Synthesis of Carbocyclic Compounds via a Nickel-Catalyzed Carboiodination Reaction

A scalable nickel-catalyzed carboiodination reaction generating 6-membered carbocycles is reported. NiI2 and P(OEt)(3), as the ligand and reducing agent, provided decorated iodo-tetrahydronaphthalenes in up to 94% yield. The impact of varying electronic and steric parameters on the reaction are reported and a non-linear Hammett plot was obtained, supporting a change in the rate-determining step from oxidative addition to reductive elimination. Experimental and DFT studies suggest that the malonate group may stabilize a nickel oxidative-addition complex. A variety of heteroatom-containing nucleophiles and medicinally relevant heterocycles were easily incorporated into the products via simple S(N)2 chemistry.