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Belokon et al.
2.67—2.92 (m, 1 H, βꢀH Pro); 3.26—3.48 (m, 3 H, δꢀH,
αꢀH Pro); 3.68, 3.75 (AB system, 2 H, CH2 Gly, JA,B = 19.6 Hz);
4.02 (s, 3 H, OMe); 4.12, 4.41 (AB system, 2 H, NCH2Ar,
JA,B = 12.3 Hz); 6.61—7.48 (m, 7 H, Ar); 8.38 (m, 1 H, Ar).
Alkylation of complexes 6 with BnBr and MeI (general proꢀ
cedure). Complex 6 (0.53 mmol), DMF (2 mL), and alkylating
reagent (0.53 mmol) were placed in an argonꢀfilled flask, the
mixture was cooled, the argon was pumped out, the flask was
filled again with argon, and NaH (0.053 g, 1.325 mmol) was
added. The mixture was stirred under argon for 5—10 min.
The reaction was monitored by TLC (SiO2, elution with
AcOEt—CHCl3, 4 : 1). After completion of the reaction, 2 mL
of a 3 M solution of MeONa in MeOH was added, and the
mixture was stirred for an additional 10—15 min, neutralized
with AcOH, and diluted with 20 mL of H2O. The precipitate
was washed with water, and in the case of BnBr, additionally
with hexane. The (S,S)ꢀ/(S,R)ꢀisomer ratio was determined by
1H NMR spectroscopy.
2.51, 3.61 (AB system, 2 H, CH2Ph, JA,B = 17.5 Hz); 3.00,
3.16 (AB system, 2 H, CH2Ph, JA,B = 14.6 Hz); 3.61, 4.50
(AB system, 2 H, NCH2Ar, JA,B = 13.2 Hz); 4.51 (m, 1 H,
Me2CHO); 6.49—7.63 (m, 18 H, Ar); 7.96 (m, 1 H, Ar).
2ꢀBenzylphenylalanine was isolated from complexes 8b,c in
68% yield, m.p. 288—290 °C. Found (%): C, 72.93; H, 6.63;
N, 5.11. C16H18NO2•0.5 H2O. Calculated (%): C, 72.73;
H, 6.59; N, 5.30. 1H NMR (D2O), δ: 2.86, 3.23 (AB system,
4 H, CH2Ph, JA,B = 14.4 Hz); 6.94—7.12 (m, 10 H, Ar).
Alkylation of complexes 5 with alkyl halides (general proceꢀ
dure). The reaction was carried out by a procedure similar to
that described above for the alkylation of complexes 6. Comꢀ
plex 5a (0.34 mmol), DMF (1 mL), alkyl halide (0.68 mmol),
and NaH (0.041 g, 1.02 mmol) were used. After completion of
the reaction (2 h), the reaction mixture was neutralized
with AcOH, diluted with water, and extracted with CHCl3
(3×10 mL). The chloroform extracts were concentrated and
the residue was treated with hexane (to remove traces of the
alkylating reagent) and Et2O. The precipitate was filtered off.
(S)ꢀ{({2ꢀ[1ꢀ(3,4ꢀDichlorobenzyl)pyrrolidineꢀ2ꢀcarboxꢀ
amide]phenyl}phenylmethylene)ꢀ(S)ꢀ2ꢀbenzylalaninatoꢀ
N,N´,N″,O}nickel(II) ((S)ꢀ9a). Yield 0.17 g (85%) (96% degree
of conversion according to 1H NMR spectroscopy), m.p. 191 °C,
(S)ꢀ{({2ꢀ[1ꢀ(3,4ꢀDichlorobenzyl)pyrrolidineꢀ2ꢀcarboxꢀ
amide]phenyl}phenylmethylene)ꢀ(S)ꢀphenylalaninatoꢀ
N,N´,N″,O}nickel(II) ((S)ꢀ7a). Yield 75%, m.p. 144—145 °C,
25
[α]D +2273 (c 0.3, MeOH). Found (%): C, 62.03; H, 4.37;
N, 6.11. C34H29Cl2N3NiO3. Calculated (%): C, 62.10; H, 4.41;
N, 6.39. 1H NMR, δ: 1.71 (m, 1 H, βꢀH Pro); 1.88 (m, 1 H,
γꢀH Pro); 2.30 (m, 3 H, γꢀH, βꢀH, δꢀH Pro); 2.82, 3.08 (AB part
25
[α]D +1860 (c 0.3, MeOH). Found (%): C, 62.76; H, 4.75;
N, 6.18. C35H31Cl2N3NiO3. Calculated (%): C, 62.59; H, 4.62;
N, 6.30. 1H NMR, δ: 1.15 (s, 3 H, Me αꢀMePhe); 1.55—1.78
(m, 1 H, βꢀH Pro); 1.80—1.89 (m, 1 H, γꢀH Pro); 2.00—2.12
(m, 1 H, βꢀH Pro); 2.15—2.39 (m, 2 H, γꢀH, δꢀH Pro);
3.07—3.25 (m, 4 H, αꢀH, δꢀH Pro, CCH2Ph); 3.19, 4.16
(AB system, 1 H, NCH2Ar, JA,B = 13.0 Hz); 6.57—6.70 (m,
2 H, Ar); 6.79 (m, 1 H, Ar); 7.10—7.65 (m, 12 H, Ar); 8.05 (m,
1 H, Ar); 8.95 (s, 1 H, Ar).
of an ABX system, 2 H, CH2 Phe, JA,B = 13.6 Hz, JA,X
=
5.6 Hz, JB,X = 4.0 Hz); 3.00—3.22 (m, 2 H, αꢀH, δꢀH Pro);
3.11, 4.16 (AB system, 2 H, NCH2Ph, JA,B = 12.4 Hz); 4.28
(X part of an ABX system, 1 H, αꢀH Phe); 6.65 (m, 2 H, Ar);
6.80 (m, 1 H, Ar); 7.10—7.68 (m, 12 H, Ar); 8.12 (m, 1 H, Ar);
8.89 (s, 1 H, Ar).
25
(S)ꢀ5a. Yield 74%, m.p. 327 °C, [α]D +2821 (c 0.3,
MeOH). Found (%): C, 57.85; H, 4.70; N, 6.89.
C28H25Cl2N3NiO3. Calculated (%): C, 57.87; H, 4.34; N, 7.23.
1H NMR, δ: 1.61 (d, 3 H, Me Ala, J = 7.0 Hz); 2.09 (m, 1 H,
γꢀH Pro); 2.29 (m, 1 H, βꢀH Pro); 2.63 (m, 1 H, γꢀH Pro);
2.75 (m, 1 H, βꢀH Pro); 3.43 (m, 1 H, αꢀH Pro); 3.59 (m, 1 H,
δꢀH Pro); 3.77 (m, 1 H, δꢀH Pro); 3.94 (m, 1 H, αꢀH Ala);
4.32, 4.35 (AB system, 2 H, NCH2Ar, JA,B = 12.5 Hz); 6.65
(m, 2 H, Ar); 6.92 (m, 1 H, Ar); 7.17 (m, 1 H, Ar); 7.32—7.57
(m, 5 H, Ar); 7.82 (m, 1 H, Ar); 8.00 (m, 1 H, Ar); 8.84
(s, 1 H, Ar).
(S)ꢀ{({2ꢀ[1ꢀ(4ꢀIsopropoxytetrafluorobenzyl)pyrrolidineꢀ2ꢀ
carboxamide]phenyl}phenylmethylene)ꢀ(S)ꢀ2ꢀbenzylalaninatoꢀ
N,N´,N″,O}nickel(II) ((S)ꢀ9c). Yield 77%. H NMR, δ: 1.15 (s,
3 H, Me αꢀMePhe); 1.32 (m, 6 H, Me2CHO); 1.48—1.76 (m,
2 H, βꢀH, γꢀH Pro); 1.77—2.10 (m, 1 H, γꢀH Pro); 2.21—2.48
(m, 2 H, βꢀH, δꢀH Pro); 2.91—3.29 (m, 2 H, αꢀH, δꢀH Pro);
3.05 (s, 2 H, CH2Ph); 4.04, 4.13 (AB system, 2 H, NCH2Ar,
JA,B = 13.5 Hz); 4.41—4.68 (m, 1 H, Me2CHO); 6.66 (m, 2 H,
Ar); 7.05 (m, 1 H, Ar); 7.19—7.61 (m, 10 H, Ar); 8.35
(m, 1 H, Ar).
1
Alkylation of complexes 6b,c with BnBr. These reactions
(for reaction conditions, see above) afford bisꢀalkylated prodꢀ
ucts, i.e., complexes of αꢀaminoisobutyric acid 8b,c (with a
15% impurity of the initial glycine complex according to
1H NMR data).
(S)ꢀ{({2ꢀ[1ꢀ(4ꢀMethoxytetrafluorobenzyl)pyrrolidineꢀ2ꢀ
carboxamide]phenyl}phenylmethylene)ꢀ(S)ꢀ2ꢀbenzylalaninatoꢀ
N,N´,N″,O}nickel(II) ((S)ꢀ9d). Yield 81%. H NMR, δ: 1.14 (s,
1
3 H, Me αꢀMePhe); 1.51—1.74 (m, 2 H, βꢀH, γꢀH Pro);
1.77—2.14 (m, 1 H, γꢀH Pro); 2.23—2.45 (m, 2 H, βꢀH, δꢀH
Pro); 2.89—3.32 (m, 2 H, αꢀH, δꢀH Pro); 3.08 (s, 2 H, CH2Ph);
3.91, 4.19 (AB system, 2 H, NCH2Ar, JA,B = 13.2 Hz); 3.98 (s,
3 H, OMe); 6.65 (m, 2 H, Ar); 6.95 (m, 1 H, Ar); 7.17—7.51
(m, 10 H, Ar); 8.29 (m, 1 H, Ar).
(S)ꢀ{({2ꢀ[1ꢀ(4ꢀMethoxytetrafluorobenzyl)pyrrolidineꢀ2ꢀ
carboxamide]phenyl}phenylmethylene)ꢀ(S)ꢀ2ꢀethylalaninatoꢀ
N,N´,N″,O}nickel(II) ((S)ꢀ10d). Yield 35%. 1H NMR, δ: 1.19
(s, 3 H, αꢀMe Iva); 1.50 (m, 3 H, MeCH2, Iva); 1.71 (m, 2 H,
MeCH2, Iva); 1.81—1.94 (m, 1 H, γꢀH Pro); 2.07—2.21 (m,
1 H, βꢀH Pro); 2.55—2.69 (m, 1 H, γꢀH Pro); 2.88—3.03 (m,
1 H, βꢀH Pro); 3.19—3.39 (m, 2 H, αꢀH, δꢀH Pro); 3.40—3.49
(m, 1 H, δꢀH Pro); 4.03 (s, 3 H, OMe); 4.13, 4.36 (AB system,
2 H, NCH2Ar, JA,B = 13.4 Hz); 6.68 (m, 2 H, Ar); 6.97 (m,
1 H, Ar); 7.15—7.55 (m, 5 H, Ar); 8.17 (m, 1 H, Ar).
(S)ꢀ{({2ꢀ[1ꢀ(Pentafluorobenzyl)pyrrolidineꢀ2ꢀcarboxꢀ
amide]phenyl}phenylmethylene)ꢀ2ꢀbenzylphenylalaninatoꢀ
N,N´,N″,O}nickel(II) (8b). Yield 78%. 1H NMR, δ: 1.63—1.84
(m, 1 H, γꢀH Pro); 2.03—2.22 (m, 1 H, βꢀH Pro); 2.23—2.41
(m, 1 H, γꢀH Pro); 2.42—2.65 (m, 3 H, βꢀH, δꢀH Pro);
2.62, 3.29 (AB system, 2 H, CH2Ph, JA,B = 16.6 Hz); 3.02,
3.12 (AB system, 2 H, CH2Ph, JA,B = 10.0 Hz); 3.83, 4.76
(AB system, 2 H, NCH2Ar, JA,B = 13.2 Hz); 3.52—3.64 (m,
1 H, αꢀH Pro); 6.52—7.53 (m, 18 H, Ar); 8.26 (m, 1 H, Ar).
(S)ꢀ{({2ꢀ[1ꢀ(4ꢀIsopropoxytetrafluorobenzyl)pyrrolidineꢀ2ꢀ
carboxamide]phenyl}phenylmethylene)ꢀ2ꢀbenzylphenylalaninatoꢀ
N,N´,N″,O}nickel(II) (8c). Yield 74%. 1H NMR, δ: 1.22—1.31
(m, 6 H, CHMe2); 1.50—1.64 (m, 1 H, γꢀH Pro); 1.64—2.05
(m, 2 H, βꢀH, γꢀH Pro); 2.11—2.46 (m, 3 H, βꢀH, δꢀH Pro);