Electronegativity palladium chemistry

Pyridine is a jt-electron-deficient heterocycle. Due to the electronegativity of the nitrogen atom, the a and y positions bear a partial positive charge, making the C(2), C(4), and C(6) positions prone to nucleophilic attacks. A similar trend occurs in the context of palladium chemistry. The a and y positions of halopyridines are more susceptible to the oxidative addition to Pd(0) relative to simple carbocyclic aryl halides. Even a- and y-chloropyridines are viable electrophilic substrates for Pd-catalyzed reactions under standard conditions. 

Thiazole is a jt-electron-excessive heterocycle. The electronegativity of the N-atom at the 3-position makes C(2) partially electropositive and therefore susceptible to nucleophilic attack. In contrast, electrophilic substitution of thiazoles preferentially takes place at the electron-rich C(5) position. More relevant to palladium chemistry, 2-halothiazoles and 2-halobenzothiazoles are prone to undergo oxidative addition to Pd(0) and the resulting o-heteroaryl palladium complexes participate in various coupling reactions. Even 2-chlorothiazole and 2-chlorobenzothiazole are viable substrates for Pd-catalyzed reactions. 

To summarize, both chloropyrazines and chloroquinoxalines are sufficiently activated to serve as viable substrates for palladium chemistry under standard conditions. In contrast to chlorobenzene, the inductive effect of the two nitrogen atoms polarizes the C—N bonds. Therefore, oxidative additions of both chloropyrazines and chloroquinoxalines to Pd(0) occur readily. One exception is 2-chloropyrazine A-oxide, which does not behave as a simple chloropyrazine. All Pd-catalyzed reactions with 2-chloropyrazine A-oxide failed, presumably because the nitrogen atom no longer possesses the electronegativity required for activation. 

Due to the electronegativity of the two nitrogen atoms, pyrimidine is a deactivated, rc-electron-deficient heterocycle. Its chemical behavior is comparable to that of 1,3-dinitrobenzene or 3-nitropyridine. One or more electron-donating substituents on the pyrimidine ring is required for electrophilic substitution to occur. In contrast, nucleophilic displacement takes place on pyrimidine more readily than pyridine. The trend also translates to palladium chemistry 4-chloropyrimidine oxidatively adds to Pd(0) more readily than does 2-chloropyridine. 

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