Novel chiral C1-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolines: synthesis, resolution, and applications in catalytic enantioselective reactions

A straightforward synthesis of a structurally constrained C1-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline 1 is described. Resolution of this compound has been achieved successfully. The preparation of chiral N-alkyl, urea, and thiourea derivatives as potential new chiral ligands, based on the parent compound 1, is reported. Chiral compound 1 induced very good selectivity and yield in the addition of either Et2Zn (85% ee, 96% yield) or nitromethane (85% ee, 60% yield) to benzaldehyde.

Graphical abstractThe structurally constrained C1-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline (+)-1 was synthesized and resolved. Various derivatives were prepared from (+)-1. Application of (+)-1 in asymmetric C–C bond forming reactions gave very good enantioselectivity and yield in either the addition of Et2Zn (85% ee, 96% yield) or CH3NO2 (85% ee, 60% yield) to benzaldehyde.Figure optionsDownload full-size imageDownload as PowerPoint slide