Coupling agents aryl chlorides

Another system, a mixture of Pd(OAc)2 and IPr HC1, can mediate this reaction in the presence of a fluorine source [121]. The use of TBAF is essential for this reaction as it can act as a base, deprotonating the imidazolium salt, as a fluorous medium for tin extraction and as a fluorinating agent. In fact, the in situ formation of a hypervalent organnostannate speeds up the trans-metallation step and therefore eases the coupling reaction. Unfortunately, the reaction is limited to aryl bromides and activated aryl chlorides, on the other hand vinylstannates can also be used as coupling partners (Scheme 14). 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

Zim and Buchwald synthesized the palladacyclic phosphine complex 44 based on their ligand P(Bu-f)2(o-biphenyl) 13 (equation 46)157. This air- and moisture-stable palladium complex is a convenient one-component precatalyst for animation of aryl chlorides when combined with sodium tert-butoxide or sodium methoxide. For coupling of anilines, the addition of NEt3, which is possibly acting as the reducing agent to produce Pd(0), is necessary. 

An alternative is to use a pre-prepared stable ate complex, so that no Lewis base needs to be added to the mixture. One simple example is the tetraphenylborate ion, as in NaBPh4, which can acts as a phenyl transfer agent. A wide range of palladium catalysts have been used. While complexes with simple phosphines, such as triphenylphosphine, work well in many cases, the use of more sophisticated ligands is required in more difficult cases including the coupling of unactivated aryl chlorides. ... 

The last example reports the CuO-catalyzed N-aiylation of nitrogen heterocycles (and also anilines and ammonia) in water. The procedure, reported by Wan et al., is quite complex. It indeed requires the presence of a very large excess of the nucleophiles, a phase transfer agent (NBu4Br) and two ligands L13 (50%) and L14 (100%). It however represents one of the rare examples of copper-catalyzed coupling applied to nonactivated aryl chlorides [61]. 

Pyridylstannanes have been cross-coupled with numerous aryl- and heteroaryl halides as well as various other electrophiles. For example, an extension of Stille s original methodology to 3-trimethylstannylpyridine and acid chloride 73 gave the corresponding ketone 74, which was then converted to 2S-(+)-nicotinylalanine 75, a neuroprotection agent [62],... 

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