TY - JOUR
T1 - Diastereoselective synthesis of highly functionalized β 2,2,3-substituted amino acids from 4-substituted-1,3-oxazinan-6-ones
AU - Nguyen, Nghi H.
AU - Sleebs, Brad E
AU - White, Jonathan M.
AU - Hughes, Andrew B
PY - 2012/6/17
Y1 - 2012/6/17
N2 - 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.
AB - 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.
KW - Beta-amino acids
KW - Enolate
KW - N-Methyl amino acids
KW - Oxazinanones
KW - Stereoselective
UR - http://www.scopus.com/inward/record.url?scp=84861221239&partnerID=8YFLogxK
U2 - 10.1016/j.tet.2012.04.012
DO - 10.1016/j.tet.2012.04.012
M3 - Article
AN - SCOPUS:84861221239
SN - 0040-4020
VL - 68
SP - 4745
EP - 4756
JO - Tetrahedron
JF - Tetrahedron
IS - 24
ER -