Synthesis of L-[4,5,5,5-D-4] isoleucine: Determination of approximate rotamer population about the C-beta-C-gamma bond

An asymmetric synthesis of regio- and stereoselectively deuterium-labelled L-isoleucine was examined. An unsaturated gamma -lactam readily available f rom L-pyroglutamic acid was stereoselectively methylated by the Gilman reag ent and subsequent oxidation of the hydroxymethyl moiety afforded a 3-methy lpyroglutamate derivative. Introduction of a deuterium atom into the gamma -position was achieved via a radical-based deuteriation of the correspondin g phenyl selenide by tributyltin deuteride. Then, the deuteriated 3-methylp yroglutamate derivative was converted to L-[4,5,5,5-D-4]isoleucine via a ba se-promoted ring opening and a reductive deuteriation of the terminal carbo xyl. moiety.