Strategy intramolecular Stille coupling

Our strategy is based on the premise that the 31-membered ring and the conjugated triene array of the natural product could be fashioned simultaneously by a tandem inter-/intramolecular Stille coupling. Moreover, the mild conditions under which Stille couplings can be performed fueled hopes that the crucial stitching cycliza-tion could be conducted on a fully deprotected seco bis(vinyl iodide) (see 145, Schemes 40 and 54) the stitching cyclization would thus be the final operation in the synthesis. 

Scheme 7.3 Intramolecular Stille coupling in macrocyclization. (a) Solution-phase synthesis [54]. (b) Solid-phase synthesis by a cyclorelease strategy [55].

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

In 2006, Bout and Suffert combined Stille coupling with a preceding intramolecular alkyne insertion into a vinylic palladium bond and developed a new application of the 4-exo-dig cyclocarbopalladation of acyclic y-bromopropargylic diols 120 [48] (Scheme 6.30). This strategy is an efficient route to cyclobutanediol derivatives 121. The efficiency of the reaction is improved greatly by the use of brief microwave irradiation at 130 °C. Further 6ii-electrocyclization occurred, providing new bicyclic systems 123 instead of trienes 122, when the reaction was conducted in the presence... 

Another palladium-catalysed process that has proven utility for cyclic structures is the Stille coupling between organostannanes and aiyl or vinyl halides/triflates. Specifically for the macrocyclic framework, this chemistry was applied to the preparation of cyclic trienes (102) with defined geometry (Scheme 11.11) that were intermediates for transannular Diels-Alder reactions. The intramolecular Stille reaction also has been efficiently conducted on solid phase to form 104, an advanced intermediate in the synthesis of (S)-zearalenone, from 103 by a cyclization-release strategy. ... 

Scheme 16.17b [37, 34]. Although the substrate scope of these reactions is still narrow, this intramolecular Ar-H/Ar-H coupling strategy is beginning to flourish in the synthesis of natural products and pharmaceuticals.

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