Multicomponent Synthesis of Spiro-dihydropyridine Oxindoles Cascade Spiro-cyclization of Knoevenagel/Aza-Michael Adducts.

An efficient, straightforward, and one-pot synthesis of biologically relevant spiro-dihydropyridine oxindoles was described readily available isatin, malononitrile, allenoate, and amines. The metal/organocatalyst-free, EtN-mediated reaction proceeds cascade spiro-cyclization of generated Knoevenagel/aza-Michael adducts. The reaction has great flexibility over electron-rich and electron-poor substituents affording desired products in good to excellent yields. We have also demonstrated the selected spiro-dihydropyridines for late-stage diversification into new spiro-dihydropyridine hybrids of pharmaceutical relevance.