Hiyama

The Hiyama reaction, or Hiyama coupling, is a palladium-catalyzed cross-coupling that forms carbon–carbon bonds by joining organosilanes with organic electrophiles such as aryl, vinyl, or alkyl halides and pseudohalides. The reaction is distinguished by the use of a fluoride source to activate the silicon atom, enabling transmetalation to palladium under relatively mild conditions. It was developed by the Japanese chemist Hiyama and coworkers in the 1980s and has since become a versatile tool in organic synthesis.

The scope includes aryl-, vinyl-, and alkylsilicon reagents bearing various substituents, coupled with aryl or vinyl halides (iodides, bromides, and chlorides with modern catalysts) or triflates. Variants use different silicon groups (silanols, silanes, silsesquioxanes) and different fluoride activators such as tetrabutylammonium fluoride, cesium fluoride, or fluoride in combination with amines. The catalytic system is typically palladium-based, with phosphine ligands, N-heterocyclic carbenes, or bulky ligands; copper may act as a co-catalyst in some variants.

Conditions can tolerate air and moisture to some extent, and many reactions operate at ambient to moderately elevated temperatures.

Despite its advantages, the Hiyama coupling can be slower than other cross-couplings, especially with alkylsilicon reagents, and often requires optimized fluoride activation and ligands. Nevertheless, it remains valued for its use of abundant, stable organosilanes and its compatibility with a range of functional groups. It has found applications in the synthesis of biaryl motifs, natural products, and pharmaceutical intermediates, and has inspired further developments such as Hiyama–Denmark variants and nickel-catalyzed versions.