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.