Nickel-Catalyzed Reductive 1,4-Alkylarylation of 1,3-Enynes to Access Tetra-Substituted Allenes

Abstract

Allenes are one of pi-conjugated system that has a carbon atom with two doubles. This unique structure causes our interest in allenes as a useful synthetic intermediate for asymmetric synthesis of natural products. The classical synthetic methodologies to access allene include sigmatropic rearrangements, nucleophilic substitution, 1,2-eliminations, olefinations and 1,4-additions with help of organometallic reagents and strong bases. As the transition-metal catalysis evoked as a mild and efficient synthetic methodology, the modern synthesis of allenes are also being focused on the development of useful and efficient catalytic system. The novel breakthrough for the synthesis of allenes was reported by the Hayashi group through ligand controlled remote 1,4-hydroboration of 1,3-enynes with palladium catalyst. Later, the radical introduction of alkyl iodide to 1,3-enyne followed by formation of allenyl radical shows remarkable possibility of transition metal-catalyzed allene synthesis. However, the usage of organometallic reagent remains as limitation. The reductive difunctionalization of pi-conjugated system arises as an alternative strategy since it only uses organic halide without formation of reactive organometallic reagents. The reductive difunctionalization of 1,3-enyne has not been studied because of its variety of possible undesired products including homo-coupling, di-alky- or di-arylation of 1,3-enyne, vicinal functionalization of 1,3-enyne. Here in, the novel nickel-catalyzed reductive 1,4-alkylarylation of 1,3-enyne to access structurally diverse tetrasubstituted allenes with high efficiency and regioselectivity is described