Stille cross coupling
From Biocrawler, the free encyclopedia.
A Stille cross coupling is a cross coupling reaction of an aryl halide with an aryl or alkenyl tin compound using a zero-valent palladium complex such as tetrakis(triphenylphosphine)palladium(0) as a catalyst. This reaction was discovered by John K. Stille in 19861.
The reaction mechanism of the reaction can be explained as follows. First, oxidative addition of a palladium(0) catalyst into the carbon-halogen bond of the aryl halide occurs; then the transmetalation of the aryl or alkenyl group proceeds and organic tin halide is generated. Finally, reductive elimination of the catalyst affords a product of the coupling reaction.
The reaction is usually performed under inert atmosphere using dehydrated and degassed solvent. This is because oxygen causes the oxidation of the palladium catalyst and promotes homo coupling of organic stannyl compounds, and these side reactions lead to a decrease in the yield of the cross coupling reaction.
As the organic tin compound, a trimethylstannyl or tributylstannyl compound is normally used. Although trimethylstannyl compounds show higher reactivity compared with tributylstanny compounds, the toxicity of the former is about 1000 times larger than that of the latter. Therefore it is better to avoid using trimethylstanny compounds unless necessary.
To improve the yield of the reaction, lithium chloride is often added to the reaction mixture. This reagent stabilizes the intermediate complex formed by the oxidative addition of a catalyst and accelerates the reaction.
1. J. K. Stille, Angew. Chem. Int. Ed., 25, 508 (1986).
