Lord of the Rings: Catalytic Isocyanide Insertion as a Platform for Cascade Reactions toward Complex and Diverse heterocycles
Palladium-catalyzed CO-insertive cross-coupling reactions have been undoubtedly beneficial to the industrial-scale synthesis of a myriad of valuable chemical intermediates. In terms of step-economy, overall waste-production and atom-economy, carbonylative cross-coupling has proven to be a valuable synthetic tool in the synthesis of nearly all carbonyl-containing compound classes. The isoelectronic properties of isocyanides and carbon monoxide have long been known. However, the implementation of isocyanide insertive (imidoylative) palladium-catalyzed cross coupling reactions has only recently taken up interest.
The main advantage point of imidoylative cross-coupling reactions is the addition of a diversity point on the isocyanide-derived nitrogen atom. This diversity point leads to increased complexity in the final product, but can also be applied towards further derivatization of the coupling product in a cascade manner. We attempt to facilitate multi-bond-forming transformations (MBFTs) by isocyanide insertion/ intramolecular cyclization cascades, employing the isocyanide substituent as a reactive handle. These cascade sequences are capable of delivering highly complex nitrogenous heterocycles without intermediate isolation and purification.
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