Yuri N. Belokon

Improved procedures for the synthesis of (S)-2-[N-(N′-benzylprolyl)amino]benzophenone (BPB) and Ni(II) complexes of Schiff's bases derived from BPB and amino acids

(S)-N-Benzylproline (BP) was obtained by the reaction of (S)-proline and benzylchloride in high chemical yield (89%). (S)-2-[N-(N′-Benzylprolyl)amino]benzophenone (BPB) was synthesized in amounts greater than 100 g by the SOCl2 promoted condensation of BP with 2-aminobenzophenone (yield 82%). Ni(II) complexes of Schiffs bases derived from BPB and amino acids were prepared by an improved procedure involving the use of KOH as a base and MeOH as solvent (yield 90–91%).

The asymmetric addition of trimethylsilyl cyanide to ketones catalysed by a bimetallic, chiral (salen)titanium complex

Abstract The use of a bimetallic titanium salen complex as a catalyst for the asymmetric addition of trimethylsilylcyanide to ketones is reported. The cyanohydrin trimethylsilyl ethers are obtained with enantiomeric excesses of up to 72% from reactions carried out at room temperature and atmospheric pressure employing 0.5 mol% of the catalyst.

Mechanistic Investigation of the Asymmetric Addition of Trimethylsilyl Cyanide to Aldehydes Catalysed by Dinuclear Chiral (Salen)titanium Complexes

Titanium complexes 1 derived from chiral salen ligands are highly active precatalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and ketones. Based on spectroscopic studies and the identification of adducts between complexes 1 and carbonyl compounds or trimethylsilyl cyanide, a catalytic cycle which explains the origin of the asymmetric induction is proposed. Kinetics studies have been carried out, the results of which are consistent with the proposed catalytic cycle.

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.

Asymmetric trimethylsilylcyanation of benzaldehyde catalyzed by (salen)Ti(IV) complexes derived from (R)- and/or (S)-4-hydroxy-5-formyl[2.2]paracyclophane and diamines

Benzaldehyde has been asymmetrically trimethylsilylcyanated, using chiral (salen)Ti(IV) catalysts 1a and 1b, 2a and 2b, 3a and 3b prepared in situ from titanium tetraisopropoxide and the Schiffs bases derived from (R)- or (S)-4-hydroxy-5-formyl[2.2]paracyclophane [(R)- and (S)-FHPC] and diaminoethane (EDA) (catalysts 1a or 1b); (R)- or (S)-FHPC and 1,3-diaminopropane (PDA) (catalysts 2a or 2b); (R)- or (S)-FHPC and (1R,2R)-1,2-diaminocyclohexane [(1R,2R)-CHDA] (catalysts 3a and 3b). Surprisingly, 1a and 1b were found to be the most efficient catalysts whereas both enantiomers of 2 were completely inactive. The maximum e.e. of 84% (S) at −78°C was obtained in the reaction catalysed by 1b at 5–10 mol%. The catalyst could be precipitated with hexane from the reaction mixture and reused.

Regioselective Fries Rearrangement and Friedel−Crafts Acylation as Efficient Routes to Novel Enantiomerically Enriched ortho-Acylhydroxy[2.2]paracyclophanes

Two useful approaches to ortho-acylhydroxy[2.2]paracyclophanes, starting from 4-hydroxy[2.2]paracyclophane, have been developed. TiCl4-catalyzed Fries rearrangement and direct acylation occur regioselectively (to the ortho position with respect to the hydroxy group), leading to 4-acetyl-5-hydroxy[2.2]paracyclophane (3) and 4-benzoyl-5-hydroxy[2.2]paracyclophane (4) in high to excellent chemical yields. For compound 4, an X-ray investigation has been performed. ortho-Acylhydroxy[2.2]paracyclophanes 3 and 4 have been obtained in enantiomerically enriched forms (ee 92−99%) and the absolute configurations of their enantiomers have been determined.

A new synthesis of enantiomerically pure syn-(S)-β-hydroxy-α-amino acids via asymmetric aldol reactions of aldehydes with a homochiral Ni(II)-glycine/(S)-BPB Schiff base complex

syn-(S)-β-Hydroxy-α-amino acids were synthesised stereoselectively via elaboration of the asymmetric aldol reactions of aldehydes with a chiral Ni(II)-(S)-BPB/glycine Schiff base complex in the presence of equimolar NaH in THF. The stereoselectivity of the reaction was studied as a function of time, the reaction conditions, the nature of the carbonyl compounds and the base used. The synthetic potential of this asymmetric method was demonstrated in the preparation of syn-(S)-β-hydroxyleucine on a multi-gram scale.

An improved synthesis of (S)-(+)- and (R)-(−)-[2.2]paracyclophane-4-carboxylic acid

Abstract Treatment of 4-bromo[2.2]paracyclophane with n-butyllithium followed by CO2 produced [2.2]paracyclophane-4-carboxylic acid, 1. Both enantiomeric forms [63% of (+)-(S)-1 and 48% of (−)-(R)-1] were obtained by resolution via the corresponding diastereomeric α-(p-nitrophenylethylammonium salts.

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.