Synthesis of All Distinct α-Methyl-Substituted Isomers of Amino Bis(2,2′-Ethanoic Acid) Diethyl Ester and Ethylene Diamine Tetraacetic Acid Tetraethyl Ester Scaffolds

The syntheses of three dialkylated and six tetraalkylated ethylene diamine tetraacetic acid tetraesters is described. The dialkylated derivatives were synthesized by a convergent non-racemizing route to yield three enantiomerically and diastereomerically pure tetraesters (SS)-3a, (RR)-3b and (R∗S∗)-3c in 55–57% yields from alanine ethyl ester 1. Enantiomerically and diastereomerically pure tetraalkylated derivatives (SSSS)-8a, (RRRR)-8b, (2R∗,2′S∗,2″R∗,2‴S∗)-8c, (2R∗,2′R∗,2″S∗,2‴S∗)-8d, (2R,2′R,2″R,2‴S)-8e and (2S,2′S,2″S,2‴R)-8f were synthesized in two to five steps and 22–49% overall yields from alanine ethyl ester 1.