Enantiodivergent syntheses of (+)- and (−)-1-(2,6-dimethylphenoxy)propan-2-ol: A way to access (+)- and (−)-mexiletine from D-(+)-mannitol.

Chiron approach was used to acquire optically pure (R)- and (S)-1-(2,6-dimethylphenoxy)propan-2-ol, immediate precursors of (S)- and (R)-mexiletines, respectively. Two different routes were followed from a D-mannitol-derived optically pure common precursor to get the enantiomeric alcohols separately. Comparison of their specific rotation values with the corresponding literature values as well as exact mirror-image relationship between their CD curves proved their high enantiopurity. These alcohols were then transformed to the corresponding amine-drugs in an efficient one-step process instead of two steps described in the literature. Image 1 • Chiron approach conveyed stereochemistry from D-mannitol to alcohol enantiomers. • Different routes from a chiral intermediate gave enantiomeric alcohols separately. • First report of one-step conversion of alcohols to corresponding mexiletines. • CD curves of alcohol and amine enantiomers showed exact mirror image relationship. [ABSTRACT FROM AUTHOR]