2-Bromopyridine, reaction with palladium complexes

While carefully isolating all products from a reaction of 2-bromopyridine 19 with palladium catalyst, bimetallic complex 148 was isolated and determined to be a pre-catalyst for the Suzuki reaction [52]. Upon examining the utility of this complex, it was found to be able to carry out Suzuki reactions, such as the conversion of 149 and 150 into 151. 

The obvious limitation of this reaction so far is in the electrophile as we have suggested naturally electrophilic enones as ideal partners for aryl or vinyl palladium o-complexes. In fact, complexation with palladium makes all alkenes electrophilic and nucleophilic addition can in principle occur to a simple alkene while it and the nucleophile are both bound to the palladium atom. Such reactions are known for aryl halides. Even ethylene itself does satisfactory Heck reactions and its reaction with the bromopyridine 132 is the basis for a large scale process leading to a drug.21... 

High yields (90 and 86%) of 2-chloro- and 2-bromo-pyridine are obtained by low-temperature (0—5 °C) halogenation of a palladium(ii) chloride complex of pyridine 2-chloropyridine is converted into 2-bromopyridine by its reaction with gaseous hydrogen bromide. A quantitative conversion of 2-chloro- into 2-methyl-pyridine is achieved by its reaction with methylmagnesium bromide in the presence of a catalyst, readily prepared from 2-chloropyridine and... 

Examples of the formylation of aryl halides with synthesis gas catalyzed by palladium complexes are summarized in Equation 19.90. These reactions relied upon the development of ligands with particular steric and electronic properties. The dia-damantyl-n-butyl phosphine shown in the equation, in combination with palladium acetate, leads to the formation of aromatic aldehydes in high yields from electron-rich and electron-poor aryl bromides. Reactions of nitroarenes and 2-bromopyridine provided the aldehydes in low yield, but other examples occurred in satisfactor) yield with only 0.1-0.75 mol % catalyst. The identity of the base is important in this process, and TMEDA was the most effective base. The mechanism of this process was not proposed in the initial work, but is likely to occur by oxidative addition of the aryl halide, insertion of the carbon monoxide into the palladium-aryl bond, and a combination of hydrogenolysis of the acyl intermediate and elimination of hydrogen halide to regenerate palladium(O). The base would then be involved in the hydrogenol5 sis and consumption of hydrogen halide. 

Suzuki coupling reaction of phenylboronic acids such as 74 with 4-bromopyridine [34]. Inada and Miyuara [35] have extended the method to 2-chloroquinoline 25. Therefore, the coupling between 25 and phenylboronic acid 74 led to 2-tolylquinoline 75 in 91% yield. The catalyst was recovered with ease and used in further coupling reactions. Not surprisingly, the couplings of phenylboronic acids with electron-rich chloroarenes were ineffective due to their slow oxidative addition to the palladium(O) complex. This reaction is an example where even quinolinyl chloride is a good substrate for the oxidative addition of Pd(0) if the chlorine atom is at the activated position (a or 8). 

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