Highly Regioselective Difluoroalkylarylation of Butadiene through a Nickel-Catalyzed Tandem Radical Process

A nickel-catalyzed reaction of 1,3-butadiene with easily accessible difluoroalkyl bromides and arylboronic acids has been realized, affording the corresponding 1,4-difluoroalkylarylation products in good yields with high regioselectivities. The procedure can also be successfully extended to nonfluorinated alkyl bromides. A radical clock experiment suggests that a key alkyl radical is involved in the catalysis. The operational simplicity, excellent functional-group compatibility, and high efficiency should make this nickel-catalyzed three-component reaction highly promising for the cost-efficient synthesis of difluoroalkylated compounds.

Automated summary

A nickel-catalyzed reaction has been developed for the synthesis of 1,4-difluoroalkylarylation products from 1,3-butadiene with easily accessible difluoroalkyl bromides and arylboronic acids. The involvement of a key alkyl radical in the catalysis was demonstrated by a radical clock experiment. The operational simplicity, excellent functional-group compatibility, and high efficiency of this three-component reaction make it highly promising for the cost-efficient synthesis of difluoroalkylated compounds.