Reaction of ω-nitrostyrene with diethyl malonate in the presence of chiral nickel(II) complexes

Article abstract of DOI:10.1134/S1070428012120056

Single-ligand complexes of nickel(II) with chiral diamines based on L-proline and (S)-camphor efficiently catalyze addition of diethyl malonate to ω-nitrostyrene in the presence of 1 equiv of triethylamine as co-catalyst. The reaction enantioselectivity d

Full text of DOI:10.1134/S1070428012120056

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1526–1529. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.N. Reznikov, Yu.N. Klimochkin, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 12, pp. 1555–1558.
Reaction of ω-Nitrostyrene with Diethyl Malonate
in the Presence of Chiral Nickel(II) Complexes
A. N. Reznikov and Yu. N. Klimochkin
Samara State Technical University, ul. Molodogvardeiskaya 244, Samara, 443100 Russia
e-mail: orgchem@samgtu.ru
Received February 8, 2012
Abstract—Single-ligand complexes of nickel(II) with chiral diamines based on L-proline and (S)-camphor
efficiently catalyze addition of diethyl malonate to ω-nitrostyrene in the presence of 1 equiv of triethylamine as
co-catalyst. The reaction enantioselectivity depends on the chiral ligand structure.
DOI: 10.1134/S1070428012120056
Addition of diethyl malonate to nitroalkenes under-
lies procedures for the synthesis of a number of neuro-
tropic agents, specifically γ-aminobutyric acid deriva-
tives, and provides a convenient synthetic approach to
five-membered nitrogen-containing heterocycles via
subsequent reduction and cyclization of the addition
products [1–3]. Enantioselectivity of the addition is
achieved by the use of organocatalysts (mainly difunc-
tional thiourea derivatives) [4] or chiral transition
metal complexes [5]. However, the required metal
catalysts have a complex structure and are therefore
difficultly accessible, whereas high concentrations
mixed-ligand complex III (Scheme 1). Thus one di-
amine ligand acts as a base. With a view to reduce
consumption of a chiral ligand it seemed promising to
use an achiral base as co-catalyst in enantioselective
Michael addition. In the present work we examined the
catalytic activity of nickel(II) complexes with diamine
ligands V, VII, and IX based on accessible natural
compounds [L-proline and (S)-camphor] in order to
verify the above assumption and elucidate the effect of
ligand environment on the catalytic properties.
Nickel(II) complexes VI, VIII, and X were syn-
thesized by reactions of chiral diamines V, VII, and IX
with NiCl or NiBr (Scheme 2). The catalytic activity
(
5 mol % and more) of organocatalysts are necessary.
2
2
of complexes VI, VIII, and X was assessed using the
reaction of ω-nitrostyrene (XI) with diethyl malonate
It is known that the nickel(II) complex with
R,R)-trans-N,N′-dibenzylcyclohexane-1,2-diamine as
catalyst ensures high enantioselectivity in the addition
of some 1,3-dicarbonyl compounds to nitroalkenes
6, 7]. It was shown that Ni(II) complexes like I having
two chiral ligands exhibit a high catalytic activity in
the above reaction and that single-ligand complexes
are weakly active. The authors presumed that the
second ligand deprotonates 1,3-dicarbonyl compounds
(
(II) as model process (see table; Scheme 3). This reac-
tion was selected taking into account that it may be
regarded as the key step in the synthesis of such phar-
maceuticals as (R)-phenibut and (R)-phenotropil [7]
and that the use of substituted ω-nitrostyrene deriva-
tives in analogous reaction ensures preparation of
intermediate products for the synthesis of (R)-rolipram
[
[1] and (R)-baclofen [2].
(
e.g., II) with simultaneous removal of one of the two
chiral ligands from the coordination sphere as onium
All the examined complexes turned out to be
cation IV and formation of acetylacetonate-type
inactive in the Michael addition of diethyl malonate to
Scheme 1.
Bzl
Bzl Bzl
Bzl
NH
OEt
OEt
Br
Ni
Br
O
O
NH2
NH
NH
O
O
+
Br–
+
Ni
EtO
OEt
NH
NH
NH
Bzl
NH
Bzl
Bzl Bzl
I
II
III
IV
1
526

REACTION OF ω-NITROSTYRENE WITH DIETHYL MALONATE
1527
Scheme 2.
N
NiCl2
NH
N
Ni
Cl
Cl
N
H
V
VI
N
NiCl2
NH
N
Ni
Cl
N
H
Cl
VIII
Me
VII
Me
Me
Me
Br
Br
Me
Me
Me
Me
NiBr2
Me
Me
Me
Me
Ni
NH HN
NH
NH
IX
X
ω-nitrostyrene. However, addition to the reaction mix-
ture of 1 equiv of an achiral base (triethylamine)
sharply enhanced the catalytic activity of complexes
VI, VIII, and X. In a control experiment, i.e., in the
reaction of ω-nitrostyrene with diethyl malonate in the
presence of 2 mol % of triethylamine, the conversion
of ω-nitrostyrene was less than 5%. This means that
the contribution of base catalysis to the overall process
is small. The use of the catalytic system magnesium
bisoxazoline complex–N-methylmorpholine showed
that coordination of dicarbonyl compound to the metal
complex (which is a Lewis acid) increases acidity of
the former, thus facilitating its deprotonation with
amine (co-catalyst) with formation of the correspond-
ing enolate [1]. Activation of Ni(II) complexes with
triethylamine may be rationalized by the action of the
latter as enolizing agent in the formation of acetyl-
acetonate-type coordination compounds that are the
true catalysts in the addition of ω-nitrostyrene to
diethyl malonate according to the mechanism proposed
previously [7].
to predominant formation of (S)-enantiomer (S)-XII.
Its enantiomeric excess (ee) depends on the chiral
ligand nature. The highest ee value was obtained using
complexes with L-proline-based ligands V and VII,
while the size of the second nitrogen-containing ring in
the ligand (pyrrolidine or piperidine) was insignificant.
The reaction catalyzed by complex X with (S)-cam-
phor ligand IX was characterized by lower enantio-
selectivity. Presumably, the reduction of ee in going
from ligands V and VII to IX is related to lower con-
formational rigidity of the chelate ring in Ni(II) com-
plexes with a longer linker connecting the coordination
centers in the diamine ligand.
To conclude, we have demonstrated that nickel(II)
complexes with chiral diamine ligands based on acces-
sible natural compounds [L-proline and (S)-camphor]
effectively catalyze Michael addition of diethyl malo-
nate to ω-nitrostyrene; in this reaction, activation of
Catalytic activity of Ni(II) complexes in the reaction of
ω-nitrostyrene with diethyl malonate (20°C, 72 h, 2 mol %
of the catalyst with respect to ω-nitrostyrene)
Addition of diethyl malonate to ω-nitrostyrene,
catalyzed by Ni(II) complexes VI, VIII, and X, leads
a
Catalyst
VI
Conversion, % Yield, % ee (S)-XII, %
Scheme 3.
0<5
100
0<5
100
0<5
100
0<5
00
90
00
87
00
88
00
–
64.6
–
O
O
NO2
3
VI + Et N
+
Ph
EtO
OEt
VIII
XI
II
VIII + Et
3
N
65.0
–
O
O
O
O
X
[
Ni]
EtO
OEt
+
EtO
OEt
X + Et
Et
3
N
30.4
–
NO2
NO2
3
N
Ph
(
Ph
(S)-XII
a
R)-XII
After isolation by flash chromatography.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

1
528
REZNIKOV, KLIMOCHKIN
single-ligand Ni(II) complexes via addition of 1 equiv
of an achiral base (triethylamine) is required. The
reaction enantioselectivity is determined by the chiral
diamine ligand nature, and conformational rigidity of
the resulting chelates is a necessary condition ensuring
high enantioselectivity.
1040, 860, 780. Found, %: C 40.49; H 7.24; N 9.21.
C H Cl N Ni. Calculated, %: C 40.32; H 6.77;
N 9.40.
1
0
20
2
2
Dibromo{N,N′-bis[(1S,2S,4S)-1,7,7-trimethylbicy-
clo[2.2.1]heptan-2-yl]ethane-1,2-diamine}nickel(II)
(
(
X) was synthesized in a similar way from 103 mg
0.31 mmol) of compound IX and 60 mg (0.27 mmol)
EXPERIMENTAL
of nickel(II) bromide. Yield 50 mg (34%), violet
–
1
crystals. IR spectrum (KBr), ν, cm : 3435, 3032,
920, 1552, 1379, 1066. Found, %: C 48.01; H 7.44;
N 5.01. C H Br N Ni. Calculated, %: C 47.95;
The enantiomeric composition of the addition prod-
ucts was determined by HPLC using a Waters chro-
matograph equipped with a Waters 2487 UV detector
and a Waters 2414 refractive index detector (stationary
chiral phase Chiralcel AD; analysis conditions for
compound XII: eluent hexane−propan-2-ol, 95:5, flow
rate 1.0 ml/min). The elemental compositions were
determined on a EuroVector EA 3000 analyzer. The IR
spectra were measured on a Shimadzu IR Affinity-1
2
2
2
40
2
2
H 7.32; N 5.08.
Catalytic addition of diethyl malonate to ω-ni-
trostyrene. Nickel(II) complex VI, VIII, or X, 4.42×
–2
–2
1
0 mol, and triethylamine, 4.5 mg (4.42×10 mmol),
were added to a solution of 0.33 g (2.21 mmol) of
ω-nitrostyrene and 0.4 ml (0.42 g, 2.63 mmol) of
diethyl malonate in 1 ml of toluene. The mixture was
kept for 72 h at 20°C, the solvent was distilled off
under reduced pressure, and the residue was subjected
to flash chromatography on silica gel (Kieselgel 60,
1
13
instrument. The H and C NMR spectra were record-
ed on a Jeol JNM-ECX400 spectrometer at 399.78 and
1
00.53 MHz, respectively, using CDCl as solvent and
3
reference. The mass spectra (electron impact, 70 eV)
were obtained on a Finnigan Trace DCQ GC–MS
system (SGE BPX-5 capillary column, 30 m×0.32 mm).
The optical rotations were determined on a Rudolph
Research Analytical polarimeter.
0
.04–0.063 mm) using methylene chloride as eluent.
The results of control experiment with triethylamine
are given in table.
Diethyl 2-(2-nitro-1-phenylethyl)malonate (XII).
1
13
The H and C NMR spectra of XII were consistent
Compounds V, VII, and IX were prepared accord-
ing to the procedures described in [8–10].
with those reported in [7]. Mass spectrum, m/z (I , %):
rel
+
3
09 [M] , 263 (12), 218 (12), 190 (13), 189 (100), 171
Dichloro{1-[(2S)-pyrrolidin-2-ylmethyl]pyrroli-
dine}nickel(II) (VI). A solution of 51.2 mg
(58), 161 (56), 145 (30), 133 (22), 131 (20), 117 (28),
115 (70), 105 (15), 104 (55), 103 (34), 91 (26), 78
(15), 77 (20). Retention time, min: (R)-XII), 18.5;
(S)-XII, 43.1.
(
0.33 mmol) of compound V and 69.0 mg (0.29 mmol)
of nickel(II) chloride hexahydrate in 5 ml of aceto-
nitrile was heated for 30 min under reflux. The mixture
was evaporated under reduced pressure, the residue
was dissolved in 25 ml of methylene chloride, the solu-
tion was filtered from a small amount of undissolved
material, and the filtrate was evaporated. The residue
was ground with 20 ml of diethyl ether, and the bright
yellow precipitate was filtered off, washed with 10 ml
of diethyl ether, and dried. Yield 50 mg (39%). IR
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (Federal Special-Puprose Program
“
Studies and Developments in the Priority Fields of
Russian Science and Technology 2007–2013,” state
contract no. 16.512.11.2011, Feb 10, 2011) with the
use of facilities provided by the Shared Use Center at
the Samara State Technical University (program
“Study on Physicochemical Properties of Substances
and Materials”).
–
1
spectrum (KBr), ν, cm : 3250, 2950, 2866, 2780,
460, 1400, 1345, 1310, 1290, 1140, 870. Found, %:
C 38.27; H 6.80; N 9.72. C H Cl N Ni. Calculated,
1
9
18
2
2
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REACTION OF ω-NITROSTYRENE WITH DIETHYL MALONATE
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