Heterocyclic synthesis, intramolecular carbopalladation

In 2005, Ohno et al. reported a cascade intramolecular carbopalladation/aromatic C-H bond activation for the synthesis of tri- or tetracyclic heterocycles 174 in the presence of palladium species [70] (Scheme 6.48). The authors proposed that this domino reaction might proceed through the oxidative addition of bromoenyne 173 to Pd(0), insertion of the alkyne into the C-Pd bond of intermediate 175, followed by C-H bond functionalization of the aromatic ring. Not only benzene-substituted substrates but also heteroaromatic rings such as benzofuran and indole, could be introduced efficiently to this reaction. Similar work was reported by Chernyak and Gevorgyan [71]. 

A new total synthesis of morphine 409 employing a palladium-catalyzed cou-phng as a key step started from the hydroisoquinoline derivative 407 to give dihydrocodeinone 408 (Scheme 8.81). This transformation constitutes a cascade of an intramolecular Heck carbopalladation and subsequent heterocyclization. The initially formed arylpalladium iodide species attacks the bridgehead position of the diene functionality in 407 to form a r-allylpalladium complex that is trapped by the internal nucleophilic phenol moiety (cf. Scheme 8.30). 

The oxidative addition reactions to alkenes promoted or catalyzed by PdCl2(CH3CN)2 have been classified based on the nature of the attacking species. Oxygen nucleophiles such as water, alcohols and carboxylic acids undergo oxypalladation, while ammonia, amines and their derivatives are typical nucleophiles for aminopalladation. Carbopalladation with active methylene compounds is also discussed The palladium-catalyzed intramolecular hetero- and carbopalladation of olefins is extensively used as the ring-forming step in the synthesis of a variety of heterocyclic and carbocyclic systems, and representative examples are provided. 

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