Synthesis of Carbocyclic Compounds via a Nickel-Catalyzed Carboiodination Reaction

Abstract

A scalable nickel-catalyzed carboiodination reaction generating 6-membered carbocycles is reported. NiI 2 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.

Iron‐Catalyzed Alkene Trifluoromethylation in Tandem with Phenol Dearomatizing Spirocyclization: Regioselective Construction of Trifluoromethylated Spirocarbocycles

“…The linker with an unsymmetrical ethyl acetoacetate gave the product 2 u in 67% yield, while the reaction was completely inhibited from the substrate with a α‐cyano ester linker ( 1 v ). This is possibly due to the formation of a inactive complex between the Lewis basic nitrile group and Iron [16] . The N ‐isopropylacrylamide‐tethered substrates also resulted in the dearomatized products 2 w‐y in 61–78% yields.…”

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…[74] In 2021, the Lautens group reported an ickel-catalyzed carboiodination reaction generating carbocycles using malonate-containing substrates. [75] Again NiI 2 with an alkyl phosphite (P(OEt) 3 )p roved to be optimal for the reaction. Experimental and computational evidence supported the hypothesis of the malonate group being essential for coordination of ac atalytically relevant nickel oxidative addition complex.…”

“…In 2021, the Lautens group reported a nickel‐catalyzed carboiodination reaction generating carbocycles using malonate‐containing substrates [75] . Again NiI 2 with an alkyl phosphite (P(OEt) 3 ) proved to be optimal for the reaction.…”

“… Hammett Analysis and mechanistic studies of the carbocyclic carboiodination reaction catalyzed by nickel [75] …”

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…[74] In 2021, the Lautens group reported a nickel-catalyzed carboiodination reaction generating carbocycles using malonate-containing substrates. [75] Again NiI 2 with an alkyl phosphite (P(OEt) 3 ) proved to be optimal for the reaction. Experimental and computational evidence supported the hypothesis of the malonate group being essential for coordination of a catalytically relevant nickel oxidative addition complex.…”