Condition-Controlled Divergent Synthesis of Imidazoindolone Spiroisoquinolinones from N-Alkoxycarboxamide Indoles and Diazo Homophthalimides

Presented herein is a condition-controlled divergent synthesis of imidazoindolone spiro-isoquinolinones (IISIQs) via the cascade reactions of N-alkoxycarboxamide indoles with diazo homophthalimides. When the reaction is carried out under air and in the absence of an acid additive, IISIQ tethered with a N-alkoxy moiety (IISIQ-OR) is formed through Rh(III)-catalyzed C-H/N-H metalation, carbene formation/ migratory insertion followed by reductive elimination, in which air acts as an oxidant to regenerate the Rh(III) catalyst. When the reaction is run under argon and in the presence of MesCO(2)H, on the other hand, IISIQ-H is formed through rhodacycle intermediate formation, carbene insertion followed by acid-assisted intramolecular substitution/annulation and N-O bond cleavge. In general, this method provides a divergent approach toward spiroheterocyclic scaffolds and features accessible substrates, functional group compatibility and air as an external oxidant. Moreover, the value of this developed protocol is further showcased by gram-scale synthesis and structural transformation of products.