Cascade cyclizations carbopalladation

Tricyclic skeletons such as 85, 87, 89 with a central benzene ring are formed in the fully intramolecular Pd-catalyzed cascade cyclization of 2-bromo-l-ene-//,w-diynes 84, 86, 88 and analogs (Scheme 24). This process involves two alkyne relays in a row and a final 67r-electrocyclization or 6-endo-trig carbopalladation with ensuing / -dehydropalladation. 

Scheme 37 Two cascade cyclizations involving inter- or intramolecular carbopalladations of allenes.

DumbbeM"-Mode and Related Circular Cascade Cyclization Processes via Carbopalladation... 

Selective synthesis of benzene derivatives via partially intramolecular cyclic carbopalladation is considerably more complex than the corresponding all-intramolecular processes. As it is generally difficult to specify the cascade-initiation point in the Type Ha cyclization process, it would generally be the least selective path. A priori, the most favorable might be the intra-inter cascade cyclization process (Type lib), since both the point of initiation and the queuing order between the two alkynes is sharply differentiated by the fact that one is intramolecular, while the other is intermolecular. Still, in-... 

Both spiro-mode and linear-fused-mode cascade cyclization processes via carbopalladation were introduced in 1988 [20,21,131]. In addition to the... 

The propagation steps of the zipper -mode cascade cyclization are by definition all-intramolecular processes. Some prototypical examples of the zip-per -mode cascade cyclic carbopalladation producing two to five fused rings in one step are summarized in Scheme 40 [11,113-116,122]. One of the major attractive features of this synthetic methodology is the ease of retrosynthetic analysis, which involves finding a linear line of dissection indicated in bro-... 

A 2-bromotetradeca-l,13-dien-7-yne with a terminal phenyl group apparently also prefers to cascade-cyclize via a neopentylpalladium intermediate with attack on the proximal phenyl group to yield a pentacyclic system (Scheme 41) rather than following the carbopalladation sequence to yield a tetracycle with a bridging cyclopropane ring as observed for other 2-bromo-l,13-diene-7-ynes (see above, Scheme 33). 

Three simpler ort/to-substituted iodobenzene derivatives with two alkene moieties in the side chains have been cascade cyclized to give methylenespiroalkane-annelated indanes (Scheme 26) and bicyclic systems (Scheme 27). This outcome clearly demonstrates that the intramolecular carbopalladations are determined by entropic factors, which always favor the formation of the smaller possible ring sizes. 

As indicated in Scheme 6, alkynes are well-suited for the zipper -mode and dumbbelF -mode cascades, the latter of which can be extended to circular cascades. Although some other modes of cyclizations are conceivable, the two mentioned above appear to be the two representative ones involving syn-carbopalladation. 

Palladium-Catalyzed Cyclization via Carbopalladation and Acylpalladation Zipper"-mode cascade cylclization... 

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. ... 

On the other hand, an alkenylpalladium intermediate formed by intramolecular carbopalladation from a 2-bromo-l-en-6-yne carbopalladates an external mono-or disubstituted alkyne, and the cascade process is terminated by cyclization of the 1,3,5-hexatrienylpalladium intermediate through intramolecular carbopalladation or 67T-electrocyclization and ensuing dehydropalladation (Scheme... 

The octahydrophenanthrene skeleton is also formed from 2-bromotetradeca-l-ene-7,13-diynes with a trialkylsilyl-substituted terminal triple bond (Scheme 46, Eq. 1). With an unsubstituted terminal acetylene, the same bromoenediynes yield bisannelated ful-venes by a completely different cascade carbopalladation mode involving a 5-exo-trig cy-clization and a [l,5]-sigmatropic shift of the CH2PdBr group or a 3-exo-trig cyclization... 

In principle, carbonylative cyclization, that is, acylpalladation or Ac—Pd process, or noncarbonylative cyclization, that is, sample carbopalladation or C—Pd process, in the presence of CO and a Pd catalyst. Various possibilities with halo alkenes as representative substrates are shown in Scheme 2P Those processes that incorporate CO in the cyclization processes are discussed in Part VI including Sects. VI.4-VI.6. hi this section, those cases that do not incorporate CO during the cychzation processes but do so only after cyclization will be discussed. Such cychc carbopalladation-carbonylative termination tandem and cascade processes are represented by the Type II C—Pd process in Scheme 2, which may take place in competition with the other processes shown in Scheme 2, especially the cyclic Heck reaction (Type 1 C—Pd process) and cyclic carbopalladation involving cyclopropa-nation (Type 111 C— Pd process). 

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