Stereo? and Regioselective [3+3] Annulation Reaction Catalyzed by Ytterbium: Synthesis of Bicyclic 1,4?Dihydropyridines

An ytterbium catalyzed formal [3+3] cycloaddition of cyclic enamines and ?,?-unsaturated ketones is reported. The reaction proceeds with a ‘head to tail’ regioselectivity through conjugate addition the enamine moiety followed by an amine-carbonyl condensation. In use chiral provided high degree stereoselectivity, driven possible balance between steric ?-stacking effects. resulting bicyclic 1,4-dihydropyridines were evaluated as antiproliferative agents against A549 (carcinomic human alveolar basal epithelial cell) SKOV3 (human ovarian carcinoma) tumor cell lines. Good toxicities found for some compounds lines, best IC50 values 0.89 ?M 6.69 SKOV3, very good selectivity was observed towards MRC5 (non-malignant)