Reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with enamines derived from cycloalkanones. A new type of ring-chain tautomerism in a series of cyclobutane derivatives and stereochemistry of the products

Article abstract of DOI:10.1007/s11172-012-0240-1

Depending on the reaction conditions, the reactions of (E)-3,3,3-trichloro- 1-nitropropene with cyclohexanone enamines led to bicyclo[4.2.0]octanes or trisubstituted enamines, which are the ring-chain tautomers capable of reversible transformations. Diast

Full text of DOI:10.1007/s11172-012-0240-1

Russian Chemical Bulletin, International Edition, Vol. 61, No. 9, pp. 1736—1749, September, 2012
1736
Reactions of (E)ꢀ3,3,3ꢀtrichloro(trifluoro)ꢀ1ꢀnitropropenes with enamines
derived from cycloalkanones. A new type of ringꢀchain tautomerism in
a series of cyclobutane derivatives and stereochemistry of the products
V. Yu. Korotaev, A. Yu. Barkov, and V. Ya. Sosnovskikh
B. N. Eltsin Ural Federal University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vyacheslav.Sosnovskikh@usu.ru
Depending on the reaction conditions, the reactions of (E)ꢀ3,3,3ꢀtrichloroꢀ1ꢀnitropropene
with cyclohexanone enamines led to bicyclo[4.2.0]octanes or trisubstituted enamines, which
are the ringꢀchain tautomers capable of reversible transformations. Diastereoselectivity of the
reactions of (E)ꢀ3,3,3ꢀtrichloro(trifluoro)ꢀ1ꢀnitropropenes with cycloalkanone enamines were
studied, a series of hitherto unknown CX3ꢀcontaining nitroalkylated enamines and ꢀnitro
ketones were synthesized, the structures of novel compounds were determined by NMR spectroꢀ
scopy and Xꢀray diffraction.
Key words: 3,3,3ꢀtrihaloꢀ1ꢀnitropropenes, enamines, cyclobutanes, ꢀnitro ketones, organoꢀ
fluorine and organochlorine compounds, Xꢀray diffraction.
Reactions of ketone enamines with conjugated nitroꢀ
alkenes proceeds via nucleophilic 1,4ꢀcycloaddition, which
involved the diastereoselective C—C bond formation and
resulted in dipolar intermediate A. This intermediate
through the proton transfer usually provides nitroalkylatꢀ
ed enamine B, which is readily hydrolyzed into ꢀnitro
ketone C.1—3 However, depending on the nature of the
reactants and the reaction conditions, the initially formed
betaine A can give rise to the cyclic products, cyclobutanes
D ([2+2] carbocyclization)4—6 and 1,2ꢀoxazine Nꢀoxides
E ([4+2] heterocyclization),7—9 resulting from intraꢀ
molecular attack of an iminium carbon atom onto
the ambident nitronat anion (Scheme 1). The cycloꢀ
addition reactions have been studied in detail on the exꢀ
ample of 1(2)ꢀnitropropenes, ()ꢀnitrostyrenes, and
cycloalkanone enamines;1—9 in some cases 1,2ꢀoxꢀ
azine Nꢀoxides were isolated. These compounds are
highly reactive 1,3ꢀdipole species, which are able to add to
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1720—1733, September, 2012.
1066ꢀ5285/12/6109ꢀ1736 © 2012 Springer Science+Business Media, Inc.

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1737
the multiple bonds and are readily react with nucleoꢀ
philes.10—13
Results and Discussion
At the same time, the data on the reactions of polyhaꢀ
loalkylated nitroolefins with enamines are scares. It is
known14—16 that they react with enamines of cycloalkanꢀ
ones, pinacoline, and acetophenone to give the corresꢀ
ponding nitroalkylated enamines and ꢀpolyhaloꢀꢀnitro
ketones, the promising starting material for the chemoꢀ and
stereoselective synthesis of the functionalized RFꢀ and
CCl3ꢀcontaining carbinols.15 Recently,17 we have demonꢀ
strated that the reactions of ethyl 3ꢀmorpholinocrotonate
with ꢀ(trifluoroethylidene)nitroalkanes give the cycloꢀ
butane derivatives resulting from [2+2] carbocyclization,
while in the case of ꢀ(trichloroethylidene)nitroalkanes,
products of nucleophilic 1,4ꢀaddition to the methyl group
of enamine are formed.
In the present work, stereochemistry of reaction prodꢀ
ucts of (E)ꢀ3,3,3ꢀtrichloroꢀ1ꢀnitroꢀ and (E)ꢀ3,3,3ꢀtriꢀ
fluoroꢀ1ꢀnitropropenes 1a,b with enamines 2a—d derived
from cycloalkanones (cyclohexanone, cyclopentanone)
and cyclic amines (Nꢀmethylpiperazine, morpholine, piꢀ
peridine) were studied; a novel type of ringꢀchain tautoꢀ
merism in a series of CCl3ꢀcontaining bicyclo[4.2.0]ꢀ
octanes were found (see preliminary communication18).
The data on the impact of the nature of substituents on
ringꢀchain tautomeric equilibria of the reaction products
of conjugated nitroalkenes with enamines are scares. The
only known example is the tautomeric equilibrium beꢀ
tween 1,2ꢀoxazine Nꢀoxides and the corresponding trisubꢀ
stituted enamines synthesized based on 2ꢀnitroꢀ1ꢀphenylꢀ
propene and cyclohexenyl amines.19,20 It is worthy to note
that earlier the ring opening of cyclobutane derivatives
to give nitroalkylated enamines was considered irreꢀ
versible.4,5,21
We found that the reaction of CCl3ꢀcontaining nitroꢀ
propene 1a with cyclohexanone enamines 2a—c in anꢀ
hydrous hexane at 10—15 C for 15 min and at ~20 C for
0.5 h under kinetic control resulted stereoselectively in
substituted bicyclo[4.2.0]octanes 3a—c in the yields of
61—76% (Scheme 2).
It should be emphasized that cyclobutanes 3 contain
four stereogenic centers, but only one diastereomer was
found in the crude product by 1H NMR spectroscopy.
Stereochemistry of cyclobutane 3b was unambiguously
confirmed by Xꢀray diffraction18 being in good agreement
with the known data22,23 for related molecules. Structures
Scheme 2
X = NMe (a), O (b), CH2 (c)

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Korotaev et al.
of compounds 3a,c were established by comparison of their
1H NMR spectra with that of compound 3b in C6D6, in
freshly prepared solution of the latter only signals for the
cyclobutane form were found evidencing the relative staꢀ
bility of the obtained products in this solvent. All resoꢀ
nance signals were attributed based on 2D NMR experiꢀ
ments HSQC and HMBC. The characteristic feature of
1H NMR spectra of cyclobutanes 3 are two low field sigꢀ
nals of the H(7) ( 3.76—3.81, dd, J = 9.8 Hz, J = 8.3 Hz)
and H(8) protons ( 4.83—4.90, d, J = 8.3 Hz).
cyclic (3) and open (4 and 5) forms was determined by
integration of wellꢀresolved signals of the H(7) and H(8)
ring protons and the H(1´) and H(2´) chain protons (see
Scheme 2).
Almost immediately after dissolution of Nꢀmethylꢀ
piperazine derivative 3a in CDCl3, 1H NMR spectrum
exhibits signals of compounds 3a and 4a in a 90 : 10 ratio
(Fig. 1, a). After 40 min, tautomeric mixture contains
equal amounts of cyclobutane 3a and enamine 4a (Fig. 1, b),
while after 280 min, the ratio of 3a : 4b was equal to 18 : 82
(Fig. 1, c) and did not change within 1 day. However, over
time, the third product (5a) accumulates in the mixture
indicating that under conditions used compounds 3a and
4a irreversibly isomerize into tetrasubstituted enamine 5a
(4% after 7 days and 7% after 2 weeks) via intermediate A
(Fig. 2). It should be emphasized that tautomeric mixture
of the same composition (4a : 3a = 82 : 18) is also formed
from pure synꢀenamine 4a upon keeping its solution in
CDCl3 for 290 min (Fig. 3, a—c).
When bicyclo[4.2.0]octanes 3a,b were kept in the soluꢀ
tion in anhydrous chloroform at ~20 C for 2 h, they
underwent ring opening to give trisubstituted synꢀenamꢀ
ines 4a,b (50—53%), compound 3c yielded tetrasubstitutꢀ
ed enamine 5c (98%) within 2 days. Compounds 4a,b can
be obtained under the same conditions and in the same
yields directly from nitroalkene 1a and enamines 2a,b,
however pure trisubstituted enamine 4c was not isolated
due to its low stability. Regardless the synthesis procedure
used, enamines 4a,b always formed as one synꢀdiastereoꢀ
mer, which relative configuration (1´R*,6R*) was rigorꢀ
ously determined by Xꢀray diffraction of crystals of 4b.18
Morpholineꢀcontaining enamine 5b was synthesized in
nearly quantitative yield by keeping cyclobutane 3b in soꢀ
lution in chloroform at ~20 C for 2 days. Piperazine deꢀ
rivative 5a was detected in the reaction mixture only by
1H NMR spectroscopy. Pure triꢀ and tetrasubstituted
enamines 4b and 5b were isolated only in one case, when
Nꢀcyclohexenylmorpholine (2b) was used as enamine.
In a series of morpholine derivatives, the monitoring
of the ring opening of cyclobutane 3b into trisubstituted
enamine 4b was complicated by formation of tetrasubstiꢀ
H(7) (3a)
a
H(8) (3a)
1
The H NMR spectra of compounds 5 exhibit no sigꢀ
nals for the vinyl (H(2)) and the methyne (H(6)) protons
characteristic of trisubstituted enamines 4, and the most
low field shifted signal of the methyne proton of the side
chain (H(1´)) resonates as doublet of doublets at  5.9—6.0
with J = 10.5 Hz and J = 3.0 Hz. Unusually strong down
field shift of this proton as compared to that of the same
proton of trisubstituted enamines 4 ( 3.6—3.7) can be
explained by deshielding effect of the neighboring double
bond; the spinꢀspin coupling constant values indicate in
favor of conformations with trans and gauche arrangement
of the hydrogen atoms.
0.90
0.10
5.00
4.85
4.00
3.85
3.70

b
0.50
0.50
Cyclobutanes 3a—c are relatively stable compounds in
the crystalline state and suitable for long term storage in
refrigerator at –10 C. However, in the CDCl3 at room
temperature, equilibrium between ring (3a—c) and chain
(4a—c) tautomers are established. Enamines 4a,b are also
stable in the crystalline state, but being dissolved in CDCl3,
they spontaneously transform into cyclobutanes 3a,b until
thermodynamic equilibrium between cyclic and open
forms is established. Since both direct and reverse reacꢀ
tions are diastereoselective and do not lead to the mixtures
of stereoisomers, it is possible to suggest that the ring
opening of the cyclobutane 3 and its formation from the
open form 4 proceed via betaine A. This process was monꢀ
itored by the 1H NMR spectroscopy at 25 C, the ratio of
5.00
4.85
4.00
3.85
3.70

c
0.82
0.18
5.00
4.85
4.00
3.85
3.70

1

Fig. 1 H NMR spectra of a mixture 3a
and 280 min (c) after dissolution of compound 3a.
4a after 3 (a), 40 (b),


Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1739
by studying the reverse reaction, namely, the ring closure
of enamine 4b to cyclobutane 3b. As in the case of
Nꢀmethylpiperazine derivatives, the equilibrium mixture
contains 4b : 3b = 82 : 18 and equilibrium was achieved
in 6 h. In the case of reverse reaction, the transformaꢀ
tion of compound 4b into product 5b proceeds much slower
(a ratio of 4b : 3b : 5b = 64 : 20 : 16 was achieved afꢀ
ter 32 h).
H(2´a,b) (5a)
H(1´) (5a)
In studying the behavior of cyclobutane 3c in the
1
0.19
0.81
CDCl3 solution by H NMR spectroscopy it was found
that the piperidine derivative is less stable and undergoes
ring opening to give trisubstituted enamine 4c more rapidꢀ
ly. The spectrum of cyclobutane 3c recorded immediately
after dissolution of the sample revealed the presence of
compounds 3c and 4c in a ratio of 38 : 62, after 30 min as
in the two previous cases, the ratio was already 18 : 82 and
does not change over three next hours. Therefore, the conꢀ
tent of more thermodynamically stable tetrasubstituted
enamine 5c increased to 3 and 14%, respectively 1 and 3 h
after (see Scheme 2). Thus, the nature of amine has no
effect on the ration of cyclic and opened tautomeric forms
existing in the dynamic equilibrium, and the vast content
of enamine 4 (82% in all three cases) is due to the highest
stability of the open form as compared with cyclobutane
form. The spectral study of tetrasubstituted enamines 5 in
C6D6 and CDCl3 indicates that these compounds are relꢀ
atively stable in anhydrous solvent and do not involved in
tautomerism or isomerism of any type.
5.85
5.00
4.75
3.85 3.70

1

Fig. 2. H NMR spectrum of a mixture 3a
4a after 13 days.


tuted enamine 5b, which was more rapid than the 3b 4b

equilibration. The third set of the signals (3%) attributed
to enamine 5b was observed 4 h after dissolution of comꢀ
pound 3b in CDCl3; within 24 h its content increased up
to 44% and 48 h after 5b was the only reaction product. It
is occurred possible to establish the composition of the
tautomeric equilibrium mixture for morpholine derivatives
H(2´a) (4a)
H(2´b) (4a)
a
H(2) (4a)
H(1´) (4a)
These results clearly demonstrate a possibility of ringꢀ
chain tautomerism in a series of cyclobutane derivatives
and are of special interest since no spontaneous formation
of a strained cyclobutane system from acyclic precursor
was earlier documented. As it was expected, the solvent
nature strongly affected the rates of tautomeric equilibraꢀ
tion of this type. Thus, equilibrium between compounds
3a and 4a is nearly completely shifted to the acyclic form
4a immediately after dissolution of the sample 3a in
CD3OD. Meanwhile, in nonꢀpolar C6D6, we found the
mixtures 3a : 4a = 73 : 27 (from 3a) and 4a : 3a = 93 : 7
(from 4a) 24 h after dissolution (in CDCl3, these ratios
established within 15 and 30 min, respectively). It is noteꢀ
worthy that addition of CD3CO2D to the solutions of 3a,b
in C6D6 accelerates their transformation into compounds
5a,b. Thus, a solution of cyclobutane 3b in C6D6 in the
presence of CD3CO2D after 3 days contained only tetraꢀ
substituted enamine 5b as a mixture of approximately equal
amounts of nonꢀdeuterated form 5b and monodeuterated
at the C(2´) of the side chain form Dꢀ5b (content of diꢀ
deuterated product was no more than 5%). Interesting
that form Dꢀ5b was represent by only one diastereomer
indicating the stereoselectivity of deuteration (only the
proton of the CH2 group resonating in the strong field at
 4.20 (J = 10.7 Hz) is replaced by deuterium, while the
low field proton resonates, as it was expected, as a doublet
at  4.40 (J = 3.0 Hz)).
0.03
0.97
5.05
4.90
4.75
3.90
3.75

b
0.13
0.87
5.05
4.90
4.75
3.90
3.75

c
0.18
0.82
5.05
4.90
4.75
3.90
3.75

1

Fig. 3. H NMR spectra of a mixture 4a
3a after 3 (a), 60 (b),

and 290 min (c) after dissolution of compound 4a.

1740
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Korotaev et al.
Due to slow formation of Nꢀmethylpiperazine derivaꢀ
tive 5a (7 and 24% after 13 and 41 days, respectively), it
was not isolated pure. Apparently, it can be explained by
the fact that enamines 4 are formed from betaine A with
axially oriented substituent1 as a result of the intramolecuꢀ
lar transfer of the axial proton H(6) (route A), while the
intermolecular cleavage of the equatorial proton H(2) by
the external base yielded enamines 5 (route B). In this case,
Nꢀmethyl group in the piperazine intermediate A may
hinder the approach of the base to the H(2) proton thus
decreasing the formation rate of enamine 5a (Scheme 3).
conditions are nonꢀepimerization towards the resulting
ketone and formation of small amount of antiꢀisomer 7
can be due to relatively fast isomerization of 4b into 5b.
From the viewpoint of stereoselective ring opening of cyꢀ
clobutanes 3 into synꢀenamines 4, it is not surprising that
cyclobutane 3b is also hydrolyzes to synꢀketone 7 (CHCl3,
HCl) containing 15% of dichloro ketone 8. Detecting of
the latter among the reaction products is evidenced the
readiness of dehydrochlorination of ꢀnitro ketones 7. Inꢀ
deed, treatment of enamine 5b with morpholine excess
(2 equiv.) in MeOH (40 C, 40 h) led to pure dichloro
ketone 8 in 41% yield (Scheme 4).
Scheme 3
Scheme 4
Discovery of a new type of the ringꢀchain tautomerism in
a series of the products of the reaction between CCl3ꢀconꢀ
taining nitroalkene 1a with cyclohexanone enamines 2a—c
motivated us to study the similar reactions involving cycloꢀ
pentanone morpholine enamine 2d. It was found that in
this case the reaction in anhydrous benzene (10  20 C,
45 min) afforded bicyclo[3.2.0]heptane 9 in 78% yield.
Stereochemistry of compound 9 was confirmed by Xꢀray
diffraction (Fig. 4). Cyclobutane 9 is relatively stable in
the solid state and in solution in C6D6; while in solutions
in CDCl3 at 25 C, it undergoes the ring opening to give
a mixture of triꢀ and tetrasubstituted enamines 10 and
antiꢀ11 (Scheme 5). Detailed study of this transformation
in the NMR tube revealed that enamine 10 (5%) is apꢀ
peared first immediately after dissolution of compound 9
in CDCl3. Over time, as cyclobutane 9 is disappeared
trisubstituted antiꢀenamine 11 begins to accumulate, along
with tetrasubstituted enamine 10 (Table 1). Equilibrium
between triꢀ and tetrasubstituted enamines of cyclopenꢀ
tene series has been observed previously.24,25
It is also should be noticed that when cyclohexanone
enamines 2 react with (E)ꢀ3,3,3ꢀtrichloroꢀ1ꢀnitropropene
(1a) to give [2+2] cycloaddition adducts 3 (no cyclic nitrꢀ
onates 6 were found in any cases), their reactions with
(E)ꢀ1,1,1ꢀtrichloroꢀ3ꢀnitroꢀ2ꢀbutene (1c; R = Me) under
the similar conditions proceed differently to yield [4+2]
cycloaddition adducts, 3ꢀmethylꢀ4ꢀtrichloromethylꢀ1,2ꢀ
oxazine Nꢀoxides 6.16 The change in the direction of reacꢀ
tion with nitrobutene 1c is due apparently to the presence
of the methyl group hindering the approach of the carbꢀ
anion to the iminium carbon atom and favors its attack by
the oxygen atom of the ambident nitronate anoin (see
Scheme 3).
On the next step of our research, we studied characterꢀ
istic features of hydrolysis of triꢀ and tetrasubstituted CCl3ꢀ
containing enamines on the example of morpholine derivꢀ
atives 4b and 5b. It was found that treatment of enamine
4b, whose syn structure was determined by Xꢀray diffracꢀ
tion,18 with diluted HCl in EtOH at 40 C for 4 h resulted
in synꢀꢀnitro ketone 7 (yield was 55%) containing 6% of
antiꢀꢀnitro ketone 7 as an impurity. Apparently, these
Initially formed enamine 10 isomerizes only into antiꢀ
enamine 11 indicating the selective protonation of the
double bond in compound 10 and are in agreement with

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1741
Scheme 5
Table 1. Time dependent content of enamines 10,
antiꢀ11, and antiꢀ12 at the ring opening of cycloꢀ
butane 9 in CDCl3 solution (1H NMR data)
Time
9
10
antiꢀ11 antiꢀ12
%
2 min
1 h
6 h
25 h
92 h
95
82
32
10
10
15
18
51
62
58
10
10
17
35
35
0
0
0
3
7
chloroform (24 h, ~20 C) results in a mixture of tetraꢀ
and trisubstituted enamines 10 and antiꢀ11 in a 3 : 2 ratio.
The acid hydrolysis of this mixture (diluted HCl, 4 h,
50 C) leads to a mixture of ꢀnitro ketones 12 in the ratio
of antiꢀ12 : synꢀ12 = 3 : 1. Hydrolysis of cyclobutane 9
under the same conditions affords a similar mixture (see
Scheme 5).
We believe that hydrolysis conditions used are nonꢀ
epimerization one and formation of isomer synꢀ12 is due
to the presence of enamine 10 in the starting mixture.
Hydrolysis of the latter proceeds nonꢀstereoselectively to
give ketones synꢀ12 and antiꢀ12 in approximately equal
amounts. Thus, on going from cyclohexenylamines 2a—c
to Nꢀcyclopentenylmorpholine (2d), several significant
changes are observed. First, there is no ringꢀchain tautoꢀ
merism between cyclic (9) and open (10 and 11) forms of
enamine. Second, the ring opening of cyclobutane 9 afꢀ
fords initially not triꢀ but tetrasubstituted enamine 10,
which is in equilibrium with trisubstituted enamine 11.
Third, compound 10 isomerizes stereoselectively into antiꢀ
enamine 11, while in the case of cyclohexenyl derivatives
trisubstituted synꢀenamines 4a—c are observed, which arise
from the ring opening of cyclobutanes 3a—c via a dipolar
intermediate A.
Reaction of more reactive nitropropene 1b bearing the
CF3 group instead of the CCl3 group with Nꢀcycloꢀ
hexenylmorpholine (2b) (benzene, 2 h, ~20 C) to give the
corresponding cyclobutane derivative failed. In this case,
filtration afforded only nitroalkylated synꢀenamine 13 in
63% yield (this compound have been earlier synthesized
from 2ꢀdiazoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane26) and disꢀ
tillation of the filtrate in vacuo furnished a colorless oil
being an inseparable mixture containing tetrasubstituted
enamine 14 with an admixture of synꢀisomer 13 (18%)
(total yield 26%) (Scheme 6). Note that performing the
reaction of nitroalkene 1b with enamine 2b without solꢀ
vent increases the yield of synꢀ13 up to 86%. Acid hydrolysis
of this compound under mild conditions (diluted HCl, 2 h,
~20 C) is not accompanied by epimerization and afforded
synꢀnitro ketone 15 in 73% yield. The structure of compound
15 is determined by Xꢀray diffraction (Fig. 5). Epimer
antiꢀ15 is detected in the mixture obtained by hydrolysis
published data8 on nonꢀhalogenated analogs. This fact
excludes the participation of betaine A in isomerization,
since in the latter case one can expect formation of synꢀ
isomer. It is worthy to note that 1 day after in the studied
solution, the product of hydrolysis, antiꢀketone 12, begins
to accumulate, the content of which after 4 days increases
to 7%. As could be expected (see Table 1), the reaction of
Nꢀcyclopentenylmorpholine (2d) with nitroalkene 1a in
C(4)
C(5)
C(6)
Cl(2)
C(3)
C(2)
N(2)
C(7)
C(8)
C(12)
O(1)
C(1)
C(11)
C(9)
Cl(1)
N(1)
O(2)
Fig. 4. Molecular structure of bicyclo[3.2.0]heptane 9.
O(3) C(10)
Cl(3)

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Korotaev et al.
Scheme 6
of 14 (diluted HCl, 2 h, 40 C; antiꢀ15 : synꢀ15 : 14 =
= 46 : 45 : 9). Nitro ketone 15 have been described earliꢀ
er,14,26 however its syn configuration is first established.
We also performed the reaction of CF3ꢀcontaining
nitroalkene 1b with cyclopentanone enamine 2d in chloroꢀ
form (10  20 C, 2 h) to obtain quantitatively a mixture
of nitroalkylated enamines antiꢀ16 and 17 in a ratio of 3 : 1.
Analogously to trichloromethylated compounds 10 and
antiꢀ11, it is possible to suggest initial formation of tetraꢀ
substituted enamine 17, which exists in equilibrium with
trisubstituted enamine antiꢀ16 formed from the latter. Acid
hydrolysis of this mixture (diluted HCl, 4 h, 50 C) is
accompanied by partial epimerization to give a mixture of
approximately equal amounts of ꢀnitro ketones antiꢀ18
and synꢀ18 in the yield of 68% (see Scheme 6).
Stereochemistry of the synthesized compounds. As it
was mentioned above, for a series of acyclic derivatives
synthesized based on cyclohexanone enamines 2a—c, relꢀ
ative syn configurations were determined for trisubstituted
CCl3ꢀenamine 4b and CF3ꢀnitro ketone 15 using Xꢀray
diffraction. This fact serves for easy determination of
stereochemistry of other products of cyclohexanone series
by comparing their 1H NMR spectra (Table 2). Nevertheꢀ
less, we encountered serious problems in establishing the
relative configuration of cyclopentane derivatives syntheꢀ
sized from nitroalkenes 1a,b and Nꢀcyclopentenylmorꢀ
pholine (2d) as a mixtures of liquid isomers. The situation
is further complicated by the fact that bicyclo[3.2.0]ꢀ
heptane 9, whose structure was unambiguously determined
by Xꢀray diffraction (see Fig. 4) undergoes the ring openꢀ
ing to give not triꢀ but tetrasubstituted enamine 10, which
then partially stereoselectively transforms into one of isoꢀ
mers of trisubstituted enamine 11 (synꢀ11 or antiꢀ11).
Stereochemistry of enamine 11, the key compound in seꢀ
ries of cyclopentane products, is established due to recent
important observation.14 In studying the reaction of
nitroalkene 1b with Nꢀcyclopentenylpiperidine, bisꢀadꢀ
duct 19a was isolated as the single diastereomer and by
Xꢀray diffraction its 1´S*,5R*,1S* configuration was deꢀ
termined.
O(3)
C(4)
C(7)
F(3)
F(1)
C(2)
C(9)
C(5)
F(2)
C(3)
C(1)
C(6)
O(1)
N(1)
O(2)
C(8)
Fig. 5. Molecular structure of synꢀꢀnitro ketone 15.

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1743
In attempt at obtainꢀ
ing the crystals suitable
for Xꢀray diffraction of
the analogs of compound
19a, which can serve as
a reference in determiꢀ
nation of relative configꢀ
uration of cyclopentane
nitroalkene 1a (2 equiv.) with Nꢀcyclopentenylpiperidine
and enamine 2d in anhydrous dichloromethane (reflux,
3 h, yield of 34—49%) and compounds 19d,e were obtained
under similar conditions by subsequent addition of first
nitroalkene 1a and either 1c or 1b (yields of 19d,e were 41
and 32%, respectively). The relative 1´S*,5R*,1R*,2S*
configuration of bisꢀadduct 19d was unambiguously esꢀ
tablished by Xꢀray diffraction (Fig. 6), which allow furꢀ
ther determination of stereochemistry of compounds by
derivatives, we synthesized dialkylated adducts 19b—e.
Compounds 19b,c were synthesized by the reaction of
1
comparing their H NMR spectra (see Table 2). It was
X = CH2 (b), O (c)
Table 2. Chemical shifts and spinꢀspin coupling constants for H(1´), H(2´a), and H(2´b) protons in
1H NMR spectra of enamines 4a,b, 11, 13, 16, 19b—e and ꢀnitro ketones 7, 12, 15, 18
Comꢀ
pound
Solvent

J/Hz
H(1´)
H(2´a)
H(2´b)
J2´a,2´b
J1´,2´b
J1´,2´a
dd
synꢀ4a
synꢀ4a
synꢀ4b
synꢀ4b
synꢀ7
antiꢀ7
antiꢀ11a
antiꢀ11
antiꢀ12
synꢀ12
С6D6
CDCl3
С6D6
3.67 (td)
3.68 (q)
4.61
4.82
4.57
4.84
4.74
4.55
3.94
4.36
4.47
5.00
4.22
4.67
4.47
4.45
3.78
4.31
4.30
4.68
4.18
3.93
4.19
4.07
4.12
4.88
4.98
4.82
5.04
5.22
4.92
4.37
4.76
5.01
5.28
4.28
4.75
4.83
4.53
4.02
4.55
4.62
4.97
4.77
4.39
4.79
4.46
4.73
4.63
15.0
15.2
15.0
15.1
16.0
14.5
15.0
15.0
14.0
15.1
14.5
14.5
14.7
14.1
14.3
14.4
13.8
14.4
15.0
15.1
15.8
15.3
15.5
14.3
5.6
5.2
5.6
5.5
6.5
4.4
5.9
6.0
4.1
9.0
6.4
6.1
6.7
8.3
7.6
7.9
7.5
6.3
7.3
6.9
7.7
7.3
7.7
8.8
4.6
5.0
4.4
4.7
3.0
6.5
2.9
2.7
7.7
3.4
6.3
6.5
4.4
4.0
3.2
2.7
5.5
6.2
1.8
2.2
2.2
1.2
1.5
2.2
3.62 (dt)
3.70 (m)
3.77 (ddd)
4.67 (ddd)
4.07 (dt)
4.07 (dt)
4.19 (ddd)
3.77 (dt)
3.40 (m)
3.48 (m)
3.60 (m)
4.06 (m)
4.01 (m)
3.56 (m)
3.88 (m)
3.56 (qq)
4.14 (dt)
4.13 (dt)
4.16 (dt)
4.18 (dt)
4.14 (m)
CDCl3
CDCl3
CDCl3
С6D6
CDCl3
CDCl3
CDCl3
С6D6
CDCl3
CDCl3
CDCl3
С6D6
CDCl3
CDCl3
CDCl3
CDCl3
С6D6
synꢀ13
synꢀ13
synꢀ15
antiꢀ15
antiꢀ16b
antiꢀ16
antiꢀ18
synꢀ18
antiꢀ19bc
antiꢀ19cd
antiꢀ19c
antiꢀ19de
antiꢀ19d
antiꢀ19ef
CDCl3
C6D6
CDCl3
CDCl3
3.59 (qiuntt) 4.30
a H(5): 3.43 m (C6D6), 3.75 m (CDCl3).
b H(5): 2.97 m (C6D6), 3.39 m (CDCl3); 19F NMR (CDCl3), : 92.6 (d, CF3, J = 9.6 Hz).
c H(5): 3.87 m (CDCl3).
d H(5): 3.37 m (C6D6), 3.86 m (CDCl3).
e H(5): 3.37 br.t, J = 7.0 (C6D6), 3.80 m (CDCl3).
f H(5): 3.38 m (CDCl3); 19F NMR (CDCl3), : 92.3 (d, CF3, J = 9.3 Hz).

1744
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
Korotaev et al.
O(5)
Experimental
Cl(1)
C(1)
Cl(2)
C(15)
C(14)
IR spectra were recorded on a Perkin—Elmer Spectrum BXꢀII
instrument in the KBr pellets. 1H, 19F, and 13C NMR spectra
were run on Bruker DRXꢀ400 (working frequencies of 400, 376,
and 100 MHz, respectively) and Bruker Avance II instruments
(working frequencies of 500 and 126 MHz) in CDCl3 and C6D6
using Me4Si and C6F6 as internal standards. Nitroalkenes 1a,b
(see Refs 27, 28) and enamines 2 (see Ref. 29) were synthesized
by known procedures.
Synthesis of cyclobutanes 3a—c (general procedure). To
a stirred solution of the corresponding enamine 2 (10.0 mmol) in
anhydrous hexane (3 mL), a solution of nitropropene 1a (1.90 g,
10.0 mmol) in anhydrous hexane (3 mL) was added over a period
of 15 min at 10—15 C. The mixture was stirred at ~20 C for
0.5 h, the precipitate formed was filtered off, washed with
hexane, and recrystallized from hexane or hexane—benzene
(1 : 2, for 3b).
C(13)
N(3)
C(5)
C(16)
C(2)
Cl(4)
Cl(3)
C(9)
O(4)
C(6)
C(4)
C(8)
O(2)
C(10)
C(7)
C(3)
N(1)
O(1)
Cl(5)
Cl(6)
O(3)
C(12)
N(2)
C(11)
Fig. 6. Molecular structure of dialkylated compound 19d.
found that stereochemistry of 19b,c,e is the same as for
trifluoromethylated compound 19a (1´S*,5R*,1S*).14
A comparison of 1H NMR spectra of compounds 19b,c
and 11 recorded in C6D6 and CDCl3 reveals very similar
chemical shifts for the H(1´), H(2´a), H(2´b), and H(5)
and spinꢀspin coupling constants for the AMX spin sysꢀ
tem formed by the protons of the side chain at the C(5)
atom, thus suggesting that tetrasubstituted CCl3ꢀenamine
10 is in equilibrium with trisubstituted antiꢀenamine 11.
Similar comparison of NMR spectra of compounds 19e and
(1R*,6S*,7S*,8R*)ꢀ1ꢀ(4ꢀMethylpiperazino)ꢀ8ꢀnitroꢀ7ꢀ(triꢀ
chloromethyl)bicyclo[4.2.0]octane (3a). Yield 2.26 g (61%),
colorless prisms, m.p. 93—94 C. Found (%): C, 45.48; H, 5.94;
N, 11.33. C14H22Cl3N3O2. Calculated (%): C, 45.36; H, 5.98;
N, 11.34. IR, /cm–1: 1537, 1455, 1367. 1H NMR (C6D6),
: 0.80—1.70 (m, 8 H, 4 CH2); 2.10 (s, 3 H, Me); 2.21 (br.s, 4 H,
N(CH)2)2); 2.35 (t, 1 H, H(6), J = 8.0 Hz); 2.42 (dt, 2 H,
N(CHH)2, J = 10.5 Hz, J = 4.5 Hz); 2.63 (dt, 2 H, N(CHH)2,
J = 10.5 Hz, J = 4.5 Hz); 3.79 (dd, 1 H, H(7), J = 9.6 Hz,
J = 8.3 Hz); 4.90 (d, 1 H, H(8), J = 8.3 Hz). 1H NMR (CDCl3),
: 1.20—2.10 (m, 8 H, 4 CH2); 2.30 (s, 3 H, Me); 2.45 (br.s, 4 H,
N(CH2)2); 2.62 (t, 1 H, H(6), J = 8.0 Hz); 2.68 (dt, 2 H,
N(CHH)2, J = 10.5 Hz, J = 4.5 Hz); 2.80 (br.s, 2 H, N(CHH)2);
3.86 (dd, 1 H, H(7), J = 9.6 Hz, J = 8.5 Hz); 4.91 (d, 1 H, H(8),
J = 8.5 Hz).
(1R*,6S*,7S*,8R*)ꢀ1ꢀMorpholinoꢀ8ꢀnitroꢀ7ꢀ(trichloromethꢀ
yl)bicyclo[4.2.0]octane (3b). Yield 2.58 g (72%), colorless prisms,
m.p. 134—135 C. Found (%): C, 43.65; H, 5.51; N, 7.71.
C13H19Cl3N2O3. Calculated (%): C, 43.66; H, 5.35; N, 7.83. IR,
/cm–1: 1540, 1458, 1357. 1H NMR (500 MHz, C6D6), :
0.80—1.22 (m, 6 H, 3 CH2); 1.54—1.60 (m, 2 H, CH2); 2.17—2.22
(m, 2 H, N(CHH)2); 2.28 (ddt, 1 H, H(6), J = 9.8 Hz, J = 6.3 Hz,
J = 1.7 Hz); 2.38—2.42 (m, 2 H, N(CHH)2); 3.44 (ddd, 2 H,
O(CHH)2, J = 10.8 Hz, J = 5.8 Hz, J = 3.3 Hz); 3.47 (ddd, 2 H,
O(CHH)2, J = 10.8 Hz, J = 5.8 Hz, J = 3.3 Hz); 3.76 (dd, 1 H,
H(7), J = 9.8 Hz, J = 8.3 Hz); 4.83 (d, 1 H, H(8), J = 8.3 Hz).
1H NMR (CDCl3), : 1.20—2.10 (m, 8 H, 4 CH2); 2.60—2.70
(m, 3 H, N(CHH)2, H(6)); 2.74—2.82 (m, 2 H, N(CHH)2);
3.68—3.75 (m, 4 H, O(CH2)2); 3.87 (t, 1 H, H(7), J = 9.1 Hz);
4.95 (d, 1 H, H(8), J = 8.4 Hz). 13C NMR (C6D6), : 20.5
(C(4)), 21.0 (C(3)), 22.3 (C(2)), 24.3 (C(5)), 36.5 (C(6)), 47.1
(NCH2), 54.3 (C(7)), 64.1 (C(1)), 67.3 (OCH2), 83.7 (C(8)),
99.8 (CCl3).
16 in CDCl3 including 19F NMR spectra (CF 92.3—92.6)
3
also indicates anti configuration of enamine 16, which,
apparently, as well as antiꢀ11, is the product of isomerizaꢀ
tion of initially formed tetrasubstituted CF3ꢀenamine 17
(see Schemes 5, 6 and Table 2). Acid hydrolysis of the
mixtures of isomeric enamines antiꢀ11 : 10 = 40 : 60 and
antiꢀ16 : 17 = 75 : 25 results in the mixtures of diastereoꢀ
meric ꢀnitro ketones antiꢀ12 : synꢀ12 = 74 : 26 and
antiꢀ18 : synꢀ18 = 56 : 44, respectively. Stereochemisꢀ
try of these ꢀnitro ketones can be determined by comꢀ
1
paring their H NMR spectra in CDCl3 with the spectra
of synꢀ and antiꢀketones 7 and 15 of the cyclohexane
series (cf., for example, synꢀ7 and synꢀ12, Table 2). Reꢀ
gardless of the ring size and the nature of the CX3 group
passing from synꢀ to antiꢀketones always accompanied by
the low field shift of the signal of the H(1´) proton of
0.90—0.32 ppm.
In summary, we first shown that the reactions of
(E)ꢀ3,3,3ꢀtrichloroꢀ1ꢀnitropropene with cycloalkanone
enamines result in cyclobutanes or enamines of linear
structure depending on the reaction conditions. Novel type
of ringꢀchain tautomerism consisting in reversible transꢀ
formation of the CCl3ꢀcontaining cyclobutane derivatives
into trisubstituted enamines is found and studied by
1H NMR spectroscopy. Starting from (E)ꢀ3,3,3ꢀtriꢀ
chloro(trifluoro)ꢀ1ꢀnitropropenes, a series of hitherto
unknown CX3ꢀcontaining nitroalkylated enamines and
ꢀnitro ketones are diastereoselectively synthesized and
their relative configurations are established.
(1R*,6S*,7S*,8R*)ꢀ8ꢀNitroꢀ1ꢀpiperidinoꢀ7ꢀ(trichloromethꢀ
yl)bicyclo[4.2.0]octane (3c). Yield 2.70 g (76%), colorless
prisms, m.p. 75—76 C. Found (%): C, 47.20; H, 5.91; N, 7.95.
C14H21Cl3N2O2. Calculated (%): C, 47.28; H, 5.95; N, 7.88. IR,
/cm–1: 1549, 1442, 1367. 1H NMR (C6D6), : 0.80—1.70
(m, 14 H, 7 CH2); 2.25 (dt, 2 H, N(CHH)2, J = 10.6 Hz, J = 5.0 Hz);
2.36 (br.t, 1 H, H(6), J = 8.0 Hz); 2.48 (dt, 2 H, N(CHH)2,
J = 10.6 Hz, J = 5.0 Hz); 3.81 (dd, 1 H, H(7), J = 9.8 Hz,
J = 8.4 Hz); 4.90 (d, 1 H, H(8), J = 8.4 Hz). 1H NMR (CDCl3),
: 1.20—2.20 (m, 14 H, 7 CH2); 2.52—2.64 (m, 3 H, N(CHH)2,

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1745
H(6)); 2.67 (dt, 2 H, N(CHH)2, J = 10.5 Hz, J = 5.2 Hz); 3.84
(dd, 1 H, H(7), J = 9.8 Hz, J = 8.5 Hz); 4.91 (d, 1 H, H(8),
J = 8.5 Hz).
in vacuo, the product was purified by column chromatography
(silica gel, elution with chloroform). Yield 0.23 g (78%).
2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ethyl]ꢀ1ꢀpiperidinoꢀ1ꢀcycloꢀ
hexene (5c) was synthesized similarly to enamine 5b following
the procedure B. Yield 0.35 g (98%), white powder, m.p. 54—55 C.
Compound 5c is unstable at room temperature and within 0.5 h
is undergoes spontaneous exothermic decompositions with HCl
evolution. IR, /cm–1: 1643, 1556, 1378. 1H NMR (C6D6),
: 0.80—2.70 (m, 18 H, 9 CH2); 4.24 (t, 1 H, H(2´a), J = 10.7 Hz);
4.45 (dd, 1 H, H(2´b), J = 10.9 Hz, J = 3.1 Hz); 6.03 (dd, 1 H,
H(1´), J = 10.3 Hz, J = 2.8 Hz).
(2R*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ethyl]cyclohexꢀ
anone (synꢀ7). A suspension of enamine synꢀ4b (0.36 g, 1.0 mmol)
in 0.5 M HCl (2.5 mL) and EtOH (2 mL) was stirred at 40 C for
4 h, then the mixture was cooled and extracted with dichloroꢀ
methane (2×1 mL). The organic layer was dried with anhydrous
Na2SO4, the solvent was removed in vacuo. Recrystallization of
the residue from pentane afforded ketone synꢀ7 in a yield of
0.16 g (55%), colorless prisms, m.p. 55—56 C (content of isoꢀ
mer antiꢀ7 is 6%). Found (%): C, 37.57; H, 4.35; N, 4.76.
C9H12Cl3NO3. Calculated (%): C, 37.46; H, 4.19; N, 4.85. IR,
/cm–1: 1709, 1558, 1381. 1H NMR (CDCl3), : 1.50—2.50
(m, 8 H, 4 CH2); 3.25—3.31 (m, 1 H, H(2)); 3.77 (ddd, 1 H,
H(1´), J = 6.5 Hz, J = 3.0 Hz, J = 1.8 Hz); 4.74 (dd, 1 H,
H(2´a), J = 16.0 Hz, J = 3.0 Hz); 5.22 (dd, 1 H, H(2´b), J = 16.0 Hz,
J = 6.5 Hz). Ketone synꢀ7 was also synthesized from cycloꢀ
butane 3b in chloroform in the presence of diluted HCl (conꢀ
tent of 2ꢀ(1,1ꢀdichloroꢀ3ꢀnitropropꢀ1ꢀenꢀ2ꢀyl)cyclohexanone 8
is 15%).
(2S*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ethyl]cyclohexanꢀ
one (antiꢀ7) was synthesized as the antiꢀ7 : synꢀ7 = 62 : 38 (by
hydrolysis of synꢀenamine 4b with insufficient acid amount) and
antiꢀ7 : synꢀ7 : 8 = 46 : 13 : 41 mixtures (by hydrolysis of enamine
5b under conditions described for ketone synꢀ7). 1H NMR
(CDCl3), : 1.50—2.60 (m, 8 H, 4 CH2); 3.23 (ddd, H, H(2),
J = 13.2 Hz, J = 5.5 Hz, J = 2.7 Hz); 4.55 (dd, 1 H, H(2´a),
J = 14.5 Hz, J = 6.5 Hz); 4.67 (ddd, 1 H, H(1´), J = 6.5 Hz,
J = 4.4 Hz, J = 2.7 Hz); 4.92 (dd, 1 H, H(2´b), J = 14.5 Hz,
J = 4.4 Hz).
2ꢀ(1,1ꢀDichloroꢀ3ꢀnitropropꢀ1ꢀenꢀ2ꢀyl)cyclohexanone (8).
A solution of enamine 5b (0.36 g, 1.0 mmol) and morpholine
(0.18 g, 2.0 mmol) in MeOH (2 mL) was stirred at 40 C for
3 days, then water (3 mL) was added and stirring was continued
for 1 day. After cooling to ~20 C, the reaction mixture was
extracted with chloroform (3×1 mL), the organic layer was dried
with Na2SO4, and the solvent was removed in vacuo. Column
chromatography of the residue (silica gel, elution with chloroꢀ
form) and subsequent recrystallization afforded compound 8 in
the yield of 0.10 g (41%), m.p. 78—79 C, white powder. Found (%):
C, 43.05; H, 4.47; N, 5.42. C9H11Cl2NO3. Calculated (%):
C, 42.88; H, 4.40; N, 5.56. IR, /cm–1: 1701, 1614, 1558, 1378.
1H NMR (CDCl3), : 1.60—2.50 (m, 8 H, 4 CH2); 3.89 (dd, 1 H,
H(2), J = 12.8 Hz, J = 5.8 Hz); 4.96 (d, 1 H, H(3´a), J = 15.8 Hz);
5.35 (d, 1 H, H(3´b), J = 15.8 Hz).
(6R*,1´R*)ꢀ1ꢀ(4ꢀMethylpiperazino)ꢀ6ꢀ[2ꢀnitroꢀ1ꢀ(trichloroꢀ
methyl)ethyl]ꢀ1ꢀcyclohexene (synꢀ4a). A solution of cyclobutane
3a (0.37 g, 1.0 mmol) in chloroform (1 mL) was kept at ~20 C
for 2 h, the solvent was removed in vacio, and the residue
was recrystallized from hexane. Yield 0.20 g (53%), colorless
prisms, m.p. 126—127 C. Found (%): 45.24; H, 5.95; N, 11.39.
C14H22Cl3N3O2. Calculated (%): C, 45.36; H, 5.98; N, 11.34.
IR, /cm–1: 1652, 1553, 1457, 1375. 1H NMR (C6D6), : 1.30—1.90
(m, 6 H, 3 CH2); 2.09 (br.s, 4 H, N(CH2)2); 2.05 (s, 3 H, Me);
2.25 (br.s, 2 H, N(CHH)2); 2.68 (br.s, 1 H, H(6)); 2.76 (br.s,
2 H, N(CHH)2); 3.67 (td, 1 H, H(1´), J = 5.1 Hz, J = 4.6 Hz);
4.61 (dd, 1 H, H(2´a), J = 15.0 Hz, J = 4.6 Hz); 4.76 (dd, 1 H,
H(2), J = 4.1 Hz, J = 3.4 Hz); 4.88 (dd, 1 H, H(2´b), J = 15.0 Hz,
J = 5.6 Hz). 1H NMR (CDCl3), : 1.50—2.20 (m, 6 H, 3 CH2);
2.30 (s, 3 H, Me); 2.30—2.60 (m, 6 H, 3 CH2N); 2.88 (br.s, 1 H,
H(6)); 3.08 (br.s, 2 H, CH2N); 3.68 (q, 1 H, H(1´), J = 4.8); 4.82
(dd, 1 H, H(2´a), J = 15.2 Hz, J = 5.0 Hz); 4.98 (dd, 1 H,
H(2´b), J = 15.2 Hz, J = 5.2 Hz); 5.08 (t, 1 H, H(2), J = 3.8 Hz).
(6R*,1´R*)ꢀ1ꢀMorpholinoꢀ6ꢀ[2ꢀnitroꢀ1ꢀ(trichloromethyl)ꢀ
ethyl]ꢀ1ꢀcyclohexene (synꢀ4b) was synthesized similarly to enꢀ
amine 4a, yiled 0.18 g (50%), colorless prisms, m.p. 101—102 C.
Found (%): C, 43.64; H, 5.22; N, 7.79. C13H19Cl3N2O3. Calcuꢀ
lated (%): C, 43.66; H, 5.35; N, 7.83. IR, /cm–1: 1648, 1558,
1383. 1H NMR (500 MHz, C6D6), : 1.33—1.54 (m, 3 H, H(4a),
H(4b), H(5a)); 1.73 (m, 1 H, H(3a)); 1.83—1.90 (m, 2 H, H(3b),
H(5b)); 2.06 (ddd, 2 H, N(CHH)2, J = 11.5 Hz, J = 5.8 Hz,
J = 3.1 Hz); 2.53—2.60 (m, 3 H, N(CHH)2, H(6)); 3.32—3.42
(m, 4 H, O(CH2)2); 3.62 (dt, 1 H, H(1´), J = 5.6 Hz, J = 4.4 Hz);
4.57 (dd, 1 H, H(2´a), J = 15.0 Hz, J = 4.4 Hz); 4.67 (dd, 1 H,
H(2), J = 4.1 Hz, J = 3.5 Hz); 4.82 (dd, 1 H, H(2´b), J = 15.0 Hz,
J = 5.6 Hz). 1H NMR (CDCl3), : 1.55—2.20 (m, 6 H, 3 CH2);
2.51 (dt, 2 H, N(CHH)2, J = 11.7 Hz, J = 5.0 Hz); 2.87 (br.q,
1 H, H(6), J = 3.5 Hz); 3.05 (dt, 2 H, N(CHH)2, J = 11.7 Hz,
J = 5.0 Hz); 3.70 (m, 5 H, O(CH2)2, H(1´)); 4.84 (dd, 1 H, H(2´a),
J = 15.1 Hz, J = 4.7 Hz); 5.04 (dd, 1 H, H(2´b), J = 15.1 Hz,
J = 5.5 Hz); 5.08 (t, 1 H, H(2), J = 3.7 Hz). 13C NMR (126 MHz,
C6D6), : 17.1 (C(4)), 24.1 (C(3)), 30.5 (C(5)), 34.5 (C(6)), 50.6
(NCH2), 61.2 (C(1´)), 67.0 (OCH2), 75.6 (C(2´)), 103.0 (CCl3),
112.6 (C(2)), 145.9 (C(1)).
1ꢀMorpholinoꢀ2ꢀ[2ꢀnitroꢀ1ꢀ(trichloromethyl)ethyl]ꢀ1ꢀcycloꢀ
hexene (5b). A. To a solution of enamine 2b (0.17 g, 1.0 mmol) in
chloroform (5 mL), a solution of nitroalkene 1a in chloroform
(5 mL) was added dropwise. A mixture was stirred at ~20 C for
7 days, the solvent was removed in vacuo. Purification of the
residue by column chromatography (silica gel, elution with
chloroform) afforded 0.36 g (100%) of compound 5b, yellow oil.
Found (%): C, 43.49; H, 5.20; N, 7.77. C13H19Cl3N2O3. Calcuꢀ
lated (%): C, 43.66; H, 5.35; N, 7.83. IR, /cm–1: 1646, 1558,
1378. 1H NMR (C6D6), : 1.20—2.40 (m, 12 H, 4 CH2, N(CH2)2);
3.60—3.73 (m, 4 H, O(CH2)2); 4.20 (t, 1 H, H(2´a), J = 10.7 Hz);
4.41 (dd, 1 H, H(2´b), J = 11.0 Hz, J = 3.0 Hz); 5.93 (dd, 1 H,
H(1´), J = 10.5 Hz, J = 3.0 Hz). 1H NMR (CDCl3), : 1.50—2.40
(m, 10 H, 4 CH2, NCH2); 2.60—2.70 (m, 2 H, NCH2); 3.74
(br.s, 4 H, O(CH2)2); 4.76 (t, 1 H, H(2´a), J = 10.7 Hz); 4.98
(dd, 1 H, H(2´b), J = 10.8 Hz, J = 3.0 Hz); 5.93 (dd, 1 H, H(1´),
J = 10.3 Hz, J = 3.0 Hz).
(1R*,5S*,6S*,7R*)ꢀ1ꢀMorpholinoꢀ7ꢀnitroꢀ6ꢀ(trichloromethꢀ
yl)bicyclo[3.2.0]heptane (9). To a stirred solution of enamine 2d
(1.53 g, 10.0 mmol) in anhydrous benzene (3 mL), a solution of
nitropropene 1a (1.90 g, 10.0 mmol) in anhydrous benzene
(3 mL) was added dropwise within 15 min at 10—15 C. The
mixture was stirred at ~20 C for 0.5 h and diluted with hexane
(5 mL). The precipitate formed was filtered off, washed with
B. A solution of compound 3b (0.36 g, 1.0 mmol) in chloroꢀ
form was kept at ~20 C for 2 days. The solvent was removed

1746
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
Korotaev et al.
hexane and recrystallized from hexane—benzene (1 : 2) to give
cyclobutane 9 in the yield of 2.68 g (78%), m.p. 155—156 C,
colorless prisms. Found (%): C, 41.88; H, 5.14; N, 8.00.
C12H17Cl3N2O3. Calculated (%): C, 41.94; H, 4.99; N, 8.15. IR,
/cm–1: 1538, 1447, 1368. 1H NMR (C6D6), : 1.13—1.53 (m, 6 H,
3 CH2); 1.96 (dt, 2 H, N(CHH)2, J = 11.0 Hz, J = 4.6 Hz); 2.35
(dt, 2 H, N(CHH)2, J = 11.0 Hz, J = 4.6 Hz); 2.35 (t, 1 H, H(5),
J = 6.0 Hz); 3.44 (t, 4 H, O(CH2)2, J = 4.6 Hz); 3.58 (dd, 1 H,
H(6), J = 7.5 Hz, J = 6.7 Hz); 5.02 (d, 1 H, H(7), J = 7.5 Hz).
1H NMR (CDCl3), : 1.54—2.04 (m, 6 H, 3 CH2); 2.51 (dt, 2 H,
N(CHH)2, J = 11.5 Hz, J = 4.5 Hz); 2.77 (dt, 2 H, N(CHH)2,
J = 11.5 Hz, J = 4.5 Hz); 2.83 (t, 1 H, H(5), J = 6.0 Hz);
3.70—3.74 (m, 5 H, O(CH2)2, H(6)); 5.24 (d, 1 H, H(7),
J = 7.5 Hz). 13C NMR (126 MHz, C6D6), : 25.7 (C(3)), 27.1
(C(2)), 31.3 (C(4)), 42.8 (C(5)), 47.1 (NCH2), 55.3 (C(6)), 67.0
(OCH2), 74.2 (C(1)), 83.9 (C(7)), 99.5 (CCl3).
J = 7.7 Hz); 5.01 (dd, 1 H, H(2´b), J = 14.0 Hz, J = 4.1 Hz)
(antiꢀ12 (74%)); 1.70—2.50 (m, 6 H, 3 CH2); 2.58 (m, 1 H,
H(2)); 3.77 (dt, 1 H, H(1´), J = 8.9 Hz, J = 3.4 Hz); 5.00
(dd, 1 H, H(2´a), J = 15.1 Hz, J = 3.4 Hz); 5.28 (dd, 1 H,
H(2´b), J = 15.1 Hz, J = 9.0 Hz) (synꢀ12 (26%)).
B. To a stirred solution of enamine 2d (1.53 g, 10.0 mmol) in
chloroform or dichloromethane (3 mL), a solution of nitroproꢀ
pene 1a (1.90 g, 10.0 mmol) in chloroform or dichloromethane
(3 mL) was added dropwise over a period of 15 min at 10—15 C.
The reaction mixture was stirred at ~20 C for 2 h, the solvent
was removed in vacuo, and 0.5 M HCl (25 mL) was added to the
residue. The resulting mixture was stirred at 50 C for 4 h and
extracted with chloroform (3×3 mL), the organic layers were
dried with anhydrous Na2SO4. Purification by column chromaꢀ
tography (silica gel, elution with dichloromethane) afforded
a mixture of antiꢀ12 and synꢀ12 (3 : 1) in the yield of 1.87 g (68%).
(6R*,1´R*)ꢀ1ꢀMorpholinoꢀ6ꢀ[2ꢀnitroꢀ1ꢀ(trifluoromethyl)ꢀ
ethyl]ꢀ1ꢀcyclohexene (synꢀ13). To a stirred solution of enamine
2b (1.67 g, 10.0 mmol) in anhydrous benzene (3 mL), a solution
of nitropropene 1b (1.41 g, 10.0 mmol) in anhydrous benzene
(3 mL) was added dropwise over a period of 15 min at 10—15 C.
The reaction mixture was stirred at ~20 C for 2 h and diluted
with hexane (10 mL). The precipitate formed was filtered off
and recrystallized form hexane to give compound synꢀ13 in the
yield of 1.93 g (63%), m.p. 86—87 C (cf. Ref. 26: m.p. 88—89 C),
colorless prisms. Performing the reaction without solvent for
0.5 h led to the increase in the yield up to 86%. IR, /cm–1: 1648,
1557, 1387. 1H NMR (C6D6), : 1.20—1.90 (m, 6 H, 3 CH2);
1.97—2.04 (m, 2 H, N(CHH)2); 2.39 (br.q, 1 H, H(6), J = 4.1 Hz);
2.43—2.49 (m, 2 H, N(CHH)2); 3.29—3.48 (m, 5 H, H(1´),
O(CH2)2); 4.22 (dd, 1 H, H(2´a), J = 14.5 Hz, J = 6.3 Hz); 4.28
(dd, 1 H, H(2´b), J = 14.5 Hz, J = 6.4 Hz); 4.61 (t, 1 H, H(2),
J = 3.9 Hz). 1H NMR (CDCl3), : 1.50—2.20 (m, 6 H, 3 CH2);
2.44—2.50 (m, 2 H, N(CHH)2); 2.76 (br.q, 1 H, H(6), J = 4.6 Hz);
2.88—2.96 (m, 2 H, N(CHH)2); 3.42—3.54 (m, 1 H, H(1´));
3.67—3.77 (m, 4 H, O(CH2)2); 4.67 (dd, 1 H, H(2´a), J = 14.5 Hz,
J = 6.5 Hz); 4.75 (dd, 1 H, H(2´b), J = 14.5 Hz, J = 6.1 Hz); 5.04
(t, 1 H, H(2), J = 3.9 Hz). 19F NMR (C6D6), : 94.5 (d, CF3,
J = 9.8 Hz). 19F NMR (CDCl3), : 92.9 (d, CF3, J = 9.7 Hz).
1ꢀMorpholinoꢀ2ꢀ[2ꢀnitroꢀ1ꢀ(trifluoromethyl)ethyl]ꢀ1ꢀcycloꢀ
hexene (14) was prepared as a colorless oil by distillation of filꢀ
trate obtained in the synthesis of synꢀ13; the sample contained
18% of the latter (19F NMR data). Yield 0.81 g (26%), b.p.
110—112 C (2 Torr). Found (%): C, 50.69; H, 6.41; N, 9.37.
C13H19F3N2O3. Calculated (%): C, 50.65; H, 6.21; N, 9.09. IR,
/cm–1: 1655, 1562, 1380. 1H NMR (CDCl3), : 1.50—2.70
(m, 12 H, 4 CH2, N(CH2)2); 3.75 (m, 4 H, O(CH2)2); 4.62 (dd,
1 H, H(2´a), J = 11.9 Hz, J = 10.4 Hz); 4.68 (dd, 1 H, H(2´b),
J = 11.9 Hz, J = 4.7 Hz); 5.48 (quint.d, 1 H, H(1´), J = 10.4 Hz,
J = 4.7 Hz). 19F NMR (CDCl3), : 95.3 (d, CF3, J = 10.3 Hz).
(2R*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trifluoromethyl)ethyl]cyclohexanꢀ
one (synꢀ15) was synthesized by hydrolysis of enamine synꢀ13
(HCl, H2O, EtOH, 2 h, 20 C). Yield 73%, b.p. 121—123 C
(3 Torr), m.p. 43—44 C (pentane), colorless prisms (cf. Ref. 26:
b.p. 114—116 C (2 Torr), m.p. 43 C). IR, /cm–1: 1714, 1564,
1ꢀMorpholinoꢀ2ꢀ[2ꢀnitroꢀ1ꢀ(trichloromethyl)ethyl]ꢀ1ꢀcycloꢀ
pentene (10) and (5S*,1´R*)ꢀ1ꢀmorpholinoꢀ5ꢀ[2ꢀnitroꢀ1ꢀ(triꢀ
chloromethyl)ethyl]ꢀ1ꢀcyclopentene (antiꢀ11). A solution of
cyclobutane 9 (0.34 g, 1.0 mmol) in chloroform (2 mL) was kept
at ~20 C for 24 h. Removal of the solvent in vacuo quantitatively
afforded a mixture of isomers 10 (60%) and antiꢀ11 (40%), yelꢀ
low oil. The mixture of the same composition was obtained diꢀ
rectly from the starting compounds 1a and 2d under similar conꢀ
ditions. IR, /cm–1: 1659, 1637, 1560, 1378. Found (%): C, 41.75;
H, 5.08; N, 7.86. C12H17Cl3N2O3. Calculated (%): C, 41.94;
H, 4.99; N, 8.15. 1H NMR (C6D6), : 1.45—2.40 (m, 10 H, 3 CH2,
N(CH2)2); 3.50—3.55 (m, 4 H, O(CH2)2); 4.24 (dd, 1 H, H(2´a),
J = 11.4 Hz, J = 10.5 Hz); 4.43 (dd, 1 H, H(2´b), J = 11.4 Hz,
J = 3.2 Hz); 5.03 (dd, 1 H, H(1´), J = 10.5 Hz, J = 3.2 Hz)
(compound 10 (60%)); 1.45—2.40 (m, 6 H, 2 CH2, N(CHH)2);
2.62—2.68 (m, 2 H, N(CHH)2); 3.40—3.46 (m, 1 H, H(5));
3.55—3.60 (m, 4 H, O(CH2)2); 3.94 (dd, 1 H, H(2´a), J = 15.0 Hz,
J = 2.9 Hz); 4.07 (dt, 1 H, H(1´), J = 5.9 Hz, J = 2.6 Hz); 4.37
(dd, 1 H, H(2´b), J = 15.0 Hz, J = 5.9 Hz); 4.39 (t, 1 H, H(2),
1
J = 1.8 Hz) (antiꢀ11 (40%)). H NMR (CDCl3), : 1.78—2.48
(m, 6 H, 3 CH2); 2.55 (dt, 2 H, N(CHH)2, J = 11.6 Hz,
J = 4.6 Hz); 2.70 (dt, 2 H, N(CHH)2, J = 11.6 Hz, J = 4.6 Hz);
3.75 (t, 4 H, O(CH2)2, J = 4.6 Hz); 4.75 (dd, 1 H, H(2´a),
J = 11.7 Hz, J = 10.8 Hz); 5.01 (dd, 1 H, H(2´b), J = 11.7 Hz,
J = 3.0 Hz); 5.02 (dd, 1 H, H(1´), J = 10.8 Hz, J = 3.0 Hz)
(10 (62%)); 1.45—2.40 (m, 4 H, 2 CH2); 2.63—2.70 (m, 2 H,
N(CHH)2); 2.95—3.03 (m, 2 H, N(CHH)2); 3.70—3.80 (m, 5 H,
O(CH2)2, H(5)); 4.07 (dt, 1 H, H(1´), J = 6.0 Hz, J = 2.4 Hz);
4.36 (dd, 1 H, H(2´a), J = 15.0 Hz, J = 2.7 Hz); 4.76 (dd, 1 H,
H(2´b), J = 15.0 Hz, J = 6.0 Hz); 4.77 (m, 1 H, H(2)) (antiꢀ11
(38%)).
(2S*,1´R*ꢀ and 2R*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ꢀ
ethyl]cyclopentanones (antiꢀ12, synꢀ12). A. A suspension of cycloꢀ
butane 9 (0.34 g, 1.0 mmol) in a mixture of 0.5 M HCl (2.5 mL)
and EtOH (2 mL) was stirred at 50 C for 4 h, then the reacꢀ
tion mixture was cooled and extracted with dichloromethane
(2×1 mL). The organic layer was dried with anhydrous Na2SO4,
the solvent was removed in vacuo. Column chromatography of
the residue (silica gel, elution with dichloromethane) afforded
a mixture of antiꢀ12 and synꢀ12 (3 : 1) in the yield of 0.16 g (60%).
IR, /cm–1: 1742, 1562, 1379. Found (%): C, 35.12; H, 3.88;
N, 5.39. C8H10Cl3NO3. Calculated (%): C, 35.00; H, 3.67;
N, 5.10. 1H NMR (CDCl3), : 1.70—2.50 (m, 6 H, 3 CH2);
3.00—3.08 (m, 1 H, H(2)); 4.19 (ddd, 1 H, H(1´), J = 7.7 Hz,
J = 4.1 Hz, J = 2.0 Hz); 4.47 (dd, 1 H, H(2´a), J = 14.0 Hz,
1
1381. H NMR (CDCl3), : 1.60—2.50 (m, 8 H, 4 CH2); 2.80
(dtq, 1 H, H(2), J = 12.7 Hz, J = 5.5 Hz, J = 0.8 Hz); 3.54—3.66
(m, 1 H, H(1´)); 4.47 (dd, 1 H, H(2´a), J = 14.7 Hz, J = 4.4 Hz);
4.83 (dd, 1 H, H(2´b), J = 14.7 Hz, J = 6.7 Hz). 19F NMR
(CDCl3), : 95.5 (dd, CF3, J = 9.5 Hz, J = 0.8 Hz). On keeping
the solution of this isomer in CDCl3 at ~20 C for 4 days in the

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1747
presence of SiO2, it partially isomerizes to give a mixture of
ketones synꢀ15 (80%) and antiꢀ15 (20%).
dichloromethane (5 mL), a solution of nitroalkene 1a (1.90 g,
10.0 mmol) in anhydrous dichloromethane (5 mL) was added
dropwise over a period of 15 min at ~20 C. The reaction mixꢀ
ture was refluxed with stirring for 3 h and the solvent was reꢀ
moved in vacuo. The brown oily residue was dissolved in benzꢀ
ene (5 mL) and hexane (2 mL) was added. The precipitate formed
was filtered off and recrystallized from dichloromethane—hexꢀ
ane (1 : 2) to give compound 19b in the yield of 0.92 g (34%),
m.p. 100—111 C, white powder. Found (%): C, 36.10; H, 3.84;
N, 7.83. C16H21Cl6N3O4. Calculated (%): C, 36.12; H, 3.98;
N, 7.90. IR, /cm–1: 1625, 1573, 1563, 1453, 1417, 1375.
1H NMR (CDCl3), : 1.54—1.72 (m, 6 H, 3 CH2); 1.72—1.82
(m, 1 H, CHH); 2.12—2.23 (m, 1 H, CHH); 2.40—2.51 (m, 1 H,
CHH); 2.72—2.80 (m, 1 H, CHH); 2.80—2.88 (m, 2 H,
N(CHH)2); 3.14—3.23 (m, 2 H, N(CHH)2); 3.87 (m, 1 H, H(5));
4.14 (dt, 1 H, H(1´), J = 7.3 Hz, J = 1.8 Hz); 4.18 (dd, 1 H,
H(2´a), J = 15.0 Hz, J = 1.8 Hz); 4.76 (dd, 1 H, H(1), J = 10.3 Hz,
J = 3.3 Hz); 4.77 (dd, 1 H, H(2´b), J = 15.0 Hz, J = 7.3 Hz); 4.86
(dd, 1 H, H(2a), J = 11.8 Hz, J = 10.3 Hz); 5.09 (dd, 1 H,
H(2b), J = 11.8 Hz, J = 3.3 Hz).
(1´S*,5R*,1S*)ꢀ4ꢀ{2,5ꢀBis[2ꢀnitroꢀ1ꢀ(trichloromethyl)ꢀ
ethyl]cyclopentenꢀ1ꢀyl}morpholine (19c) was synthesized similarꢀ
ly to compound 19b starting from nitroalkene 1a and enamine
2d. Yield 1.33 g (49%), m.p. 137—138 C, white powder.
Found (%): C, 33.68; H, 3.47; N, 7.65. C15H19Cl6N3O5. Calcuꢀ
lated (%): C, 33.74; H, 3.59; N, 7.87. IR, /cm–1: 1625, 1578,
1558, 1456, 1443, 1424, 1378. 1H NMR (CDCl3), : 1.83 (ddd, 1 H,
H(3a), J = 14.6 Hz, J = 9.7 Hz, J = 4.9 Hz); 2.20 (dtd, 1 H,
H(4a), J = 15.6 Hz, J = 9.7 Hz, J = 5.8 Hz); 2.48 (dddd, 1 H,
H(4b), J = 15.6 Hz, J = 9.7 Hz, J = 5.8 Hz, J = 2.6 Hz); 2.82
(ddd, 1 H, H(3b), J = 14.6 Hz, J = 9.7 Hz, J = 4.9 Hz); 2.93
(ddd, 2 H, N(CHH)2, J = 11.2 Hz, J = 5.8 Hz, J = 3.5 Hz); 3.28
(ddd, 2 H, N(CHH)2, J = 11.2 Hz, J = 5.8 Hz, J = 3.5 Hz);
3.74—3.85 (m, 4 H, O(CH2)2); 3.86 (m, 1 H, H(5)); 4.16 (dt, 1 H,
H(1´), J = 7.7 Hz, J = 2.0 Hz); 4.19 (dd, 1 H, H(2´a), J = 15.8 Hz,
J = 2.2 Hz); 4.75 (dd, 1 H, H(1), J = 10.4 Hz, J = 3.3 Hz); 4.79
(dd, 1 H, H(2´b), J = 15.8 Hz, J = 7.7 Hz); 4.87 (dd, 1 H,
H(2a), J = 12.1 Hz, J = 10.4 Hz); 5.10 (dd, 1 H, H(2b),
J = 12.1 Hz, J = 3.3 Hz). 1H NMR (C6D6), : 1.24—1.32 (m, 1 H,
H(3a)); 1.56 (dtd, 1 H, H(4a), J = 15.6 Hz, J = 9.8 Hz,
J = 5.9 Hz); 1.97 (dddd, 1 H, H(4b), J = 15.6 Hz, J = 9.8 Hz,
J = 5.9 Hz, J = 2.6 Hz); 2.32 (ddd, 1 H, H(3b), J = 14.6 Hz,
J = 9.8 Hz, J = 4.7 Hz); 2.65 (ddd, 2 H, N(CHH)2, J = 11.4 Hz,
J = 5.8 Hz, J = 3.5 Hz); 2.93 (ddd, 2 H, N(CHH)2, J = 11.4 Hz,
J = 5.8 Hz, J = 3.5 Hz); 3.37 (m, 1 H, H(5)); 3.47—3.56 (m, 4 H,
O(CH2)2); 3.93 (dd, 1 H, H(2´a), J = 15.1 Hz, J = 2.2 Hz); 4.13
(dt, 1 H, H(1´), J = 6.9 Hz, J = 2.2 Hz); 4.24 (dd, 1 H, H(2a),
J = 12.4 Hz, J = 10.3 Hz); 4.39 (dd, 1 H, H(2´b), J = 15.1 Hz,
J = 6.9 Hz); 4.40 (dd, 1 H, H(2b), J = 12.4 Hz, J = 3.6 Hz); 4.58
(dd, 1 H, H(1), J = 10.3 Hz, J = 3.6 Hz).
(2S*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trifluoromethyl)ethyl]cyclohexanꢀ
one (antiꢀ15) was not isolated in individual state. Hydrolysis of
enamine 14 containing 18% of isomer synꢀ13 (HCl, H2O, EtOH,
4 h, 40 C) resulted in a mixture of antiꢀ15, synꢀ15, and 14 in
a ratio of 46 : 45 : 9, yellowish oil (yield of 96%, 19F NMR data).
1H NMR (CDCl3), : 1.41 (qd, 1 H, CHH, J= 12.9 Hz, J = 3.6 Hz);
1.50—2.50 (m, 7 H, CHH, 3 CH2); 2.89—2.96 (m, 1 H, H(2));
4.00—4.12 (m, 1 H, H(1´)); 4.45 (dd, 1 H, H(2´a), J = 14.1 Hz,
J = 4.0 Hz); 4.53 (dd, 1 H, H(2´b), J = 14.1 Hz, J = 8.3 Hz).
19F NMR (CDCl3), : 93.3 (d, CF3, J = 9.6 Hz).
(5S*,1´R*)ꢀ1ꢀMorpholinoꢀ5ꢀ[2ꢀnitroꢀ1ꢀ(trifluoromethyl)ꢀ
ethyl]ꢀ1ꢀcyclopentene (antiꢀ16) and 1ꢀmorpholinoꢀ2ꢀ[2ꢀnitroꢀ1ꢀ
(trifluoromethyl)ethyl]ꢀ1ꢀcyclopentene (17). To a stirred soluꢀ
tion of enamine 2d (1.53 g, 10.0 mmol) in anhydrous chloroform
(3 mL), a solution of nitropropene 1b (1.41 g, 10.0 mmol) in
anhydrous chloroform (3 mL) was added dropwise over a period
of 15 min at 10—15 C. The reaction mixture was stirred at
~20 C for 2 h. The removal of the solvent in vacuo quantitativeꢀ
ly afforded a mixture of antiꢀ16 and 17 in a ratio of 3 : 1, yellow
oil. IR, /cm–1: 1637, 1564, 1379. 1H NMR (C6D6), : 1.20—2.10
(m, 4 H, 2 CH2); 2.18 (ddd, 2 H, N(CHH)2, J = 11.7 Hz,
J = 6.1 Hz, J = 3.4 Hz); 2.41 (ddd, 2 H, N(CHH)2, J = 11.7 Hz,
J = 6.1 Hz, J = 3.4 Hz); 2.94—3.00 (m, 1 H, H(5)); 3.37—3.52
(m, 4 H, O(CH2)2); 3.78 (dd, 1 H, H(2´a), J = 14.3 Hz, J = 3.2 Hz);
3.97—4.06 (m, 1 H, H(1´)); 4.02 (dd, 1 H, H(2´b), J = 14.3 Hz,
J = 7.6 Hz); 4.30 (dd, 1 H, H(2), J = 3.8 Hz, J = 2.2 Hz) (antiꢀ16);
1.20—2.10 (m, 6 H, 3 CH2); 2.32 (t, 4 H, N(CH2)2, J = 4.6 Hz);
3.35—3.44 (m, 4 H, O(CH2)2); 3.95 (dd, 1 H, H(2´a),
J = 12.2 Hz, J = 4.8 Hz); 4.03 (dd 1 H, H(2´b), J = 12.2 Hz,
J = 10.2 Hz); 4.52 (quintd, 1 H, H(1´), J = 9.9 Hz, J = 4.8 Hz)
(17). 1H NMR (CDCl3), : 1.70—2.70 (m, 6 H, 2 CH2, N(CHH)2);
2.87—2.94 (m, 2 H, N(CHH)2); 3.36—3.42 (m, 1 H, H(5));
3.50—3.62 (m, 1 H, H(1´)); 3.68—3.80 (m, 4 H, O(CH2)2); 4.31
(dd, 1 H, H(2´a), J = 14.4 Hz, J = 2.7 Hz); 4.55 (dd, 1 H,
H(2´b), J = 14.4 Hz, J = 7.9 Hz); 4.76 (dd, 1 H, H(2), J = 3.9 Hz,
J = 2.3 Hz) (antiꢀ16). 19F NMR (C6D6), : 94.1 (d, CF3,
J = 9.8 Hz) (antiꢀ16); 95.5 (d, CF3, J = 9.6 Hz) (17). 19F NMR
(CDCl3), : 92.6 (d, CF3, J = 9.6 Hz) (antiꢀ16); 94.3 (d, CF3,
J = 8.8 Hz) (17).
(2S*,1´R*ꢀ and 2R*,1´R*)ꢀ2ꢀ[2ꢀNitroꢀ1ꢀ(trifluoromethyl)ꢀ
ethyl]cyclopentanones (antiꢀ18, synꢀ18). A mixture of diastereoꢀ
meric ketones were obtained from compounds 2d and 1b followꢀ
ing the procedure B described for isomers 12. Yield 1.53 g (68%),
yellowish oil, b.p. 108—110 C (2 Torr) (cf. Ref. 30: b.p.
105—107 C (3 Torr)). Found (%): C, 42.14; H, 4.48; N, 6.47.
C8H10F3NO3. Calculated (%): C, 42.67; H, 4.47; N, 6.22. IR,
/cm–1: 1746, 1565, 1381. 1H NMR (CDCl3), : 1.60—2.50
(m, 6 H, 3 CH2); 2.62 (ddd, 1 H, H(2), J = 11.3 Hz, J = 8.3 Hz,
J = 2.7 Hz); 3.83—3.94 (m, 1 H, H(1´)); 4.30 (dd, 1 H, H(2´a),
J = 13.8 Hz, J = 5.5 Hz); 4.62 (dd, 1 H, H(2´b), J = 13.8 Hz,
J = 7.5 Hz) (antiꢀ18 (54%)); 1.60—2.50 (m, 7 H, 3 CH2, H(2));
3.56 (qq, 1 H, H(1´), J = 8.8 Hz, J = 6.3 Hz); 4.68 (dd, 1 H,
H(2´a), J = 14.4 Hz, J = 6.2 Hz); 4.97 (dd, 1 H, H(2´b), J = 14.4 Hz,
J = 6.3 Hz) (synꢀ18 (46%)). 19F NMR (CDCl3), : 92.7 (d, CF3,
J = 9.2 Hz) (antiꢀ18 (54%)); 94.5 (d, CF3, J = 8.8 Hz) (synꢀ18
(46%)).
(1´S*,5R*,1R*,2´S)ꢀ4ꢀ{2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ꢀ
propyl]ꢀ5ꢀ[2ꢀnitroꢀ1ꢀ(trichloromethyl)ethyl]cyclopentenꢀ1ꢀyl}ꢀ
morpholine (19d). To a stirred solution of enamine 2d (0.77 g,
5.0 mmol) in anhydrous dichloromethane (5 mL), a solution of
nitroalkene 1a (0.95 g, 5.0 mmol) in anhydrous dichloromethane
(5 mL) was added dropwise over a period of 15 min at ~20 C.
The mixture was stirred for 30 min followed by dropwise addiꢀ
tion of a solution of nitroalkene 1c (1.02 g, 5.0 mmol) in anhydrꢀ
ous dichloromethane (5 mL) within 15 min at ~20 C. The reacꢀ
tion mixture was refluxed for 3 h and the solvent was removed
in vacuo. Ethanol (5 mL) was added to the brown oily residue;
(1´S*,5R*,1S*)ꢀ1ꢀ{2,5ꢀBis[2ꢀnitroꢀ1ꢀ(trichloromethyl)ꢀ
ethyl]cyclopentenꢀ1ꢀyl}piperidine (19b). To a stirred solution of
Nꢀcyclopentenylpiperidine (0.76 g, 5.0 mmol) in anhydrous

1748
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
Korotaev et al.
the precipitate fromed was filtered off, and washed with hexane.
Yield 1.13 g (41%), m.p. 163—164 C, colorless prisms.
Found (%): C, 35.05; H, 3.95; N, 7.84. C16H21Cl6N3O5. Calcuꢀ
lated (%): C, 35.06; H, 3.86; N, 7.67. IR, /cm–1: 1632, 1554,
1454, 1420, 1381, 1359. 1H NMR (CDCl3), : 1.62—1.72 (m, 1 H,
CHH); 1.93 (d, 3 H, Me, J = 6.7 Hz); 2.17 (dtd, 1 H, CHH,
J = 14.3 Hz, J = 9.5 Hz, J = 4.7 Hz); 2.50—2.70 (m, 2 H, CH2);
2.98 (ddd, 2 H, N(CHH)2, J = 11.2 Hz, J = 6.0 Hz, J = 3.0 Hz);
3.22 (ddd, 2 H, N(CHH)2, J = 11.2 Hz, J = 5.8 Hz, J = 3.2 Hz);
3.74—3.85 (m, 5 H, O(CH2)2, H(5)); 4.12 (dd, 1 H, H(2a´),
J = 15.5 Hz, J = 1.5 Hz); 4.14 (m, 1 H, H(1´)); 4.59 (d, 1 H, H(1),
J = 9.6 Hz); 4.73 (dd, 1 H, H(2b´), J = 15.5 Hz, J = 7.7 Hz); 5.24
(dq, 1 H, H(2), J = 9.6 Hz, J = 6.7 Hz). 1H NMR (C6D6),
: 1.22—1.35 (m, 1 H, CHH); 1.33 (d, 3 H, Me, J = 6.7 Hz);
1.64 (dtd, 1 H, CHH, J = 14.6 Hz, J = 9.5 Hz, J = 5.0 Hz);
2.20—2.37 (m, 2 H, CH2); 2.76 (dt, 2 H, N(CHH)2, J = 11.7 Hz,
J = 4.5 Hz); 2.93 (dt, 2 H, N(CHH)2, J = 11.7 Hz, J = 4.5 Hz);
3.37 (br.t, 1 H, H(5), J = 7.0 Hz); 3.56 (t, 4 H, O(CH2)2, J = 4.5 Hz);
4.07 (dd, 1 H, H(2a´), J = 15.3 Hz, J = 1.2 Hz); 4.18 (dt, 1 H,
H(1´), J = 7.3 Hz, J = 1.2 Hz); 4.46 (dd, 1 H, H(2b´), J = 15.3 Hz,
J = 7.3 Hz); 4.47 (d, 1 H, H(1), J = 9.4 Hz); 4.79 (dq, 1 H,
H(2), J = 9.4 Hz, J = 6.7 Hz).
ine (19e) was synthesized similarly to compound 19d with addiꢀ
tion of nitroalkene 1b (0.71 g, 5.0 mmol) on the second step.
Yield 1.56 g (32%), m.p. 173—174 C, white powder. Found (%):
C, 37.20; H, 3.80; N, 8.62. C15H19Cl3F3N3O5. Calculated (%):
C, 37.17; H, 3.95; N, 8.67. IR, /cm–1: 1635, 1566, 1558, 1434,
1380. 1H NMR (CDCl3), : 1.68—2.10 (m, 2 H, CH2); 2.42—2.62
(m, 2 H, CH2); 2.97 (ddd, 2 H, N(CHH)2, J = 11.2 Hz,
J = 5.8 Hz, J = 3.2 Hz); 3.20 (ddd, 2 H, N(CHH)2, J = 11.2 Hz,
J = 5.8 Hz, J = 3.2 Hz); 3.38 (m, 1 H, H(5)); 3.59 (quintt, 1 H,
H(1´), J = 9.1 Hz, J = 2.5 Hz); 3.68—3.80 (m, 4 H, O(CH2)2);
4.30 (dd, 1 H, H(2´a), J = 14.3 Hz, J = 2.2 Hz); 4.63 (dd, 1 H,
H(2´b), J = 14.3 Hz, J = 8.8 Hz); 4.73 (dd, 1 H, H(2a),
J = 11.3 Hz, J = 10.3 Hz); 4.92 (dd, 1 H, H(1), J = 10.3 Hz,
J = 3.1 Hz); 4.98 (dd, 1 H, H(2b), J = 11.3 Hz, J = 3.1 Hz).
19F NMR (CDCl3), : 92.3 (d, CF3, J = 9.3 Hz).
Xꢀray diffraction analyses of compounds 9, synꢀ15 and 19d
were performed on a single crystal automatized Xcalibur 3 difꢀ
fractometer equipped with CCD detector following the standard
procedure (T = 295(2) K for compounds 9, 19d and 120(2) K for
compound synꢀ15), MoꢀK irradiation, graphite monochromaꢀ
tor,  scanning mode, scanning step of 1). The structures were
solved by direct method using the SHELX97 program packꢀ
age.31 All nonꢀhydrogen atoms were positioned independently
by anisotropic approximation, the hydrogen atoms were placed
(1´S*,5R*,1S*)ꢀ4ꢀ{2ꢀ[2ꢀNitroꢀ1ꢀ(trichloromethyl)ethyl]ꢀ5ꢀ
[2ꢀnitroꢀ1ꢀ(trifluoromethyl)ethyl]cyclopentenꢀ1ꢀyl}morpholꢀ
Table 3. Crystallographic data and Xꢀray diffraction experiment parameters for compounds 9, synꢀ15, and 19d
Parameter
9
synꢀ15
19d
Crystal system
Space group
Monoclinic
P21/c
Triclinic
P–1
Triclinic
P–1
a/Å
b/Å
c/Å
/deg
7.6720(3)
26.3710(7)
7.7406
5.6773(6)
9.3221(16)
10.8453(10)
65.899(13)
81.626(8)
82.085(11)
516.41(11)
2
11.7494(17)
14.8139(13)
14.870(2)
87.897(12)
67.026(12)
80.397(10)
2348.3(5)
4
90
/deg
109.149(3)
90
1479.41(8)
4
1.543
0.627
/deg
V/Å3
Z
dcalc/g cm–3
/mm–1
1.538
0.148
1.550
0.764
F(000)
712
248
1120
Scanning rang on /deg
h, k, l Indices
2.89—28.28
–7 < h < 10,
–35 < k < 33,
–10 < l < 10
7869
3.64—30.51
–8 < h < 7,
–13 < k < 13,
–13 < l < 15
3546
2.84—26.37
–14 < h < 14,
–18 < k < 16,
–18 < l < 17
10948
Number of measured reflections
Number of independent
3542
3071
9333
reflections
Reflections with I > 2(I)
(Rint = 0.0533)
2587
(Rint = 0.0133)
2105
(Rint = 0.0418)
3015
Completeness of
96.4
97.3
97.2
data collection (%)
S on F2
( = 26.00)
1.003
( = 26.00)
1.007
( = 26.37)
1.002
R Factors (I > 2(I))
R1
wR2
0.0439
0.1153
0.0324
0.0791
0.0541
0.0990
R Factors (on all reflections)
R1
wR2
0.0574
0.1196
0.393/–0.446
0.0518
0.0823
0.391/–0.247
0.1738
0.1077
0.467/–0.294
 (max/min)/e Å–3
e

Reactions of trihalonitropropenes with enamines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 9, September, 2012
1749
in geometrically calculated positions and refined in the riding
model with fixed thermal parameters. The main parameters of
Xꢀray diffraction experiments are given in Table 3. In structure
19d, the morpholine cycle of one of the crystallographically inꢀ
dependent molecule are in the chair conformation. The cycle of
the second independent molecule are disordered in two posiꢀ
tions with population of 0.5, in which the substituent at the morꢀ
pholine nitrogen adopts pseudoꢀaxial and pseudoꢀequatorial
positions. The details of Xꢀray experiments for compounds 9,
synꢀ15, and 19d were deposited with the Cambridge Crystalloꢀ
graphic Data Center (CCDC 860867, 860866, 863734, resꢀ
pectively).
13. M. S. Klenov, A. V. Lesiv, Yu. A. Khomutova, I. D. Nesteꢀ
rov, S. L. Ioffe, Synthesis, 2004, 1159.
14. M. Molteni, R. Consonni, T. Giovenzana, L. Malpezzi,
M. Zanda, J. Fluorine Chem., 2006, 127, 901.
15. V. Yu. Korotaev, A. Yu. Barkov, P. A. Slepukhin, V. Ya.
Sosnovskikh, Russ. Chem. Bull. (Int. Ed.), 2011, 60, 143
[Izv. Akad. Nauk, Ser. Khim., 2011, 137].
16. V. Yu. Korotaev, A. Yu. Barkov, P. A. Slepukhin, M. I.
Kodess, V. Ya. Sosnovskikh, Mendeleev Commun., 2011,
21, 112.
17. V. Yu. Korotaev, A. Yu. Barkov, P. A. Slepukhin, M. I.
Kodess, V. Ya. Sosnovskikh, Tetrahedron Lett., 2011, 52, 5764.
18. V. Yu. Korotaev, A. Yu. Barkov, P. A. Slepukhin, M. I.
Kodess, V. Ya. Sosnovskikh, Tetrahedron Lett., 2011,
52, 3029.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 11ꢀ03ꢀ00126).
19. G. Pitacco, E. Valentin, Tetrahedron Lett., 1978, 2339.
20. P. Nitti, G. Pitacco, V. Rinaldi, E. Valentin, Croat. Chem.
Acta, 1986, 59, 165.
References
21. F. P. Colonna, E. Valentin, G. Pitacco, A. Risaliti, Tetraꢀ
hedron, 1973, 29, 3011.
22. S. Brückner, G. Pitacco, E. Valentin, J. Chem. Soc., Perkin
Trans. 2, 1975, 1804.
23. M. Calligaris, G. Pitacco, E. Valentin, E. Zotti, J. Org. Chem.,
1977, 42, 2720.
24. F. Asaro, G. Pitacco, E. Valentin, Tetrahedron, 1987,
43, 3279.
25. S. Daneo, G. Pitacco, A. Risaliti, E. Valentin, Tetrahedron,
1982, 38, 1499.
26. A. Ya. Aizikovich, V. Yu. Korotaev, L. E. Yaroslavtseva,
Zh. Org. Khim., 1994, 30, 989 [Russ. J. Org. Chem.
(Engl. Transl.), 1994, 30, 1045].
27. F. Brower, H. Burkett, J. Am. Chem. Soc., 1953, 75, 1082.
28. H. Shechter, D. E. Ley, E. B. Jr. Roberson, J. Am. Chem.
Soc., 1956, 78, 4984.
1. A. Risaliti, M. Forchiassin, E. Valentin, Tetrahedron Lett.,
1966, 6331.
2. A. Risaliti, M. Forchiassin, E. Valentin, Tetrahedron, 1966,
24, 1889.
3. G. Pitacco, A. Pizzioli, E. Valentin, Synthesis, 1996, 242.
4. M. E. Kuehne, L. Foley, J. Org. Chem., 1965, 30, 4280.
5. K. C. Brannock, A. Bell, R. D. Burpitt, C. A. Kelly, J. Org.
Chem., 1964, 29, 801.
6. F. Felluga, P. Nitti, G. Pitacco, E. Valentin, Tetrahedron,
1989, 45, 5667.
7. A. T. Nielsen, T. G. Archibald, Tetrahedron, 1970, 26, 3475.
8. F. Felluga, P. Nitti, G. Pitacco, E. Valentin, Tetrahedron,
1989, 45, 2099.
9. P. Bradamante, G. Pitacco, A. Risaliti, E. Valentin, Tetraꢀ
hedron Lett., 1982, 23, 2683.
10. S. L. Ioffe, in Nitrile Oxides, Nitrones and Nitronates in Orꢀ
ganic Synthesis: Novel Strategies in Synthesis, 2 ed., Ed.
H. Feuer, J. Wiley and Sons, Chichester, 2008, 435.
11. D. Seebach, I. M. Lyapkalo, R. Dahinden, Helv. Chim. Acta,
1999, 82, 1829.
29. S. Hünig, W. Lendle, Chem. Ber., 1960, 93, 909.
30. A. Ya. Aizikovich, I. T. Bazyl´, Zh. Org. Khim., 1987, 23,
1330 [J. Org. Chem. USSR (Engl. Transl.), 1987, 23, 1203].
31. G. M. Sheldrick, Acta Crystallogr., Sect. A, 2008, 64, 112.
12. V. O. Smirnov, S. L. Ioffe, A. A. Tishkov, Yu. A. Khomuꢀ
tova, I. D. Nesterov, M. Yu. Antipin, W. A. Smit, V. A.
Tartakovsky, J. Org. Chem., 2004, 69, 8485.
Received February 1, 2012;
in revised form June 27, 2012