Synthesis of 12b‐Methyl‐Isoindoloisoquinolin‐8‐ones via Iridium‐Catalyzed Intramolecular Hydroarylation of Phenacyl Enamides

Our iridium-catalyzed hydroarylation methodology affords high product yields and does not require pre-functionalized substrates – a distinct advantage over conventional Heck-type cyclization protocols. Substrate scope and mechanistic investigations reveal that electron-donating substituents on the ring D moiety are critical for successful cyclization.These observations are consistent with a reaction pathway involving electrophilic aromatic substitution of an iridium species onto ring D.

An intramolecular iridium-catalyzed hydroarylation process is described for the synthesis of the title scaffold from phenacyl enamide substrates. This method achieves high yields while eliminating the requirement for prefunctionalized substrates, as compared to Heck-type cyclization methodologies. Substrate scope and mechanistic studies indicate that the presence of electron-donating substituents in the incipient ring D moiety is essential for the cyclization, consistent with a pathway involving electrophilic aromatic substitution of iridium in ring D.

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