Chiral Amino Alcohols As Intermediates in the Stereocontrolled Synthesis of 1,3-Disubstituted Tetrahydroisoquinolines and Protoberberines

An efficient stereocontrolled synthetic approach to (3 S )-3-aryltetrahydroisoquinoline 3d and (1 S,3 S )-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 obtaining the epimeric derivative of 3a, tetrahydroisoquinoline (1 R,3 S )- 6, was also achieved by a stereocontrolled ring opening process carried out on the oxazolotetrahydroisoquinoline 9 . Tetrahydroisoquinoline 8 was employed for the stereoselective preparation of (5 S,6 S,14 S )-6-phenyl-2,3,10,11-tetramethoxyprotoberberin-5-ol (12), a new type of 5,6-disubstituted protoberberine derivative with excellent (d.e>95% by 1 H NMR) stereoselection.