Heteroaromatics 3-hetero-substituted compounds

All o-hetero-substituted arylmetals and aryl electrophiles (1) as well as heteroaromatic compounds represented by 2 and 3 are /3-hetero-substituted aryl derivatives. In most cases, /3-heteroatoms merely exert some rate-enhancing or -retarding influences on the Pd-catalyzed cross-coupling process. In some cases, however, their presence offers additional synthetic opportunities of potential significance. Synthesis of arene-fused heterocyclic compounds is particularly noteworthy, as indicated by the results presented below. However, most of the known examples involve cross-coupling-heteropalladation tandem processes, which are also discussed in Sect. V.3. So, they are very briefly mentioned in this section. 

Reactions of aromatic and heteroaromatic rings are usually only found with highly reactive compounds containing strongly electron donating substituents or hetero atoms (e.g. phenols, anilines, pyrroles, indoles). Such molecules can be substituted by weak electrophiles, and the reagent of choice in nature as well as in the laboratory is usually a Mannich reagent or... 

The radical alkylation of protonated heteroaromatic compounds-the so-called Minisci reaction-has been intensively investigated [2e, g, 111]. Protonated hetero-arenes are electron-deficient substrates, which react with nucleophilic radicals with high regioselectivity to yield the corresponding homolytic aromahc substitution products. For para-substituted pyridine derivatives the reaction occurs with complete regioselectivity at the 2-position, whereas for nonprotonated pyridines, arylations occur with low regioselectivity and in low yields. 

---