Studies on Intramolecular Higher-Order Cycloaddition Reactions

Thermal, metal-free, and metal-promoted intramolecular higher-order cycloadditions are described. Substrates in which the tropone (2,4,6-cycloheptatrien-1-one) nucleus is tethered to various diene moieties undergo exo-selective [6π + 4π] cycloaddition under thermal conditions to afford stereochemically defined tricyclic products. The substrates employed in this study were prepared by addition of the Grignard derivative of the given diene side-chain unit to 2-chlorotropone. In each instance, the requisite 2-substituted tropone was obtained directly from these reaction sequences. A similar study was conducted on the corresponding chromium(0) complexes of related tropone and cycloheptatriene-based substrates. In the cases involving metal mediation both thermal and photochemical activation were effective for delivering cycloadducts. The metal-promoted reactions were shown to proceed exclusively via an endo-selective pathway, which is stereocomplementary to the course of the thermal, metal-free reactions. A tandem Cr(0)-promoted 1,5-H shift-[6π + 2π] cycloaddition protocol is also reported with several systems.