Palladium catalysed cyclizations for N-Heterocycle synthesis: Recent developments


*Corresponding author
1. LAQV-REQUIMTE, University of Évora, Rua Romão Ramalho, Évora, Portugal
2. Department of Chemistry, School of Science and Technology, University of Évora, Évora, Portugal


In this paper we address the synthesis of important heterocycles via palladium catalyzed cyclizations of appropriate starting materials. Many important active pharmaceutical ingredients (APIs), biologically active compounds and chemicals applied in electronics contain heterocyclic units, and thus efficient routes to such chemicals are vital. In this article we will focus on some key Pd-catalyzed cyclizations affording such compounds over the last 5 years or so. The focus will be on the common 5- and 6-membered N-containing heterocycles. There will be a strong emphasis on cyclizations that rely on both functional group and C-H activation as the preliminary step in the cyclization process.


Due to their vast array of pharmacological properties, nitrogen heterocycles are among the most prominent structural features in medicinal chemistry. Over the past century, nitrogen heterocycles have emerged as an essential backbone to diverse bioactive molecules and commercial drugs, as it was reported that 59% of drugs contain a nitrogen heterocyclic unit (1). Consequently, development of novel strategies to access these structural units are in great demand.


Chemocatalysis has become a powerful tool in the medicinal chemist’s toolbox. Over the last century, a broad spectrum of bioactive heterocyclic compounds was accessed using various types of chemocatalyst, that generally were either a coordination or organometallic complex (2). Amongst all the types of chemocatalysts that have been used, palladium based catalysts have shown outstanding applications, due to their versatility, high activity, selectivity and more importantly their ability to generate carbon-carbon and carbon-heteroatom bonds through reactions like the Suzuki–Miyaura, Mizoroki–Heck, Sonogashira and Buchwald-Hartwig cross-coupling reactions. However, pall ...