New route to enantiopure MαNP acid, a powerful resolution and chiral 1 H NMR anisotropy reagent

MαNP 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 MαNP acid ( R )‐(−)‐ 1 was recovered. In a similar way, enantiopure MαNP acid ( S )‐(+)‐ 1 was obtained from amide ( S;S )‐(+)‐ 5b . These reactions provide a new route for the large‐scale preparation of enantiopure MαNP acid, a powerful chiral reagent for the enantioresolution of alcohols and simultaneous determination of their absolute configurations by 1 H NMR anisotropy. Chirality, 2007. © 2007 Wiley‐Liss, Inc.