title: New route to enantiopure MalphaNP acid, a powerful resolution and chiral 1H NMR anisotropy reagent.
abstract: MalphaNP acid (+/-)-1, 2-methoxy-2-(1-naphthyl)propionic acid, was enantioresolved by the use of phenylalaninol (S)-(-)-4; a diastereomeric mixture of amides formed from acid (+/-)-1 and amine (S)-(-)-4 was easily separated by fractional recrystallization and/or HPLC on silica gel, yielding amides (R;S)-(-)-5a and (S;S)-(+)-5b. Their absolute configurations were determined by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-5a was converted to oxazoline (R;S)-(+)-8a, from which enantiopure MalphaNP acid (R)-(-)-1 was recovered. In a similar way, enantiopure MalphaNP acid (S)-(+)-1 was obtained from amide (S;S)-(+)-5b. These reactions provide a new route for the large-scale preparation of enantiopure MalphaNP acid, a powerful chiral reagent for the enantioresolution of alcohols and simultaneous determination of their absolute configurations by (1)H NMR anisotropy.
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Naito
authors.forename: Hiromi
authors.initials: H
authors.lastname: Taji
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Miwa
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kuwahara
authors.forename: Masataka
authors.initials: M
authors.lastname: Watanabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada