Metal-Catalyzed Cross-Coupling Reactions on Azaindole Synthesis and Functionalization

Abstract

Azaindoles are rare in nature but extremely attractive for drug discovery programs. Azaindoles can be obtained by diverse methods, including those involving metal-catalyzed reactions. This important core has been fascinating the scientific community due to their challenging synthesis and relevant bioactivity. This paper highlights the diverse synthetic methodologies developed to date involving metal-catalyzed reaction to attain azaindoles and its functionalization.

Advances in Green Catalysis for the Synthesis of Medicinally Relevant N-Heterocycles

“…Marques' group has also been focused on the application of Sonogashira reaction as a way of developing new and improved routes to achieve important privileged structures such as azaindoles [48]. The previous methodology reported by the team involved a palladium-catalyzed cascade C-N cross-coupling/Heck reaction that allowed for a straightforward synthesis of substituted 4-, 5-, 6-and 7-azaindoles but did not work when applied to N-aryl amino-o-bromopyridines.…”

“…Azaindoles are considered privileged structures, and their pharmacologic properties have enticed the interest of the scientific community [48,51,52]. On the follow-up of our previous work on the one-pot synthesis of azaindoles [45], novel palladium nanocatalysts were developed by J. Palomo's group [53] and in a joint collaboration were applied to the C-N cross-coupling/Heck reaction to synthesize several azaindole derivatives (Scheme 17).…”

“…The use of transition metals as catalysts has revolutionized modern organic chemistry and contributed to the development of more sustainable approaches. The metal-catalyzed synthesis of azaindole is no exception, since the application of metal-catalyzed reactions to synthesize this scaffold has continuously been improving [48]. Reactions such as Sonogashira [49] and Heck [45] and the methods reported by Lautens and Larock have been extensively applied.…”

Investigação de Aminopiridinas Não Halogenadas como Substratos Promissores para a Síntese de Azaindoles

“…Até ao momento, diversas vias sintéticas têm sido reportadas para a preparação de azaindoles a partir de aminopiridinas, incluindo a reação de Sonogashira, do tipo-Larock, a reação de Heck, e o acoplamento de Suzuki, bem como outras reações catalisadas por paládio, incluindo os protocolos mais recentes de Cacchi e Lautens. Outras abordagens, como a reação de ativação C-H catalisada por metal, têm sido escassamente exploradas para síntese e funcionalização de azaindoles (Esquema 4) [20]. O nosso grupo tem desenvolvido procedimentos para a síntese de azaindoles, em particular métodos de etapa-única, envolvendo catalisadores de paládio.…”

Solvent-Free C-3 Coupling of Azaindoles with Cyclic Imines

“…Thanks to the close similarity of azaindoles to the indole skeleton, C-3 functionalization of these compounds has been postulated [13,14]. Most of the methods known already for the synthesis of 3-functionalized 7-azaindole derivatives have applied multistep transformations.…”