Palladium‐Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with 1,3‐Indanedione: Approach to Spiro‐Tetrahydroquinoline Scaffolds

Abstract

AbstractA palladium catalyzed decarboxylative [4+2] cycloaddition of vinyl benzoxazinanones with 2‐arylidene indan‐1,3‐dione has been established, which afford a series of bioactive spiro‐tetrahydroquinolines (27 examples) in moderate to good yield (up to 87 %) with high diastereoselectivities. The synthetic utility of this reaction was demonstrated by gram‐scale synthesis. Compounds synthesized by this method potently inhibited proliferation in a panel of cancer cell lines. Particularly, the most potent compounds 3 ae, 3 ah, 3 aj and 3 fa displayed selective inhibition of MDA‐MB‐231 breast carcinoma cells with IC50 values of 1.292, 0.6118, 0.6558, 1.656 and 2.215 μM, respectively.