Carbopalladation intramolecular trapping

Based upon the studies on the mechanism of the Cl sequence we rationalized that the elusive allenol intermediate 19 (Chap. 2.2) could participate in intramolecular trapping reactions as an allenyl ether. Furthermore, vinyl allenes are perfectly suited as dienes in Diels-Alder reactions. Considering both reactive functionalities, allenyl ethers and vinyl allenes, which are perfectly suited for domino processes, we designed an insertion sequence based upon cyclizing carbopalladation [76], where the vinyl aUene results from an isomerization of an alkynylation of a vinyl... 

Two types of reactions are summarized in this section (i) the intermolecular carbopalladation leads to a Pd functionality such as alkyl-, alkenyl-, or allylpalladium complexes, which is intramolecularly trapped by a heteroatom (again Wacker-type processes are mechanistic alternatives) (ii) the palladium catalyst is not directly involved in the hetero-cyclization step, but the carbopalladation builds up a suitable functionality or changes bond angles so that the heterocyclization can take place. 

In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

Cascade intermolecular carbopalladations of alkynes followed by intramolecular trapping with electrophiles represent not only a novel type of organic transformation involving vinylpalladium intermediates, but also provide synthetically useful routes toward differently substituted indenols, indanones, indenones, and naphthy-lamines." Although these protocols are restricted to the intramolecular trapping with electrophiles, a wide application of this methodology toward the synthesis of various types of complex carbocychc compounds may be anticipated in the near future. 

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. 

Pyrrolidine derivatives 152 are accessible by cascade carbopalladation of a diene 151 and intramolecular trapping of the intermediate it-allylpalladium species by a secondary amine moiety. In this case, an eflBcient enantiocontrol has been achieved using chiral phosphine ligands (Scheme 8.36) [340]. 

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. 

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). 

Over the last fifteen years or so the domino process involving the intermolecular and intramolecular carbopalladation of alkynes followed by trapping of the resultant... 

The intramolecular carbopalladation starting from a 2-halo-1,6-enyne leads to a terminal aUcenylpalladium halide relay that can be trapped by an external alkene or alkyne. With the former, the cascade process leads to a 1,3,5-hexatriene that undergoes rapid 67T-electrocyclization to a flve-ring-annelated cyclohexadiene and this, in turn, is easily dehydrogenated to the corresponding aromatic compound (Scheme 15). With an external alkyne trapping the intermediate, a 1,3,5-hexatrienylpalladium intermediate will be formed and can either cyclize by intramolecular carbopalladation or 67r-electrocycliza-tion before termination by dehydropalladation will occur. ... 

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

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

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). 

Intermolecular carbopalladation of a triple bond as in 457 by an in sitw-formed organopalladium triflate and subsequent intramolecular nucleophibc trapping gives rise to indoles 458 (Scheme 8.86) [600]. The versatihty of this approach derives from the fact that the triflate may be varied in a wide range. 

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