Heteroaryl Heck reaction imidazoles

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

Oxazoles and benzoxazoles are viable participants in the heteroaryl Heck reactions. In their monumental work published in 1992, Ohta and colleagues demonstrated that oxazoles and benzoxazoles, along with other rc-sufficient aromatic heterocycles such as furans, benzofurans, thiophenes, benzothiophenes, pyrroles, thiazole and imidazoles, are acceptable recipient partners for the heteroaryl Heck reactions of chloropyrazines [22b]. Therefore, treatment of 2-chloro-3,6-diethylpyrazine (27) with oxazole led to regioselective addition at C(5), giving rise to adduct 28. By contrast, a similar reaction between 2-chloro-3,6-diisobutylpyrazine (29) and benz[fc]oxazole took place at C(2) exclusively to afford pyrazinylbezoxazole 30. 

Ohta s group thoroughly studied the heteroaryl Heck reactions of chloropyrazines and jt-electron-rich heteroaryls [42-44], The substitution occurred at the electron-rich C(5) position of the imidazole ring for the heteroaryl Heck reaction of 2-chloro-3,6-dimethylpyrazine and N-methylimidazole. 

The heteroaryl Heck reaction is an efficient tool for the introduction of other five membered heteroaromatic systems too (for more details see Chapter 6.4.). Chloropyrazines reacted readily with oxazole to give the coupled product (7.57.), consisting solely of the 5-oxazolyl isomer.77 Extension of the reaction to imidazole led to a similar observation,78 and the expected 5-pyrazyl-imidazole derivative was isolated in acceptable yield. Reactions using thiophene as the masked olefin gave similar results. Under forcing conditions the 2,5-diarylation of fiiran was also observed.77... 

In contrast to facile reactions of aryl halides with alkenes and alkynes, reactions of aromatic compounds with aryl halides have received less attention. Only intramolecular arylation of benzene derivatives, except phenols, is known [1]. On the other hand, electron-rich heterocycles such as ffirans, thiophenes, pyrroles, oxa-zoles, imidazoles, and thiazoles undergo facile inter- and intramolecular arylation with aryl halides. These are called heteroaryl Heck reactions [2]. 

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