2-Methoxy-2-(1-naphthyl)propionic acid, a powerful chiral auxiliary for enantioresolution of alcohols and determination of their absolute configurations by the 1H NMR anisotropy method

Abstract

Racemic 2-methoxy-2-(1-naphthyl)propionic acid ( 1, MαNP acid) was enantioresolved as its esters derived from various chiral alcohols. For example, a diastereomeric mixture of esters prepared from (±)- 1 and (1 R,3 R,4 S)-(−)-menthol was easily separated by HPLC on silica gel yielding esters (−)- 2a and (−)- 2b, the separation factor α=1.83 being unusually large. The 1H NMR chemical shift differences, Δδ=δ( R)–δ( S), between diastereomers 2a and 2b, are much larger than those of conventional chiral auxiliaries, e.g. Mosher’s MTPA and Trost’s MPA acids. This acid 1 is therefore very powerful for determining the absolute configuration of chiral alcohols by the 1H NMR anisotropy method. Solvolysis of the separated esters yielded enantiopure acids ( S)-(+)- 1 and ( R)-(−)- 1, which are useful for enantioresolution of racemic alcohols.