Synthesis of complex hexacyclic compounds via a tandem Rh(II)-catalyzed double-cyclopropanation/Cope rearrangement/Diels-Alder reaction.

Treatment of (E)-1-(methoxymethylene)-1,2,3,4-tetrahydronaphthalene with styryl diazoacetates in the presence of catalytic amounts of the dirhodium complex Rh2(S-DOSP)4 provides a highly enantioenriched hexacyclic product with 10 new stereogenic centers. The transformation proceeds by a cascade sequence starting with a double cyclopropanation of a benzene ring, followed by a Cope rearrangement of a divinylcyclopropane and then an intramolecular Diels-Alder cycloaddition.

Divergent reaction pathways of homologous and isosteric propargyl amides in sequential Ru/Pd-catalyzed annulations for the synthesis of heterocycles.

Cu-catalyzed three-component coupling of imines with benzoyl chloride and terminal arylalkynes followed by enyne ring-closing metathesis (RCM) and Heck cyclization afforded medicinally relevant benzoindolines, cyclopropane-fused indenopyridines, pyrroloquinolines, or 1,7-tetrahydrophenanthrolines via divergent cyclization pathways. Unexpectedly, the Pd-catalyzed cyclization of heterocyclic dienes proceeded via regiodivergent 5-exo or 6-endo pathways depending on the ring size (n = 1, 2) or the presence of isosteric groups (CH vs N). A one-pot protocol for the enyne-RCM/Heck annulation featuring a sequential addition of the Ru and Pd catalysts was developed maximizing the synthetic efficiency.