S. A. Orlova

Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines

Abstract Stereoselectivity of aldol reactions between aliphatic aldehydes and Ni(II)-complex of chiral non-racemic Schiff base of glycine with ( S )- o -[ N -( N -benzylprolyl)amino]benzophenone (BPB) in the presence of excess of MeONa, has been studied as a function of time, reaction conditions and nature of an aldehyde. Two salient features of the reaction, very high pseudokinetic syn -(2 S )-diastereoselectivity, and dependence of thermodynamic syn -(2 R )-diastereoselectivity on the steric bulk of an aldehyde side chain, were disclosed and used for efficient (more than 90% de and ee) asymmetric synthesis of both syn -(2 S ) and syn -(2 R )-3-alkyl substituted serines. Synthetic potential and reliability of this asymmetric method are demonstrated with the large scale (2–20 g) preparation of enantiomerically pure amino acids.

Asymmetric trimethylsilylcyanation of aldehydes catalyzed by chiral (salen)Ti(IV) complexes

Abstract A set of aromatic, aliphatic and α,β-unsaturated aldehydes has been asymmetrically trimethylsilylcyanated with e.e.s ranging from 40% to 80% using a chiral (salen)Ti(IV) catalyst prepared in situ from titanium tetraisopropoxide and (1R,2R)[N,N′-bis(2′-hydroxy-3′-t-butyl-benzylidene)]-1,2-diaminocyclohexane or (1R,2R)-[N,N′-bis(2′-hydroxybenzylidene)]-1,2-diaminocyclohexane.

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%.

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.

Stereoselective radical addition of carbon-centred radicals to the dehydroalanine moiety of the chiral nickel(II) complex of the Schiff′s base derived from (S)-2-[N-(N′-benzylprolyl)amino]benzophenone and dehydroalanine

A new approach to the asymmetric synthesis of β-substituted α-aminopropanoic acids by 2,2′-azoisobutyronitrile (AIBN) and Bu3SnH-initiated radical addition of Etl, PriBr, ButBr, and PhCH2Br to the dehydroalanine moiety of the NiII complex 1 of a Schiff′s base derived from (S)-o-[N-(N′-benzylprolyl)amino]benzophenone (BPB) and dehydroalanine is described. The radical addition produced a mixture of diastereoisomeric complexes 4a–d with a 40–90% excess of (S,S)diastereoisomers over the (S,R)-ones, giving the reaction products in almost quantitative yields. The diastereoselectivity of the reaction depended on the size of the entering radicals, the most effective asymmetric induction being achieved for the But radical addition. Enantiomerically pure ‘(S)-2-amino3-(tert-butyl)propanoic acid’[(S)-γ-methylleucine] and the chiral auxiliary BPB were recovered from compound 4d after its decomposition with HCl. The reactivities of the carbon–centred radicals towards the carbon-carbon double bond in the amino acid moiety of the complex 1 was quantitatively established by using ESR spectroscopy in the spin-trap technique.

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.

The first example of asymmetric Michael reaction catalyzed by chiral alkali metal alkoxides

Some chiral sodium alkoxides can be used as catalysts in the asymmetric Michael reaction as exemplified by the 1,4-addition of an achiral NiII complex of the Schiff base derived from glycine andN-(2-pyridylcarbonyl)-o-aminobenzophenone (1) to methyl methacrylate (2) or methyl acrylate (14). The products of the reaction of1 with2,viz., the corresponding diastereomeric complexes of 4-methylglutamic acid, are formed in dissimilar amounts (de 26–85%); theee value for the major diastereomer (2S,4R)-3a is 28%. After recrystallization, the enantiomeric purity of complex3a increases toee>85%. Acidcatalyzed hydrolysis of the enantiomerically enriched complex3a affords (2S,4R)-4-methylglutamic acid (ee>85%). The complex of glutamic acid15 resulting from the reaction of1 with14 is formed with anee of 45%. After recrystallization, the enantiomeric purities of complex15 and glutamic acid increase toee>90%.

Determination of stability constants of intermediates by coordination capillary GLC. Chiral complexes of NiII and CuII with Schiff's bases (1R, 2R)-N,N′-bis(3′-tert-butylsalycilidene)diaminocyclohexane and (1R,2R)-N,N′-bis[(4-hydroxy[2.2]paracyclophanyl)-5-methylene]diaminocyclohexane as GLC phases

Chiral NiII and CuII salen complexes dissolved in the polymethylphenylsiloxane phase OV-17 were used as the phases for capillary chromatography. Chiral salen lignads are Schiffs bases obtained from salicylaldehyde (SA) and (1R,2R)-diaminocyclohexane and Schiffs bases obtained by condensation of (1R,2R)- or (1S,2S)-diaminocyclohexane with (R)-4-hydroxy-5-formyl[2.2]paracyclophane (HFPC). The stability constants of the intermediates were calculated from the retention times. The complexes based on HFPC are stronger Lewis acids than those based on SA. The ability of the substrates to form intermediates decreases in the sequence: aromatic aldehydes>halogen-substituted aromatic compounds>halogen-substituted aliphatic compounds.