N. S. Ikonnikov

Synthesis, resolution and absolute configuration determination of (S)- and (R)-4-formyl-5-hydroxy [2.2]paracyclophane and its application in the asymmetric synthesis of α-amino acids

Racemic (R,S)-4-formyl-5-hydroxy[2.2]paracyclophane (FHPC) was resolved into enantiomers via its Schiffs base with (S)- and (R)-α-phenylethylamine (α-PEAM) and its absolute configuration was determined by an X-ray diffraction structural study. Scalemic FHPC or its derivatives can be used as chiral auxiliaries for the asymmetric synthesis of β-hydroxy-α-amino acids and α-methylphenylalanine with ees ranging mostly from 45 to 98%.

Elaboration of a novel type of planar-chiral methylene bridged biphenols based on [2.2]paracyclophanes

Abstract A new class of chiral methylene bridged biphenols with planar chirality has been designed and elaborated. The synthetic approach is based on the use of 4-hydroxy-5-hydroxymethyl[2.2]paracyclophane 9 derived from either racemic or enantiomerically pure ( S ) - 4 - formyl-5-hydroxy[2.2.]paracyclophane (FHPC) by reduction with LiAlH 4 . The condensation of 9 with chiral racemic 4-hydroxy[2.2]paracyclophane 4 and achiral phenols, such as 2,5-dimethylphenol 10 and 2-isopropyl-5-methylphenol 11 , afforded the target bridged biphenols 6 , 12 and 13 , respectively. The preliminary results on the asymmetric addition of Et 2 Zn to benzaldehyde promoted by ( S,S ) - 6 are reported.

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using NiII complexes of their Schiffs bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of α-methyl-α-amino acids with high enatiomeric purity (ee >95%).

Synthesis of both enantiomers of β,β-diphenyl-α-alanine (Dip) from glycine using (S)- or (R)-2-[(N-benzylprolyl)amino]benzophenone as a reusable chiral auxiliary

Abstract Preparative syntheses of enantiopure (S)- and (R)-Dip by α-C-alkylation with Ph2CHX (X=Cl or Br) of the glycine moiety in a Ni(II) Schiffs base complex 1 derived from glycine and (S)- or (R)-[(N-benzylprolyl)amino]benzophenone (BPB) is described. The diastereoselectivity of the alkylation with PhCH2Br in DMF in the presence of NaOH is both kinetically and thermodynamically controlled.

Asymmetric alkylation catalyzed by chiral alkali metal alkoxides of TADDOL. Synthesis of α-methyl amino acids

It is shown that sodium alkoxides formed from (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-bis(diphenylmethanol) ((R,R)-TADDOL) and some of its derivatives can be used as chiral catalysts for enantioselective alkylation of Schiffs bases derived from alanine with reactive alkyl halides. Acid hydrolysis of the reaction products affords (R)-α-methylphenyl-alanine, (R)-α-allylalanine, and (R)-α-methylnaphthylalanine in 61–93% yields and withee 69–94%. When (S,S)-TADDOL is used, the (S)-amino acid is formed. A mechanism explaning the observed features of the reaction is proposed.

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.

Effects of the temperature and substituents in chiral TiIV(salen) catalysts on the enantioselectivity of the addition of Me3SiCN to PhCHO

The enantiomeric purity (ee) of the addition product of Me3SiCN to PhCHO at ∼20 °C catalyzed by chiral TiIV complexes, which were preparedin situ from Ti(OPri)4 and the Schiff bases (condensation products of substituted salicylaldehydes with (1R, 2R)-1,2-diaminocyclohexane), was, on the average, 20–30% lower than that achieved at −80 °C. The substituents at position 5 of 3-tert-butylsalicylaldehyde exert only the steric effect. It was shown that the stereochemical result of the reaction is controlled by the stage which involves the formation of the C−C bond rather than the transfer of the Me3Si group.

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.

Metal-dependent stereochemistry of C—C bond formation under the asymmetric phase transfer catalysis by chiral salen complexes

The effect of the nature of the central metal atom in chiral salen type complexes on the stereodifferentiating capacity of these complexes as catalysts in phase transfer asymmetric alkylation of Schiffs base derived from alanine isopropyl ester and benzaldehyde by benzyl bromide. The nature of the central metal atom in the complex has a pronounced influence on the stereochemistry of alkylation; copper(ii) complexes exhibit the highest activity combined with a high stereoselectivity.