Diastereoselective synthesis of highly functionalized I22,2,3-substituted amino acids from 4-substituted-1,3-oxazinan-6-ones

1,3-Oxazinan-6-ones were used to generate substituted I22,2,3-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. T...

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Bibliographic Details
Published in:Tetrahedron 2012-06, Vol.68 (24), p.4745-4756
Main Authors: Nguyen, Nghi H, Sleebs, Brad E, White, Jonathan M, Hughes, Andrew B
Format: Article
Language:English
Subjects:
Amino acids
Cleavage
Derivatives
Esters
Hydrolysis
Solvolysis
Synthesis
Tetrahedrons
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Summary:1,3-Oxazinan-6-ones were used to generate substituted I22,2,3-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 I22,2,3-substituted amino acids by reductive cleavage. Hydrolysis or solvolysis of the oxazinanones afforded I22,2,3-substituted amino acids or esters, respectively. The chemistry thus provides access to a range of symmetrical and stereopure I22,2,3-substituted amino acids and further establishes 1,3-oxazinan-6-ones as useful intermediates.
ISSN:0040-4020
DOI:10.1016/j.tet.2012.04.012