Halides, aryl, arylation heteroaryl, coupling with

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]. 

Like most aryl halides, furyl halides and furyl triflates couple with a var iety of organos-tannanes including alkenyl, aryl, and heteroaryl starmanes in the presence of catalytic palladium. Carbamoylstannane 122 is prepared by treating lithiated piperidine with carbon monoxide and tributyltin chloride sequentially. The Stille reaction of 122 and 3-bromofuran then gives rise to amide 123 [116]. In another example, lithiation of 4,4-dimethyl-2-oxazo-line followed by quenching with Me,SnCl results in 2-(tt ibufylstannyl)-4,4-dimethyl-2-oxa-zoline (124) in 70-80% yield [117]. Subsequent Stille reaction of 124 with 3-bromofuran affords 2-(3 -fuiyl)-4,4-dimethyl-2-oxazoline (125). 

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... 

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 furyl- and benzofurylstannanes can be coupled with a variety of electrophiles including aryl [53] and heteroaryl halides [54, 55]. In their synthetic studies towards lophotoxin and pukalide, Paterson and coworkers explored both intermolecular and intramolecular Stiile coupling reactions [56], The intermolecular approach between vinyl iodide 54 and furylstannane 55 was... 

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). 

Both diethyl (3-pyridyl)borane and diethyl (4-pyridyl)borane are readily accessible from 3-bromopyridine and 4-bromopyridine, respectively, via halogen-metal exchange and reaction with triethylborane [29-32], The two pyridylboranes have been coupled with a variety of aryl and heteroaryl halides, as exemplified by the coupling of diethyl (3-pyridyl)borane and 2-nitrophenylbromide to form phenylpyridine 39 [30, 31]. 

The copper-catalysed, Ullman-type coupling of aryl, heteroaryl and alkenyl halides may be achieved at ambient temperature using copper(I) thiophene-2-carboxylate as catalyst.60 A new semiconducting poly(anthraquinone-l,5-diyl) with nitro groups at the 4- and 8-positions has been prepared by Ullman-type coupling using metallic copper or a zerovalent nickel complex as catalyst.61... 

Wang and Scott [189] have described a two-step reaction in which an iodopyrrole is reacted first with hexabutylditin and subsequently with an aryl or heteroaryl halide unfortunately two different catalysts are required. Bates and Parker [190] have carried out the two-step synthesis of a ligand designed to impose a tetrahedral coordination geometry, the product of the initial ditin/aryl iodide coupling reacting further with a heteroaryl halide without change of catalyst (Scheme 4-49). 

The majority of reported reactions of aryl and heteroaryl substrates with organocopper reagents are examples of Stephens-Castro coupling or the more recent catalytic version of that reaction. The reaction has found recent application in syntheses of C-(6)-substituted pterins and pteridines, substituted pyridines, and the antitumor antibiotic fredericamycin A," to name a few. Aryl iodide can be che-mospecifically displaced in the presence of bromide," and 2,5-dibromopyridine is regioselectively substituted at the 2-position. Substitution of halobenzenes by propargyl alcohol, followed by oxidative cleavage, provides a convenient route to terminal arylalkynes. " Fused heterocycles are formed in reactions of aryl halides bearing nucleophilic ortho substituents. - "... 

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