Directing group and substrate control strategies have frequently been employed for the regioselective C-H alkenylation of acid- and oxidant-sensitive pyrrole heterocycles. We developed an undirected, aerobic strategy for the C-H alkenylation of N-alkylpyrroles by ligand control. For C2-alkenylation of electron-rich N-alkylpyrroles, an electrophilic palladium catalyst derived from Pd(OAc) and 4,5-diazafluoren-9-one (DAF) was used. Alternatively, a combination of Pd(OAc) and a mono-protected amino acid ligand, Ac-Val-OH, was useful for C5-alkenylation of N-alkylpyrroles possessing electron-withdrawing groups at the C2 position. This approach based on the electronic effects of heterocycles and catalysts can rapidly provide a wide range of alkenyl pyrroles from readily available N-alkylpyrroles and alkenes.

Complementary to Catellani-type reactions and 1:1 coupling of six-membered halo­(hetero)­arenes and norbornene (NBE) derivatives, Pd-catalyzed 1:2 coupling of five-membered haloheteroarenes with NBEs was achieved to afford rigid nonplanar heterocycles. Pyrazole, thiophene, furan, and indole underwent exo- and trans-selective annulation. Two strained alkene groups of the resulting products were further manipulated to afford 1-alkylindazoles and ladder polymers. The type of heteroarenes and position of halides along with the choice of ligands and bases were critical to set a preference between C–H annulation and Catellani reactions, which will be useful for the development of Pd-catalyzed, NBE-mediated reactions of heteroarenes.

Pd-catalyzed multicomponent coupling reactions of five-membered heteroaryl halides and norbornadiene (NBD) were developed. Either direct addition of (benzo)­azoles or 2:1 annulation was achieved depending on the propensity of the intermediate complex to undergo palladacycle formation, determined by the nature and substitution pattern of the heteroarene. The obtained exo- and cis-diheteroaryl norbornenes underwent epimerization and retro-Diels–Alder reactions to afford the corresponding trans-isomers and π-extended heteroaromatic systems, respectively, demonstrating the versatility of NBD as an acetylene synthon.

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