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Synthesis of isoquinolin-4-ols by palladium-catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes

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A palladium‐catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes leading to tetrahydroisoquinolin‐4‐ols is reported. A variety of products were isolated in good to excellent yields. The joint experimental‐computational study shows that although two competitive reaction pathways can be promoted by Pd(0) starting from α‐(2‐iodobenzylamino)‐aldehydes, the selectivity of the process can be controlled by the proper selection of the base. While the nucleophilic addition of the aryl‐Pd(II) intermediate to the carbonyl group is selectively promoted by using the base triethylamine (Et3N), the CH bond activation at the formyl group competes with the nucleophilic addition only when the base is replaced by cesium carbonate (Cs2CO3). Keywords: catalysis; cyclization; density functional theory (DFT) calculations; nucleophilic addition; palladium

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SOLÉ ARJÓ, Daniel, MARIANI, Francesco, FERNÁNDEZ CADENAS, Israel. Synthesis of isoquinolin-4-ols by palladium-catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes. _Advanced Synthesis & Catalysis_. 2014. Vol. 356, núm. 14-15, pàgs. 3237-3243. [consulta: 20 de gener de 2026]. ISSN: 1615-4150. [Disponible a: https://hdl.handle.net/2445/127725]

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