Palladium Catalysis in the Intramolecular Carbene C–H Insertion of α‐Diazo‐α‐(methoxycarbonyl)acetamides to Form β‐Lactams

• Published in: European journal of organic chemistry Vol. 2018; no. 32; pp. 4446 - 4455
• Main Authors: Solé, Daniel, Pérez‐Janer, Ferran, Bennasar, M.‐Lluïsa, Fernández, Israel
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 31.08.2018; Wiley-VCH
• Subjects: Carbenes; Catalysis; Catalysts; Catàlisi; Complexitat computacional; Computational complexity; Density functional calculations; Diazo compounds; Insertion; Organic synthesis; Palladium; Pal·ladi (Element químic); Reaction products; Síntesi orgànica; β‐Lactams
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201800666

The intramolecular carbene C–H insertion of α‐diazo‐α‐(methoxycarbonyl)acetamides leading to β‐lactams is effectively catalyzed by palladium complexes. It is found that although Pd0 catalysts typically produce mixtures of β‐lactams together with Buchner‐type reaction products, the use of PdII catalysts results in highly chemoselective transformations. According to DFT calculations, this insertion reaction occurs stepwise and involves an unprecedented PdII‐promoted Mannich‐type reaction through a metallacarbene‐induced zwitterionic intermediate. The intramolecular carbene C–H insertion of α‐diazo‐α‐(methoxycarbonyl)acetamides leading to β‐lactams is effectively catalyzed by PdII complexes. According to DFT calculations, this insertion reaction occurs stepwise through a metallacarbene‐induced zwitterionic intermediate.