The secret to the palladium-catalyzed cross-coupling reactions is often the judicious choice of catalyst ligand. Michael G. Organ’s group at York University, in Toronto, in collaboration with researchers at Dow Chemical and Eli Lilly & Co., have revealed a bit more of that secret by learning how to tweak the structure of a pyridine-N-heterocyclic-carbene-based ligand system called PEPPSI to carry out selective Negishi couplings of secondary alkyl groups with five-membered heterocyclic rings, a reaction not possible before (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201503941). Negishi coupling works for adding branched alkyl groups to six-membered rings, but attempts to do the same with five-membered rings gave a mixture of linear and branched isomers. Organ’s group found that adjusting the structure of a commercial PEPPSI ligand they previously developed, by switching from isopentyl to isoheptyl substituents and adding chlorines, increases the bulk and alters the electronic properties to favor the desired branched isomers.