Synthesis of Indenopiperidinone Derivatives Achieved through the Aza-Semipinacol-Type Rearrangement of Iodobenzomorphanones

The synthesis of 2,4,4a,9-tetrahydro-3H-indeno[2,1-c]pyridin-3-ones 7 is achieved through the aza-semipinacol-type rearrangement of readily available iodobenzomorphanones when treated with silver salts. A comprehensive study was performed on the optimization of the synthesis of iodobenzomorphans and subsequent rearrangement products, while addressing the scope and limitations of both reactions. It has been shown that the resulting indeno[2,1-c]pyridine-3-ones, acting as enelactams, are suitable precursors for further stereoselective functionalization, e.g., reduction, using an NaBH₄/NiCl₂ system, and arylation activated by TIPSOTf.