Palladium-Catalyzed Stille Couplings with Fluorous Tin Reactants

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Abstract
A new class of “fluorous” aryl tin reactants was investigated for use in the Stille coupling. Fluorous compounds partition into a fluorocarbon (fluorous) phase in a fluorous/organic extraction. The coupling of tris[(perfluorohexyl)ethyl]phenyl tin [(C6F13CH2CH2)3SnPh] with bromobenzene occurs smoothly in DMF/THF (1/1) at 80 °C in the presence of a catalytic amount of PdCl2(PPh3)2 and 3 equiv of LiCl. Partitioning between CH2Cl2 and FC-72 (a mixture of perfluorohexanes) provided biphenyl in 90% yield from the organic phase and tris[(perfluorohexyl)ethyl]tin chloride in >90% yield from the fluorous phase. The tin chloride was reacted with phenylmagnesium bromide to regenerate the starting tin reactant. A study to optimize reaction conditions is described, and the scope of the method is illustrated with 20 coupling reactions. The beneficial effect of lithium choride is an unusual feature of the reaction, but it also promotes the formation of some fluoroalkyl-coupled products. These can be suppressed by adding CuI. The paper describes a prototypical example of how to render a tin reactant fluorous. This process should be advantageous in small- and large-scale synthesis, as well as in automated synthesis.