Sequential annulation and isomerisation reaction of 3-acylmethylidene oxindoles with Huisgen zwitterions and synthesis of 5-(3-oxindolyl)oxazoles

• Published in: Organic & biomolecular chemistry Vol. 21; no. 4; pp. 8176 - 8181
• Main Authors: Xue, Feixue, Yang, Chang-Jiang, Tang, Tong, He, Zhengjie
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 18.10.2023; Royal Society of Chemistry
• Subjects: Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Organic; Functional groups; Isomerization; Organic chemistry; Oxazole; Oxazoles; Physical Sciences; Science & Technology; Zwitterions; NATURAL-PRODUCT; FACILE SYNTHESIS; CONSTRUCTION; 1ST TOTAL-SYNTHESIS; 2,5-DISUBSTITUTED OXAZOLES; NOMINAL DIAZONAMIDES; CYTOTOXIC METABOLITES; RED ALGA; PIMPRININE; ALKALOIDS
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d3ob01199b

Herein, we report a facile synthesis of 5-(3-oxindolyl)oxazole derivatives via a sequential annulation and isomerisation reaction of 3-acylmethylidene oxindoles with in situ generated Huisgen zwitterions (HZs) from PPh 3 and azodicarboxylates. This reaction exhibits good functional group tolerance with 30 examples of structurally diverse products prepared with moderate to good efficiencies (up to 88% yield), thus providing a generally applicable route to the biologically important 5-(3-indolyl)oxazole structural motifs. Key to the success of this sequential one-pot strategy is the utilization of DBU as a base to promote the isomerisation process of the corresponding intermediate annulation products. A one-pot synthesis of 5-(3-oxindolyl)oxazoles has been developed by a sequential annulation/isomerization strategy.