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

New chiral NiII 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.

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C28H24N3O3NiF[α]D20=+2337.5 (c 0.08, CH3OH/СНCl3 (3:1))Source of chirality: asymmetric synthesisAbsolute configuration: (S)

l-β-(N-Isopropylamino)-α-alanineC6H14N2O2Ee pure[α]D20=-32.5 (c 0.16, 6M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Carboxy-4-N-mesyl-pyperazineC6H12N2O4SEe pure[α]D20=+1813 (c 0.058, МеОН)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C31H33N4O3ClNi[α]D20=+1985.3 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C31H28ClN5NiO3Ee pure[α]D20=+2333.4 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C29H29ClN4NiO3Ee pure[α]D20=+2876.2 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C30H31ClN4NiO4Ee pure[α]D20=+1896.4 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C32H35ClN4NiO5Ee pure[α]D20=+1653.3 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C31H33ClN4NiO3Ee pure[α]D20=+2186.3 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C30H30N3O4SNiClEe pure[α]D20=+1940 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

C35H33N4NiO3F[α]D20=+1678.0 (c 0.05, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C31H28N5O3NiFEe pure[α]D20=+1940 (c 0.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C29H29N4NiO3FEe pure[α]D20=+3969.9 (c 0.18, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C30H31N4NiO4FEe pure[α]D20=+2384.8 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C32H35N5O4NiFEe pure[α]D20=+2941.7 (c 0.42, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C31H33N4NiO3FEe pure[α]D20=+3585.3 (c 0.19, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

C30H30N3NiO3SFEe pure[α]D20=+3192.8 (c 0.32, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)