Pyrrole—continued reactivity

Here, the parallels with benzenoid counterparts continue, for these compounds have no special properties - their reactivities are those typical of benzenoid aldehydes, ketones, acids and esters. For example, in contrast to the easy decarboxylation of a-acids observed for pyrrole and furan, thiophene-2-acids do not easily lose carbon dioxide nevertheless, high-temperatme decarboxylations are of preparative value (see also 17.12.1.2). "... 

Side chain lithiation is a major source of reactivity in terms of the elaboration of pyrroles and indoles, and new examples and developments continue to be reported. One major development has been the lithiation of 2-alkyl groups of 2-alkylindole-1 -carboxylate lithium salts. The carboxyl group protects the nitrogen atom, directs the lithiation, and can easily be removed after alkylation (Scheme 121) <86JA6808>. Similarly, lithiation of 2,3-dialkylindoles takes place at the 2-methylene position via the C,7V-dilithio derivative, using three equivalents of butyllithium <9UOC2256>. 

Hydrogen borrowing and dehydrogenative condensations provide new opportunities for the preparation of both saturated and aromatic heterocycles respectively. The ability to directly access azacycles from stable species such as alcohols and amines allows chemists to circumvent the preparation and use of relatively unstable carbonyls and alkyl halides that conventional methods require. Pyridines, pyrazines, pyrroles, as well as fused bicyclic heteroaromatics, may all be prepared by dehydrogenative condensation this reactivity will likely be extended to pyrimidines, imidazoles, pyrazoles, and triazoles in the near future. Continuous advances in scope and scalability will expand the role of hydrogen transfer in the discovery and production of small molecule therapeutics. 

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