Haloiminolactonization of cyclopentene α,α-dichlorocarboxamides. Tandem rearrangement of iminolactones in epoxylactones

Article abstract of DOI:10.1134/S1070428015110020

Electrophilic cyclization initiated by NBS and I₂ of 2,2-dichloro-2-[(1R,5S)- and 2,2-dichloro-2-[(1S,5R)-5-hydroxy-2-cyclopent-2-en-1-yl]-N-[(1R)-1-phenylethyl]acetamides was investigated. Stable under conditions of chromatography on SiO₂ bicyclic iminoesters, (2Z,3aS,4S,6S,6aS)-6-bromo-3,3-dichloro- and (2Z,3aS,4S,6S,6aS)-3,3-dichloro-6-iodo-2-{[(1R)-1-phenylethyl]imino}hexahydro-2H-cyclopenta[b]furan-4-ols were isolated and characterized, and a possible version was suggested of their step-by-step recyclization transformations. The halocyclization of carboxamides in water-organic mixtures afforded bicyclic epoxylactones (1aR,2aS,5aS,5bS)- and (1aS,2aR,5aR,5bR)-5,5-dichlorohexahydro-4H-oxireno[3,4]cyclopenta-[1,2-b]furan-4-ones, whose reductive dechlorination proceeded stepwise with successive removal of Cl atoms and led to the formation of (1aR,2aS,5aS,5bS)- and (1aS,2aR,5aR,5bR)-hexahydro-4H-oxireno[3,4]cyclopenta-[1,2-b]furan-4-ones.

Full text of DOI:10.1134/S1070428015110020

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 11, pp. 1524–1531. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © Z.R. Valiullina, V.A. Akhmet’yanova, N.A. Ivanova, A.S. Erastov, E.S. Meshcheryakova, M.S. Miftakhov, 2015, published in
Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 11, pp. 1558–1564.
Haloiminolactonization of Cyclopentene
α,α-Dichlorocarboxamides. Tandem Rearrangement
of Iminolactones in Epoxylactones
Z. R. Valiullinaa, V. A. Akhmet’yanovaa, N. A. Ivanovaa, A. S. Erastova,
E. S. Meshcheryakovab, and M. S. Miftakhova
a Ufa Institute of Chemistry, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, Bashkortostan, 450054 Russia
e-mail: bioreg@anrb.ru
b Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, Bashkortostan, Russia
Received July 17, 2015
Abstract—Electrophilic cyclization initiated by NBS and I2 of 2,2-dichloro-2-[(1R,5S)- and 2,2-dichloro-2-
[(1S,5R)-5-hydroxy-2-cyclopent-2-en-1-yl]-N-[(1R)-1-phenylethyl]acetamides was investigated. Stable under
conditions of chromatography on SiO2 bicyclic iminoesters, (2Z,3aS,4S,6S,6aS)-6-bromo-3,3-dichloro- and
(2Z,3aS,4S,6S,6aS)-3,3-dichloro-6-iodo-2-{[(1R)-1-phenylethyl]imino}hexahydro-2H-cyclopenta[b]furan-4-ols
were isolated and characterized, and a possible version was suggested of their step-by-step recyclization
transformations. The halocyclization of carboxamides in water-organic mixtures afforded bicyclic
epoxylactones (1aR,2aS,5aS,5bS)- and (1aS,2aR,5aR,5bR)-5,5-dichlorohexahydro-4H-oxireno[3,4]cyclopenta-
[1,2-b]furan-4-ones, whose reductive dechlorination proceeded stepwise with successive removal of Cl atoms
and led to the formation of (1aR,2aS,5aS,5bS)- and (1aS,2aR,5aR,5bR)-hexahydro-4H-oxireno[3,4]cyclopenta-
[1,2-b]furan-4-ones.
DOI: 10.1134/S1070428015110020
Electrophilic cyclizations of α,β-, β,γ-, γ,δ-unsatu-
rated amides initiated by sources of a positive halogen
atom are well known [1–6]. Cyclization proceeds mainly
along the permitted Baldwin [7] routes, the structure of
the compound and the substituents at the double bond
influence the stereo- and regioselectivity of the process
[8, 9]. The carbonium intermediate generated by the
attack of the electrophile on the double bond depen-
ding on conditions can intra-molecularly react both
with the oxygen atom (О-attack) and the N-function
(N-attack) resulting in lactams, amines, lactones, esters
etc. [1]. Due to the low nucleophilicity of the amide
nitrogen atom the N-cyclization is difficult under common
conditions, and mainly the О-alkylation products are
obtained. A successful halolactamization of unsaturated
carboxamides requires a preliminary activation (increase
in the nucleophilicity) of the amide nitrogen atom that
is provided by the preparation of N-, O-bis-TMS-imidates
(Knapp method [10]), or through N-lithium salts
(Corey method [11]) followed by the treatment with
the halogen source (NBS, I2, Br2). Enantioselective
reactions of halolactonization, haloesterification, and
haloamination were developed [12–16]. These
reactions are widely applied to the directional synthetic
approaches to bioactive and other structures [1, 11].
In this work aiming to obtain vicinally tetrasub-
stituted chiral cyclopentane blocks we investigated the
electrophilic cyclization of cyclopentene carboxamides
2 and 3 prepared from dichlorolactone 1 [13] with
NBS and I2 in MeCN and THF in the presence or
absence of NaHCO3 and water.
Carboxamides 2 and 3 were prepared in ~34% yield
by the opening of the lactone ring of compound 1 at
treating with (+)-α-methylbenzyl amine. Carboxami-
des 2 and 3 have different Rf values and are easily
separated by chromatography on SiO2 (Scheme 1).
The cyclization of carboxamides for the preparation
of the most popular 5- and 6-membered rings are
carried out in a mixture THF–H2O to obtain therewith
the corresponding lactones, however, the postulated
intermediates of the intramolecular О-attack, iminium
salts or iminoesters, were not isolated [1]. The lability
of γ-iminolactones obtained in another way is also
1524

HALOIMINOLACTONIZATION OF CYCLOPENTENE α,α-DICHLOROCARBOXAMIDES.
1525
Scheme 1.
H2N
OH
OH
O
O
O
C6H6
+
+
O
2-pyridinol
N
Ph
N
Ph
H
H
Cl
Cl
Cl
Cl
Cl
Cl
1
2
3
Scheme 2.
OH
Br
O
NBS
Cl
Cl
DBU
C6H6
Ph
O
O
N
CH3CN
OH
N
Cl
Cl
Ph
Br
O
5
4
N
H
Ph
Cl
Cl
O
2
O
NBS
THF_H2O
+
O
O
O
HO
Cl
Cl
Cl
Cl
7
6
DBU
mentioned in [14]. The intramolecular electrophilic
cyclization of compound 2 with NBS in MeCN
afforded in good yield iminoester 4, whose structure
was confirmed by NMR and mass spectra, and also by
the data of 2D 1H NMR spectrum (Scheme 2, Fig. 1).
dichloroepoxylactone 7 with the minor less polar
compound 6. At the dehydrobromination of this crude
mixture by stirring with DBU (20°С, 3 h) minor
compound 6 was converted in epoxylactone 7, which
was obtained in over 60% yield.
The dehydrobromination of compound 4 using
DBU in boiling benzene or t-BuOK in THF at room
temperature occurred cleanly giving epoxyiminolac-
tone 5. The anti-configuration of imine 5 was proved
by X-ray diffraction analysis (Fig. 2).
The result of the electrophilic cyclization of amide
2 under the action of I2 also depends on the reaction
conditions. For instance, in MeCN in the presence of
C13
C4
The reaction of carboxamide 2 with NBS in a
medium THF–H2O led to the formation of a mixture of
C12
C7
C14
O1
C2
H
O
H
C10
C9
H
H
C11
C15
C3
O4
C5
C6
OH
Br
N2
H
H
Cl
Cl
C1
Cl1
C8
Cl2
N
Fig. 1. NOE-interactions in (2Z,3aS,4S,6S,6aS)-6-bromo-
3,3-dichloro-2-{[(1R)-1-phenylethyl]imino}hexahydro-2H-
cyclopenta[b]furan-4-ol 4.
Fig. 2. Molecular arrangement of (1R)-N-[(1aR,2aS,4Z,5aS,5bS)-
5,5-dichlorohexahydro-4H-oxireno[3,4]cyclopenta[1,2-b]-
furan-4-ylidene]-1-phenylethanamine
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

VALIULLINA et al.
1526
NaHCO3 along with the expected iminoester 8 the
formation of epoxylactone 5 obtained in the previous
experiment was observed, and in aqueous THF a
mixture of dichloroepoxylactone 7 with iodolactone 9
appeared; its treatment with DBU provided exclusively
epoxylactone 7 in 75% yield (Scheme 3).
epoxy ring complete the formation of stable
epoxylactone 5 (Scheme 4).
The exocyclic oxyimino esters are fairly labile [14],
and the relative stability of the exocyclic iminoester 5
is evidently due to steric and electronic effects of the
gem-dichloro function.
Scheme 3.
It may be stated that we have discovered a new
tandem rearrangement of γ-hydroxyiminolactones into
epoxyiminolactones followed by hydrolysis (in the
presence of water) to the corresponding epoxylactones.
We have found in the literature only three “distant”
precedents of this rearrangement reminding the
conversions “oxyimino→lactam” [8, 9].
OH
I
I2, NaHCO3
CH3CN
Cl
Cl
5
+
O
N
Ph
2
In the study of reductive dechlorination of
compound 5 with Zn-Cu couple in MeOH in the
presence of NH4Cl we found that the reaction
proceeded stepwise with the formation of the
dechlorination and hydration products in the imine part
of molecule 7 and 13–15. The latter products we
succeeded to isolate in the individual state by treating
the reaction mixture just after total consumption of
initial iminolactone 5. If the reaction is not stopped the
intermediate compounds 7 and 13 are gradually
converted into the main epoxylactone 14 that forms in
50% yield. The reaction of the individual dichloro
derivative 7 made it possible to considerably reduce its
duration and to increase the yield of epoxylactone 14
to 60% (Scheme 5).
8
I
O
I2
7
O
+
THF_H2O
HO
Cl
Cl
9
DBU
In the studied transformations of compound 2
especially interesting is the formation in anhydrous
conditions of stable at chromatography on SiO2
exocyclic iminoesters 4 and 8, and also their
recyclization into epoxyimine 5.
The structure of monochlorolactone 13 presented in
Presumably the formation of epoxyiminoester 5
1
Scheme 5 follows unambiguously from the data of Н
from halohydrins
4
and
8
begins with the
and 13С NMR spectra. The strong NOE-interaction
between the cis-protons at the atoms C5 and C5а
(J 8.6 Hz) indicates the exo-orientation of the C5–Cl
bond (Fig. 3). Consequently, the reductive dechlori-
nation with zinc occurs first of all with the sterically
more accessible atom 5β-Сl of dichlorolactone 7.
intramolecular attack of γ-hydroxide-anion on the
spatially available imine bond in compound 10 and
with the generation of a charged tricyclic intermediate
11. The subsequent selective cleavage of one C–O
bond in the latter and the SN2-substitution of the
halogen in the arising imine 12 with the closure of the
Scheme 4.
_
O
X
X
O
X
DBU
or t-BuOK
O
Cl
Cl
Cl
Cl
Ph
4 or 8
O
O
5
_
N
O
_
Cl
Cl
N
N
Ph
Ph
10
11
12
X = I, Br.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

HALOIMINOLACTONIZATION OF CYCLOPENTENE α,α-DICHLOROCARBOXAMIDES.
1527
Scheme 5.
OH
Cl
O
O
O
Zn-Cu, NH4Cl
O
O
N
+
O
Ph
MeOH, Δ
HO
N
H
Ph
Cl
Cl
5
14
15
O
O
O
O
O
+
O
Cl
Cl
Cl
7
13
Scheme 6.
1. NBS or I2,
THF_H2O
2. DBU
O
O
Zn-Cu, NH4Cl
O
O
O
O
2
MeOH, Δ
Cl
Cl
7
14
1. NBS or I2,
THF_H2O
O
O
Zn-Cu, NH4Cl
2. DBU
O
O
3
O
O
MeOH, Δ
Cl
ent-7
Cl
ent-14
As seen from the structure of epoxylactone 14 the
vicinally tetrasubstituted cyclopentane block is
obviously of synthetic interest for developing approach
to cyclopentanoids [19–23]. Chiral epoxylactone 14
was described for the first time and applied to
prostaglandins synthesis in [24]. In [25] compound 14
was obtained from 5-substituted cyclopentadiene
derivative via a fairly whimsy stage of chirality
introduction resulting in the preparation of Grieco (–)-
lactone. This compound was obtained by a multistage
synthesis from D-glucose [26]. In [27] the spectral data
of compound 14, prepared from racemic Grieco
lactone in the course of the synthesis of natural
macrolide auriside were published.
tion: iminolactones 4 and 8, described their recycliza-
tion transformations promoted by γ-hydroxy-anion and
the reactions of reductive dechlorination of 5, dichloro-
lactones 7 and ent-7 with the preparation of correct
configuration of chiral sites of the bicyclic blocks for
cyclopentanoids: epoxylactones 14 and ent-14.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Shimadzu IR Prestige-21 from films or mulls in
mineral oil. NMR spectra were registered on
spectrometers Bruker AM-300 [operating frequencies
The output of our study consists in the development
of a new practical procedure for the preparation of
synthetically important epoxylactone 14 and its
enantiomer ent-14 proceeding from easily accessible
carboxamides 2 and 3 in two stages with an overall
yield 40% (Scheme 6).
H
H
H
O
O
O
H
H
Cl
Fig. 3. NOE-interactions in 2,2-dichloro-2-[(1S,5R)-5-hyd-
roxycyclopent-2-en-1-yl]-N-[(1R)-1-phenylethyl]acetamide
13.
Thus as a result of our investigation we characteri-
zed the primary adducts of carboxamide 2 О-cycliza-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

VALIULLINA et al.
1528
300.13 (1H) and 75.47 (13С) MHz] or Bruker Avance-
500 [operating frequencies 500.13 (1H) and 125.77
(13С) MHz] in CDCl3 (δН 7.27, δС 77.00 ppm) or
acetone-d6 (δН 2.07, δС 28.83 ppm). Mass spectra were
obtained on an instrument Thermo Finnigan MАT
95XP, ionizing electrons energy 70 eV. XRD
experiment on a single crystal of compound 5 was
performed on a diffractometer Xcalibur E (Agilent
Technologies). The reaction progress was monitored
by TLC on Sorbfil plates, spots visualized with 10%
solution of anisealdehyde in ethanol with sulfuric acid
added, or with alkaline solution of KMnO4. Rotation
angles were measured on a polarimeter Perkin-Elmer
241 MC. We used (+)-α-methylbenzylamine purchased
from Fluka, [α]D25 +38.5°.
2,2-Dichloro-2-[(1S,5R)-5-hydroxycyclopent-2-
en-1-yl]-N-[(1R)-1-phenylethyl]acetamide (3). Light
yellow oily substance, Rf 0.45 (petroleum ether–ethyl
acetate, 8 : 2, triple elution), [α]D20 +106.8° (c 1.0,
CHCl3). IR spectrum, ν, cm–1: 3312 (NH), 3313 (ОН),
1
2951, 2853, 1922, 1635 (С=О), 692 (ССl2). Н NMR
spectrum (CDCl3, 300 MHz), δ, ppm: 1.26 d (1H, Me,
J 7.1 Hz), 2.14 br.d (1H, ОH, J 5.6 Hz), 2.42 d.d.q
(1H, H5а, J 16.9, 4.6, 2.3 Hz), 2.63 d.d.t (1H, H5b, J
16.9, 7.4, 1.0 Hz), 3.96 d.q (1Н, Н2, J 6.2, 0.9 Hz), 4.61
d.d.d.d (1Н, Н1, J 7.4, 4.6, 6.2, 7.1 Hz), 5.04 quintet
(1Н, Н2', J 7.1 Hz), 5.88 d.q (1Н, Н3, J 6.2, 2.0 Hz), 5.99
d.q (1Н, Н4, J 6.2, 2.3 Hz), 7.13 d (1Н, NН, J 7.1 Hz),
7.26–7.32 m (5H, C6H5). 13С NMR spectrum (CDCl3,
75 MHz), δ, ppm: 21.57 (Me), 40.99 (C5), 50.33
(CHCl2), 60.08 (C2), 72.66 (C1), 87.21 (C1'); 126.01,
127.65, 128.80, 142.16 (C6H5); 122.96 (C4), 128.26
(C3), 166.30 (CО).
Reaction of lactone (1) with (+)-α-methylbenzyl-
amine. To a solution of 0.3 g (1.6 mmol) of compound
1 in 10 mL of anhydrous C6Н6 in an argon atmosphere
at 20°С while stirring was added 0.15 g (1.60 mmol) of
2-pyridinol and 0.4 mL (3.2 mmol) of (+)-α-methyl-
benzylamine. The reaction mixture was stirred for 48 h,
the end of the process was determined by TLC
monitoring. The reaction mixture was diluted with
ethyl acetate (30 mL), washed with H2O (3 × 5 mL),
dried with Na2SO4, concentrated in a vacuum, and the
residue was chromatographed on a column packed with
SiO2 (eluent petroleum ether–ethyl acetate, 20 : 1).
Yield 0.33 g (34%) of compound 2 and 0.33 g (34%)
of compound 3.
(2Z,3aS,4S,6S,6aS)-6-Bromo-3,3-dichloro-2-
{[(1R)-1-phenylethyl]imino}hexahydro-2H-cyclo-
penta[b]furan-4-ol (4). To a solution of 0.25 g
(0.80 mmol) of amide 2 in 8 mL of CH3CN was added
0.31 g (1.75 mmol) of NBS, and the mixture was
stirred for 2 h at 20°С, the solvent was evaporated, the
residue was chromatographed on a column packed
with SiO2 (petroleum ether–ethyl acetate, 9 : 1). Yield
0.30 g (95%), Rf 0.26 (eluent petroleum ether–ethyl
acetate, 8 : 2, double elution). Light yellow crystals,
mp 180°C, [α]D20 +77.7° (c 1.0, CH2Cl2). IR spectrum, ν,
cm–1: 3228, 1689, 1456, 1035. 1Н NMR spectrum (ace-
tone-d6, 500 MHz), δ, ppm: 1.25 d (3H, СН3, J 6.7 Hz),
2.82 d.d (1Н, Н5А, J 7.3, 16.3 Hz), 3.00 d.d.d (1H, Н5B,
J 2.8, 6.0, 16.3 Hz), 3.76 d.d (1Н, Н3а, J 4.3, 5.8 Hz),
4.46 d (1Н, Н6, J 6.0 Hz), 4.58 d (1Н, Н6а, J 4.0 Hz),
4.77 q (1Н, СНN, J 6.7 Hz), 5.25 m (1Н, Н4); 7.25
(1Н), 7.30 (2Н), 7.40 (2Н, С6Н5). 13С NMR spectrum
(acetone-d6, 125 MHz), δ, ppm: 23.49 (CH3), 41.88
(С5), 54.16 (C6), 55.54 (СНN), 59.60 (C3a), 77.83 (C4),
82.37 (C6a), 82.78 (C3); 126.22, 126.28, 126.30,
127.80, 128.00, 145.08 (С6Н5); 156.94 (С2). Mass
spectrum, m/z (Irel, %): 391 (60) [M]+, 376 (20) [M –
СН3]+, 105 (100) [C6H5CHCH3]+. Found: 391.9742
[M]+. С15Н16BrCl2NO2. Calculated 391.9736.
2,2-Dichloro-2-[(1R,5S)-5-hydroxy-2-cyclopent-
2-en-1-yl]-N-[(1R)-1-phenylethyl]acetamide (2).
Light-yellow crystals, Rf 0.31 (petroleum ether–ethyl
acetate, 8 : 2, triple elution), mp 35°C, [α]D20 –10°
(c 1.0, CH2Cl2). IR spectrum, ν, cm–1: 3312 (NH), 3313
1
(ОН), 2951, 2853, 1922, 1635 (С=О), 692 (ССl2). Н
NMR spectrum (CDCl3, 300 MHz), δ, ppm: 1.26 d
(3H, Me, J 7.1 Hz), 2.38 br.d (1H, ОH, J 7.0 Hz), 2.45
d.d.q (1H, H5а, J 17.1, 4.4, 2.3 Hz), 2.68 d.d.t.d (H5b, J
17.1, 7.4, 1.1, 2.3 Hz), 3.91 d.d.q (1Н, Н2, J 6.2, 1.1,
2.3 Hz), 4.60 d.d.d.d (1Н, Н1, J 7.4, 4.6, 7.0, 6.2 Hz),
5.07 quintet (1Н, Н2', J 7.1 Hz), 5.88 d.q (1Н, Н3, J
6.0, 2.2 Hz), 6.00 d.q (1Н, Н4, J 6.0, 2.3 Hz), 7.11 d
(1Н, NН, J 7.1 Hz), 7.26–7.32 m (5H, С6Н5). 13С
NMR spectrum (CDCl3, 75 MHz), δ, ppm: 21.38 (Me),
41.13 (C5), 50.17 (CHCl2), 60.31 (C2), 72.55 (C1),
87.16 (C1'); 126.01, 127.69, 128.97, 141.95 (C6H5);
128.35 (C3), 132.75 (C4), 166.18 (CОО). Found, %: С
57.51; Н 5.15; Сl 22.37; N 4.51. С15Н17NCl2O3.
Calculated, %: С 57.34; Н 5.35; Сl 22.47; N 4.46.
(1R)-N-{(1aR,2aS,4Z,5aS,5bS)-5,5-Dichloro-
hexahydro-4H-oxireno[3,4]cyclopenta[1,2-b]furan-
4-ylidene}-1-phenylethanamine (5). a. To a solution
of 0.20 g (0.51 mmol) of bromide 4 in 7 mL of
anhydrous С6Н6 was added 0.083 mL (0.56 mmol) of
DBU. The reaction mixture was boiled for 1 h (TLC
monitoring), concentrated, the residue was chroma-
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HALOIMINOLACTONIZATION OF CYCLOPENTENE α,α-DICHLOROCARBOXAMIDES.
1529
tographed on a column packed with SiO2 eluent pet-
roleum ether–ethyl acetate, 9 : 1). Yield 0.12 g (76%).
57.58, 57.76, 59.68 (С5а, С5b, С1а); 78.18 (С5), 79.99
(С2а), 167.40 (С4). Mass spectrum, m/z (Irel, %): [M]+
was not observed, 296 (60) [M – СО2 – Сl]+, 65 (100).
Found, %: С 40.10; Н 2.71; Сl 33.18. С7Н6Cl2O3.
Calculated, %: С 40.22; Н 2.89; Сl 33.92.
b. To a solution of 0.78 g (0.2 mmol) of bromide 4
in 6 mL of anhydrous THF at 0°С was added by
portions 0.034 mg (0.3 mmol) of t-BuOK. The reaction
mixture was stirred for 10 min (TLC monitoring), THF
was evaporated, the residue was diluted with ethyl
acetate (20 mL), washed with Н2О, with brine, dried
with Na2SO4, concentrated in a vacuum, and the
residue was chromatographed on a column packed
with SiO2 (eluent petroleum ether–ethyl acetate, 8 : 2).
Yield 0.025 g (40%). White crystals, mp 160ºC, [α]D20
+53.4° (c 1.0, CH2Cl2). Rf 0.31 (petroleum ether–ethyl
acetate, 8 : 2, triple elution). IR spectrum, ν, cm–1: 1705,
1464, 1451, 1042, 705. 1Н NMR spectrum (acetone-d6,
500 MHz), δ, ppm: 1.35 d (3Н, СН3, J 6.6 Hz), 2.30
d.d.d (1Н, Н2А, J 0.9, 16.0 Hz), 2.45 d (1Н, Н2В, J
16.0 Hz), 3.70 br.s (1Н, Н5b), 3.74 d.d (1Н, Н5а, J 1.3,
6.0 Hz), 3.80 br.s (1Н, Н1а), 4.75 q (1Н, СНN, J 6.6 Hz),
5.06 t (1Н, Н2а); 7.15–7.20 m (1Н, Ph), 7.30 t (2Н, Ph,
J 7.3 Hz), 7.40 d (2Н, Ph, J 7.5 Hz). 13С NMR
spectrum (CDCl3, 75 MHz), δ, ppm: 23.34 (Me), 34.52
(C2), 56.51 (C5a), 58.41 (CHN), 59.70, 59.95 (C1a, C5b),
82.52 (C2a), 83.57 (C5); 127.16, 127.25, 128.3, 146.76
(С6Н5); 157.45 (С4). Mass spectrum, m/z (Irel, %): 311
(60) [M]+, 296 (100) [M – СН3]+, 276 (10) [M – Сl]+,
105 (92) [C6H5CHCH3]+. Found: 311.0470 [M]+.
С15Н15Cl2NO2. Calculated: M 311.0474.
Reaction of amide (2) with I2 in the presence of
NaHCO3. To a solution of 0.3 g (0.96 mmol) of amide
2 in 15 mL of CH3CN was added 0.98 g (3.90 mmol)
of I2 and 1.23 g (14.40 mmol) of NaHCO3, and the
mixture was stirred for 72 h at 20°С. The reaction
mixture was quenched by adding 7 mL of a saturated
solution of Na2SO3, concentrated to a 1/3 of volume,
and extracted with ethyl acetate (3 × 40 mL), the
combined organic extracts were washed with water,
with brine, dried with MgSO4. After concentrating the
solution and column chromatography of the residue on
SiO2 (eluent petroleum ether–ethyl acetate, 9 : 1) we
obtained 0.074 g (17%) of iodide 8 and 0.12 g (41%)
of iminolactone 5.
(2Z,3aS,4S,6S,6aS)-3,3-Dichloro-6-iodo-2-{[(1R)-
1-phenylethyl]imino}hexahydro-2H-cyclopenta[b]-
furan-4-ol (8). White crystals, mp 65°C, Rf 0.58 (pet-
roleum ether–ethyl acetate, 8 : 2, triple elution), [α]D20
–66° (c 0.2, CH2Cl2). IR spectrum, ν, cm–1: 3223, 1691,
1458, 1036. 1Н, NMR spectrum (CDCl3, 300 MHz), δ,
ppm: 1.42 d (3H, СН3, J 6.6 Hz), 2.75 d.d (1Н, Н5А, J
7.2, 15.8 Hz), 3.10 d.d.d (1H, Н5В, J 3.1, 6.8, 15.8 Hz),
4.10 d.d (1Н, Н3а, J 3.8, 4.6 Hz), 4.25 d (1Н, Н6, J 6.6 Hz),
4.80 q (1Н, СНN, J 6.6 Hz), 5.15 m (1Н, Н6а); 7.25
(1Н), 7.30 (2Н), 7.40 (2Н, С6Н5). 13С NMR spectrum
(CDCl3, 75 MHz), δ, ppm: 23.47 (CH3), 27.10 (C6),
43.87 (С5), 55.70 (C3a), 59.80 (СНN), 79.92 (C4), 81.91
(C3), 82.42 (C6a); 126.22, 126.28, 126.30, 127.80, 128.00,
145.08 (С6Н5); 154.57 (С2). Found, %: C 40.22; H
3.89; Cl 15.92; I 28.35; N 3.03. С15Н16Cl2INО2. Calcu-
lated, %: С 40.94; Н 3.66; Cl 16.11; I 28.84; N 3.18.
(1aR,2aS,5aS,5bS)-5,5-Dichlorohexahydro-4H-
oxireno[3,4]cyclopenta[1,2-b]furan-4-one (7). a. To a
solution of 0.21 g (0.68 mmol) of amide 2 in 10 mL of a
mixture THF–H2O, 8 : 2, was added 0.37 g (2.10 mmol)
of NBS, the mixture was stirred for 12 h (TLC
monitoring). THF was evaporated, the residue was
extracted with ethyl acetate (3 × 40 mL), the combined
organic extracts were washed with brine, dried with
Na2SO4, concentrated in a vacuum. The residue was
diluted with benzene, 0.2 mL (1.30 mmol) of DBU
was added, and the mixture was stirred for 2 h. Then
benzene was evaporated, the residue was
chromatographed on a column packed with SiO2
(eluent petroleum ether–ethyl acetate, 8 : 2). Yield
0.084 g (65%), Rf 0.44 (petroleum ether–ethyl acetate,
1 : 1), light yellow crystals, mp 121°C, [α]D20 –94.2° (c
1.0, CH2Cl2). IR spectrum, ν, cm–1: 1791, 1135, 1180,
Reaction of carboxamide (2) with I2 in the system
THF–H2O. To a solution of 0.23 g (0.73 mmol) of
amide 2 in 20 mL of a mixture THF–H2O, 8 : 2, was
added 1.90 g (7.30 mmol) of I2. The mixture was
stirred for 2 h (TLC monitoring), THF was evaporated, the
residue was extracted with ethyl acetate (3 × 50 mL),
the combined organic extracts were washed with
saturated solution of Na2SO3 and with brine, dried with
Na2SO4, concentrated in a vacuum, and the residue
was chromatographed on a column packed with SiO2
(eluent petroleum ether–ethyl acetate, 8 : 2). Yield
0.031 g (31%) of iodide 9 and 0.096 g (63%) of di-
chloroepoxylactone 7.
1
1025. Н NMR spectrum (CDCl3, 300 MHz), δ, ppm:
2.20 d.d (1Н, Н2А, J 6.1, 16.1 Hz), 2.64 d.d (1Н, Н2В, J
16.1 Hz), 3.61 d (1Н, Н5а, J 6.1 Hz); 3.74 s (1Н) and
3.80 s (1Н, Н1а, Н5b); 5.05 d (1Н, Н2а, J 6.1 Hz). 13С
NMR spectrum (CDCl3, 75 MHz), δ, ppm: 33.67 (С2);
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

VALIULLINA et al.
1530
(3aR,4S,5S,6aS)-3,3-Dichloro-4-hydroxy-5-
(1aR,2aS,5aS,5bS)-Hexahydro-4H-oxireno[3,4]-
cyclopenta[1,2-b]furan-4-one (14). White crystals,
mp 77°C (76–77°C [24, 25]), [α]D20 –107°С (c 1.0,
CH2Cl2) {–115°С (c 1.0, CHCl3) [24], –108°С (c 1.0,
CHCl3) [25]}, Rf 0.27 (petroleum ether–ethyl acetate,
1 : 1, triple elution). IR spectrum, ν, cm–1: 1751, 1031.
1Н NMR spectrum (CDCl3), δ, ppm: 2.10 d.d.d (1Н,
H2A, J 1.6, 7.1, 16.2 Hz), 2.50 d (1Н, Н2B, J 16.2 Hz),
2.70 d (2Н, Н5, J 5.3 Hz), 3.00 m (1Н, Н5а), 3.60 br.s
(1Н) and 3.70 br.s (1Н, Н1а, Н5b), 5.00 t (1Н, Н2а, J
6.6 Hz). 13С NMR spectrum (CDCl3, 125 MHz), δ, ppm:
30.20 (C5), 34.38 (C2), 40.08 (C5a), 60.06 and 60.78
(C1a and C5b), 83.38 (C2a), 176.21 (CO). Mass spectrum,
m/z (Irel, %): 140 (70) [M]+, 112 (20) [M – H2O]+, 97
(100). Found: 140.0467 [M]+. С7Н8О3. Calculated M
140.0468.
iodohexahydro-2H-cyclopenta[b]furan-2-one (9).
Light yellow oily substance, Rf 0.36 (petroleum ether–
ethyl acetate, 8 : 2, double elution). IR spectrum, ν, cm–1:
1
3600–3200, 1793, 1023, 973. Н NMR spectrum (ace-
tone-d6, 300 MHz), δ, ppm: 2.95 d.d (1Н, Н6A, J 7.0,
16.3 Hz), 3.15 d.d.d (1Н, Н6B, J 2.8, 6.0, 16.3 Hz), 4.10
t (1Н, Н3a, J 4.5 Hz), 4.45 d (1Н, Н6, J 6.7 Hz), 4.65 m
(1Н, Н4), 5.40 m (1Н, Н6а). 13С NMR spectrum (acetone-
d6, 75 MHz), δ, ppm: 28.86 (C5), 43.12 (C6), 58.66 (C3a),
79.67 (C4), 80.17 (C3), 82.84 (C6а), 176.40 (CO). Found,
%: C 25.01; H 1.95; Cl 21.53; I 37.35. C7H7Cl2IO3.
Calculated, %: С 24.95; Н 2.09; Cl 21.04; I 37.66.
Compound 7. b. To a solution of 0.076 g (0.23 mmol)
of iodohydrin 9 in 5 mL of anhydrous С6Н6 was added
0.068 mL (0.45 mmol) of DBU. The reaction mixture
was stirred for 3 h at room temperature (TLC monito-
ring), concentrated, and the residue was chromatogra-
phed on a column packed with SiO2 (eluent petroleum
ether–ethyl acetate, 8 : 2). Yield 0.019 g (40%).
2-[(1S,2S,3S,5S)-3-Chloro-2,5-dihydroxycyclo-
pentyl]-N-[(1R)-1-phenylethyl]acetamide (15).
Transparent oily substance, Rf 0.11 (petroleum ether–
ethyl acetate, 1 : 1, double elution), [α]D20 +51.7°С
(c 1.0, CH2Cl2). IR spectrum, ν, cm–1: 3400–3200,
Reaction of epoxyiminoester (5) with Zn-Cu
couple. To a solution of 0.18 g (0.59 mmol) of
compound 5 in 8 mL of anhydrous MeOH in an argon
atmosphere at stirring was added 0.02 g (0.3 mmol) of
NH4Cl and 0.19 g (3 mmol) of Zn-Cu couple. The
reaction mixture was stirred for 2 h at boiling (TLC
monitoring), the precipitate was filtered off, the mother
liquor was concentrated, and the residue was chroma-
tographed on a column packed with SiO2 (eluent petro-
leum ether–ethyl acetate, 8 : 2). Yield 0.006 g (5%) of
dichlorolactone 7, 0.025 g (25%) of monochloro-
lactone 13, 0.018 g (22%) of dechlorinated lactone 14,
and 0.013 g (8%) of compound 15.
1
1632, 1560, 1100. Н NMR spectrum (CDCl3, 300
MHz), δ, ppm: 1.50 d.d.d (3Н, CH3, J 3.9, 6.1, 15.0
Hz), 1.80–1.90 m (1Н, H4A), 2.20–2.30 m (1Н, Н4B),
2.40–2.60 m (2Н, Н2), 3.25 m (1H, H1), 3.42 br.s
(2Н, 2ОН), 3.85 d.d.d (1Н, Н3, J 2.7, 3.7, 7.3 Hz), 3.97
br.s (1Н, Н5), 4.40 br.s (1Н, Н2), 5.20 quintet (1Н,
СHN, J 7.0 Hz), 6.30 d (1Н, NH, J 7.6 Hz), 7.25–7.20
m (5Н, С6Н5). 13С NMR spectrum (CDCl3, 75 MHz),
δ, ppm: 21.77 (CH3), 32.07 (C2), 40.45 (C4), 44.62
(C6а), 49.00 (CHN), 57.06 (C3), 74.07 (C5), 87.05 (C2),
126.01, 127.41, 128.68, 142.94 (C6H5), 172.69 (CO).
Found, %: C 60.08; H 6.59; Cl 11.33; N 4.92.
С15Н20ClNО3. Calculated, %: С 60.50; Н 6.77; Cl
11.97; N 4.70.
(1aR,2aS,5aS,5bS)-5-Chlorohexahydro-4H-
oxireno[3,4]cyclopenta[1,2-b]furan-4-one (13).
White crystals, mp 133°C, Rf 0.31 (petroleum ether–
ethyl acetate, 1 : 1, triple elution), [α]D20 –126.2°С (c 0.5,
CH2Cl2). IR spectrum, ν, cm–1: 1767, 1262, 1377, 1172,
Dechlorination of dichloroepoxylactone (7). To a
solution of 0.24 g (1.15 mmol) of compound 7 in 8 mL
of anhydrous MeOH in argon atmosphere at stirring
was added 0.02 g (0.34 mmol) of NH4Cl and 0.52 g
(8.0 mmol) of Zn-Cu couple. The reaction mixture was
stirred for 2 h at boiling (TLC monitoring), the
precipitate was filtered off, the mother liquor was
concentrated, and the residue was chromatographed on
a column packed with SiO2 (eluent petroleum ether–
ethyl acetate, 8 : 2). Yield 0.096 g (60%) dechlorinated
lactone 14.
1
1022, 837. Н NMR spectrum (CDCl3, 500 MHz), δ,
ppm: 2.15 d.d.d (1Н, Н2А, J 1.4, 6.1, 16.1 Hz), 2.53 d
(1Н, Н2В, J 16.1 Hz), 3.30 d.d.d (1Н, Н5а, J 1.6, 6.4,
8.8 Hz), 3.65 t (1Н, Н2а, J 1.4 Hz), 3.72 d.d (1Н, Н1а, J
1.4, 1.6 Hz), 4.69 d (1Н, Н5, J 8.8 Hz), 4.86 t (1Н, Н2а,
J 6.4 Hz). 13С NMR spectrum (CDCl3, 125 MHz), δ,
ppm: 34.69 (C2), 46.41 (C5a), 52.32 (C5), 57.92 (C5b),
59.39 (C1a), 80.08 (C2a), 171.08 (CO). Mass spectrum,
m/z (Irel, %): [M]+ was not observed, 139 (4) [M – Сl]+,
95 (88) [M – Сl – CO2]+, 67 (100). Found: 139.0393
[M – Сl]+. С7Н7О3. Calculated [M – Сl] 139.0390.
(1aS,2aR,5aR,5bR)-5,5-Dichlorohexahydro-4H-
oxireno[3,4]cyclopenta[1,2-b]furan-4-one (ent-7).
[α]D20 +90.7° (c 1.0, CH2Cl2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

HALOIMINOLACTONIZATION OF CYCLOPENTENE α,α-DICHLOROCARBOXAMIDES.
1531
14. Tan, C.K., Zhou, L., and Yeung, Y.-Y., Synlett., 2011,
(1aS,2aR,5aR,5bR)-Hexahydro-4H-oxireno[3,4]-
cyclopenta[1,2-b]furan-4-one (ent-14). [α]D20 +107.6°
(c 1.0, CH2Cl2).
p. 1335.
15. Tan, C.K. and Yeung, Y.-Y., Chem. Commun., 2013,
vol. 49, p. 7985.
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