Coupling reactions with heteroaryl compounds

As described in Section in.B.4.d, a palladium catalyst was required to couple ArZnX with AFX. Indeed, the remaining nickel(II) complex in the medium was unable to catalyze this coupling reaction even if it was reduced to the corresponding zero-valent nickel complex. In contrast, with 2-chloropyridine as the heteroaryl halide added in the second stage, the coupling reaction was efficiently catalyzed by Ni°(bpy). 2-Arylpyridine compounds were obtained in good yields. Results are reported in Table 5. 

A similar electrophile, iodosyl triflate, CF3S020I0, was employed with arylsi-lanes [98]. The same reagent upon reaction with Me3SiCN formed (CN)2I+ TfO" which was coupled with tributyltin substituted arenes or heterocycles to afford bis(heteroaryl)iodonium triflates, e.g. dithienyl and difuryl derivatives [99]. However, this method gave poor results with nitrogen heterocycles. For them another approach was developed based on the reaction of the appropriate lithium compound with / -(dichloroiodo)chloroethylene (Scheme 33). Pyridine and quinoline compounds were formed in this way in moderate yield (23-71 %) [100]. 

The organometallic-substituted 85 (M = a derivative of B, Zn, Sn) and halogeno-substituted siloles 85 (M = C1, Br, I) are suitable starting compounds for cross-coupling reactions. Pd-catalyzed coupling of 91 (R = Me, Ph) with 4-amino- and 4-heteroaryl-bromobenzenes affords the siloles 92 in high yield <20040M6205>. 

One class of transformations that illustrate the striking difference in reactivity between heteroarenes and carbocyclic arenes is the heteroaryl Heck reaction, in which an aryl or heteroaryl halide is coupled directly with a heteroaromatic compound to afford a biaryl product (formally a C—H bond functionalization process). Intermolecular Heck reactions involving the functionalization of aromatic carbocycles with aryVheteroaryl halides are rare [70], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles. 

A number of ligand coupling reactions involving the treatment of an heteroaryllithium reagent with triphenylsulfonium salts leading to phenyl-heteroaryl compounds [(14) - (17) for example] have also... 

Heteroaryl zinc compounds are particularly useful in palladium-catalysed coupling, being compatible with many functional groups. They are often prepared in situ via lithiation, followed by reaction with zinc halides, but direct zincation of halides can be carried out, using either Riecke zinc, as in the example below, or, more conveniently, ordinary zinc dust, with various means of activation. 

Organoindium(III) compounds can be prepared under very similar conditions to these organozincs and have an even greater tolerance of functional groups they are compatible with alcohols and phenols. Di-(heteroaryl) zincs, for use in coupling reactions, can be prepared by direct exchange of iodides, for example 5-iodofurfural, with (i-Pr)2Zn in the presence of a Li(acac) catalyst. ... 

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