168297-86-7

An alternative methodology for the synthesis of chiral 3-(p-tolyl) butanoic acids is presented. This was accomplished through the diastereoselective hydrogenation reaction of different chiral N-3-(p-tolyl) but-2-enamides, using Pd/C in EtOH, to produce the corresponding chiral N-3-(p-tolyl) butanamides with high chemical yields and moderate diastereomeric ratios. Removal of the chiral auxiliary from N-3-(p-tolyl) butanamides gave the respective enantiomerically pure acids.

A highly efficient chiral auxiliary-based strategy for the asymmetric synthesis of P-chiral phosphine oxides in >98:2 er has been developed. The methodology involves the highly stereoselective formation of P-chiral oxazolidinones that then undergo displacement with a variety of Grignard reagents to prepare the desired phosphine oxides.

Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4- isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium β-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2′-alkylacryloyl)-4-isopropyl-5,5- dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of β-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of β-amino- β′-hydroxy N-acyl oxazolidinones. The Royal Society of Chemistry.

(2S,3S,1′R)-2-(α-Methoxybenzyl)-3-phenyl-3- sulfanylpropionamides were diastereoselectively prepared by the reactions of N-cinnamoyl-4S-isopropyl-5,5-dimethyloxazolidinethione with acetals in the presence of SnCl4. The absolute configuration of the three newly created contiguous stereocenters was determined by the X-ray analysis of the disulfide. The amides were transformed into propanols by the reductive removal of the oxazolidinone moiety.

The proclivity of α-branched N-2′-benzyl-3′-phenylpropionyl derivatives of (S)-4-benzyl-5,5-dimethyl-, (S)-4-phenyl-5,5-dimethyl-, (S)-4-isopropyl-5,5-dimethyl-, (S)-4-benzyl- and (S)-4-benzyl-5,5-diphenyl-oxazolidin-2-ones to generate directly 2-benzyl-3-phenylpropionaldehyde upon hydride reduction with DIBAL is investigated. The (S)-4-benzyl-5,5-dimethyl-derivative proved optimal for inhibition of endocyclic nucleophilic attack, giving 2-benzyl-3-phenylpropionaldehyde in good yield upon reduction. Application of this methodology for the asymmetric synthesis of chiral aldehydes via diastereoselective enolate alkylation of a range of (S)-N-acyl-4-benzyl-5,5-dimethyloxazolidin-2-ones to afford an array of α-substituted-N-acyl-5,5-dimethyloxazolidin-2-ones (85-94% de) and subsequent reduction with DIBAL afforded directly non-racemic α-substituted aldehydes without loss of stereochemical integrity (87-94% ee). The extension of this protocol for the asymmetric synthesis of β-substituted aldehydes is demonstrated, via the diastereoselective conjugate addition of a range of organocuprates to (S)-N-acyl-4-phenyl-5,5-dimethyloxazolidin-2-ones which proceeds with high diastereoselectivity (generally >95% de). Reduction of the conjugate addition products with DIBAL gives non-racemic β-substituted aldehydes in high yields and in high ee (generally >95% ee). This methodology is exemplified by the asymmetric synthesis of (R)-3-isopropenylhept-6-enal, which has previously been used in the synthesis of (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate, a component of the sex pheromones of the California red scale.

The 1,3-oxazolidinethione 4 has been synthesized from (S)-valine and used in the intramolecular sulfur transfer in its N-enoyl derivatives in the presence of NbCl5 as catalyst, which, moreover, works as an indicator of the course of the reactio