Chiral amino alcohols as intermediates in the stereocontrolled synthesis of 1,3-disubstituted tetrahydroisoquinolines and protoberberines

An efficient stereocontrolled synthetic approach to (3S)-3-aryltetrahydrois oquinoline Sd and (1S,3S)-3-aryl-1-methyltetrahydroisoquinolines 3a-c by a Pictet-Spengler heterocyclization reaction of optically active (95% ee) (S) -1,2-diarylethylamines 2a-c is presented. An alternative route toward obtai ning the epimeric derivative of 3a, tetrahydroisoquinoline (1R,3S)-6, was a lso achieved by a stereocontrolled ring opening process carried out on the oxazolotetrahydroisoquinoline 9. Tetrahydroisoquinoline 8 was employed for the stereoselective preparation of(5S,6S, 14S)-6-phenyl-2,3,10,11-tetrameth oxyprotoberberin-5-ol (12), a new type of 5,6-disubstituted protoberberine derivative with excellent (d.e>95% by H-1 NMR) stereoselection.