Direct Suzuki–Miyaura cross-coupling of C(sp2)–B(dan) bonds: designed in pursuit of usability†

Abstract

We developed practical reaction conditions and a procedure for the direct Suzuki–Miyaura cross-coupling (SMCC) of C(sp²)–B(dan) bonds. Below are important notes to successfully execute the direct SMCC: (1) dehydrated conditions that exclude as much H₂O as possible are required, (2) LiOH is the base of choice, (3) dppf is the ligand of choice when using electron-deficient (hetero)aryl halides [(Het)ArX], (4) P(t-Bu)₃ is the ligand of choice when using electron-rich (Het)ArX, and (5) COD is the ligand of choice when using (Het)ArX with a protic functional group such as NH₂ and OH. Taking heed of these notes enables the direct SMCC of the C(sp²)–B(dan) bond by using a wide range of substrates with diverse functional groups, affording the following series of coupling products: Ar–Ar, Ar–HetAr, HetAr–HetAr, alkenyl–Ar, and alkenyl–alkenyl. Sequentially executing distinct types of palladium-catalyzed CCs, such as Buchwald–Hartwig CC + SMCC, Mizoroki–Heck reaction + SMCC, and Sonogashira–Hagihara CC + SMCC, allows access to complex π-conjugated molecules. The B(dan) moiety also exhibits outstanding compatibility with Wittig olefination and Sc(OTf)₃-catalyzed acetal-forming reactions, enabling molecular transformations that are otherwise impracticable when using ArB(OH)₂. Mechanistic studies suggest the involvement of both path A, wherein a boronate species reacts with an arylpalladium halide, and path B, wherein a boron compound reacts with an arylpalladium hydroxide, at the stage of the transmetalation.