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

An efficient, straightforward, and one-pot synthesis of biologically relevant spiro-dihydropyridine oxindoles was described via readily available isatin, malononitrile, allenoate, and amines. The metal/organocatalyst-free, Et3N-mediated reaction proceeds via cascade spiro-cyclization of in situ 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.

Automated summary

This article describes an efficient, straightforward, and one-pot synthesis method for biologically active spiro-dihydropyridine oxindoles. The method has great flexibility and yields good results, and the resulting products can be further modified into new compounds of pharmaceutical relevance.