Friedel-Crafts cyclization Bischler-Napieralski

The asymmetric syntheses of tetrahydroisoquinoline derivatives were also reported. Optically pure 3,4-disubstituted tetrahydroisoquinolines such as 78 were prepared by Friedel-Crafts cyclization of amino alcohols 77 <02TL1885>. Enantioselective syntheses of dihydropyrrolo[2,l-a]isoquinolines via a highly diastereoselective, chiral auxiliary assisted N-acyliminium cyclization was disclosed <02SL593>. The enantioselective synthesis (-)-tejedine, a seco-bisbenzyltetrahydroisoquinoline was also reported. One key step in this synthesis involved a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization <02OL2675>. Additionally, an asymmetric Bischler-Napieralski was reported for the preparation of 1,3,4-trisubstituted 1,2,3,4-tetrahydroisoquinolines <02JCS(P1)116>. 

To reach our target molecule, the routes involving the cyclization step looked particularly attractive. The Bischler-Napieralski or related Friedel-Crafts route offers the potential for an asymmetric synthesis through enantio- or diastereoselective reduction of the imine penultimate intermediate, whereas the Pictet-Spengler approach is the shortest possible pathway. 

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