The unnatural amino acid analogue, 4-(phosphonomethyl)phenylalanine (Pmp, 2), has proven to be a valuable tool for studying protein-tyrosine kinase dependent signal transduction, where it is most often incorporated into peptides or peptide mimetics as a phosphatase-stable phosphotyrosyl mimetic. Although Pmp has been prepared previously bearing a number of protection strategies, the N α-Fmoc 4-[di-( tert-butyl)phosphonomethyl] phenylalanine form [( N α-Fmoc- l-Pmp( t Bu 2)-OH, 3] is particularly attractive since it can be cleanly introduced into peptides using standard Fmoc protocols. Synthesis of 3 was first reported as its ( d/ l)-racemate, and subsequently as its l- 3 enantiomer, with the latter synthesis having relied on induction of chirality using a camphor sultam auxillary. Reported herein is an alternate enantioselective synthesis of l- 3 in high enantiomeric purity by procedures which derive the stereochemistry of the final product directly from the starting amino acid, without the need for chiral induction. A key feature of the route is the racemization-free nucleophilic substitution of lithium di- tert-butyl phosphite onto protected 4-bromomethylphenylalanine ( 17).