Toward the improvement of the tandem halide displacement/amide coupling spiro-cyclization as a new route to γ-lactam and pyrroloisoquinoline templates

Two efficient and rapid accesses to spiro-oxindole entities bearing an imide function were presented, and their performance was compared. The key components are N-substituted α-bromoacetamides to reach these derivatives in tandem process. The resulting spiro-imides from these methodologies were regioselectively reduced into corresponding N-acyliminium precursors, which were subsequently submitted to an intramolecular cyclization to provide pentacyclic spiro-oxindole architecture analogues to pteropodine and spirotryprostatin-B alkaloids with high diastereoselective control.

Graphical abstractTwo expedient approaches for the synthesis of spiro-oxindoles containing succinimide were investigated. From these results, the tandem halide displacement/amide coupling spiro-cyclization approach that extends our recent findings in this subject seems to be simple and effective. The spiro-cyclic systems obtained were then used to provide spiro-oxindoles containing γ-lactams and pyrroloisoquinolines by using reduction processes followed or not by π-cationic cyclization in acidic medium.Figure optionsDownload full-size imageDownload as PowerPoint slide