Zipper-mode

Regarding efficiency in terms of achieving a maximum increase of molecular complexity in a minimum number of operational steps, the zipper-mode tetracyclization of the open-chain trienediyne 102 leading to the tetracyclic steroidal skeleton 103, as accomplished by Negishi et al. is particularly impressive (Scheme 28). This transformation involves four intramolecular carbopalladations with two alkyne relays forming four new G,G-bonds with the creation of four rings. 

The ultimate in the so-called zipper-mode carbopalladations has been demonstrated by Trost and Shi with the oligocyclization of the heptaenyne 130c to the heptacyclic hexaspirane... 

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. 

The propagation steps of the zipper -mode cascade cydization 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-... 

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

Even the tetracyclic steroid skeleton was successfully assembled in a zipper mode from an open-chain trienediyne with two alkynyl groups and a 2,2-disubstituted terminal double bond functioning as relays, as demonstrated by Negishi and co-workers (Scheme 30). "... 

It is noteworthy that, although Pd-catalyzed zipper mode cyclization under the Heck reaction conditions has widely been used for the construction of polycyclic systans, it would not be suitable for the construction of the capnellene skeleton with the cis-anti-cis stereochemistry, since the Heck reaction involves syn addition of an organopaUadium species to the carbon-carbon double bond followed by the syn elimination of a palladium hydride. Indeed, only the cis-syn-cis triquinane skeleton would be formed, and this has indeed been the case.f" ... 

Zipper-Mode Cascade Carbometallation for Construction of Polycyclic Structures. 

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