Kumada Coupling
The Kumada cross-coupling is the transition metal-catalyzed carbon-carbon bond-forming reaction of alkenyl or aryl halides and organomagnesium or organolithium reagents.
General features: 1. The coupling is stereoselective, and the stereochemistry of the starting vinyl halides is preserved. 2. The reaction can be catalyzed by Ni and Pd catalysts. The Pd-catalyzed process is more chemo- and stereoselective and has a much broader scope. 3. The coupling takes place with aryl bromides and iodides, but not with aryl chlorides when Pd catalysts are employed. 4. Organomagnesium and organolithium reagents are used most often. 5. Base-sensitive functional groups are not tolerated because of the polar nature of the organomagnesium and organolithium compounds. 6. Possible side-reactions include homocoupled and reduction products. 7. The reaction is often carried out in tetrahydrofuran or diethyl ether, which are the typical solvents for generating the Grignard reagent. 8. As in many coupling reactions, the palladium catalyst is often air-sensitive, requiring an inert reaction environment.
Kumada Coupling
Reaction Mechanism
1. Initially, the electron-rich Pd(0) catalyst inserts into the R–X bond of the organic halide. This oxidative addition forms an organo-Pd(II)-complex. 2. Subsequent transmetallation with the Grignard or the organolithium reagent forms a hetero-organometallic complex. 3. Before the next step, isomerization is necessary to bring the organic ligands next to each other into cis positions. 4. Finally, reductive elimination leads to the formation of a C–C bond and releases the cross-coupled product while regenerating the Pd(0) catalyst.
Example
Experimental Procedure
To a stirred solution of the alkenyl iodide (3.07 mmol, 1.0 eq) in degassed Et2O (50 mL) at 0 °C was added PdCl2(dppf) (0.1 eq) followed by allylmagnesium chloride (1.5 M in Et2O, 3.0 eq) dropwise. The resultant mixture was allowed to warm to room temperature over 18 hours before the reaction was then diluted with Et2O and quenched with water at 0 °C. The mixture was extracted with Et2O, and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was passed through a short plug of SiO2, and the crude product was submitted directly to the next step without further purification.
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