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

Feixue Xue; Chang-Jiang Yang; Tong Tang; Zhengjie He

doi:10.1039/d3ob01199b

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

Org Biomol Chem. 2023 Oct 18;21(40):8176-8181. doi: 10.1039/d3ob01199b.

Authors

Feixue Xue^{1

2}, Chang-Jiang Yang^{3

4}, Tong Tang^{1

2}, Zhengjie He^{1

2}

Affiliations

¹ The State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
² Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China. zhengjiehe@nankai.edu.cn.
³ Department of Chemistry, School of Sciences, Great Bay University, Dongguan 523000, China.
⁴ The Dongguan Key Laboratory for Data Science and Intelligent Medicine, Dongguan 523000, China. yangcj@gbu.edu.cn.

PMID: 37786314
DOI: 10.1039/d3ob01199b

Abstract

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 PPh₃ 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.