Kinetic Resolution Conditions Research Articles

N-Phthaloyl-( S)-alanyl chloride as a chiral resolving agent for the kinetic resolution of heterocyclic amines

Acylation of heterocyclic amines with N-phthaloyl-( S)-alanyl chloride under kinetic resolution conditions resulted in the predominant formation of ( S, S)-amides. The diastereoselectivity of resolution depended heavily on the structure of the resolved amine.

Enzymatic reactions in ionic liquids: lipase-catalysed kinetic resolution of racemic, P-chiral hydroxymethanephosphinates and hydroxymethylphosphine oxides

Lipase-mediated acetylation of racemic P-chiral hydroxymethanephosphinates and hydroxymethylphosphine oxides was performed in ionic liquids under kinetic resolution conditions. Lipase AK (Amano) and lipase from Pseudomonas fluorescens (Fluka) were up to six times more enantioselective in BMIM·PF6 solutions than in common organic solvents. On the contrary, the analogous reactions performed in BMIM·BF4 were practically non-stereoselective.

Biocatalytic syntheses of chiral non-racemic 2-hydroxyalkanephosphonates

A series of 2-oxoalkanephosphonates 2 were screened for reduction with Geotrichum candidum. Only diethyl 2-oxopropanephosphonate 2a underwent asymmetric reduction to give (+)-( R)-diethyl 2-hydroxypropanephosphonate 3a with 98% e.e. In turn, a series of racemic 2-hydroxyalkanephosphonates 3 were acetylated under kinetic resolution conditions in the presence of various lipases to give the corresponding 2-acetoxyalkanephosphonates 4 and recovered alcohols 3 in good yields and with e.e. up to 93%.

Kinetic resolution of P-chiral tertiary phosphines and chlorophosphines: a new approach to optically active phosphoryl and thiophosphoryl compounds

Treatment of racemic P-stereogenic tertiary phosphines with enantiomerically pure bis-phosphoryl and bis-thiophosphoryl disulfides under kinetic resolution conditions (2:1 ratio) afforded enantiomerically enriched tertiary phosphine oxides or phosphine sulfides with ee values up to 39%. In a similar way from racemic tert-butylphenylchlorophosphine, optically active tert-butylphenylphosphinoyl chloride with 50% ee was obtained. The same reaction performed under dynamic kinetic resolution conditions (1:1 ratio of reagents) in the presence of chloride ions gave phosphinoyl chloride with 70% ee.

Enzymatic Reduction of Hydrophobic β,δ-Diketo Esters

The regio- and enantioselective reduction of two hydrophobic β,δ-diketo esters is presented. Enzymatic reduction of racemic tert-butyl 4-methyl-3,5-dioxohexanoate (rac-1) with alcohol dehydrogenase from Lactobacillus brevis (recLBADH) gave δ-hydroxy-β-keto ester syn-(4S,5R)-4 under dynamic kinetic resolution conditions (99.2% ee, syn:anti = 97:3, 66% isolated yield). The highly lipophilic tert-butyl-3,5-dioxoheptanoate (2) was reduced with the same sense of enantio- and regioselectivity by recLBADH. A biphasic system was applied in this case. The product, δ-hydroxy-β-keto ester (R)-9 (98.5% ee, 66% isolated yield), was converted into (R)-6-ethyl-5,6-dihydropyran-2-one [(R)-10], which is a naturally occurring fragrance.

On the applicability of the Jones active site model of pig liver esterase to S-chiral and prochiral sulfinyl substrates

A series of racemic methyl sulfinylacetates was hydrolyzed in the presence of pig liver esterase (PLE) under kinetic resolution conditions to give the corresponding S-chiral sulfinylacetic acids and recovered esters in moderate enantiomeric purity. The Jones active site model was found to be suitable for explaining the enantioselectivity of the above reaction and for the PLE-mediated desymmetrization of prochiral sulfinyldicarboxylates.

N-Carbamylamino Alcohols as the Precursors of Oxazolidinones via Nitrosation-Deamination Reaction

Oxazolidinones were effectively prepared from N-carbamylamino alcohols by treatment with nitrous acid, via N-nitroso compound as the intermediate. A new route to (R)-4-benzyloxazolidinone was developed starting from dl-phenylalanine, utilizing d-hydantoinase-catalyzed enantioselective hydrolysis of 5-benzylhydantoin under the dynamic kinetic resolution conditions, and the subsequent reduction to the precursor for the above-mentioned cyclization reaction, by taking advantage of the intermediates bearing an N-carbamylamino functionality.

Lipase-promoted kinetic resolution of racemic, P-chiral hydroxymethylphosphonates and phosphinates

Lipase-mediated acetylation of racemic P-chiral hydroxymethylphosphonates and phosphinates, and hydrolysis of their O-acetyl derivatives have been conducted under kinetic resolution conditions to give the enantiomerically enriched title products with up to 92% ee. Their absolute configuration has been determined by means of chemical correlation and CD measurements.

Enzyme-promoted kinetic resolution of racemic, P-chiral phosphonyl and phosphorylacetates

A series of racemic methyl phosphonyl- and phosphorylacetates were hydrolyzed in the presence of porcine liver esterase (PLE) under kinetic resolution conditions to give the corresponding P-chiral phosphonyl- and phosphorylacetic acids and recovered esters in moderate to high enantiomeric purity (up to 95% ee). The Jones PLE active site model was applied to explain the enantioselectivity of this reaction.