SuperQuat N-acyl-5,5-dimethyloxazolidin-2-ones for the asymmetric synthesis of α-alkyl and β-alkyl aldehydes

Steven D. Bull, Stephen G. Davies*, Rebecca L. Nicholson, Hitesh J. Sanganee, Andrew D. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2886-2899
Number of pages14
JournalOrganic and Biomolecular Chemistry
Volume1
Issue number16
DOIs
Publication statusPublished - 21 Aug 2003

Fingerprint

Dive into the research topics of 'SuperQuat N-acyl-5,5-dimethyloxazolidin-2-ones for the asymmetric synthesis of α-alkyl and β-alkyl aldehydes'. Together they form a unique fingerprint.

Cite this