Cross-coupling reactions aryl chlorides

Activated aryl chlorides, which are close in reactivity to unactivated aryl bromides, underwent reaction with the original P(o-tol)3-ligated catalyst.58 Nickel complexes, which catalyze classic C—C bond-forming cross-couplings of aryl chlorides, 9-64 also catalyzed aminations of aryl chlorides under mild conditions.65,66 However, the nickel-catalyzed chemistry generally occurred with lower turnover numbers and with a narrower substrate scope than the most efficient palladium-catalyzed reactions. 

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. 

One limitation to the scope of the Suzuki reaction has been its inefficiency when aryl chlorides are employed as substrates. Recently, Buchwald and Fu have discovered the palladium-catalyzed cross-coupling of aryl chlorides with organoboron reagents, employing highly active palladium catalysts mediated by special ligands. These are discussed in Section 3.4. 

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. 

Cross-coupling Reactions. Trimethylsilylmethylmagnesium chloride reacts with organic halides (or pseudohalides), especially aryl and alkenyl halides, in the presence of transition metal catalysts. The reactions directly provide allylic or benzylic trimethyl-silanes of significant synthetic use. 

Recently, studies in urea synthesis have focused on transition-metal-catalyzed reactions. Buchwald et al. reported a Pd-catalyzed cross-coupling of aryl chlorides with sodium cyanate, which represented a practical way to synthesize unsymmet-rical ureas [50]. The protocol allows for the synthesis of unsymmetrical N,N -di-and A. A. A -trisubstituted ureas in one pot and is tolerant of a wide range of functional groups (Scheme 5.19). Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive... 

FuNn iONAL Group Tolerance of PdildbrO VIMes.HCI Catalyzed Suzuki Cross-Coupling Reactions of Aryl Chlorides with Phenyi.boronic Acid Derivatives... 

In the context of NHC/metal catalysed cross-coupling reactions, the only example of a Hiyama reaction was reported by Nolan using an in situ protocol by mixing Pd(OAc)j and IPr HCl for the formation of the catalyst. Activated aryl bromides and chlorides, such as 2-chloropyridine, were coupled with phenyl and vinyl-trimethoxysilane in good yields [123] (Scheme 6.39). 

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

The generated palladium chlorides possessing phosphinous acid ligands were found to be remarkably active and efficient catalysts in the presence of bases for a variety of cross-coupling reactions of aryl halides with aiylboronic... 

In summary, these results demonstrate that air-stable POPd, POPdl and POPd2 complexes can be directly employed to mediate the rate-limiting oxidative addition of unactivated aryl chlorides in the presence of bases, and that such processes can be incorporated into efficient catalytic cycles for a variety of cross-coupling reactions. Noteworthy are the efficiency for unactivated aryl chlorides simplicity of use, low cost, air- and moisture-stability, and ready accessibility of these complexes. Additional applications of these air-stable palladium complexes for catalysis are currently under investigation. 

The low catalytic reactivity of aryl chlorides in cross-coupling reactions is usually attributed to their reluctance towards oxidative addition to Pd(0). For a discussion, see V. V. Grushin and H. Alper, Chem. Rev., 94, 1047-1062 (1994), and reference therein. 

---