Exploring the Solid-Phase Synthesis of 3,4-Disubstituted β-Lactams:  Scope and Limitations

• Published in: Journal of combinatorial chemistry Vol. 7; no. 2; pp. 331 - 344
• Main Authors: Delpiccolo, Carina M. L, Méndez, Luciana, Fraga, M. Amelia, Mata, Ernesto G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2005
• Subjects: beta-Lactams - chemical synthesis; beta-Lactams - chemistry; Combinatorial Chemistry Techniques - methods; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Spectroscopy, Fourier Transform Infrared
• ISSN: 1520-4766; 1520-4774
• DOI: 10.1021/cc049825l

This work describes a comprehensive study on the solid-phase synthesis of 3,4-disubstituted β-lactams. In situ generated ketenes react with immobilized aldimines under mild conditions to generate libraries of β-lactams in good to very good overall isolated yields. Different commercially available solid supports were studied, with the cost-effective Wang resin proving to be the most effective. The utility of the protocol was also demonstrated by the highly efficient asymmetric versions when homochiral ketenes or homochiral aldimines were used. A practical technique for the preparation of manual solid-phase parallel libraries of biologically interesting β-lactam compounds, using Mukaiyama's salt as dehydrating agent, is also presented. Reactions were easily monitored by FT-IR and gel-phase 13C NMR using conventional equipment.