A Rhodium-Catalyzed [(4+2)+2] Cycloaddition of Allenediene for the Synthesis of Medium-Sized Rings

The synthesis of the compounds with medium-sized rings, especially those with a 5,8-fused ring system embedded into the structure, had long been pursued due to their ubiquitousness in numerous natural products and pharmaceutical molecules. These rings could be efficiently synthesized using metal-catalyzed higher order cycloaddition. In our studies, a previously-reported Rh-catalyzed [4+2+2] cycloaddition was developed and optimized to generate fused systems with a cyclooctadiene core from allenedienes and external alkynes. Upon screening of various metal complexes, ligands and solvents, a rhodium-BozPHOS complex was found to have the best reactivity. This cycloaddition between allenedienes and alkynes showed moderate yield and good substrate tolerance, showing good synthetic potential.