Final answer:
Pd(II)/Lewis acid-catalyzed intramolecular annulation of indolecarboxamides involves dual C-H activation to form diverse heterocyclic structures. Oxidative addition, coordination of the nucleophile, and reductive elimination are key steps controlled by regioselectivity in the reaction. Palladium catalysis and oxidants like PhI(OAc)2 are commonly employed.
Step-by-step explanation:
The intramolecular annulation of indolecarboxamides with dioxygen through dual C-H activation typically involves Pd(II)/Lewis acid catalysis. C-H bond activation enables the functionalization of organic molecules in the presence of palladium, which acts as a catalyst. For instance, the Pd(II)-catalyzed C-H bond activation and oxidation of certain nucleosides using stoichiometric oxidants in acetonitrile can provide access to acetoxylated products. The system often relies on purine nitrogen atoms to direct the C-H bond activation, as shown in protocols synthesizing phenylated purine nucleosides.
In such transformations, the catalytic cycle begins with the oxidative addition of Pd(0) to the substrate, followed by coordination of the nucleophile and reductive elimination, forming the desired product and regenerating the Pd(0) catalyst. Regioselectivity, crucial in these reactions, can be controlled via substrate design or reaction conditions. PhI(OAc)2 often serves as the necessary oxidant, promoting the formation of multiple products, with diacetoxylated products formed under increased oxidant loading. These methodologies enable the synthesis of diverse heterocyclic structures featuring the indole core, pivotal in many biologically active compounds.