Pyridyl halide

Scheme 149 Cathodic heterocoupling of aryl halides and pyridyl halides.

In a formal total synthesis of matrine (116), Yamanaka and coworkers used the Sonogashira reaction of pyridyl halides as the means to form C—C bonds <86CPB2018>. For instance, bromonaphthyridinone 114 was coupled with 3-butyn-l-ol to furnish alkynylnaphthyridinone 115, an intermediate towards matrine (116). 

Table 7.3 Palladium-catalyzed amination of pyridyl halides...

Results on the amination of pyridyl halides conducted with two phosphine ligands and two different palladium precursors have been published (Table 2) [123]. The most general palladium precursor proved to be palladium acetate. Again, BINAP was found to be generally effective for amination with either primary or secondary amines. However, yields were lower with unbranched primary amines than those with branched amines, such as cydo-... 

Hydrazinopyridines are important in the preparation of triazines and as intermediates in the production of agrochemicals and pharmaceuticals. Thus, Arterburn et al. investigated the reaction between hydrazine derivatives and pyridyl halides and triflates [124]. These workers found that 2-bromo- and 2-chloropyridine reacted with benzophenone hydrazone... 

Most of the mechanistic work on this reaction has been devoted to determining the role of the base. Its most obvious function would be to complex the Lewis-acidic boron reagent, rendering it nucleophihc and thus activating it toward transmetallation. However, Miyaura, Suzuki, and coworkers noted that an electron-rich tetracoordinate boronate complex was less reactive than a bivalent boronic ester. From this, they surmised that the role of the base was not to activate the boron toward transmetallation, but rather to transform the palladium halide intermediate to the hydroxide or alkoxide species, which would then be more reactive toward boron. However, in a mass spectrometry study of a reaction between a pyridyl halide substrate and an aryl boroiuc acid, Aliprantis and Canary saw no evidence of palladium hydroxide or alkoxide intermediates, despite observing signals in the mass spectra assignable to every other palladium intermediate of the proposed catalytic cycle. ... 

Activated aromatic halides and 2- or 4-pyridyl halides can be used for the N-arylation of 1,2,4-triazoles, best achieved by the Ullmann technique (70JCS(C)8s). Preference for annular arylation on N-1 rather than N-4 is observed but arylations of 3-aminotriazoles with picryl chloride are anomalous the parent triazole itself is substituted on N-1 but in... 

Multiple aminations are possible when polyfunctionalized pyridyl halides 30 are coupled with 69 to generate 411. 

Coupling reactions of polyfunctional organomagnesium reagents with alkyl [123], alkenyl [124], or pyridyl halides [125] are achieved by use of Cu, Fe, or Pd catalysis (Scheme 3.100). 

Coupling reactions. Electrochemical coupling reactions with (bpy)NiBr2 catalysis include those between alkenyl bromides and a-halo esters, aryl and pyridyl halides, as well as aryl and chlorophosphines. ... 

Couplings requiring pyridyl organometallic species are best achieved with boron, zinc, or tin compounds the last are available either by reaction of pyridyl halides with sodium trialkylstannate or, in the opposite sense, by the reaction of a pyridyllithium with chlorotrimethylstannane. " Pyridyltin compounds have been coupled for example with haloarenes and with halopyridine A -oxides. ... 

Arylpyridines can be obtained by the electrochemical reduction of the corresponding aryl and pyridyl halides using a sacrificial anode (Mg, Zn or Fe) in the presence of NiBr2bpy as a catalyst (Scheme 149) [265, 266]. 

Attempts to hydrolyze the ester group in the o-nitro-2- and 4-pyridyl acetates XI-19, synthesized by treating the corresponding pyridyl halide with a malonic acid derivative, were unsuccessful using either basic or acidic conditions. The... 

Scheme 3.18 Pd-catalyzed reaction of pyridyl halides S3 with phenylboronic acids 55a-c after dilution with MeOH for ESI-MS monitoring.

Scheme 5.12 Pd-catalyzed reaction (0.27(imol L ) of pyridyl halides 27 (8.9 tmol L ) with phenylboronic acids 29a-c (5.48pmol L ) after dilution with MeOH for analysis.

Canary used pyridyl halides (1 and 2) instead of the typically used phenyl derivatives to introduce a protonable group into the complexes, tvhich othertvise might not be detected by the ESI-MS (Scheme 7.2). 

Scheme 7.2 Suzuki-Miyaura cross-coupling reactions of pyridyl halides 1 and 2 with arylboronic acids 3 studied by ESI-MS.

Entry Pyridyl halide Arylboronic acid R R Species observed by ESI-MS... 

In 2007, Castanet reported an efficient carbonylative Suzuki reaction of pyridyl halides with different boronic acids using 50 bar of carbon monoxide. The catalyst used is a combination of Pd(OAc)2 and imidazolium salt precursors NHC-Cl. In all cases, carbonylated species 72 were obtained as the major products (Scheme 5.52). The best results were found with ligand precursor IMes-Cl, being also active in... 

The reaction is greatly affected by steric hindrance. The reactivity of the alkene decreases with its degree of substitution. Ethylene is a good partner in Heck reactions, but infrequently used. The Heck reaction of a pyridyl halide 5.63 with ethylene was employed on a 5.4 kg scale for the preparation of a pharmaceutical intermediate 5.64 (Scheme 5.20). °... 

Craig, L. C. (1934). A study of the preparation of alpha-pyridyl halides from alpha-aminopyridine by the diazo reaction. J Am Chem Soc 56, 231-232. 

---