder,
mp 150–151°С. IR spectrum, ν, cm–1: 1732, 1667 (NCO,
1
OCO), 600 (CI). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.83 (1H, dd, J = 12.8, J = 4.3, 7-CH2); 2.13 (3Н,
s, СН3); 2.35 (3H, s, CH3); 2.40 (1Н, t, J = 12.8, 7-CH2);
3.07 (1Н, dt, J = 12.8, J = 4.3, 7a-CH); 3.72 (1Н, d,
J = 4.3, 4a-CH); 3.91 (1Н, br. s, 5-CH); 4.13 (1Н, d,
J = 13.1, 3-СН2); 4.17 (1Н, d, J = 13.1, 3-СН2); 4.71 (1H,
br. s, 6-CH); 7.12 (2H, d, J = 8.1, H Ar); 7.21 (2H, d,
J = 8.1, Н Ar). 13C NMR spectrum (CDCl3), δ, ppm: 18.0;
21.0; 22.3; 36.9; 38.0; 46.6; 54.8; 84.3; 104.2; 125.9;
130.0; 137.4; 138.2; 169.1; 169.2. Mass spectrum, m/z 428
[M+H]+. Found, %: С 47.71; H 4.18; N 3.40. C17H18INO4.
Calculated, %: С 47.79; H 4.25; N 3.28.
(4SR,4aRS,5SR,6RS,7aSR)-5-Iodo-2-(4-methoxyphenyl)-
1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl
acetate (13f). Yield 0.63 g (71%), colorless prisms,
mp 168–170°С. IR spectrum, ν, cm–1: 1729, 1654 (NCO,
1
OCO). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.81
(1H, dd, J = 13.3, J = 4.3, 7-CH2); 2.12 (3Н, s, СН3); 2.39
(1Н, dt, J = 13.3, J = 11.6, 7-CH2); 3.07 (1Н, dt, J = 11.6,
J = 4.3, 7a-CH); 3.71 (1Н, d, J = 4.3, 4a-CH); 3.80 (3Н, s,
ОCH3); 3.90 (1Н, br. s, 5-CH); 4.11 (1Н, d, J = 13.1,
3-СН2); 4.16 (1Н, d, J = 13.1, 3-СН2); 4.70 (1H, br. s,
6-CH); 6.91 (2H, d, J = 8.8, H Ar); 7.16 (2H, d, J = 8.8,
Н Ar). 13C NMR spectrum (CDCl3), δ, ppm: 18.0; 22.3;
36.9; 37.9; 46.5; 55.1; 55.4; 77.2; 84.3; 104.1; 114.6;
127.3; 133.5; 158.6; 169.2. Mass spectrum, m/z: 444
[M+H]+. Found, %: С 46.00; H 4.01; N 3.27. C17H18INO5.
Calculated, %: С 46.07; H 4.09; N 3.16.
(4SR,4aRS,5SR,6RS,7aSR)-2-(4-Chlorophenyl)-5-iodo-
1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl
acetate (13c). Yield 0.67 g (75%), colorless plates, mp 172–
173°С (decomp.). IR spectrum, ν, cm–1: 1735, 1661 (NCO,
1
OCO), 599 (CI). H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 1.58 (1H, dd, J = 12.6, J = 4.3, 7-CH2); 2.03 (3Н,
s, СН3); 2.33 (1Н, dd, J = 12.6, J = 11.6, 7-CH2); 2.97 (1Н,
dt, J = 11.6, J = 4.3, 7a-CH); 3.55 (1Н, d, J = 4.3, 4a-CH);
4.10 (1H, d, J = 12.8, 3-CH2); 4.15 (1H, d, J = 12.8,
3-CH2); 4.22 (1Н, br. s, 5-CH); 4.66 (1H, br. s, 6-CH); 7.33
(4SR,4aRS,5SR,6RS,7aSR)-5-Iodo-7а-methyl-2-phenyl-
1-oxooctahydro-4Н-4,6-epoxycyclopenta[c]pyridin-4-yl
acetate (13g). Yield 0.57 g (67 %), light-orange powder,
mp 151–152°С (decomp.). IR spectrum, ν, cm–1: 1730,
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Chemistry of Heterocyclic Compounds 2020, 56(7), 930–935
1
1653 (NCO, OCO), 602 (CI). H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 1.51 (3Н, s, СН3); 1.86 (1H, d, J = 13.3,
7-CH2); 2.05 (1Н, d, J = 13.3, 7-CH2); 2.14 (3Н, s, СН3);
3.49 (1Н, br. s, 4a-CH); 4.07 (1Н, d, J = 12.6, 3-CH2); 4.25
(1Н, d, J = 12.6, 3-CH2); 4.26 (1Н, br. s, 5-CH); 4.69 (1H,
br. s, 6-CH); 7.23 (2H, d, J = 8.6, Н Ar); 7.28 (1H, t,
J = 8.6, Н Ar); 7.40 (2H, t, J = 8.6, Н Ar). 13C NMR
spectrum (CDCl3), δ, ppm: 17.5; 22.4; 23.9; 41.5; 46.0;
52.3; 53.2; 84.5; 104.1; 126.0; 127.3; 129.2; 141.4; 169.4;
171.4. Mass spectrum, m/z: 428 [M+H]+. Found, %:
С 47.73; H 4.20; N 3.37. C17H18INO4. Calculated, %:
С 47.79; H 4.25; N 3.28.
Investigation, Frumkin Institute of Physical Chemistry and
Electrochemistry (CKP FMI IPCE RAS).
References
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J. Am. Chem. Soc. 2011, 133, 10768. (h) Zubkov, F. I.;
Zaytsev, V. P.; Nikitina, E. V.; Khrustalev, V. N.; Gozun, S. V.;
Boltukhina, E. V.; Varlamov, A. V. Tetrahedron 2011, 67,
9148. (i) Zaytsev, V. P.; Zubkov, F. I.; Nadirova, M. A.;
Mertsalov, D. F.; Nikitina, E. V.; Novikov, R. A.; Varlamov, A. V.
Methyl (4SR,4aRS,5SR,6RS,7RS,7aSR)-4-acetoxy-5-iodo-
2-phenyl-1-oxooctahydro-1Н-4,6-epoxycyclopenta[c]pyri-
dine-7-carboxylate (13h). Yield 0.62 g (66%), colorless
powder, mp 146–147°С. IR spectrum, ν, cm–1: 1745, 1658
(NCO, OCO), 599 (CI). 1H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 2.13 (3Н, s, СН3); 3.30–3.35 (2H, m,
7а,4а-CH); 3.67 (1Н, d, J = 3.0, 7-CH); 3.74 (3Н, s,
OСН3); 3.97 (1H, d, J = 13.6, 3-СН2); 4.43 (1Н, d,
J = 13.6, 3-СН2); 4.03 (1Н, br. s, 5-CH); 4.86 (1H, br. s,
6-CH); 7.29–7.32 (1H, m, H Ar); 7.40–7.44 (4Н, m, H Ar).
13C NMR spectrum (CDCl3), δ, ppm: 14.1; 16.4; 21.0;
21.9; 40.5; 48.3; 52.4; 58.4; 86.5; 104.7; 126.5; 127.5;
129.3; 141.1; 167.7; 168.8. Mass spectrum, m/z: 472
[M+H]+. Found, %: С 45.82; H 3.78; N 3.06. C18H18INO6.
Calculated, %: С 45.88; H 3.85; N 2.97.
Chem. Heterocycl. Compd. 2016, 52, 736. [Khim.
Geterotsikl. Soedin. 2016, 52, 736.]
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X-ray structural analysis of compound 13d was
carried out at room temperature on a Bruker Kappa Apex II
automatic four-circle diffractometer with
a
two-
dimensional detector. The cell parameters were refined
over the whole data set.9 The experimental reflection
intensities were corrected for absorption using the
SADABS program.10 The structures were solved with the
direct method according to the SHELXS program11 and
refined against F2 by the least-squares technique in the full-
matrix anisotropic approximation for all non-hydrogen
atoms using the SHELXL-2018 program.12 The positions
of H atoms were calculated geometrically with isotropic
temperature factors equal to 1.2 (CH or CH2 groups) or 1.5
(CH3 group) of the equivalent isotropic factor of the
C atom with which the H atoms are bonded. The
experimental parameters and the final probability factor
values are given in Table 2 (Supplementary information
file). Atomic coordinates and temperature parameters of the
crystalline structure were deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1994943).
6. (a) Hokamp, T.; Storm, A. T.; Yusubov, M.; Wirth, T. Synlett
2018, 415. (b) Giri, R.; Yu, J.-Q. Iodine Monoacetate,
e-EROS Encyclopedia of Reagents for Organic Synthesis;
John Wiley and Sons: Hoboken, 2008. (с) Heasley, V. L.;
Holstein, L. S., III; Moreland, R. J.; Rosbrugh, J. W., Jr.;
Shellhamer, D. F. J. Chem. Soc., Perkin Trans. 2 1991, 8,
1271. (d) Clarke, P. A.; Grist, M.; Ebden, M. Tetrahedron
Lett. 2004, 45, 927. (e) Cambie, R. C.; Rutledge, P. S.;
Stewart, G. M.; Woodgate, P. D.; Woodgate, S. D. Aust. J.
Chem. 1984, 37, 1689. (f) Urbanaitė, A.; Čikotienė, I. Eur. J.
Org. Chem. 2016, 31, 5294. (g) Srivastava, P. C.; Singh, P.;
Tangri, M.; Sinha, A.; Bajpai, S. J. Ind. Chem. Soc. 1997, 74,
443.
7. Zubkov, F. I.; Mertsalov, D. F.; Zaytsev, V. P.; Varlamov, A. V.;
Gurbanov, A. V.; Dorovatovskii, P. V.; Timofeeva, T. V.;
Khrustalev, V. N.; Mahmudov, K. T. J. Mol. Liq. 2018, 249,
949.
8. Zaytsev, V. P.; Zubkov, F. I.; Mertsalov, D. F.; Orlova, D. N.;
Sorokina, E. A.; Nikitina, E. V.; Varlamov, A. V. Russ.
Chem. Bull., Int. Ed. 2015, 64, 112. [Izv. Akad. Nauk, Ser.
Khim. 2015, 112.]
Supplementary information file containing H and 13C
NMR spectra of compounds 12b–f and 13a–h, as well as
crystallographic data of compound 3d is available at the
journal website at http://link.springer.com/journal/10593.
1
9. SAINT-Plus, Version 7.68.; Bruker AXS Inc.: Madison,
Wisconsin, USA, 2007.
10. SADABS; Bruker AXS Inc.: Madison, Wisconsin, USA,
2008.
This work was supported by the Russian Science
Foundation (grant 18-13-00456).
11. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
12. Sheldrick, G. M. Acta Crystallogr., Sect. C: Struct. Chem.
2015, C71, 3.
X-ray structural analysis of compound 13d was carried
out at the Center for Collective Use of Physical Methods of
935