Synthesis of enantiopure alpha-deuteriated Boc-L-amino acids

An alternative scheme for the synthesis of enantiopure alpha-deuteriated amino acids from a common intermediate is presented. Methyl bis(methylsulfanyl)methylene [2,2-H-2(2)] glycinate was prepared in a mixture of MeOD and D2O with a catalytic amount of Na2CO3 and attached to (2R)-bornane-10,2-sultam. Alkylation of the corresponding enolate provided intermediates which after careful purification were first deprotected on nitrogen and then cleaved from the auxiliary to give deuteriated alpha-amino acids of very high purity (> 99% ee and > 98% D). These were directly converted into the corresponding Boc-L-[2-H-2]-Ala, -Leu,-Phe and -(O-Bzl)Tyr derivatives, suitable for application in peptide synthesis, Boc-[2,2-H-2(2)]Gly was also prepared.