Efficient Synthesis of Ephedra Alkaloid Analogues Using an Enantiomerically Pure N-[(R)-(+)-α-Methylbenzyl]aziridine-2-carboxaldehyde

Abstract

Efficient preparation of enantiomerically pure (2S)-aziridine-2-carboxaldehyde 9 and its 2(R) isomer and highly diastereoselective addition of organolithium reagents to the aldehyde 9 are described. The diastereoselectivity in additions of the lithium reagents seems to come from "chelation-controlled" carbon-carbon bond formation and is influenced by the source of the organometallic compound, solvent, and the presence of a Li salt. The C(3)-N bond of the aziridine ring of the addition 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 comparison with those of commercially available norpseudoephedrine.

A scalable and expedient method of preparing diastereomerically and enantiomerically enriched pseudonorephedrine from norephedrine

“…The diastereomeric ratios obtained ranged from 91:9 to 94:6 and required flash chromatography to further enhance them. 5 In addition to these methods, Claremon et al carried out the addition of methyllithium to a chiral, non-racemic a-substituted hydrazone to prepare pseudonorephedrine. 6 involved multiple steps as well as a kinetic resolution protocol to generate the key starting material.…”

Microwave-assisted regioselective ring opening of non-activated aziridines by lithium aluminium hydride

“…literature, [31][32][33] some of these approaches suffer from (minor) drawbacks such as low regioselectivity, cumbrous substrate synthesis or low substrate stability. …”

“…In the literature, only a few studies have been made on ring opening reactions of non-activated enantiomerically pure 2-(hydroxymethyl)aziridines. 32,[49][50][51][52] For example, the catalytic hydrogenation of aziridine methanols 8a and 8b in EtOH using Pd(OH) 2 has provided β-amino alcohols 9a and 9b in good yields. 49 Recently, the preparation of chiral β-amino alcohols via regio-and stereocontrolled ring opening reactions of chiral aziridines was examined.…”

Regioselective Opening of Epoxides Catalyzed by Sn (IV). A New Method for the Synthesis of Halohydrins?

“…Many different organotin reagents have been employed to effect the regio-and stereoselective cleavage of oxiranes in the presence of nucleophiles affording 1,2-alcoxialcohols, 1,2-aminoalcohols, 1, 2-azidoalcohols, etc [3].…”