Design, synthesis, and optical resolution of a novel non-natural chiral auxiliary, 1-(2,5-dimethoxyphenyl)ethylamine. Application to diastereoselective alkylation of aldimines

Abstract

A chiral amine, 1-(2,5-dimethoxyphenyl)ethylamine, was found to be an effective chiral auxiliary for the diastereoselective alkylation of its aldimines with alkylmetals. The 1-(2,5-dimethoxyphenyl)ethyl group of the chiral auxiliary could be removed by the acetylation and then oxidation of the resultant alkylated product, accompanying an amino-transfer from the chiral auxiliary to the final product. Racemic 1-(2,5-dimethoxyphenyl)ethylamine could be easily synthesized from 1,4-dimethoxybenzene and resolved by the diastereomeric salt formation with mandelic acid to give both enantiomers in pure forms.