Hiyama Coupling - Reaction History

Reaction History

The Hiyama-coupling was developed to combat the issues associated with other organometallic reagents. The initial reactivity of organosilicon was not actually first reported by Hiyama, as Kumada reported a coupling reaction using organofluorosilicates shown below. Organosilanes were then discovered, by Hiyama, to have reactivity when activated by a fluoride source. This reactivity, when combined with a palladium salt, creates a carbon-carbon bond with an electrophillic carbon, like an organic halide. Compared to the inherent issues of well-used organometalics reagents, such as organomagnesium (Grignard Reagents) and organocopper reagents, which are very reactive and are known to have low chemoselectivity, enough to destroy functional groups on both coupling partners, organosilicon compounds are inactive. Other organometallic reagents using metals such as zinc, tin, and boron, reduce the reactivity issue, but have other problems associated with each reagent. Organozinc reagents are moisture sensitive, organotin compounds are toxic, and organoboron reagents are not readily available, are expensive, and aren't often stable. Organosilanes are readily available compounds that, upon activation (much like organotin or organoboron compounds) from fluoride or a base, can react with organohalides to form C-C bonds in a chemo- and regioselective manner. The reaction first reported was used to couple easily made (and activated) organosilicon nucleophiles and organohalides (electrophiles) in the presence of a palladium catalyst. Since this discovery, work has been done by various groups to expand the scope of this reaction and to "fix" the issues with this first coupling, such as the need for fluoride activation of the organosilane.