Site Selectivity in Pd-Catalyzed Reactions of α-Diazo-α-(methoxycarbonyl)acetamides: Effects of Catalysts and Substrate Substitution in the Synthesis of Oxindoles and β-Lactams

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 19; p. 3551
• Main Authors: Solé, Daniel, Pérez-Janer, Ferran, Amenta, Arianna, Bennasar, M-Lluïsa, Fernández, Israel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.09.2019; MDPI
• Subjects: Acetamides - chemistry; beta-Lactams - metabolism; carbenes; Catalysis; Catalysts; Chemical reactions; density functional calculations; diazo compounds; Diazonium Compounds - chemistry; Efficiency; Insertion; Ligands; Models, Molecular; Molecular Structure; Natural products; Nitrogen; Oxidation; oxindoles; Oxindoles - metabolism; Palladium; Palladium - chemistry; Palladium - metabolism; Reaction mechanisms; Selectivity; Substitution reactions; Substrates; β-Lactam antibiotics; β-lactams; oxindoles; carbenes; density functional calculations; palladium; diazo compounds; β-Lactams
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24193551

The Pd-catalyzed intramolecular carbene C-H insertion of α-diazo-α-(methoxycarbonyl)acetamides to prepare oxindoles as well as β-lactams was studied. In order to identify what factors influence the selectivity of the processes, we explored how the reactions are affected by the catalyst type, using two oxidation states of Pd and a variety of ligands. It was found that, in the synthesis of oxindoles, ((IMes)Pd(NQ)) can be used as an alternative to Pd (dba) to catalyze the carbene C sp -H insertion, although it was less versatile. On the other hand, it was demonstrated that the Csp -H insertion leading to β-lactams can be effectively promoted by both Pd(0) and Pd(II) catalysts, the latter being most efficient. Insight into the reaction mechanisms involved in these transformations was provided by DFT calculations.