Enal Transfer via Piano-Stool Rh-Enalcarbenoids: Rapid Construction of Enal-Functionalized Isoquinolones, Application Toward Benzo[c]phenanthridinone Scaffolds

Herein, we disclosed a Rh-catalyzed site-selective enal transfer reaction of benzamides with diazoenals leading to multisubstituted enal-functionalized isoquinolone derivatives. The reaction involves arene ortho C-H activation, migratory insertion of a new class of N-heterocyclic Piano-stool Rh-enalcarbenoid, and metal-templated cyclization. The synthetic utility of enal-functionalized isoquinolones has been demonstrated by the short synthesis of valuable benzo[c]phenanthridinone scaffolds, which are present in many naturally occurring alkaloids with broad pharmacological properties and an analogue of oxyavicine natural product used for ophthalmic disorders.