Regio- and Diastereoselective Synthesis of β‑Lactam-Triazole Hybrids via Passerini/CuAAC Sequence

• Published in: Journal of organic chemistry Vol. 77; no. 16; pp. 6917 - 6928
• Main Authors: Alcaide, Benito, Almendros, Pedro, Aragoncillo, Cristina, Callejo, Ricardo, Ruiz, M. Pilar, Torres, M. Rosario
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.08.2012; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; MULTICOMPONENT REACTIONS; AZETIDINE-2,3-DIONES; PEPTIDOMIMETICS; CLICK CHEMISTRY; 1,2,3-TRIAZOLE; WATER; Regioselectivity; Organic azide; Nitrogen heterocycle; β-Lactams; Lactam; Diketone; Diastereoselectivity; Functionalization; Carboxylic acid; Azetidine derivatives; Triazole derivatives; Phenols; Click chemistry; Chemical synthesis; Isocyanide; Passerini reaction
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo301113g

Passerini (P-3CR) and Passerini–Smiles reactions were investigated in azetidine-2,3-diones, affording the corresponding 3,3-disubstituted-β-lactams with complete diastereoselectivity in high yields. The study has been carried out using different isocyanides, carboxylic acids, and phenols showing the scope of both reactions. In addition, the regioselective synthesis of highly functionalized β-lactam-triazole hybrids has been developed via a Passerini/CuAAC sequence. Interestingly, the use of dialkynes/diazides or trialkynes/triazides as linkers in the CuAAC step has allowed the synthesis of C 2 and C 3 symmetric β-lactam-triazole hybrids, respectively.