Reppe-Type Regioselective Assembly of Meta-Teraryls using Phenyl Vinyl Sulfone as a Traceless Acetylene Surrogate

Abstract

Benzene rings are among the most frequently encountered ring systems in small-molecule drugs, but only a few substitution patterns (1-, 1,2-, 1,4-, and 1,2,4-) predominate. Here, regioselective nickel-catalyzed three-component cyclotrimerization of terminal alkynes and phenyl vinyl sulfone was used to synthesize an underrepresented substitution pattern, the 1,3-arene. Phenyl vinyl sulfone serves as an acetylene surrogate for the regiocontrolled synthesis of meta-terphenyl derivatives. The reaction demonstrated wide functional group tolerance with moderate to good yields. Stoichiometric reactivity studies with catalytically relevant nickel complexes established the mechanistic origin of the observed regioselectivity.