Synthesis of novel chiral NiII complexes of dehydroalanine Schiff bases and their reactivity in asymmetric nucleophilic addition reactions. Novel synthesis of (S)-2-carboxypiperazine

Article abstract of DOI:10.1016/j.tetasy.2010.10.015

New chiral Ni^II complexes of Schiff bases of dehydroalanine with modified chiral auxiliaries (S)-2-N-[N′-(3,4-dichlorobenzyl)prolyl] aminobenzophenone (3,4-DCBPB), (S)-2-N-[N′-(3,4-dimethylbenzyl)prolyl] aminobenzophenone (3,4-DMBPB), (S)-2-N-[N′-(2-chlorobenzyl)prolyl] aminobenzophenone (2-CBPB), and (S)-2-N-[N′-(2-fluorobenzyl)prolyl]- aminobenzophenone (2-FBPB) have been synthesized. Asymmetric Michael addition reactions of primary and secondary amines and thiols to the dehydroalanine moieties of the complexes were studied. (S)-2-FBPB was found to be the best chiral auxiliary in terms of both selectivity of the reactions (de ～92-96%) and reactivity of the complexes. A novel synthetic route toward (S)-2-carboxypiperazine was developed based on the auxiliary.

Full text of DOI:10.1016/j.tetasy.2010.10.015

Tetrahedron: Asymmetry 21 (2010) 2638–2645
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of novel chiral NiII complexes of dehydroalanine Schiff bases
and their reactivity in asymmetric nucleophilic addition reactions. Novel
synthesis of (S)-2-carboxypiperazine
Ashot S. Saghiyan a, , Lala A. Stepanyan a, Luiza L. Manasyan a, Arpine V. Geolchanyan a,
⇑
Silva M. Djamgaryan a, Hrant R. Ajvazyan a, Henry A. Panosyan b, Viktor I. Maleev c, , Tatiana F. Saveleva c,
a Institute of Biotechnology of National Academy of Sciences, Republic of Armenia, 14 Gjurdjan, 0056 Yerevan, Armenia
b Molecule Structure Research Centere of National Academy of Sciences, Republic of Armenia, 26 Azatutyan, 0014 Yerevan, Armenia
c Nesmeyanov Institute of Organoelement Compounds, Vavilov 28, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
New chiral NiII complexes of Schiff bases of dehydroalanine with modified chiral auxiliaries (S)-2-N-[N0-
(3,4-dichlorobenzyl)prolyl]aminobenzophenone (3,4-DCBPB), (S)-2-N-[N0-(3,4-dimethylbenzyl)prolyl]-
aminobenzophenone (3,4-DMBPB), (S)-2-N-[N0-(2-chlorobenzyl)prolyl]aminobenzophenone (2-CBPB),
and (S)-2-N-[N0-(2-fluorobenzyl)prolyl]-aminobenzophenone (2-FBPB) have been synthesized. Asymmet-
ric Michael addition reactions of primary and secondary amines and thiols to the dehydroalanine moie-
ties of the complexes were studied. (S)-2-FBPB was found to be the best chiral auxiliary in terms of both
selectivity of the reactions (de ꢀ92–96%) and reactivity of the complexes. A novel synthetic route toward
(S)-2-carboxypiperazine was developed based on the auxiliary.
Article history:
Received 8 September 2010
Accepted 11 October 2010
Available online 20 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
of the addition of nucleophiles (amines, thiols and alcoholate ions)
to the C@C bond of the dehydroalanine moiety in the NiII com-
Non-proteinogenic
a
-amino acids can serve as building blocks
plexes of a Schiff base of dehydroalanine with a chiral auxiliary
or surrogates of proteinogenic amino acids in known physiologi-
cally active peptides, some of which possess biological activity. In
recent years, a great deal of effort has been focused on the synthe-
sis of enantiomerically pure non-proteinogenic as well as rare
(S)-2-N-[N0-benzylprolyl)aminobenzophenone (BPB)—NiII-(S)-BPB-
D
-Ala. Usually, the stereoselectivities (de) of the addition reactions
were in the range of 84–90% while the reaction took from 3 to
120 h to go to completion at ambient temperature.6–8
proteinogenic
ogenic family includes b-N-amino-substituted derivatives of
amino acids,
,b-diamino acids.2 This structural motif is widespread
a
-amino acids.1 A special branch of the non-protein-
Later we reported on the synthesis of modified chiral auxili-
aries (S)-2-N-[N0-(3,4-dichlorobenzyl)prolyl]aminobenzophenone
(3,4-DCBPB), (S)-2-[N-(N0-3,4-dimethylbenzyl) prolyl]aminobenzo-
phenone (S)-3,4-DMBPB), and (S)-2-[N-(N0-2-chlorobenzyl)prolyl]
aminobenzophenone (S)-2-CBPB) and NiII complexes of their Schiff
bases with glycine, alanine, and dehydroaminobutanoic acid. The
study of the complexes in the alkylation and nucleophilic addition
reactions clearly indicated their superior performance than the
original complexes derived from BPB in terms of both better reac-
tivity and stereoselectivity of the reactions.9,10 The best results
were found for the complexes with chiral auxiliary (S)-2-CBPB).
Even better performances were found for another auxiliary (S)-2-
N-[N0-(2-fluorobenzyl)prolyl]aminobenzophenone (2-FBPB).11 The
auxiliary derived glycine NiII complex was even more active and
its alkylation reaction with C6H5CH2Br was complete within
3 min at room temperature under standard conditions.11
L
-a-
a
among a number of molecules with therapeutic applications. Some
of the compounds are neurotoxic to animals,3a and some represent
important constituents of natural peptidic antibiotics such as
viomycin, bleomycin, Sch37137, napsamycin, lavendomycin, and
others.2 An important anti-HIV drug, indinavir is a derivative of
2-carboxypiperazine.2 Some of the amino acids have been used in
the synthesis of drugs,3b,4 in microbiology for selection of highly
active strain-producers of proteinogenic amino acids,5 etc.
A method which was previously described by us for the asym-
metric synthesis of b-substituted L-a-amino acids with aliphatic,
aromatic, and heterocyclic substituents in the side chain consisted
It could be assumed that the dehydroalanine complexes derived
from these modified chiral auxiliaries would also provide the ini-
tial material for better selectivity and efficiency of b-substituted
⇑
Corresponding author. Tel./fax: +3741 559355; fax: +3741 654183.
E-mail addresses: saghiyan@netsys.am, sagysu@netsys.am (A.S. Saghiyan),
vim@ineos.ac.ru (V.I. Maleev).
L-a-amino acid synthesis.
Fax: +7 095 1355085.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.10.015

A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
2639
Herein we report the asymmetric synthesis of b-substituted
-a
-amino acids using new modified NiII complexes of Schiff bases
L
of dehydroalanine with auxiliaries (S)-3,4-DCBPB, (S)-3,4-DMBPB,
(S)-2-CBPB, and (S)-2-FBPB. In addition, a novel synthetic route to-
ward (S)-2-carboxypiperazine has been developed.
2. Results and discussion
The dehydroalanine complexes were prepared from the initial
(R)-serine complexes 1–4, according to the earlier developed pro-
cedure for the synthesis of NiII-(S)-BPB- -Ala (see Scheme 1).9
D
The synthesis of 1–3 was described earlier9 and 4 was prepared
for the first time. Compounds NiII-(S)-3,4-DCBPB- -Ala 5, NiII-(S)-
3,4-DMBPB-
-Ala 6, NiII-(S)-2-CBPB- -Ala 7, and NiII-(S)-2-FBPB-
-Ala 8 were prepared and isolated by crystallization from a mix-
ture of acetone/heptane (1:1).
D
D
D
D
The structures of the complexes were confirmed by physical
and chemical analytical methods (see Section 4). The ORTEP draw-
ing of the X-ray determined structure of complex NiII-(S)-2-CBPB-
Figure 1. The ORTEP drawing of the X-ray determined structure of NiII-(S)-2-CBPB-
D
-Ala 7.
D
-Ala 7 is presented in Figure 1.
An important feature of the complex NiII-(S)-2-CBPB-
D-Ala is
the significant puckering of the chelate rings and a short Cl–Ni dis-
tance.3.086 Å. The latter may hint at a kind of electrostatic interac-
tion of the partially positively charged Ni-atom and negatively
charged end of the C–Cl bond dipole.
suring the sign of the specific rotation of the complexes at
589 nm, as was previously done for similar complexes of the same
amino acids based on the unmodified auxiliary (S)-BPB.6,7
The diastereomeric compositions of the products of the nucleo-
philic additions were determined by chiral GLC or HPLC enantio-
meric analyses of the amino acids recovered from the reaction
mixture of diastereomeric complexes before their separation by
chromatography. 1H NMR spectroscopy was also employed for
the same purpose. In this case, the ratio of the integral intensities
of the resonances of methylene protons of N-benzyl groups reflects
the ratio of the diastereoisomers in the mixture. The results are
shown in Table 1.
The Michael additions of imidazole, methylamine, benzylamine,
ethanolamine, diethanolamine, isopropylamine, and 2-mercap-
toethanol to the C@C bond of dehydroalanine moieties of complexes
5–8 were conducted in acetonitrile at 22 and 50 °C (Scheme 2). The
reactions were monitored by TLC [SiO2, CH3COCH3/CHCl3 (1:3) or
CH3COOC2H5/CHCl3 (1:3)], following the disappearance of traces of
the initial complexes 5–8 and establishment of the thermodynamic
equilibrium between the diastereoisomeric complexes of the addi-
tion products 9–12a–g. The addition could also be monitored by
1H NMR spectroscopy following the disappearance of the vinyl
hydrogen atom resonances of dehydroalanine moieties of the initial
complexes 5–8.
The major diastereomeric complexes 9a–g, 11a–g, and 12a–g
were separated by preparative chromatography [SiO2, 20 ꢁ
30 cm, CHCl3/CH3COCH3 (3:1)]. Compounds 10c–f could not be iso-
lated in the analytically pure form due to some decomposition on
SiO2 during chromatography with partial regeneration of the initial
complex 6.
For the sake of comparison, Table 1 also presents similar data
obtained earlier with the unmodified complex NiII-(S)-BPB-
D-Ala
(runs 28–33).6,7
The data summarized in Table 1 (runs 14–20 and 21–27) clearly
indicated that the dehydroalanine complexes 7 and 8 were the best
starting material for the b-substituted amino acid synthesis in
terms of both diastereoselectivity (de 94–96%) and reactivity
(shorter reaction times), when compared to 5 and 6 (runs1–13)
and the unmodified complex NiII-(S)-BPB-
D-Ala (runs 28–33).
The results obtained on the asymmetric addition of the nucleo-
philes to the C@C bond of dehydroalanine in the modified complex
The absolute configurations of the amino acid moieties in the
diastereomeric complexes 9a–g–12a–g were determined by mea-
Y
Y
Y
Y
X
O
O
N
N
N
X
O
70oC
O
N
N
N
Ac2O,Na2CO3/MeCN
25oC
H
O
Ni
CH2OH
H
O
Ni
CH2
H
5-8
1-4
X = H, Y = Cl, NiII-(S)-3,4-DCBPB-(R)-Ser 1, NiII-(S)-3,4-DCBPB-Δ-Ala 5;
II
II
2
X = H, Y = CH3, Ni -(S)-3,4-DMBPB-(R)-Ser , Ni -(S)-3,4-DMBPB-Δ-Ala 6;
X = Cl, Y = H, NiII-(S)-2-CBPB-(R)-Ser 3, NiII-(S)-2-CBPB-Δ-Ala 7;
X = F, Y = H, Ni -(S)-2-FBPB-(R)-Ser , Ni -(S)-2-FBPB-Δ-Ala 8
II
II
4
Scheme 1.

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A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
Y
Y
Y
Y
re-side
BH+
X
X
O
O
N
O
(S) N
O
N
NuH, B:
H
O
Ni
Ni
º
º
25 C, 50 C
CH2
N
N
CH2Nu
BH+
Ph
si-side
Sp2 carbanion
5-8
BH+
BH+
si-attack
re-attack
(S)-3,4-DCBPB·HCI
(S)-3,4-DMBPB·HCI
(S)-2-CBPB·HCI
Y
Y
Y
Y
(S)-2-FBPB·HCI
X
X
O
(S)
O
N
N
O
O
N
2M HCI
ion-exchange
EtOH/H2O(1/1)
(S)
N
N
O
H
O
H
Ni
H
O
Ni
CH2Nu
H
CH2Nu
N
Nu
OH
NH2
13a-g
(S,R) in case of 12
(S,S)
(S,S) in the case of 12
(S,R)
X=H, Y=C l9; X=H, Y=Me 10, X=Cl, Y=H 11, X=F, Y=H 12
Nu = C6H5CH2NH (a); Imidazol-1-yl (b); CH3NH (c); HOCH2CH2NH (d);
(HOCH2CH2)2N (e); (CH3)2CHNH (f); HOCH2CH2S (g).
Scheme 2.
7 clearly correlated with the previously obtained data on the asym-
metric C-alkylation of glycine and alanine moieties in the com-
plexes derived from the chiral auxiliary 2-CBPB.9
3. Conclusion
Herein, a universal method for the highly selective and rela-
The recovery of the amino acids and the chiral auxiliaries (S)-
3,4-DCBPB, (S)-3,4-DMBPB, (S)-2-CBPB and (S)-2-FBPB was carried
out similar to the previously reported procedure.6,11 The decom-
posing of the diastereoisomerically pure complexes 9a,g–12a–g
was brought about with aqueous HCl, followed by the recovery
the insoluble hydrochlorides of the auxiliaries (95%) and purifica-
tion of the amino acids by an ion-exchange protocol.6,11 The target
tively rapid asymmetric synthesis of optically active b-substi-
tuted
nucleophilic addition to the C@C bond of the modified chiral dehy-
droalanine complexes. As a result, the amino acid - or (S)-b-(N-iso-
propylamino)- -alanine has been synthesized for the first time. A
L-a-amino acids has been elaborated through a Michael
L
a
novel synthetic route toward (S)-2-carboxypiperazine was also
elaborated.
amino acids, b-substituted
L-a,b-diamino acids 13a–e and (S)-
(2-hydroxyethyl)- -cysteine 13g were isolated with high enantio-
L
4. Experimental
meric purity (ee >99%) after crystallization from an aqueous/
ethanol (1:1) solution. It should be noted that an alternative asym-
metric synthesis by a known Zeebach procedure in the case of
amino acid 13c only gives the racemic product.12 Some synthe-
The amino acids were produced by the CJSC ‘SRI of Biotechnol-
ogy’ (Armenia); silica gel L-40/100 from ‘Merk’ (Germany), (CH2O)n,
CHCl3, (CH3CO)2O, CH3COOH, (CH3)2CO, CH3COOC2H5, CH3CN, DMF,
i-PrOH, Na2CO3, NH4OH, HCl and KOH from ‘Reakhim’ (Russia);
imidazole, CH3NH2ꢂHCl, HOCH2CH2NH2, (HOCH2CH2)2NH, C6H5CH2
NH2, HOCH2CH2SH, and 2-aminobenzophenone from Aldrich (USA).
All solvents used were freshly distilled.
The enantiomeric GLC analysis of the amino acids as their N-tri-
fluoroacetyl derivatives of their isopropyl esters was performed
using a ‘Chiral Val’ type with 0.12
sized b-substituted
amino)- -alanine 13c, b-(N-ethanolamino)-
b-(N,N-diethanolamino)- -alanine 13e were isolated in the form
L
-a
,b-diamino acids, in particular b-(N-methyl-
a
a-alanine 13d, and
a
of hydrochlorides, since in the free form these amino acids are
unstable and on storage gradually darkened and acquired an
unpleasant smell.
The adduct of 8 and ethanolamine (see Table 1, run 24) served
as the initial material for the preparation of (S)-2-carboxypiper-
azine, according to Scheme 3.
lm film thickness at column tem-
perature 125 °C, using helium as the carrier gas. The enantiomeric

A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
2641
Table 1
Results of the asymmetric addition of nucleophiles to chiral complexes 5–8 in CH3CN at 50 °Ca
Run
Initial dehydroalanine complex
NuH
Duration (min)
(S,S)/(S,R)b (%)
Yieldc (%)
1a
2
NiII-(S)-3,4-DCBPB-
D
-Ala 5
C6H5CH2NH2
Imidazole
180
480
360
120
180
10
150
480
360
780
510
720
900
15
88.5/11.5 (92/8)
(95/5)
89.4/10.6
85/15
96.5/3.5
3.8/96.2
92/8
94/6
89/11
92/8
88/12
86/14
8/92
97/3
94.6/5.4
96.81/3.19 (97.5/3.5)
97.5/2.5 (94/6)
96/4
94.5/5.5
3.8/96.2 (1/99)
97/3
98/2
97/3
98/2
98/2
99/1
99/1
93/7
94/6
93/7
90/10
94/6
7/93
65
20
45
60
60
90
30
20
15
40
40
20
10
75
60
65
50
40
40
50
55
60
50
80
75
60
60
20
20
>5
>5
>5
91
‘—’
‘—’
‘—’
‘—’
‘—’
3e
CH3NH2 ꢁ HCl
HOCH2CH2NH2
(HOCH2CH2)2NH
HOCH2CH2SH
C6H5CH2NH2
Imidazole
4
5
6e
7a
NiII-(S)-3,4-DMBPB-
D
-Ala 6
8
‘—’
‘—’
‘—’
‘—’
‘—’
‘—’
9e
CH3NH2ꢂHCl
10
11
HOCH2CH2NH2
(HOCH2CH2)2NH
(CH3)2CHNH2
HOCH2CH2SH
C6H5CH2NH2
Imidazole
12
13e
14a
15
NiII-(S)-2-CBPB-
D
-Ala 7
‘—’
‘—’
‘—’
‘—’
‘—’
‘—’
110
90
16e
17
CH3NH2ꢂHCl
HOCH2CH2NH2
(HOCH2CH2)2NH
(CH3)2CHNH2
HOCH2CH2SH
C6H5CH2NH2
Imidazole
180
240
220
180
100
90
210
20
60
18
19
20e
21a
22
NiII-(S)-2-FBPB-
D-Ala 8
‘—’
‘—’
‘—’
‘—’
‘—’
‘—’
23e
24
CH3NH2ꢂHCl
HOCH2CH2NH2
(HOCH2CH2)2NH
(CH3)2CHNH2
HOCH2CH2SH
C6H5CH2NH2
Imidazole
25
26
200
25
27e
28b,d
29d
30d,e
31d
32d
33d,e
NiII-(S)-BPB-
D
-Ala
240
300
ꢀ50 hr
ꢀ50 hr
ꢀ50 hr
300
‘—’
‘—’
‘—’
‘—’
‘—’
CH3NH2 ꢁ HCl
HOCH2CH2NH2
(HOCH2CH2)2NH
HOCH2CH2SH
a
The addition of benzylamine (runs 1, 7, 14, 21 and 28) was carried out in the presence of NaOH (complex/benzylamine/NaOH = 1:1:1).
b
Determined by chiral GLC or HPLC and 1H NMR (in brackets).
c
Chemical yield at the stage of nucleophile addition after 10 min at the beginning of the reaction.
d
Literature data.6,11
e
The addition of 2-mercaptoethanol and the hydrochlorides of the amines (runs 3, 6, 9, 13, 16, 20, 23, 27, 30, 33) was carried out in
CH3CN/K2CO3 (complex/NuH/K2CO3 = 1:2:3).
HO
MesO
F
O
F
HN
O
H
H MesN
O
MesCl
CH2Cl2, Et3N, 0oC
O
N
Ph
Ni
N
N
Ph
Ni
N
N
N
H
H
O
O
14
12d
SO2Me
N
N
H
COOH
15
Scheme 3.
purity of the amino acids was determined by HPLC on the chiral
phase Diaspher-110-Chirasel-E-PA 6.0 mkm 4.0 ꢁ 250 mm with
20%-MeOH—80%-0.1 M NaH2PO4 ꢁ 2H2O was used as an eluent.
1H NMR spectra were recorded on
‘Mercury-300 Varian’
a

2642
A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
(300 MHz) in DMSO-d6/CCl4: 1:3 (unless otherwise indicated). Opti-
cal rotations were measured on a ‘Perkin Elmer-341’ polarimeter.
The modified complexes of (R)-serine 1–4 were synthesized in
accordance with the previously developed procedure.9 Modified
N, 3J = 11.3, 3J = 5.1), 4.37 (1H, d, CH2C6H3Cl2, 2J = 12.5), 6.65–6.74
(2H, m, Ar), 6.97 (1H, dt, Ar, 3J = 7.6, 4J = 1.5), 7.21 (1H, ddd, Ar,
3J = 8.7, 3J = 6.5, 4J = 2.2), 7.38 (1H, dt, Ar, 3J = 7.5, 4J = 1.5), 7.40
(1H, d, Ar, 3J = 8.1), 7.48 (1H, td, Ar, 3J = 7.5, 4J = 1.5) 7.56 (1H, tt,
Ar, 3J = 7.5, 4J = 1.4), 7.65 (1H, td, Ar, 3J = 7.5, 4J = 1.5), 7.82 (1H,
dd, Ar, 3J = 8.1, 4J = 2.1), 8.06 (1H, dd, Ar, 3J = 8.7, 4J = 1.1) 8.76
(1H, d, Ar, 4J = 2.1).
complexes of dehydroalanine NiII-(S)-3,4-DCBPB-
D
-Ala 5, NiII-(S)-
-Ala 7, and NiII-(S)-2-FBPB-
-Ala 8 were synthesized in accordance with the procedure.11
3,4-DMBPB-D D
-Ala 6, NiII-(S)-2-CBPB-
D
Complex 9f. Yield: 90% (0.21 g, 0.342 mmol). Calcd for
4.1. The synthesis of complex 8 was carried out according to the
previously described method11
C31H32N4O3NiCl2 (638.21): C, 58.34; H, 5.05; N, 8.78. Found: C,
58.51; H, 5.08; N, 8.85. Mp 155–157 °C. ½a D20
¼ þ2104:8 (c 0.05,
ꢃ
CHCl3). 1H NMR: (CDCl3) 0.95 (3H, d, CH3, 3J = 6.2), 1.06 (3H, d,
CH3, 3J = 6.2), 1.50 (1H, m, NH), 2.06 (1H, m, Pro), 2.21 (1H, m,
Pro), 2.53–2.67 (2H, m, Pro), 2.79 (1H, m, CH(CH3)2), 2.88 (1H,
dd, CH–CH2–NH, 2J = 12.8, 3J = 4.2), 3.28 (1H, d, CH2C6H3Cl2,
2J = 12.6), 3.31–3.41 (2H, m, CH–CH2–NH, Pro), 3.58 (1H, m, Pro),
3.85 (1H, m, Pro), 4.02 (1H, dd, CH–CH2–NH, 3J = 7.2, 3J = 4.2),
4.33 (1H, d, CH2C6H3Cl2, 2J = 12.6), 6.60–6.71 (2H, m, Ar), 6.96
(1H, m, Ar), 7.20 (1H, m, Ar), 7.33 (1H, m, Ar), 7.38 (1H, d, Ar,
3J = 8.2), 7.46–7.58 (3H, m, Ar), 7.76 (dd, 1H, Ar, 3J = 8.2, 4J = 1.7),
8.13 (1H, d, Ar, 3J = 8.6), 8.85 (1H, d, Ar, 4J = 1.7).
Complex 8. Calcd for C28H24N3O3NiF (528.2): C, 63.67; H, 4.58; N,
7.96. Found: C, 63.69; H, 4.60; N, 7.94. Mp 158–160 °C.
½
a 2D0
ꢃ
¼ þ2337:5 (c 0.08, CH3OH/CHCl3 (3:1)). 1H NMR (CDCl3/CCl4
ꢀ1:1): 2.09 (1H, ddd, Pro, 2J = 10.8, 3J = 9.8, 3J = 6.5), 2.20 (1H, m,
Pro), 2.55 (1H, m, Pro), 2.79 (1H, m, Pro), 3.47 (1H, dd, Pro,
3J = 10.7, 3J = 5.7), 3.57 (1H, m, Pro), 3.66 (1H, m, Pro), 3.75 (1H,
dd, NCH2C6H5F, 2J = 12.9, JH,F = 1.1), 4.13 (1H, d, C@CH2, 2J = 1.2),
4
4.32 (1H, dd, NCH2C6H5F, 2J = 12.9, JH,F = 1.5), 5.60 (1H, d, C@CH2,
4
2J = 1.2), 6.70 (1H, ddd, Ar, 3J = 8.3, 3J = 6.9, 4J = 1.4), 6.86 (1H, dd,
Ar, 3J = 8.3, 4J = 1.8), 7.04 (1H, ddd, Ar, JH,F = 10.2, 3J = 7.9,
Complex 9g. Yield: 90% (0.22 g, 0.34 mmol). Calcd for C30H29
Cl2N3 Ni O4S (657.23): C, 54.52; H, 4.45; N, 6.39. Found: C, 54.47;
3
4J = 1.8), 7.14–7.23 (5H, m, Ar), 7.42–7.50 (3H, m, Ar), 8.20 (1H,
dd, Ar, 3J = 8.7, 4J = 1.2), 8.41 (1H, ddd, Ar, JH,F = 7.3, 3J = 7.3,
H, 4.57; N, 6.45. Mp 167–169 °C. ½a D20
¼ þ2892:8 (c 0.05, CHCl3).
ꢃ
4
4J = 2.0). 13C NMR: (CDCl3/CCl4 ꢀ1:1): 24.15 (
c-Pro), 30.86 (b-
1H NMR (CDCl3) 2.04–2.20 (2H, m, Pro), 2.47–2.66 (2H, m, Pro),
2.77 (1H, dd, CH–CH2–S, 2J = 13.8, 3J = 5.8), 2.80 (1H, m,
SCH2CH2OH)2.86 (dd, 1H, CH–CH2–S, 2J = 13.8, 3J = 3.3), 2.88 (1H,
m, SCH2CH2OH), 3.30 (1H, d, CH2C6H3Cl2, 2J = 12.5), 3.37 (1H, dd,
Pro, 3J = 10.8, 3J = 6.2), 3.65 (1H, m, Pro), 3.69 (2H, dd, OCH2,
3J = 5.9, 3J = 5.3), 3.79 (1H, m, Pro), 4.24 (1H, dd, CH–CH2–S,
3J = 5.8, 3J = 3.3), 4.35 (1H, d, CH2C6H3Cl2, 2J = 12.5), 6.62–6.71
(2H, m, Ar), 6.97 (1H, m, Ar), 7.20 (1H, ddd, Ar, 3J = 8.6, 3J = 6.5,
4J = 2.2), 7.32 (1H, dt, Ar, 3J = 6.7, 4J = 1.8), 7.38 (1H, d, Ar,
3J = 8.2), 7.46–7.61 (3H, m, Ar), 7.75 (1H, dd, Ar, 3J = 8.2, 4J = 2.1),
8.17 (1H, dd, Ar, 3J = 8.6, 4J = 1.0), 8.90 (1H, d, Ar, 3J = 2.1).
Pro), 55.73 (NCH2C6H5F), 57.50 (d-Pro), 70.69
(a-Pro, d,
5JC,F = 2.7), 114.94 (C@CH2), 116.31 (Ar, d, JC,F = 22.3), 120.81
2
2
(Ar), 120.84 (Ar, d, JC,F = 14.4), 123.87 (Ar), 124.74 (Ar, d,
4JC,F = 3.7), 127.26 (Ar), 128.5 (Ar, br), 130.18 (Ar, br), 131.29 (Ar,
3
3
d, JC,F = 8.5), 134.23 (Ar), 134.30 (Ar, d, JC,F = 3.3), 135.66 (Ar),
143.98 (Ar), 161.77 (Ar, d, JC,F = 247.5), 169.09 (Ar), 170.20 (Ar),
1
179.98 (Ar).
4.2. The synthesis of complexes 9–12a–f
The addition of C6H5CH2NH2 (0.38 mmol) to complexes 5–8
(0.38 mmol) was carried out in CH3CN (5 ml) in the presence of
NaOH (0.38 mmol), while the addition of imidazole, methylamine,
ethanolamine, diethanolamine, isopropylamine, and 2-mercap-
toethanol to complexes 5–8 was carried out in CH3CN in the pres-
ence of K2CO3 (1.7 mol) at 50 °C according to the previously
described methods.6,11 The individually pure major diastereomeric
complexes 9–12g were isolated from the reaction mixture by TLC
[SiO2, 20 ꢁ 30 cm, CHCI3/CH3COOC2H5 (1:2)] and characterized
by spectroscopic methods of analysis.
Complex 10a. Yield: 69% (0.16 g, 0.26 mmol). Calcd for
C
37H38N4O3Ni (645.42): C, 68.85; H, 5.93; N, 8.68. Found: C,
68.83; H, 5.98; N, 8.70. Mp 183–185 °C. ½a D20
¼ þ3002:8 (c 0.05,
ꢃ
CHCl3). 1H NMR (CDCl3) 1.78 (3H, s, Me), 1.98 (3H, s, Me), 2.02
(2H, m, Pro), 2.08 (1H, m, CH2NHCH2Ph), 2.55 (1H, m, Pro), 2.63
(1H, m, Pro), 2.88 (1H, dd, CHCH2NH, 2J = 12.5, 3J = 5.6), 2.91 (1H,
dd, CHCH2NH, 2J = 12.5, 3J = 3.4), 3.50–3.52 (2H, m, Pro), 3.85 (1H,
d, HNCH2Ph, 2J = 13.1), 3.65 (1H, m, Pro), 3.77 (1H, dd, NCH2Ar,
2J = 12.4), 3.92 (1H, d, HNCH2Ph, 2J = 13.1), 3.99 (1H, dd, CHCH2NH,
3J = 5.6, 3J = 3.4), 4.8 (1H, dd, NCH2Ar, 2J = 12.4), 6.6–8.6 (17H, m,
Ar).
Complex 9a. Mp 100–102 °C, ½a D25
ꢃ
¼ þ1956 (c 0.046, CHCl3).
Complex 9b. Mp 199–201 °C, ½a D25
ꢃ
¼ þ2094:1 (c 0.051, CHCl3).
Complex 10b. Calcd for C33H33N5O3Ni (606.34): C, 65.37; H,
5.49; N, 11.55. Found: C, 65.42; H, 5.58; N, 11.50. Mp 155–
Complex 9c. Yield: 65% (0.15 g, 0.24 mmol). Calcd for
C
29H28N4O3NiCl2 (610.16): C, 57.09; H, 4.63; N, 9.18. Found: C,
157 °C, ½a 2D0
ꢃ
¼ þ2566:6 (c 0.05, CHCl3). 1H NMR: (CDCl3): 1.95
57.12; H, 4.66; N, 9.14. Mp 132–134 °C. ½a D20
ꢃ
¼ þ1998:5 (c 0.05,
(3H, s, Me), 1.98 (2H, m, H Pro), 2.07 (3H, s, Me), 2.49 (1H, m,
Pro), 2.55 (1H, m, Pro), 2.58 (1H, m, Pro), 3.22 (2H, m, H Pro),
3.24 (2H, dd, NCH2Ar, 2J = 12.5), 3.66 (1H, m, CHCH2imidazole),
4.21 (2H, dd, NCH2Ar, 2J = 12.5), 4.24 (1H, m, CHCH2imidazole),
4.40 (1H, m, CHCH2N), 6.66–8.98 (12H, m, Ar).
CHCl3). 1H NMR (CDCl3/CCl4 ꢀ1:1): 1.62 (3H, s, CH3NH–), 2.00
(2H, m, Pro), 2.51 (1H, m, Pro), 2.56 (1H, m, Pro), 2.68 (1H, m,
Pro), 2.92 (1H, dd, CHCH2NH, 2J = 12.3, 3J = 6.9), 3.12 (2H, m, Pro),
3.22 (1H, dd, NCH2C6H3Cl2, 2J = 12.5), 3.32 (1H, dd, CHCH2NH,
2J = 12.3, 3J = 3.6); 4.20 (1H, dd, NCH2C6H3Cl2, 2J = 12.5), 4.45 (1H,
dd, CHCH2N, 3J = 6.9, 3J = 3.6), 6.65–8.69 (12H, m, Ar).
Complex 11a. Calcd for C31H33N4O3ClNi: C, 61.67; H, 5.51; N,
9.28. Found: C, 61.69; H, 5.52; N, 9.30. Mp 108–110 °C.
Complex 9d. Mp 135–137 °C, ½a D25
ꢃ
¼ þ1969:2 (c 0.052, CHCl3).
½
a 2D0
ꢃ
¼ þ1985:3 (c 0.05, CHCl3). 1H NMR: (CDCl3): 2.00 (2H, m,
Complex 9e. Yield: 90% (0.23 g, 0.342 mmol). Calcd for
Pro), 2.02 (1H, m, CH2NHCH2Ph), 2.51 (1H, m, Pro), 2.73 (1H, m,
Pro), 2.90 (1H, dd, CH2NH, 2J = 12.6, 3J = 5.6), 2.91 (1H, dd, CH2NH,
2J = 12.6, 3J = 3.6), 3.49–3.51 (2H, m, Pro), 3.85 (1H, d, HNCH2Ph,
2J = 13.2), 3.65 (1H, m, Pro), 3.73 (1H, dd, NCH2PhCl, 2J = 12.4),
3.95 (1H, d, HNCH2Ph, 2J = 13.2), 3.98 (1H, dd, NCHCH2NH,
3J = 5.6, 3J = 3.6), 4.5 (1H, dd, NCH2PhCl, 2J = 12.4) 6.4–8.3 (18H,
m, Ar).
C
32H34N4O5NiCl2 (684.24): C, 56.17; H, 5.01; N, 8.19. Found: C,
56.21; H, 5.05; N, 8.28. Mp 138–140 °C. ½a D20
¼ þ1856:3 (c 0.05,
ꢃ
CHCl3). 1H NMR (CDCl3): 2.00–2.15 (3H, m, Pro), 2.31 (1H, m,
Pro), 2.53 (2H, m, N(CH2CH2OH)2), 2.60–2.78 (2H, m,
N
(CH2CH2OH)2), 2.66 (1H, dd, CH–CH2–N, 3J = 11.3, 3J = 5.1), 3.18–
3.26 (2H, m, N(CH2CH2OH)2), 3.30 (1H, d, 2J = 12.5, CH2C6H3Cl2),
3.41 (1H, dd, Pro, 3J = 11.1, 3J = 5.6), 3.48 (2H, ddd, N(CH2CH2OH)2,
2J = 11.8, 3J = 9.3, 3J = 2.4), 3.56–3.75 (2H, m, Pro), 3.63 (1H, dd, CH–
CH2–N, 2J = 12.7, 3J = 11.3), 3.77 (2H, m, OH), 4.00 (1H, dd, CH–CH2–
Complex 11b. Calcd for C31H28ClN5NiO3: C, 60.77; H, 4.61; N,
11.43. Found: C, 61.69; H, 4.65; N, 11.40. Mp 123–125 °C.
½
a 2D0
ꢃ
¼ þ2333:4 (c 0.05, CHCl3). 1H NMR: (CDCl3): 1.97 (2H, m, H

A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
2643
Pro), 2.50 (1H, m, Pro), 2.54 (1H, m, Pro), 2.58 (1H, m, Pro), 3.20
(2H, m, H Pro), 3.21 (1H, dd, NCH2PhCl, 2J = 12.5), 3.65 (1H, m,
CHCH2imidazole), 4.19 (1H, dd, NCH2PhCl, 2J = 12.5), 4.20 (1H, m,
CHCH2imidazole), 4.35 (1H, m, CHCH2N), 6.67–8.92 (16H, v, Ar).
Complex 11c. Calcd for C29H29ClN4NiO3 (575.71): C, 60.50; H,
5.08; N, 9.73. Found: C, 60.53; H, 5.14; N, 9.65. Mp 156–158 °C.
Ar), 7.37 (2H, m, Ar), 7.43 (1H, m, Ar), 7.48 (1H, m, Ar), 8.26 (1H,
dd, Ar, 3J = 8.7, 4J = 1.3), 8.37 (1H, td, 3J = 7.4, 4J = 2.0).
13C NMR (CDCl3/CCl4 ꢀ1:1): 23.62 (Pro), 30.87 (Pro), 52.16
(CHCH2NH), 53.33 (CH2C6H5), 55.78 (CH2C6H4F), 57.12 (Pro),
5
70.54 (
a
-CH, Pro, d, JC,F = 2.1) 70.65 (CHCH2NH), 116.26 (C6H4F,
2
2
d, JC,F = 22.4), 120.65 (C6H4F, d, JC,F = 14.3), 120.71 (C6H4),
124.00 (C6H4), 124.60 (C6H4F, d, JC,F = 3.5) 126.68 (C), 127.19 (C),
½
a 2D0
ꢃ
¼ þ2876:2 (c 0.05, CHCl3). 1H NMR: (CDCl3): 1.68 (3H, s,
4
CH3NH), 1.88 (2H, m, Pro), 2.47 (1H, m, Pro), 2.57 (1H, m, Pro),
2.68 (1H, m, Pro), 2.89 (1H, dd, CHCH2N, 2J = 12.28, 3J = 6.9), 3.10
(2H, m, Pro), 3.19 (1H, dd, NCH2PhCl, 2J = 12.5), 3.27 (1H, dd,
CHCH2N, 2J = 12.28, 3J = 3.6), 4.22 (1H, dd, NCH2PhCl, 2J = 12.5),
4.41 (dd, 1H, CHCH2N, 3J = 6.9, 3J = 3.6), 6.69–8.94 (13H, m, Ar).
Complex 11d. Calcd for C30H31ClN4NiO4 (605.74): C, 59.48; H,
5.16; N, 9.73. Found: C, 59.51; H, 5.21; N, 9.75. Mp 143–145 °C.
127.26 (C), 127.93 (C6H5), 128.41 (CH2C6H5), 128.56 (CH2C6H5),
128.98 (C), 129.03 (C), 129.72 (C), 129.72 (C), 131.28 (C6H4F, d,
3JC,F = 8.4), 132.31 (C), 133.31 (C), 134.03 (C), 134.48 (C6H4F, d,
3JC,F = 3.3), 139.96 (C), 142.88 (C), 161.89 (C6H4F, d), 170.64 (C),
178.57 (C), 180.13 (C).
Complex 12b. Calcd for C31H28N5O3NiF: C, 62.48; H, 4.80; N,
3.22. Found: C, 62.44; H, 4.73; N, 3.19. Mp 165–167 °C.
½
a 2D0
ꢃ
¼ þ1896:4 (c 0.05, CHCl3). 1H NMR: (CDCl3): 2.12 (2H, m,
½
a 2D5
ꢃ
¼ þ1940 (c 0.05, CHCl3). 1H NMR: (CDCl3): 1.81 (1H, m, Pro),
Pro), 2.39 (1H, m, Pro), 2.46 (1H, m, Pro), 2.27 (1H, m, CHCH2N),
2.35 (2H, m, NHCH2CH2OH), 2.56 (1H, m, Pro), 2.71 (1H, m, Pro),
4.11 (1H, m, CHCH2N), 3.28 (1H, dd, NCH2PhCl, 2J = 12.76), 3.40
(2H, m, NHCH2CH2OH), 3.50 (1H, m, Pro), 3.73 (1H, dd, CHCH2N,
3J = 8.0, 3J = 3.9), 4.32 (1H, dd, NCH2PhCl, 2J = 12.76), 6.67–8.03
(13H, m, Ar).
1.95 (1H, ddd, Pro, 2J = 10.8, 3J = 9.6, 3J = 7.0), 2.38 (1H, m, Pro),
2.52 (1H, m, Pro), 2.62 (1H, m, Pro), 3.26 (1H, dd, Pro, 3J = 9.8,
3J = 7.0), 3.47 (1H, ddd, Pro, 2J = 10.8, 3J = 6.6, 3J = 3.3), 3.70 (1H,
dd, CH2C6H4F, 2J = 12.9, JH,F = 1.0), 3.77 (1H, m, CHCH2imidazol),
4
3.98 (1H, dd, CH2C6H4F, 2J = 12.9, JH,F = 1.0), 4.20 (2H, m,
4
CHCH2imidazol), 6.65 (1H, m, Ar), 6.66 (1H, m, Ar), 6.95 (1H, m,
CHimidazol), 6.96 (1H, s, CHimidazol), 6.98 (1H, ddd, Ar, 3J = 10.1,
3J = 8.2, 4J = 1.5), 7.10 (1H, m, Ar), 7.14 (1H, m, Ar), 7.17 (1H, m,
Ar), 7.23 (1H, s, CHimidazol), 7.31 (1H, m, Ar), 7.53 (1H, m, Ar),
7.47–7.61 (3H, m, Ar), 8.16 (1H, m, Ar), 8.31 (1H, m, Ar).
Complex 12c. Calcd for C29H29N4NiO3F: C, 62.28; H, 5.22; N,
10.02. Found: C, 62.32; H, 5.18; N, 10.04. Mp 166–168 °C.
Complex 11e. Calcd for C32H35ClN4NiO5 (649.79): C, 59.15; H,
5.43; N, 8.62. Found: C, 59.19; H, 5.51; N, 8.65. Mp 123–125 °C.
½
a 2D0
ꢃ
¼ þ1653:3 (c 0.05, CHCl3). 1H NMR: (CDCl3): 1.98 (2H, m,
Pro), 2.32 (2H, ddd, CH2N, 2J = 12.8, 3J = 9.6, 3J = 4.1), 2.38 (1H, m,
Pro), 2.43 (2H, ddd, CH2N, 2J = 13.8, 3J = 3.0, 3J = 2.1), 2.56 (1H, m,
Pro), 2.60 (1H, m, Pro), 2.65 (1H, dd, CHCH2N, 2J = 12.7, 3J = 5.0),
2.81 (1H, m, Pro), 3.20 (2H, dt, OCH2, 2J = 11.8, 3J = 3.5), 3.22 (1H,
dd, NCH2PhCl, 2J = 12.78), 3.45 (2H, m, CH2O), 3.56 (1H, dd,
CHCH2N, 2J = 12.7, 2J = 11.2), 3.69 (1H, m, Pro), 4.09 (1H, dd,
CHCH2N, 2J = 11.3, 3J = 5.0,), 4.18 (1H, dd, NCH2PhCl, 2J = 12.78),
6.63–8.21 (13H, m, Ar).
½
a 2D0
ꢃ
¼ þ3969:9 (c 0.18, CHCl3). 1H NMR (CDCl3/CCl4 ꢀ1:1): 1.90
(1H, br, NH), 2.02 (1H, m, Pro), 2.15 (1H, m, Pro), 2.17 (3H, s,
CH3), 2.52 (1H, m, CH2, Pro), 2.77 (1H, dd, CH2NH, 2J = 12.9,
3J = 3.7), 2.82 (1H, m, Pro), 3.15 (1H, dd, CH2NH, 2J = 12.9,
3J = 7.2), 3.42 (1H, dd, Pro, 3J = 10.8, 3J = 6.0), 3.47 (1H, dd, Pro,
2J = 10.0, 3J = 6.0), 3.73 (1H, m, Pro), 3.82 (1H, dd, CH2, 2J = 13.0,
4JH,F = 1.0), 3.98 (1H, dd, CH, 3J = 7.2, 3J = 3.7), 4.38 (1H, dd, CH2,
Complex 11f. Calcd for C31H33ClN4NiO3 (03.77): C, 61.67; H,
5.51; N, 9.28. Found: C, 61.71; H, 5.66; N, 9.55. Mp 137–139 °C.
a 2D0
ꢃ
¼ þ2186:3 (c 0.05, CHCl3). 1H NMR: (CDCl3): 0.92 (3H, d,
2J = 13.0, JH,F = 1.5), 6.62 (1H, dd, Ar, 3J = 8.2, 4J = 2.2), 6.65 (1H,
4
½
CH3, 3J = 6.2), 1.04 (3H, d, CH3, 3J = 6.2), 1.53 (1H, m, NH), 2.06
(1H, m, Pro), 2.18 (1H, m, Pro), 2.54–2.69 (2H, m, Pro), 2.86 (1H,
dd, CHCH2N), 2.98 (1H, m, CH(CH3)2), 3.11 (1H, m, Pro), 3.47–
3.54 (2H, m, CHCH2N, Pro), 3.83 (1H, m, Pro), 3.88 (1H, d,
CH2C6H4Cl, 2J = 12.9), 4.00 (1H, dd, 3J = 7.1, 3J = 4.0, CHCH2N), 4.50
(1H, d, 2J = 12.9, CH2C6H4Cl), 6.60–6.71 (2H, m, Ar), 6.98 (1H, m,
Ar), 7.12–7.22 (2H, m, Ar), 7.27–7.37 (3H, m, Ar), 7.46–7.57 (3H,
m, Ar), 8.08 (1H, dd, 3J = 8.6, 3J = 0.9, Ar), 8.21 (1H, d, 3J = 7.5, Ar).
Complex 11g. Calcd for C30H30N3O4SNiCl: C, 57.86; H, 4.86; N,
6.75. Found: C, 57.83; H, 4.90; N, 6.71. Mp 165–167 °C.
ddd, Ar, 3J = 8.2, 3J = 6.6, 4J = 1.2), 6.97 (1H, m, Ar), 7.04 (1H, ddd,Ar,
3JH,F = 9.9, 3J = 8.0, 4J = 1.5), 7.13 (1H, m, Ar), 7.17 (1H, m, Ar), 7.20
(1H, m, Ar), 7.28 (1H, m, Ar), 7.43–7.55 (3H, m, Ar), 8.18 (1H, dd,
Ar, 3J = 8.6, 4J = 1.2), 8.33 (1H, ddd, Ar, JH,F = 7.4, 3J = 7.4, 4J = 2.1).
4
13C NMR (CDCl3/CCl4 ꢀ1:1): 23.72 (Pro), 30.84 (Pro), 35.92 (CH3),
55.72 (CH2), 55.89 (CH2NH), 57.13 (Pro), 69.47 (CHCH2NH), 70.51
5
2
(Pro, d, JC,F = 2.5), 116.21 (C, d, JC,F = 22.0), 120.60 (C, d,
2JC,F = 14.7), 120.76 (C), 124.01 (C), 124.59 (CH, d, JC,F = 3.7),
4
126.67 (C), 127.55 (CH), 128.02 (CH), 129.07 (C), 129.07(C),
3
129.86 (C), 131.24 (C, d, JC,F = 8.5), 132.27 (CH), 133.29 (CH),
a 2D5
ꢃ
¼ þ1940 (c 0.05, CHCl3). 1H NMR: (CDCl3): 2.0–2.20 (2H, m,
133.99 (C), 134.37 (CH, d, JC,F = 3.6), 142.69 (C), 161.77 (C, d,
3
½
Pro), 2.40–2.71 (2H, m, Pro), 2.78 (1H, dd, 2J = 13.6, 3J = 5.8, CH–
CH2–S), 2.86 (1H, dd, 2J = 13.6, 3J = 3.2, CH–CH2–S), 3.0–3.12 (2H,
m, CH–CH2–SCH2), 3.41–3.56 (2H, m, Pro), 3.69 (2H, dd, 3J = 5.8,
3J = 5.2, OCH2), 3.80 (1H, m, Pro), 3.89 (1H, d, 2J = 12.6, CH2–
C6H4Cl), 4.20 (1H, dd, 3J = 5.8, 3J = 3.3, CH–CH2–S), 4.55 (1H, d,
2J = 12.6, CH2–C6H4Cl), 6.62–8.20 (13H, m, Ar).
1JC,F = 247.8), 170.48 (C), 178.51 (C), 180.09 (C).
Complex 12d. Calcd for C30H31N4NiO4F: C, 61.16; H, 5.30; N,
9.51. Found: C, 61.21; H, 5.28; N, 9.52. Mp 159–161 °C.
½
a 2D0
ꢃ
¼ þ2384:8 (c 0.25, CHCl3). 1H NMR (CDCl3/CCl4 ꢀ1:1): 2.06
(1H, ddd, Pro, 2J = 11.6, 3J = 10.2, 3J = 6.3), 2.15 (2H, m, Pro), 2.33
(1H, m, NHCH2CH2O), 2.43 (1H, m, NHCH2CH2O), 2.53 (1H, m,
Pro), 2.80 (1H, m, Pro), 3.30 (1H, dd, CHCH2N, 2J = 12.9, 3J = 8.0),
3.38 (2H, m, OCH2), 3.41 (1H, m, Pro), 3.47 (1H, dd, Pro, 3J = 10.2,
3J = 6.3), 3.67 (1H, m, CHCH2N), 3.80 (1H, dd, CH2, 2J = 13.0,
4JH,F = 0.9), 3.96 (1H, dd, CHCH2N, 3J = 8.0, 3J = 3.9), 4.37 (1H, dd,
Complex 12a. Calcd for C35H33N4NiO3F: C, 66.17; H, 5.24; N,
8.82. Found: C, 66.21; H, 5.26; N, 8.80. Mp 158–160 °C,
½
a 2D5
ꢃ
¼ þ1678:0 (c 0.05, CH3OH): 1H NMR: (CDCl3/CCl4 ꢀ1:1):
2.02 (1H, m, Pro), 2.02 (1H, m, Pro), 2.02 (1H, br, NHbz), 2.46 (1H,
m, Pro), 2.75 (1H, m, Pro), 2.86 (1H, dd, CHCH2NH, 2J = 12.6,
3J = 5.6), 2.90 (dd, 1H, CHCH2NH, 2J = 12.6, 3J = 3.7), 3.43 (1H, dd,
CH2, 2J = 13.0, JH,F = 1.4), 6.62 (1H, dd, Ar, 3J = 8.2, 4J = 2.3), 6.65
4
(1H, ddd, Ar, 3J = 8.2, 3J = 6.3, 4J = 1.2), 6.97 (1H, ddd, Ar, 3J = 6.1,
3
a
-Pro, 3J = 10.8, 3J = 6.0), 3.48 (1H, m, Pro), 3.55 (1H, d, NHCH2C6H5,
4J = 2.2, 4J = 1.6), 7.03 (1H, ddd, Ar, JH,F = 10.1, 3J = 8.0, 4J = 1.5),
2J = 13.3), 3.63 (1H, m, Pro), 3.85 (1H, dd, 2J = 13.0, JH,F = 1.1,
7.11–7.30 (4H, m, Ar), 7.43–7.56 (3H, m, Ar), 8.16 (1H, dd, Ar,
4
CH2C6H4F), 3.95 (1H, d, NHCH2C6H5, 2J = 13.3), 3.96 (1H, dd, CHCH2,
3J = 8.6, 4J = 0.9), 8.29 (1H, ddd, Ar, JH,F = 7.3, 3J = 7.3, 4J = 2.0). 13C
4
3J = 5.6, 3J = 3.7), 4.41 (1H, dd, 2J = 13.0, JH,F = 1.4, CH2C6H4F), 6.34
NMR (CDCl3/CCl4 ꢀ1:1): 23.85 (Pro), 30.83 (Pro), 50.61
4
(1H, dt, Ar, 3J = 7.6, 4J = 1.6), 6.56 (1H, dd, Ar, 3J = 8.2, 4J = 1.9),
6.65 (1H, ddd, Ar, 3J = 8.2, 3J = 6.8, 4J = 1.0), 7.06 (1H, ddd, Ar,
3JH,F = 10.1, 3J = 8.0, 4J = 1.5), 7.17 (1H, m, Ar), 7.18 (3H, m, Ar),
7.18 (1H, m, Ar), 7.20 (1H, m, Ar), 7.24 (1H, m, Ar), 7.26 (1H, m,
(NCH2CH2O), 53.56 (NCH2CH), 55.81 (CH2), 57.22 (Pro), 60.91
5
(OCH2), 69.85 (CHCH2N), 70.45 (Pro, d, JC,F = 2.1), 116.20 (CH, d,
2
2JC,F = 22.3), 120.61 (C, d, JC,F = 14.4), 120.82 (CH), 124.01 (CH),
4
124.60 (CH, d, JC,F = 3.6), 126.52 (C), 127.45 (C), 127.88 (C),

2644
A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
3
129.14 (C), 129.14 (C), 129.92 (C), 131.27 (C, d, JC,F = 8.5), 132.37
(3H, m, Ar), 8.23 (1H, dd, Ar, 3J = 8.6, 4J = 1.0), 8.32 (1H, ddd, Ar,
4JH,F = 7.3, 4J 2.0). 13C NMR (CDCl3/CCl4 ꢀ1:1): 23.56 (Pro), 30.95
(Pro), 35.52 (SCH2CH), 36.86 (SCH2CH2O), 56.16 (CH2), 57.24
3
(C), 133.31 (C), 133.88 (C), 134.29 (C, d, JC,F = 3.3), 142.66 (C),
161.76 (C, d, JC,F = 248.2), 170.77 (C), 178.76 (C), 180.10 (C).
1
5
Complex 12e. Calcd for C32H35N5O4NiF: C, 60.69; H, 5.57; N, 8.86.
(Pro), 61.23 (OCH2), 69.89 (CHCH2S), 70.87 (Pro, d, JC,F = 2.4),
Found: C, 60.72; H, 5.54; N, 8.85. Mp 173 °C. ½a D20
ꢃ
¼ þ2941:7 (c 0.42,
116.29 (CH, d, JC,F = 22.2), 120.73 (C, d, JC,F = 13.4), 120.83 (CH),
2
2
CHCl3). 1H NMR (CDCl3/CCl4 ꢀ1:1): 2.00 (1H, ddd, NCH2, J1 = 12.5,
J2 = 9.3, J3 = 3.4), 2.07 (1H, ddd, Pro, 2J = 11.8, 3J = 9.9, 3J = 5.8),
2.22 (1H, m, Pro), 2.47 (1H, ddd, NCH2, J1 = 13.5, J2 = 3.8, J3 = 2.2),
2.55 (1H, m, Pro), 2.63 (1H, dd, CHCH2N, 2J = 12.7, 3J = 5.1), 2.74
(1H, m, Pro), 3.16 (2H, dt, OCH2, J1 = 11.8, J2 = 3.5), 3.43 (1H, m,
Pro), 3.44 (2H, m, OCH2), 3.45 (1H, dd, Pro, 3J = 10.8, 3J = 6.0), 3.57
(1H, m, Pro), 3.59 (1H, dd, CHCH2N, 2J = 12.7, 3J = 11.3), 3.77 (1H,
dd, CH2, 2J = 12.9), 3.87 (2H, br, OH), 3.93 (1H, dd, CHCH2N,
124.04 (CH), 124.65 (CH, d, JC,F = 3.8), 126.49 (C), 127.28 (CH),
4
127.89 (CH), 129.25 (C), 129.35(C), 130.10 (C), 131.34 (C, d,
3JC,F = 8.5), 132.72 (CH), 133.55 (CH), 134.23 (C), 134.41 (CH, d,
1
3JC,F = 3.5), 143.16 (C), 161.88 (C, d, JC,F = 247.5), 171.62 (C),
178.23 (C), 180.19 (C).
4.2.1. Isolation of the target amino acids 13a–g
Decomposition of the diastereomeric complexes 9–12a–g and
3J = 11.3, 3J = 5.1), 4.31 (1H, dd, CH2C6H5F, 2J = 12.9, JH,F = 1.2),
isolation of the target b-substituted a-amino acids 13a–g were car-
4
4
4.41 (1H, dd, CH2C6H5F, 2J = 12.9, JH,F = 1.4), 6.62 (1H, dd, Ar,
ried out according to the earlier procedure.6 Amino acids 13c–e
3J = 8.1, 4J = 2.1), 6.64 (1H, ddd, Ar, 3J = 8.1, 3J = 6.2, 4J = 1.2), 6.95
were isolated in the form of their hydrochlorides.
(1H, dt, Ar, 3J = 7.4, 4J = 1.6), 7.01 (1H, ddd, Ar, JH,F = 10.1, 3J = 8.0,
3
4J = 1.5), 7.13 (1H, m, Ar), 7.16 (1H, m, Ar), 7.21 (1H, m, Ar), 7.31
(1H, dt, Ar, 3J = 7.5, 4J 1.6), 7.44 (1H, td, Ar, 3J = 7.4, 4J = 1.6), 7.50
(1H, m, Ar), 7.58 (1H, m, Ar), 8.08 (1H, dd, Ar, 3J = 8.6, 4J = 1.1),
4.2.2.
L
-b-(N-Methylamino)-
a
-alanineꢂHCl [or (S)-2-amino-3-
(methylamino)propionic acid] 13c
Obtained 1.43 g (0.0121 mol) (79.2%). ½a D25
ꢃ
¼ þ23:2 (c 1, 6 M
8.29 (1H, ddd, Ar, JH,F = 7.3, 3J = 7.3, 4J = 2.0). 13C NMR (CDCl3/
HCl), Lit. ½a 2D5
¼ þ23:2 (c 1, 6 M HCl).
ꢃ
4
CCl4 ꢀ1:1): 24.29 (Pro), 30.72 (Pro), 55.97 (CH2), 57.36 (Pro),
58.04 (N(CH2)2), 59.73 (O(CH2)2), 60.08 (CHCH2N), 68.87 (CHCH2N),
4.2.3. L-b-(N-Benzylamino)-a-alanine [or (S)-2-amino-3-
5
2
70.45 (Pro, d, JC,F = 2.5), 116.11 (CH, d, JC,F = 22.2), 120.64 (C, d,
(benzylamino)propionic acid] 13a
2JC,F = 14.5), 120.85 (CH), 124.02 (CH), 124.62 (CH, d, JC,F = 3.6),
Obtained 0.24 g (0.0012 mol) (83%). ½a D25
ꢃ
¼ þ26:8 (c 10, 6 M
4
126.24 (C), 127.72 (C), 127.84 (CH), 128.82 (C), 129.39(C), 129.99
(CH), 131.26 (CH, d, JC,F = 8.4), 132.37 (CH), 133.28 (CH), 133.31
(C), 134.17 (CH, d, JC,F = 3.3), 142.41 (C), 161.64 (C, d, JC,F
HCl), Lit. ½a 2D5
¼ þ26:8 (c 10, 6 M HCl).
ꢃ
3
3
1
=
4.2.4. L-b-(N-Imidazolyl)-a-alanine [or (S)-2-amino-3-imidazol-
247.8), 170.77 (C), 179.90 (C), 180.07 (C).
1-yl)propionic acid] 13b
Complex 12f. Calcd for C31H33N4NiO3F: C, 63.40; H, 5.66; N, 9.54.
Obtained 0.177 g (0.00114 mol) (70%). ½a D20
¼ ꢄ2:2 (c 10, 6 M
ꢃ
Found: C, 63.42; H, 5.63; N, 9.57. Mp 175–177 °C. ½a D20
ꢃ
¼ þ3585:3
HCl), Lit. ½a 2D0
¼ ꢄ2:2 (c 10, 6 M HCl).
ꢃ
(c 0.19, CH3OH). 1H NMR (CDCl3/CCl4 ꢀ1:1): 0.88 (3H, d, CH3, i-Pr,
3J = 6.2), 1.00 (3H, d, CH3, i-Pr, 3J = 6.2), 1.93 (1H, br, NH), 2.02 (1H,
m, Pro), 2.11 (1H, m, Pro), 2.53 (1H, sp, CH, i-Pr, 3J = 6.2), 2.53 (1H,
m, Pro), 2.83 (1H, dd, CH2NH, 2J = 12.7, 3J = 3.8), 2.85 (1H, m, Pro),
3.06 (1H, dd, CH2NH, 2J = 12.7, 3J = 6.8), 3.41 (1H, dd, Pro,
3J = 10.8, 3J = 6.2), 3.49 (1H, dd, Pro, 2J = 9.6, 3J = 6.0), 3.77 (1H, m,
4.2.5.
L-b-(N-Ethanolamino)-
a
-alanineꢂHCl [or (S)-2-amino-3-(2-
hydroxyethylamino)propionic acid] 13d
Obtained 0.186 g (0.00126 mol) (76%). ½a D25
¼ þ15:1 (c 0.053,
ꢃ
6 M HCl), Lit. ½a 2D5
¼ þ15:1 (c 0.053, 6 M HCl).
ꢃ
4
Pro), 3.84 (1H, dd, CH2, 2J = 12.9, JH,F = 1.2), 3.97 (1H, dd, CH,
4.2.6.
L
-b-(N,N-Diethanolamino)-
a-alanineꢂHCl [or (S)-2-amino-
3J = 6.8, 3J = 3.8), 4.39 (1H, dd, CH2, 2J = 12.9, JH,F = 1.5), 6.60 (1H,
3-[bis(2-hydroxyethyl)amino]-propionic acid] 13e
4
dd, Ar, 3J = 8.2, 4J = 2.2), 6.65 (1H, ddd, Ar, 3J = 8.2, 3J = 6.6, 4J = 1.2,
Obtained 0.474 g (0.00247 mol) (80%). ½a D25
¼ þ27:2 (c 0.9, 6 M
ꢃ
6.95 (1H, m, Ar), 7.03 (1H, ddd, Ar, JH,F = 10.0, 3J = 8.0, 4J = 1.5),
HCl), Lit. ½a 2D5
¼ þ27:2 (c 0.9, 6 M HCl).
ꢃ
3
7.13 (1H, m, Ar), 7.16 (1H, m, Ar), 7.21 (1H, m, Ar), 7.27 (1H, m,
Ar), 7.42–7.54 (3H, m, Ar), 8.18 (1H, dd, Ar, 3J = 8.6, 4J = 1.0), 8.30
4.2.7. L-b-(N-Isopropylamino)-a-alanine [or (S)-2-amino-3-
(isopropylamino)-propionic acid] 13f
4
(1H, ddd, Ar, JH,F = 7.3, 3J = 7.3, 4J = 2.0). 13C NMR (CDCl3/CCl4
ꢀ1:1): 22.77 (CH3), 23.32 (CH3), 23.83 (Pro), 30.83 (Pro), 48.14
Obtained 0.58 g (0.00397 mol) (75.3%). Mp = 126–128 °C. Calcd
for C6H14N2O2: C, 49.30; H, 9.65; N, 19.16. Found: C, 49.28; H, 9.60;
N, 19.18. 1H NMR (DMSO, d, m, d, J, Hz): 1.31 (6H, d, (CH3)2CH–),
3.40 (2H, m, –NHCH2CH–), 3.51 (1H, m, –CH2CHNH2), 4.35 (1H,
(CH, i-Pr), 50.93 (CH2NH), 55.62 (CH2), 56.99 (Pro), 70.27
5
2
(CHCH2NH), 70.49 (Pro, d, JC,F = 2.4), 116.17 (CH, d, JC,F = 22.3),
2
120.52 (C, d, JC,F = 14.6), 120.71 (CH), 123.93 (CH), 124.55 (CH, d,
4JC,F = 3.6), 126.73 (C), 127.42 (CH), 127.88 (CH), 129.07(C),
m, (CH3)2CHNH–). ½a D20
¼ ꢄ32:5 (c 0.16, 6 M HCl).
ꢃ
3
129.07 (C), 129.82 (CH), 131.21 (CH, d, JC,F = 8.4), 132.24 (CH),
133.27 (CH), 134.08 (C), 134.34 (CH, d, JC,F = 3.3), 142.72 (C),
161.74 (C, d, JC,F = 248.0), 170.44 (C), 178.48 (C), 179.96 (C).
3
4.2.8. L-S-(2-Hydroxyethyl)cysteine [or (R)-2-amino-3-(2-
1
hydroxyethylthio)propionic acid] 13g
Complex 12g. Calcd for C30H30N3NiO3SF: C, 59.43; H, 4.98; N,
10.55. Found: C, 59.46; H, 4.94; N, 10.52; Mp 240–242 °C
Obtained 0.231 g (0.0014 mol) (71%). ½a D25
¼ þ12:8 (c 0.952, 6 M
ꢃ
HCl), Lit. ½a 2D5
¼ þ12:8 (c 0.952, 6 M HCl).
ꢃ
½
a 2D0
ꢃ
¼ þ3192:8 (c 0.32, CH3OH). 1H NMR (CDCl3/CCl4 ꢀ1:1): 2.07
(1H, m, Pro), 2.10 (1H, m, Pro), 2.48 (1H, dt, SCH2CH2O, 2J = 14.1,
3J = 6.1), 2.55 (1H, m, Pro), 2.75 (1H, dd, CH2S, 2J = 13.7, 3J = 5.9),
2.80 (1H, dt, SCH2CH2O, 2J = 14.1, 3J = 5.3), 2.84 (1H, dd, CH2S,
2J = 13.7, 3J = 3.4), 2.94 (1H, m, Pro), 3.45 (1H, dd, Pro, 3J = 10.6,
3J = 6.5), 3.55 (1H, dd, Pro, 2J = 9.5, 3J = 6.3), 3.65 (2H, dd, OCH2,
3J = 6.1, 3J = 5.3), 3.72 (1H, m, Pro), 3.86 (1H, dd, CH2, 2J = 12.9,
4JH,F = 1), 4.21 (1H, dd, CH, 3J = 5.9, 3J = 3.4), 4.41 (1H, dd, CH2,
4.2.9. (S)-2-Carboxy-4-N-mesyl-pyperazine 15
To a solution of the initial complex 12d (2.5 g, 0.004 mol) in
45 ml of CH2Cl2 at 0 °C was added 1.5 ml of Et3N followed by
0.5 ml of MesCl under stirring. The solution was additionally stir-
red for an additional 5 min at 0 °C and then the cooling was
stopped and the mixture was stirred for another 30 min. The reac-
tion was monitored by TLC (SiO2, CHCl3/MeOH = 95:5). Additional
amounts of MesCl and Et3N were added with stirring if the reaction
was not complete. After the initial material had disappeared, the
reaction mixture was poured into water (100 ml). The organic layer
was separated and the water layer was extracted with CHCl3
2J = 12.9, JH,F = 1.4), 6.63 (1H, dd, Ar, 3J = 8.2, 4J = 2.2), 6.67 (1H,
4
ddd, Ar, 3J = 8.2, 3J = 6.2, 4J = 1.1), 7.00 (1H, dt, Ar, 3J = 6.5, 4J = 1.8),
7.05 (1H, ddd, Ar, JH,F = 10.2, 3J = 8.0, 4J = 1.5), 7.13 (1H, m, Ar),
3
7.16 (1H, m, Ar), 7.21 (1H, m, Ar), 7.27 (1H, m, Ar), 7.45–7.58

A. S. Saghiyan et al. / Tetrahedron: Asymmetry 21 (2010) 2638–2645
2645
(3 ꢁ 10 ml). The organic solutions were combined, washed with
water, dried over MgSO4, and evaporated. The final product was
purified by chromatography (SiO2 column, CHCl3/MeOH (95:5))
to give 0.66 g (0.9 mmol) of doubly mesylated complex (see
Scheme 3).
the twofold axis. The hydrogen atoms were placed in calculated
positions and refined within riding model with fixed isotropic dis-
placement parameters (Uiso(H) = 1.2Ueq(C)). The absolute structure
of 7 was determined objectively by the refinement of Flack param-
eter which has become equal to 0.001(18). The final divergence
factors were R1 = 0.052 for 5016 independent reflections with
Complex 14. Mp 123–126 °C (decomp.). Calcd for C32H36N4-
NiO8FS2 ꢁ 0.2 EtOH ꢁ 0.2C6H6 ꢁ 0.20.4 CHCl3: C, 51.04; H, 4.89;
I > 2r(I) and wR2 = 0.136 for all independent reflections, S = 1.013.
N, 7.00. Found: C, 51.29; H, 4.81; N, 6.87. ½a D20
ꢃ
¼ þ1813 (c 0.058,
-Pro), 2.25 (m,
All calculations were carried out using the SHELXTL program. Crystal-
lographic data for 7 have been deposited with the Cambridge Crys-
tallographic Data Center, CCDC 746863. Copies of this information
may be obtained free of charge from the Director, CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (Fax: +44 1223 336033; e-mail: de-
posit@ccdc.cam.ac.uk or www.ccdc.cam.ac.uk).
MeOH). 1H NMR (CDCl3/CCl4 ꢀ1:1): 2.12 (m, 1H,
c
1H, b-Pro), 2.54 (m, 1H,
c-Pro), 2.81 (m, 1H, d-Pro), 2.95 (s, 3H,
Me), 3.10 (s, 3H, Me), 3.29 (m, 2H, b-Pro, d-Pro), 3.45 (m, 3H,
NCH2-CH2-OMs, CHCH2N), 3.56 (d, J = 12.3 Hz, 1H, NCH2Ph), 3.71
(m, 1H,
a-Pro), 4.01 (dd, J = 9.6, 5.1 Hz, 1H, CH–CH2–N), 4.06 (m,
2H, N–CH2–CH2OMs), 4.38 (d, J = 12.3, 1H, NCH2Ph), 4.67 (dd,
J = 15.0, 9.6 Hz, 1H, CH–CH2–N), 6.65 (m, 2H, Ar), 7.06 (m, 1H,
Ar), 7.15 (m, 1H, Ar), 7.21 (m, 1H, Ar), 7.27 (m, 1H, Ar), 7.36 (m,
2H, Ar), 7.56 (m, 3H, Ar), 8.07 (d, J = 7.0 Hz, 2H, Ar), 8.13 (d,
J = 9.0 Hz, 1H, Ar).
Acknowledgment
This work was supported by ISTC grants #2780 and A-1247.
References
4.2.10. Isolation of (S)-2-carboxy-4-N-mesyl-pyperazine 15
Complex 14 was decomposed as usual; the exception was that
the final neutralization before the column had to be carried out
with a concentrated solution of Na2CO3. The amino acid was then
recovered by the usual ion exchange protocol. The initial 0.66 g
of the complex gave 0.18 u (0.86 mmol) of (methylsulfonyl)pipera-
zine-2-carboxylic acid), which was recrystallized from hot water to
give (0.066 g, 0.31 mmol) of the pure amino acid. Another 0.028 g
(0.13 mmol) of the amino acid was additionally recovered from
the mother liquor.
1. (a) For reviews see: Sadovnikova, M. S.; Belikov, V. M. Application of Amino Acids
in Industry and Pharmacology; M. ONTITEM microbioprom., 1977.; (b) Izumi, Y.;
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Synthesis of Optically Active Amino Acids; Pergamon Press: Oxford, 1989; (d)
Cativiela, C.; Díaz de Villegas, M. D. Tetrahedron: Asymmetry 2000, 11, 645–732;
(e) Cativiela, C.; Dıaz de Villegas, M. D. Tetrahedron: Asymmetry 1998, 9, 3517–
3599; (f) Wirth, T. Angew. Chem., Int. Ed. 1997, 36, 225–227; (g) North, M.
Contemp. Org. Synth. 1996, 3, 323–343; (h) Duthaler, R. O. Tetrahedron 1994, 50,
1539–1650; (i) Ager, D. J.; Laneman, S. A. In Asymmetric Catalysis on Industrial
Scale; Blaser, H. U., Schmidt, E., Eds.; Wiley-VCH: Weinheim, 2004; p 259; (j)
Abellán, T.; Chinchilla, R.; Galindo, N.; Guillena, G.; Nájera, C.; Sansano, J. M.
Eur. J. Org. Chem. 2000, 3034–3041; (k) O’Donnell, M. J. Acc. Chem. Res. 2004, 37,
506–517; (l) Aurelio, L.; Brownlee, R. T. C.; Hughes, A. B. Chem. Rev. 2004, 104,
5823–5846; (m) Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, 518–525; (n)
Maruoka, K.; Ooi, T. Chem. Rev. 2003, 103, 3013–3028; (o) Ma, J.-A. Angew.
Chem., Int. Ed. 2003, 42, 4290–4299; (p) Kotha, S. Acc. Chem. Res. 2003, 36, 342–
351; (q) Nájera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584–4671.
2. For reviews see: Viso, A.; Fernandez de la Pradilla, R.; Garcia, A.; Flores, A. Chem.
Rev. 2005, 105, 3167–3196. and references cited therein.
3. (a) Cox, P. A.; Banack, S. A.; Murch, S. J. Proc. Natl. Acad. Sci. 2003, 100, 13380–
13383; (b) Yoshioka, H.; Akoi, T.; Goko, H.; Nakatsu, K.; Noda, T.; Sukakibara,
M.; Take, T.; Nagata, A.; Abe, J.; Wakamiya, T.; Shiba, T.; Kaneko, T. Tetrahedron
Lett. 1971, 12, 2043–2046.
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5. (a) Guna, A.; Mishra, A. K.; Nanda, G. Trans. Rose Res. Inst. 1992, 45, 57–62; (b)
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Coulier, A. W.; Talalay, P. Mol. Pharmacol. 1970, 6, 481–489.
4.2.11. (S)-2-Carboxy-4-N-mesyl-pyperazine 15
Mp 268–270 °C (decomp.). Calcd for C6H12N2O4S: C, 34.60; N,
13.46; H, 5.81. Found: C, 34.28; N, 13.32; H, 5.72. ½a D25
¼ þ23:5 (c
ꢃ
1, 6 M HCl). 1H NMR (DMSO): 3.01 (s, 3H, CH3), 3.09 (ddd,
J = 13.0, 9.5, 3.4 Hz, 1H NHCH2–CH2N-Ms), 3.27 (ddd, J = 12.5, 9.5,
3.0 Hz, 1H, NH–CH2–CH2N–Ms), 3.34 (ddd, J = 12.5, 3.9, 3.0 Hz,
1H, NHCH2–CH2–N-Ms), 3.52 (ddd, J = 13.0, 3.9, 3.4 Hz, 1H, NH–
CH2–CH2N-Ms), 3.40 (dd, J = 12.9, 8.9 Hz, 1H, NHCH–CH2-NMs),
3.74 (dd, J = 12.9, 3.2 Hz, 1H, NHCH–CH2-NMs), 4.31 (dd, J = 8.9,
3.2 Hz, 1H, NH–CH–CH2NMs), 9.90 and 10.2 (br s, 1H both, NH
and COOH). 13C NMR: 35.73 (CH3), 42.22 (NHCH2–CH2N-Ms),
42.29 (NHCH2–CH2N-Ms), 44.61 (NHCH–CH2N-Ms), 56.47 (NHCH–
CH2N-Ms), 167.9 (COOH).
6. Saghiyan, A. S.; Avetisyan, A. E.; Djamgaryan, S. M.; Djilavayan, L. R.;
´
Gyulumyan, E. A.; Grigoryan, S. K.; Kuzmina, N. M.; Orlova, S. A.; Ikonnikov,
N. S.; Larichev, V. S.; Tararov, V. I.; Belokon´ , Y. N. Russ. Chem. Bull. 1997, 46, 483–
486.
4.2.12. X-ray crystal structure determination
7. Saghiyan, A. S.; Geolchanyan, A. V.; Djamgaryan, S. M.; Vardapetyan, S. M.;
Tararov, V. I.; Kuz´mina, N. A.; Ikonnikov, N. S.; Belokon´ , Y. N.; North, M. Russ.
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Asymmetry 2004, 15, 705–711.
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Armenia 2009, 62, 117–131.
The crystal of 7 (C28H24N3O3ClNiꢂ0.5CCl4, M = 621.57) is mono-
clinic, space group C2, at T = 120 K: a = 22.469(2), b = 8.6483(8),
c = 16.0975(14) Å, b = 120.377(2)°, V = 2698.6(4) Å3, Z = 4, dcalc
=
1.530 g/cm3, F(0 0 0) = 1276,
tions (6437 unique reflections, Rint = 0.041) were measured on
a Bruker SMART 1000 CCD diffractometer (k(MoK )-radiation,
graphite monochromator, and
scan mode, 2hmax = 56o) and
l
= 1.053 mmꢄ1. 13,897 total reflec-
a
x
u
corrected for absorption. The structure was determined by direct
methods and refined by full-matrix least squares technique on F2
with anisotropic displacement parameters for non-hydrogen
atoms. The independent part of the unit cell of 7 contains one tet-
rachloromethane solvate molecule occupying a special position on
12. Pfammatter, E.; Seebach, D.; Liebigs. Ann. Chem. 1991, 1323–1325.