Carbopalladation intramolecular nucleophilic trapping

Both reaction modes A and B have been observed for carbopalladations of methylenecyclopropane derivatives 59a,b with subsequent intramolecular nucleophilic trapping of the intermediate allylpallatium species in or IV, respectively, depending on the tether lengths between the methylenecyclopropane and the dimethyl malonate moieties. The same carbopalladations of unsubstituted methylenecyclopropane 43 (=60a) and pentyli-dene-cyclopropane (60b) with subsequent intermolecular trapping by carbon nucleophiles were found to generally proceed by mode B via intermediates II, V, IV to yield ringopening products 61 and 62, respectively (Scheme 16). 

D. INTERMOLECULAR CARBOPALLADATION OF ALLENES FOLLOWED BY INTRAMOLECULAR NUCLEOPHILIC TRAPPING... 

As outlined in Sect. B and C, catalytic intermolecular carbopalladations of allenes followed by either /3-hydride elimination or intermolecular nucleophilic trapping provide 1,3-dienes or allyl derivatives bearing the nucleophile moiety, respectively, while an intermolecular carbopalladation followed by intramolecular trapping sequential reaction provides cyclic skeletons (Scheme 27). In Type I, the nucleophilic moiety is connected with the C—X bond, and in lype II it is attached to the allene moiety. 

Scheme 8.32 Intramolecular carbopalladation of an allene with subsequent nucleophilic trapping of the it-allylpalladium intermediate [154].

In 1995 Grigg and co-workers reported a similar cascade consisting of an intramolecular carbopalladation and intermolecular nucleophilic trapping (Scheme 44). The regioselectivity of the aUylic nucleophilic substitution can be controlled completely by using different bases. 

Negishi and co-workers demonstrated the feasibility of this carbopalladation mode on an allene in an intramolecular approach to medium and large rings [80]. The new C —C bond is fornied at the central carbon atom of the allene moiety to give a jr-allylpalladium complex, which in turn can be trapped by a variety of nucleophiles (arylstannanes to give arylated products, malonates, phenols, amines, etc.) (Scheme 3-27). The yields are remarkably good without using sophisticated nucleophile delivery techniques. 

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). 

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