Synthesis of Angularly Substituted trans-Fused Decalins by a Metallacycle-Mediated Annulative Cross-Coupling Cascade

摘要

A convergent coupling reaction is described that enables the stereoselective construction of angularly substituted trans-fused decalins from acyclic precursors. The process builds on our alkoxide-directed titanium-mediated alkyne–alkyne coupling and employs a 1,7-enyne coupling partner. Overall, the reaction is thought to proceed by initial formation of a tetrasusbstituted metallacyclopentadiene, stereoselective intramolecular [4+2] cycloaddition, elimination, isomerization, and regio- and stereoselective protonation. Distinct from our early studies directed at the synthesis of trans-fused hydrindanes, the current annulative coupling has revealed an important effect of TMSCl in controlling the final protonation – the event that establishes the ring fusion stereochemistry.