X: I, Br, Cl, or pseudohalides such as OTf; R'': typically bearing activating groups such as F, O, N, etc.
The Hiyama coupling refers to a cross-coupling reaction between an organosilicon compound and an organic halide (or pseudohalide) in the presence of a palladium catalyst to form a new C–C bond. This reaction was discovered and first reported in 1988 by the Japanese chemists Yasuo Hatanaka and Tamejiro Hiyama. Owing to the stability of its substrates and its environmental friendliness, the Hiyama coupling has found widespread application in medicinal chemistry, materials science, and natural product synthesis.
Reagents: Fluoride or base, palladium catalyst
Reactants: Organosilicon compounds, organic halides
Products: Carbon–carbon single-bond coupling products
Reaction type: Coupling reaction
Experimental Tips
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The reaction requires the addition of fluoride to activate the silicon reagent, or a base; the most commonly used is TBAF. TBAF is hygroscopic and should be dried or anhydrous reagents should be used to improve reaction efficiency.
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Fluoride can corrode glass; operations are therefore recommended in plastic bottles or PTFE-lined reaction vessels.
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For the silicon reagent, trialkoxysilanes (e.g., RSi(OEt)₃) or trifluorosilanes (RSiF₃) are preferred, as they are more readily activated. Organosilicon reagents are generally stable to air, but may undergo hydrolysis during long-term storage; drying before use is recommended.
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The reactivity of halides (or pseudohalides) follows the order I > OTf (triflate) > Br >> Cl (chlorides are difficult to react).
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Commonly used catalysts include Pd(PPh₃)₄, Pd(dba)₂ + phosphine ligands (e.g., PPh₃, XPhos), PdCl₂(dppf), etc. Nickel can also catalyze this reaction but requires the assistance of a strong reducing agent.
Reaction Mechanism
References
Hatanaka, Y.; Hiyama, T. The Journal of Organic Chemistry. 1988, 53 (4), 918-920.
Key References
Related Reactions
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