Synthesis of R- and S-MDMA via nucleophilic ring-opening of homochiral N-tosylaziridines

Homochiral (R)- and (S)-3,4-methylenedioxymethamphetamine (MDMA) were prepared in six steps (each) from the chiral pool precursors d- l-alanine, respectively. The key step, copper-catalysed regioselective ring-opening of an N-tosylaziridine with aryl Grignard reagent, proceeded high yield complete regioselectivity. Elaboration was achieved preservation configurational integrity, affording R- S-MDMA hydrochlorides enantiopurities >99.5%, as determined by enantioselective HPLC fluorescence detection. Attempts to apply synthetic methodology synthesis homochiral enantiomers α-phenyl analogue MDMA (UWA-001) thwarted a switch regioselectivity step.