Indole-2-carboxylate libraries

More recently, Somfai and coworkers have reported on the efficient coupling of a set of carboxylic acids suitable as potential scaffolds for peptide synthesis to a polymer-bound hydrazide linker [24]. Indole-like scaffolds were selected for this small library synthesis as these structures are found in numerous natural products showing interesting activities. The best results were obtained using 2-(7-aza-l H-benzo-triazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoride (HATU) and N,N-diisopropyl-ethylamine (DIEA) in N,N-dimethylformamide as a solvent. Heating the reaction mixtures at 180 °C for 10 min furnished the desired products in high yields (Scheme 7.4). In this application, no Fmoc protection of the indole nitrogen is required. 

Sulfonyl resins (23) have been developed to prepare indoles via a palladium-catalyzed cyclization. Cleavage was carried out with TBAF with excellent yields and purities (85-100%) [78]. Likewise, a library of bivalent ligands (including guanidine, pyridinium and carboxylic and sulfonic acids constituents) for a protein receptor was prepared on nitrobenzenesulfonamide resin 24. Cleavage was achieved with sodium sulfide [79]. 

Variation of the Heterocyclic Component Exchanging the indole as the heterocyclic component in the Yonemitsu reaction by imidazo[l,2-fl]pyridines 367 led to a multicomponent synthesis pathway for the preparation of a library of imidazo[l,2-a]pyridin-3-yl carboxylic acids and amides (Scheme 13.80) [138]. Heterocycles bearing a primary amine group tend to decarboxylative cyclization... 

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