β-Lactams Through Single Bond Ring Closing: Methods, Transformations and Bioactivity

• Published in: Beta-Lactams pp. 219 - 252
• Main Authors: Martín-Torres, Inmaculada, González-Muñiz, Rosario
• Format: Book Chapter
• Language: English
• Published: Switzerland Springer International Publishing AG 2017; Springer International Publishing
• Subjects: 2-Azetidinones; Alkylation; Biochemistry; Chiral auxiliaries; Chiral catalysts; Conjugate addition; C–H activation; Enolates; Memory of chirality; Organic chemistry; Pharmacology; Single bond formation; β–lactams
• ISBN: 9783319556208; 3319556207
• DOI: 10.1007/978-3-319-55621-5_7

Because the renewed interest of β–lactams in organic and medicinal chemistry, research in this field continues producing new appealing progresses. This chapter will cover significant success in the synthesis of innovative 2-azetidinones through the formation of a single bond, either C–C or N–C. While the C2–C3 bond formation has scarcely been explored, the intramolecular cyclization through the C3–C4 bond using different approaches are among the most effectively harnessed procedures. Thus, enolate-mediated alkylation and Michael conjugate additions provided quaternary β–lactams in a nice stereoselective way, through the memory of chirality phenomenon. Here, the adaptation of the procedure to solid-phase methodologies opens the possible generation of molecular diversity based on this heterocyclic skeleton. Other main C3–C4-forming strategies are the catalyzed C–H insertion of α–diazoacetamides, the oxidative bond formation and different radical cyclizations, leading to original 2-azetidinones, including some spiro derivatives. Classical methodologies, like the use of Grignard reagents, the base-induced cyclization of β–aminoesters and the application of coupling methods to β–amino acids, continued being applied for the N1–C2 ring closure. Different procedures have also been described for the β–lactam synthesis through the N1–C4 bond. In this respect, apart from the initial Mitsunobu reaction-based approaches, metal-catalyzed C–H functionalization and oxidative cyclization of amides are valuable, more recent methodologies.