Diastereoselective synthesis of highly functionalized β 2,2,3-substituted amino acids from 4-substituted-1,3-oxazinan-6-ones

Nghi H. Nguyen, Brad E Sleebs, Jonathan M. White, Andrew B Hughes

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

1,3-Oxazinan-6-ones were used to generate substituted β 2,2,3-substituted amino acid derivatives. The enolates of 1,3-oxazinan-6-ones were trans-selectively intercepted with electrophiles. This alkylation was subsequently optimized for a one-pot dialkylation to form 5,5-disubstituted oxazinanones. The initial 5-monomethylated compounds could be enolized and then diastereoselectively intercepted with different electrophiles to form differentially 5,5-disubstituted products. The 5,5-dialkylated oxazinanones were then transformed to N-methyl β2,2,3- substituted amino acids by reductive cleavage. Hydrolysis or solvolysis of the oxazinanones afforded β2,2,3-substituted amino acids or esters, respectively. The chemistry thus provides access to a range of symmetrical and stereopure β2,2,3-substituted amino acids and further establishes 1,3-oxazinan-6-ones as useful intermediates.

Original languageEnglish
Pages (from-to)4745-4756
Number of pages12
JournalTetrahedron
Volume68
Issue number24
DOIs
Publication statusPublished - 17 Jun 2012
Externally publishedYes

Keywords

  • Beta-amino acids
  • Enolate
  • N-Methyl amino acids
  • Oxazinanones
  • Stereoselective

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