N-acyl-5,5-dimethyloxazolidin-2-ones as latent aldehyde equivalents

Jordi Bach, Cécile Blachère, Steven D. Bull, Stephen G. Davies*, Rebecca L. Nicholson, Paul D. Price, Hitesh J. Sanganee, Andrew D. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

A study of the properties of N-hydrocinnamoyl- derivatives of 5,5-dimethyloxazolidin-2-one, 4,4-dimethyloxazolidin-2-one and oxazolidin-2-one upon hydride reduction with DIBAL-H demonstrates that the 5,5-dimethyl-group is essential for inhibition of endocyclic nucleophilic attack. For instance, treatment of N-hydrocinnamoyl-5,5-dimethyl-oxazolidin-2-one with DIBAL-H results in the selective formation of the stable N-1′-hydroxyalkyl derivative which may be regarded as a masked hydrocinnamaldehyde equivalent, as treatment under basic conditions affords the parent aldehyde in excellent yield. Treatment of N-hydrocinnamoyl-4,4-dimethyloxazolidin-2-one with DIBAL-H under identical conditions affords a complex mixture of products, including the formate ester product of endocyclic cleavage. As an alternate strategy, DIBAL-H reduction of straight chain and branched N-acyl-5,5-dimethyloxazolidin-2-one derivatives, followed by a Horner-Wadsworth-Emmons reaction affords α,β-unsaturated esters in good yields. Branching α- to the exocyclic carbonyl in N-acyl-oxazolidinones inhibits DIBAL-H reduction, but this can be overcome by precomplexation with ZnCl2, with subsequent fragmentation generating either the corresponding aldehyde or α,β-unsaturated esters. The addition of ZnCl2 has been shown to increase the diastereoselectivity observed in Wadsworth-Horner-Emmons reactions of lithiated phosphonates.

Original languageEnglish
Pages (from-to)2001-2010
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume1
Issue number11
DOIs
Publication statusPublished - 21 Jul 2003

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