Asymmetric synthesis of syn- and anti-α-deuterio-β 3-phenylalanine derivatives

Abstract

The conjugate addition of lithium ( S)- N-benzyl- N-(α-methylbenzyl)amide to a range of aryl substituted tert-butyl cinnamate esters followed by reaction of the resultant lithium β-amino enolates with D 2O provides access to anti configured α-deuterio-β-aminocinnamate esters in high dr. The corresponding syn configured diastereoisomers were also obtained with high diastereoselectivity via the conjugate addition of lithium ( S)- N-benzyl- N-(α-methylbenzyl)amide to a range of tert-butyl α-deuteriocinnamate esters followed by reaction of the resultant lithium β-amino enolates with 2-pyridone. After deprotection both the syn- and anti-diastereoisomers of the corresponding α-deuterio-β 3-amino acids can be isolated in high dr.