Crystalline state conformation of 2-methoxy-2-(1-naphthyl)propionic acid ester.

Abstract

The enantioresolution method using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid 1) was applied to 1,2,3,4-tetrahydro-4-phenanthrenol (4). Racemic alcohol (+/-)-4 was esterified with (S)-(+)-1, and a diastereomeric mixture of esters formed was separated by HPLC on silica gel giving the first-eluted ester 5a and the second-eluted one 5b. Ester 5a was reduced with LiAlH4 yielding enantiopure alcohol (+)-4. A single crystal of ester 5a was subjected to X-ray crystallography to determine its absolute configuration as (S,S), and therefore to assign the S absolute configuration to (+)-4. The most striking finding in the X-ray analysis is that the methoxyl oxygen atom is syn to the ester carbonyl oxygen even in the crystalline state. This is just the preferred conformation of MalphaNP acid esters assumed in the 1H NMR anisotropy method. The S absolute configuration of (+)-4 was also confirmed by the CD and 1H NMR anisotropy methods.