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Updated: May 10, 2026

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
Published on: July 30, 2017
Multicomponent synthesis of 4-aminophthalazin-1(2H)-ones by palladium-catalyzed isocyanide insertion
Tjøstil Vlaar1, Pieter Mampuys, Madeleine Helliwell
1Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Abstract:
4-Aminophthalazin-1(2H)-ones (APOs) are underexplored heterocyclic compounds with promising and diverse biological activities. The classical synthesis of these compounds is tedious and does not allow the regioselective introduction of substituents. Here, we present our full studies on the Pd-catalyzed cross-coupling of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion allowing straightforward access to diversely substituted APOs. We illustrate the advantages of this method compared to other approaches and describe solutions for the limitations we encountered. In addition, we have developed efficient diversifications of this heterocyclic scaffold that allow access to more diverse APOs as well as novel heterocyclic scaffolds.
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