Reactivity of 3‐Oxo‐β‐lactams with Respect to Primary Amines—An Experimental and Computational Approach

• Published in: Chemistry : a European journal 2017-12, Vol.23 (71), p.18002-18009
• Main Authors: Piens, Nicola, Goossens, Hannelore, Hertsen, Dietmar, Deketelaere, Sari, Crul, Lieselotte, Demeurisse, Lotte, De Moor, Jelle, Van den Broeck, Elias, Mollet, Karen, Van Hecke, Kristof, Van Speybroeck, Veronique, D'hooghe, Matthias
• Format: Article
• Language: English
• Subjects: density functional calculations; lactams; natural products; reaction mechanisms; structure elucidation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201703852

The reactivity of 3‐oxo‐β‐lactams with respect to primary amines was investigated in depth. Depending on the specific azetidin‐2‐one C4 substituent, this reaction was shown to selectively produce 3‐imino‐β‐lactams (through dehydration), α‐aminoamides (through CO elimination), or ethanediamides (through an unprecedented C3−C4 ring opening). In addition to the experimental results, the mechanisms and factors governing these peculiar transformations were also examined and elucidated by means of DFT calculations. Profiling reactivity: 3‐Oxo‐β‐lactams selectively produce 3‐imino‐β‐lactams (dehydration products), α‐aminoamides (CO‐elimination products), or unprecedented ethanediamides (C3−C4 ring‐opening products) upon reaction with primary amines (see scheme). In particular, the specific β‐lactam C4 substituent is responsible for this intriguing reactivity; an observation that is supported by DFT calculations.