Heteroaryl recipient

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]. 

Intermolecular or intramolecular Heck reaction that occurs onto a heteroaryl recipient. 

In contrast, thiazoles and benzothiazoles are suitable recipients for the heteroaryl Heck reaction. Treatment of 2-chloro-3,6-diisobutylpyrazine (103) with thiazole led to regioselective addition at C(5), giving rise to adduct 104 [57]. A similar reaction between 2-chloro-3,6-diethylpyrazine (105) and benzo[ >]thiazole took place at C(2) exclusively to afford pyrazinylbenzothiazole 106 [57]. 

Oxazoles and benzoxazoles are viable participants in the heteroaryl Heck reactions. In their important work published in 1992, Ohta and colleagues demonstrated that oxazoles and benzoxazoles, along with other rr-sufficient aromatic heterocydes such as furans, benzofurans, thiophenes, benzothiophenes, pyrroles, thiazole, and imidazoles are acceptable recipient partners for the heteroaryl Heck reactions of chloropyrazines [55]. Therefore, treatment of 2-chloro-3,6-diethylpyrazme (95) with oxazole led to regioselective addition at C(5), giving rise to oxazolylpyrazine 96. Similar results were obtained for the heteroaryl Heck reaction of iodobenzene or bromobenzene with oxazole and benzoxazole [56]. 

---