Heteroaryl halides coupling reactions

Our group has recently developed an alternative method for alkyl-(hetero)aryl- as well as aryl-heteroaryl cross coupling reactions catalyzed by iron salts.3 4 This methodology was inspired by early reports of Kochi et al.5>6 on iron-catalyzed cross coupling of vinyl halides and is distinguished by several notable advantages. 

Amide and electron-poor aniline nucleophiles have also been employed in heteroaryl halide amination reactions. For example, an organic synthesis procedure was recently reported for the synthesis of ethyl 4-[(6-chloropyridin-3-yl)amino] benzoate via Ai-arylation of ethyl 4-aminobenzoate with 2-chloro-4-iodopyridine (Eq. 32) [220]. Beletskaya has illustrated that bromoindole derivatives can be coupled with amides utilizing either Xantphos or 3,5-(Cp3)2Xantphos (22) as the ligand in good yield (Eq. 33) [169]. 

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],... 

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... 

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. 

Cross-coupling reactions between organoboranes and heteroaryl halides are effectively catalyzed by Pd(0) in the presence of a base. Couplings in simple pyrimidines are illustrated by the reaction between 2-chloropyrimidine and 2- or 3-thiophene- and selenophene-boronic acids which give the corresponding 2-substituted pyrimidines (921) (Scheme 72). In 2,4-dichloro- or 2,4-dibromo-pyrimidine it is the 4-halo substituent which is the more reactive. 

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. 

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]. 

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