Aryl chlorides, Kumada reaction

For nickel(O) complexes prepared from Ni(r -cod)2 and an excess of the free NHC, it was shown that they exhibit outstanding catalytic activity in the Kumada-Corriu reaction at room temperature toward unreactive substrates like aryl chlorides and even aryl fluorides.Again, an essential element of these catalysts is the need for sterically demanding NHC ligands as observed for the palladium catalysts. 

Low reactive aryl chlorides are converted to the respective organomagnesium species in excellent yields through transition metal catalysis using 2 mol% FeCU (4-6, equation 3). Alternatively, a safe and reproducible method for activation of aryl chlorides or bromides 7 uses microwave irradiation (equation 4). In a synthesis of a novel HIV-1 protease inhibitor, microwave irradiation was essential to generate the starting arylmagnesium halide as well as to promote the subsequent Kumada coupling reaction. ... 

The reaction of aryl electrophiles with organomagnesium compounds is known as Kumada or Kumada-Tamao-Corriu reaction. The most common leaving groups in the electrophile are halogen atoms and, among them, chlorine is the most wanted due to the good availability and the low price of aryl or heteroaryl chlorides. Unfortunately, the oxidative addition of a metal center to an aryl chloride is a difficult reaction and many efforts have been made to overcome existing limitations. 

Huang, J. Nolan, S. P. Efficient cross-coupling of aryl chlorides with aryl Grignard reagents (Kumada reaction) mediated by a Pd/imidazolium chloride system./. Am. 

Microwaves were utilized both in the preparation of the Grignard reagent and in the Kumada couplings [161] with aryl chlorides. It was noted in this case that a higher amount of homocoupling side-products was typically formed when microwaves were used as a heating source than when the reaction was carried out by employing ultrasound at ambient temperature (Scheme 74) [156]. 

MW, 175 °C, 10 min Scheme 74 Kumada reaction with aryl chlorides... 

Ni(0) carbenes are also effective for the Kumada-Corriu coupling reaction between aryhnagnesium reagents and aryl chlorides or fluorides in ca. 35 catalytic turnovers (equation 5). The yields are generally high even at room temperature (ca. 30 turnovers over 18h) only when the aryl chloride is congested (substituents ortho to Cl) does the yield suffer. It is noteworthy, however, that very similar yields were obtained when the N-heterocarbene ligands were replaced by t-BusP. 

Huang, J., Nolan, S. P. Efficient Cross-Coupling of Aryl Chlorides with Aryl Grignard Reagents (Kumada Reaction) Mediated by a Palladium/lmidazolium Chloride System. J. Am. Chem. Soc. 1999, 121,9889-9890. 

Walla, P., Kappe, C. O. Microwave-assisted Negishi and Kumada cross-coupling reactions of aryl chlorides. Chem. Common. 2004, 564-565. 

Kumada-Murahashi cross-couplings of primary alkyl bromides and tos-ylates have been described by Kambe [34]. Pd(acac)2/butadiene was employed as the catalyst, and couplings of alkyl and aryl Grignard reagents were achieved. The reactions proceed in the presence of an aryl chloride, an aryl bromide, and a styrenyl group. A typical cross-coupling is illustrated in Eq. 13. 

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