Copper/Iodine Co-catalyzed Oxygenative Transannulation of Tryptamines Enables Direct Synthesis of Donaxaridine and Its Derivatives.

We report a general copper/iodine co-catalyzed oxygenative transannulation strategy using readily available tryptamines. Molecular oxygen and water are used as oxygen sources and provide direct access to the donaxaridine scaffold and its derivatives. This methodology is applied to the efficient synthesis of the natural products donaxaridine, chimonamidine, donaxanine, donaxarine, and aline in just one or two steps. The tryptamines, albeit with oxy-sensitive dialkyl N-H groups, are selectively oxidized through a single-electron transfer dioxygenation process.

Copper-Catalyzed Selective Oxidative Cross-Coupling of Tryptophols and Tryptamines To Access Heterocyclic 3a,3a'-Bisindolines.

The first example of cyclization cross-coupling of tryptophols and tryptamines has been realized by copper catalysis with air or oxone as the terminal oxidant, resulting in the direct construction of a new class of heterocyclic 3a,3a'-bisindolines in moderate to good yields with high chemoselectivities. A series of mechanistic control experiments were also conducted, indicating that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine to initiate the oxidation, and a nucleophilic-alkylation process is proposed for the carbon-carbon bond-forming in the reaction. The novel synthetic strategies and molecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.