Heteroaryl halides, cross-coupling with

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

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],... 

The Hiyama couplings of heterocycles are still being developed to their full potential. Nevertheless, several heteroaryl halides have been cross-coupled with aryl or heteroaryl silicon reagents [52]. For example, in the presence of catalytic tt-allylpalladium chloride dimer and two equivalents of KF, the cross-coupling of ethyl(2-thienyl)difluorosilane (53) and methyl 3-iodo-2-thiophenecarboxylate led to bis-thiophene 54 under relatively forcing conditions [53]. 

Aromatic diazonium salts instead of the aryl halides also undergo Pd-catalyzed coupling of organotins, but they are less used. Aryl triflates are more popular.t The reaction of the triflate required LiCl as an additive. It was explained that triflate ligand of the oxidative adduct has to be replaced by chloride ligand before the transmetallation step. The system composed of AsPhj as ligand and NMP as solvent seems so far to be the most efficient for cross-coupling with aryl triflates. It does not require LiCl as an additive. The tolerance of heteroaryl halides and triflates is also noteworthy. Some examples are shown in Schemes 22-28. 

The applications of aryltrialkoxysilanes in Hiyama cross-couplings with heteroaryl halides have been documented in a review by DeShongJ The Hiyama cross-coupling has now been widened to include heterocyclic silanolates. 

If the stannane bears substituents at the position geminal to tin, the reaction requires activation by Cu1 (Section 9.6.3.2.1). The cross-coupling of aryl (or heteroaryl) stannanes with aryl (or heteroaryl) halides or triflates is a general route to various biaryls and their analogues, particularly useful in those cases when the Suzuki-Miyaura reaction is less effective for... 

Many examples exist for Pd-catalyzed cross-couplings of alkenylzirconocenes with simple carbocyclic aryl or alkenyl halides, whereas few precedents are seen for the coupling of alkenylzirconocenes with heteroaryl halides. Undheim and coworkers reported a Pd-catalyzed cross-coupling of 2,4-dichloropyrimidine with alkenylzirconocene [50]. Hydrozirconation of hexyne readily took place at room temperature with zirconocene chloride hydride in benzene. The resulting hexenylzirconocene chloride (76) was then coupled with 2,4-dichloropyrimidine at the more electrophilic 4 position, giving rise to 2-chloro-4-[( )-l-hexenyl]pyrimidine (77). 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

G. Cross-coupling Reactions with Aryl and Heteroaryl Halides. 1289... 

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