A General Cp*CoIII-Catalyzed Intramolecular C−H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids

5 years ago

A General Cp*CoIII-Catalyzed Intramolecular C−H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids

Frank Glorius, Maximilian Koy, Tobias Knecht, Constantin G. Daniliuc, Andreas Lerchen

Herein, we report a Cp*CoIII-catalyzed C−H activation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine, and tylophora alkaloids. This particular C−H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion. Con't get enough: A general intramolecular Cp*CoIII-catalyzed C−H activation approach for the regioselective synthesis of isoquinolone- and pyridone derivatives as highly valuable and versatile building-blocks is reported. The synthetic applicability of these building-blocks was further utilized in the total syntheses of two aromathecin alkaloids, two 8-oxyprotoberberine cores and six different tylophora alkaloids.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201702648