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

Racemic 2-methoxy-2-(l-naphthyl)propionic acid (1, M alpha NP acid) was ena ntioresolved as its esters derived from various chiral alcohols. For exampl e, a diastereomeric mixture of esters prepared from (+/-)-1 and (1R,3R,4S)- (-)-menthol was easily separated by HPLC on silica gel yielding esters (-)- 2a and (-)-2b, the separation factor alpha = 1.83 being unusually large. Th e H-1 NMR chemical shift differences, Delta delta = delta(R)-delta(S), betw een diastereomers 2a and 2b, are much larger than those of conventional chi ral auxiliaries, e.g. Mosher's MTPA and Trost's MPA acids. This acid 1 is t herefore very powerful for determining the absolute configuration of chiral alcohols by the H-1 NMR anisotropy method. Solvolysis of the separated est ers yielded enantiopure acids (S)-(+)-1 and (R)-(-)-1, which are useful for enantioresolution of racemic alcohols. (C) 2000 Elsevier Science Ltd. All rights reserved.