Swim in the Chiral Pool: MDMA and MDA Enantiomers from Alanine-Derived Precursors.

A divergent two-step process has provided access to optically pure enantiomers of MDMA and MDA, clinically relevant phenylisopropylamine entactogens. Target compounds were synthesized from commercially available alanine-derived aziridines. Critical process parameters were identified, and the reactions were optimized to avoid chromatographic purifications toward gram-scale isolations, providing ( R )-(-)-MDMA, ( S )-(+)-MDMA, ( R )-(-)-MDA, and ( S )-(+)-MDA each in greater than 98% purity by UPLC, >99% enantiomeric excess, and net yields between 50 and 60% for the complete process.