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NH2 as a directing group: from the unexpected cyclopalladation of aminoesters to the preparation of benzolactams by Pd(II)-catalyzed carbonylation of N-unprotected arylethylamines

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An unusual NH2-directed Pd(II)-catalytic carbonylation of quaternary aromatic α-amino esters to yield benzolactams has been developed. The steric hindrance around the amino group is pivotal for the success of the process. The stoichiometric cyclometallation of a variety amino esters has been studied in order to evaluate the influence of the different variables (size of the metallacycle, aromatic ring substituents, and steric bulk) in the process, and a complete kinetico-mechanistic study of the cyclopalladation process has been carried out. The experimental results indicate that the full substitution of the carbon in the α position of the amino esters plays an important role in their cyclopalladation reaction. The reaction shows a strong bias to 6-membered lactams over the 5-membered analogues, which can be explained by a greater reactivity of the six-membered palladacycles.

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ALBERT MACH, Joan, ARIZA PIQUER, Xavier, CALVET PALLÀS, Maria teresa, FONT BARDIA, Ma. mercedes, GARCÍA GÓMEZ, Jordi, GRANELL SANVICENTE, Jaime ramón, LAMELA, Andrea, LÓPEZ BARALLOBRE, Blanca, MARTÍNEZ LÓPEZ, Manuel, ORTEGA, Laura, RODRÍGUEZ RAMÍREZ, Aleix, SANTOS, David. NH2 as a directing group: from the unexpected cyclopalladation of aminoesters to the preparation of benzolactams by Pd(II)-catalyzed carbonylation of N-unprotected arylethylamines. _Organometallics_. 2013. Vol. 32, núm. 2, pàgs. 649-659. [consulta: 20 de gener de 2026]. ISSN: 0276-7333. [Disponible a: https://hdl.handle.net/2445/43589]

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