N. A. Kuz'mina

Asymmetric synthesis of phosphorus analogues of dicarboxylic α-amino acids

An efficient approach to the asymmetric synthesis of phosphorus analogues of dicarboxylic α-amino acids is described. The method of choice consists in the reaction of the nickel(II) complex (4) of the Schiffs base derived from (S)-o-[(N-benzylprolyl)amino]benzophenone 3 and glycine with the appropriate alkyl halide, substituted with an alkylphosphonate group. The reactions were carried out in MeCN at 25 °C, with solid KOH as a catalyst. Michael-type base-catalysed addition of vinyl-phosphonate and vinylphosphinate to complex 4 in dimethylformamide (DMF) at 50–70 °C could also be employed. Significant diastereoselectivity (90% d.e.) was observed for the alkylation of complex 4. Optically pure (S)-phosphinothrieine, (S)-2-amino-3-phosphonopropanoic acid, (S)-2-amino-4-phosphonobutanoic acid and (S)-2-amino-5-phosphonopentanoic acid were obtained after the alkylated diastereoisomeric complexes had been separated on SiO2 and hydrolysed with aq. HCl. The initial chiral reagent 3 was recovered (60–85%). Novel amino acids 9, having free carboxy groups and esterified phosphonic and phosphinic groups, could also be obtained as intermediates due to the mild conditions of the decomposition of the alkylated diastereoisomeric complexes.

Asymmetric addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines

The asymmetric Michael addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines was carried out. The maximum chemical yield of diastereomeric products amounted to 95 %. The best asymmetric induction (42 % e.e.) was achieved in the case of catalysis by (S)-prolinol. The diastereomeric mixture was converted to a mixture of stereoisomeric 3-methyl-2-methoxycarbonylpyrrolidines. Absolute configurations of (2S,3S)-and (2R,3S)-isomers formed in excess were determined using GLC by comparison with authentic samples of racemic and optically pure forms of 3-methylproline.

Asymmetric synthesis ofS-alkyl-substituted (R)-cysteinesvia a chiral NiII complex of the Schiff's base of dehydroalanine with (S)-2-N-(N-benzylprolyl)aminobenzophenone

An efficient procedure was developed for the asymmetric synthesis ofS-alkyl derivatives of (R)-cysteine by nucleophilic addition of alkanethiols (BunSH, ButSH, ortert-C5H11SH) to the C=C bond of the dehydroalanine fragment in the NiII complex of the Schiffs base of Δ-Ala with (S)-2-N-(N-benzylprolyl)aminobenzophenone [(S)-BPB-Δ-Ala]NiII. Under conditions of thermodynamic control of the reaction, the diastereomeric excess of the complexes with the (S.R)-configuration was 88–96%. After decomposition of the complexes,(R)-S-butylcysteine,(R)-S-tert-butylcysteine, and(R)-S-tert-pentylcysteine were isolated with an enantiomeric purity of >97%.

Asymmetric synthesis of β-N-substituted α,β-diamino acidsvia a chiral complex of NiII with a dehydroalanine derivative

Asymmetric synthesis of β-N-substituted (S)-α,β-diamino acids was accomplished by Michael addition of amines to the NiII complex of the Schiff base derived from (S)-2-[N-(N′-benzylprolyl)amino]benzophenone (BPB) and dehydroalamine. Diastereoselectivity of the reaction is kinetically and thermodynamically controlled. The chiral auxiliary reagent, BPB, can be recovered and reused.

Radical cyclization of allyl α-bromocarboxylates into λ-butyrolactones. Effect of the ester structure on the cyclization

Allyl dibromoacetate, allyl α-bromopropionate, and allyl phenylbromoacetate undergo cyclization in benzene in the presence of increased concentration of Fe(CO)5—DMF as the initiating system to give the corresponding bromo-substituted butyrolactones.

Asymmetric synthesis of organoelement analogs of natural products

Michael addition of octafluoropentyl vinylsulfonate to complexes of Ni(II) with Schiffs bases derived from 5-2-N-(N-benzylprolyl)-o-aminobenzophenone and glycine orS-2-N-(N-benzylprolyl)-o-aminobenzaldehyde and alanine is a convenient preparative method for asymmetric synthesis of previously unknown fluorinated esters ofS-homocysteic acid.

Reformatsky-type addition of esters of α-halogeno carboxylic acids to aldehydes and ketones in the presence of Fe(CO)5

Reformatsky-type addition of esters of α-halogeno carboxylic acids to aldehydes and ketones in the presence of Fe(CO)5 and an activating agent (CBrCl3 or I2) afforded the corresponding esters of β-hydroxy acids in good yields. Possible reaction mechanisms are discussed.

Addition of halogenoacetic esters to aldehydes and ketones in the presence of Fe(CO)5

The use of complex-forming solvents and variations in the reaction temperature made it possible to prepare α-halogeno β-hydroxy carboxylic esters upon addition of halogenoacetic esters to aldehydes and ketones promoted by iron pentacarbonyl.

Asymmetric synthesis of organoelemental analogs of natural compounds. 7. (2R,3S)-2-amino-3-hydroxy-5-phosphonovaleric acid

The reaction of the Ni(II) complex of the Schiff base of glycine with (S)-2-N-(N1-benzylprolyl)-o-aminobenzophenone with diethyl-3-bromo-2-hydroxypropyl phosphonate yields the corresponding complex from which (2R, 3S)-2-amino-3-hydroxy-5-phosphonovaleric acid is separated with HCl.

Asymmetrical synthesis of organometallic analogs of natural compounds. 8. Reactions of pentafluorobenzaldehyde with the Ni(II) complex of a schiff base of glycine and (S)-2-[N-(benzylprolyl)amino]benzophenone

Reaction of pentafluorobenzaldehyde with a Ni(II) complex of a Schiff base formed from glycine and (S)-2-[N-(benzylprolyl)amino]benzophenone yields, depending on the reaction conditions, the hitherto unknown, diastereo-and enantiomerically pure amino acids 2R,3S-β-(4-methoxytetrafluorophenyl)serine, 2S,3R-β-(4-methoxytetrafluorophenyl)serine, 2S,3S-β-(pentafluorophenyl)serine, and 2S,3R-β-(pentafluorophenyl)serine.