Palladium-Catalyzed One-Pot Reaction of Hydrazones, Dihaloarenes, and Organoboron Reagents: Synthesis and Cytotoxic Activity of 1,1-Diarylethylene Derivatives

A new three-component assembly reaction between <i>N</i>-tosylhydrazones, dihalogenated arenes, and boronic acids or boronate esters was developed, producing highly substituted 1,1-diarylethylenes in good yields. The two C–C bonds formed through this coupling have been catalyzed by a single Pd-catalyst in a one-pot fashion. It is noted that the one-pot pinacol boronate cross-coupling reaction generally provides products in high yields, offers an expansive substrate scope, and can address a broad range of aryl, styrene, vinyl, and heterocyclic olefinic targets. The scope of this one-pot coupling has been also extended to the synthesis of the 1,1-diarylethylene skeleton of the natural product ratanhine. The new compounds were evaluated for their cytotoxic activity, and this allowed the identification of compound <b>4ab</b> that exhibits excellent antiproliferative activity in the nanomolar concentration range against HCT116 cancer cell lines