Multicomponent Synthesis of Isoindolinones by Rh^III Relay Catalysis: Synthesis of Pagoclone and Pazinaclone from Benzaldehyde

A practical one-pot isoindolinone synthesis enabled by RhIII catalysis was developed. The advantage of this protocol is that it does not require pre-preparation of amide substrates, because RhIII participates in two reactions independently. This mild, operationally multicomponent process transforms a wide variety of commercially available aldehydes into the corresponding γ-lactams in good yields, thereby demonstrating that N-pyridin-2-yl benzamide is an effective directing group. Notably, the anxiolytic drugs pagoclone and pazinaclone can be directly prepared by this methodology.