A simple and efficient synthetic route to chiral isopavines. Synthesis of (-)-O-methylthalisopavine and (-)-amurensinine

The isopavinan alkaloids (-)-O-methylthalisopavine (7a) and (-)-amurensinine (7d) have been synthesized in good yield and high ee from the appropriate 1,2-diarylethylamine derivatives using optically active beta-amino alcohols as chiral support. This synthetic route employs as key steps the alkylation reaction of the azomethine derivatives 2 with Grignard reagents 1 and a novel one-pot double-intramolecular cyclization of the adequately functionalized 1,2-diarylethylamines 5 to afford a series of optically active isopavines 6a-d and 7a-d.