Asymmetric 1,3-Dipolar Cycloaddition Reactions

Stereoselective synthesis of quaternary α-amino acids. Part 1: Acyclic compounds

Synthetic Aspects of the Di-pi-methane Rearrangement.

Preparations of two pivotal intermediates for the synthesis of 1-β-methyl carbapenem antibiotics

Highly Enantioselective Phase Transfer Catalyzed Alkylation of a 3-Oxygenated Propionic Ester Equivalent; Applications and Mechanism

Alkylation enantioselective des dianions derives des monoesters chiraux d'acides maloniques monosubstitues avec des halogenures d'alkyles

Enantioselective construction of a quaternary asymmetric carbon center: a versatile synthesis of .alpha.-alkyl .alpha.-amino acids

Synthesis of the key intermediate of the 1β-methylcarbapenem antibiotic (1) was investigated by way of inter- and intramolecular nitrone 1,3-dipolar cycloaddition. A highly enantioselective construction of (3S,4R)-(–-)-3-[(1R)-1-(t-butyldimethylsiloxy)ethyl]-4-[(1R)-1-(hydroxymethyl)ethyl]azetidin-2-one (2) was achieved via intramolecular cycloaddition of the nitrone (6).

Enantioselective synthesis of the key intermediate of a 1β-methylcarbapenem antibiotic by way of nitrone 1,3-dipolar cycloaddition

Syntheses of chiral intermediates having one tertiary asymmetric centre were carried out via chiral half-esters of monoalkylmalonic acids. The menthyl half-ester of ethylmalonic acid afforded a single diastereoisomer through crystallisation-induced asymmetric transformation (second-order asymmetric transformation). Furthermore enantioselective preparation of unsymmetrical propane-1,3-diol derivatives was achieved by the use of 8-phenylmenthyl half-esters.

Asymmetric syntheses of chiral propane-1,3-diols starting from malonic acid

Substitution of the chiral half-esters of monosubstituted malonic acids with halides leads to the formations of mixtures of the diastereoisomeric alkyl- or benzyl-malonic half-esters. The (R)-isomers (13A and 15A–22A) were obtained from the phenylmenthyl half-ester 14 of methylmalonic acid in high diastereoisomeric excess. The same stereoisomers were also produced by reaction of the half-esters 9, 23 and 24 with methyl iodide. Their absolute configurations were determined by transforming the major products into the known α-alkyl α-amino acid derivatives 30, 33 and 35. The major product 43, prepared by allylation of the half-ester 9, was converted into two lactones 41 and 42, key intermediates for synthesis of indole alkaloids of the Hunteria and Aspidosperma types. The mechanism of the above alkylation is discussed.

Stereoselective alkylation of dianions derived from chiral half-esters of monosubstituted malonic acids: asymmetric synthesis of α-alkyl α-amino acids and key synthetic intermediates for Hunteria and Aspidosperma indole alkaloids

The key synthetic intermediate of 1β-methylcarbapenem antibiotic, (–)-(3S, 4R)-3-[(1R)-1-t- butyl-dimethylsiloxyethyl]-4-[(2R)-2-(1-hydroxypropyl)]azetidin-2-one (2), was synthesised from (R)-methyl 3-hydroxy-2-methylpropionate with high stereoselectivity via intramolecular nitrone 1,3-dipolar cycloaddition.

Masanobu Takahashi

Papers

Enantioselective construction of a quaternary asymmetric carbon center: a versatile synthesis of .alpha.-alkyl .alpha.-amino acids

Enantioselective synthesis of the key intermediate of a 1β-methylcarbapenem antibiotic by way of nitrone 1,3-dipolar cycloaddition

Asymmetric syntheses of chiral propane-1,3-diols starting from malonic acid

Stereoselective alkylation of dianions derived from chiral half-esters of monosubstituted malonic acids: asymmetric synthesis of α-alkyl α-amino acids and key synthetic intermediates for Hunteria and Aspidosperma indole alkaloids

Highly stereocontrolled synthesis of the key intermediate of 1β-methylcarbapenem antibiotic via intramolecular nitrone 1,3-dipolar cycloaddition