Racemic and diastereoselective synthesis of aryl and heteroaryl tetrahydroisoquinolines via the Pictet-Spengler reaction

Abstract

New tetrahydroisoquinolines were synthesized by the Pictet-Spengler reaction. Influence of a wide range of aryl and heteroaryl aldehydes, was investigated in the cyclization step with 3,4-dimethoxyphenylethylamine 1, L-DOPA 2 and L-3,4-dimethoxyphenylalanine methyl ester 3. Compounds 2 and 3 served as probes to assess the efficiency of two Pictet-Spengler reactions with respect to their diastereoselectivity, in order to obtain optically active diastereoisomers. Cis- and trans-diastereoisomers were obtained in short reaction times with moderate to good isolated yields (20-79%). Both nmr and X-ray analyses confirmed the expected diastereoisomer configurations.