EFFICIENT SYNTHESIS OF EPHEDRA ALKALOID ANALOGS USING AN ENANTIOMERICALLY PURE (-ALPHA-METHYLBENZYL]AZIRIDINE-2-CARBOXALDEHYDE())

Efficient preparation of enantiomerically pure (2S)-aziridine-2-carbox aldehyde 9 and its 2(R) isomer and highly diastereoselective addition of organolithium reagents to the aldehyde 9 are described. The diaster eoselectivity in additions of the lithium reagents seems to come from ''chelation-controlled'' carbon-carbon bond formation and is influence d by the source of the organometallic compound, solvent, and the prese nce of a Li salt. The C(3)-N bond of the aziridine ring of the additio n products was regioselectively reduced by catalytic hydrogenation in the presence of Pearlman's catalyst to provide enantiomerically pure 1 ,2-amino alcohols. The absolute stereochemistries of the amino alcohol 13a were assigned as (1S,2S) when the C-1 substituent was phenyl by c omparison with those of commercially available norpseudoephedrine.