Friedlander synthesis of chiral alkyl-substituted 1,10-phenanthrolines

The synthetic scope of the Friedlander condensation in the preparation of chiral alkyl-substituted 1,10-phenanthrolines has been investigated. A range of chiral [x,y-b]-cycloalkeno-condensed phenanthrolines has been prepared in one step from steroidal or other cyclic ketones from the chiral pool and 8-amino-7-quinolinecarbaldehyde (1) via base-catalyzed condensation. Phenanthroline derivatives are formed in good yields with unhindered ketones, but the reaction proceeds even with sterically congested substrates such as camphor, albeit in low yield. The utility of the Friedlander condensation has been extended to the synthesis of chiral 3-alkyl-substituted phenanthrolines from monoalkyl-substituted acetaldehydes.