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

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• 作者：Nghi H. Nguyen^a ; Brad E. Sleebs^b ; ^c ; Jonathan M. White^d ; Andrew B. Hughes^a ; ^{andrew.hughes2@optusnet.com.au}
• 关键词：Beta-amino acids ; Oxazinanones ; Stereoselective ; Enolate ; N-Methyl amino acids
• 刊名：Tetrahedron
• 出版年：2012
• 期刊代码：107_00404020
• 类别：ch
• 出版时间：17 June, 2012
• 卷：68
• 期：24
• 页码：4745-4756
• 文件大小：607 K

摘要

1,3-Oxazinan-6-ones were used to generate substituted 尾^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 尾^2,2,3-substituted amino acids by reductive cleavage. Hydrolysis or solvolysis of the oxazinanones afforded 尾^2,2,3-substituted amino acids or esters, respectively. The chemistry thus provides access to a range of symmetrical and stereopure 尾^2,2,3-substituted amino acids and further establishes 1,3-oxazinan-6-ones as useful intermediates.