Paulsen Filip, Clementson Sebastian, von Wachenfeldt Henrik, Antoszczak Michał, Fridolf Simon, Strand Daniel
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, Lund, SE-221 00, Sweden.
RG Discovery, Medicon Village, Lund, SE-223 81, Sweden.
Chemistry. 2025 Jul 17;31(40):e202501394. doi: 10.1002/chem.202501394. Epub 2025 Jun 27.
4-Alkenyl- and 4-acyloxazoles represent important substructures across a diverse array of bioactive molecules. Practical methods to synthesize these motifs are, therefore, of considerable interest. Here, we develop a novel domino process wherein a cycloisomerization is followed by a 1,2-rearrangement via an oxazolonium ion to yield 4-alkenyloxazoles from an abundant β-chloro-N-benzyl propargylamine and acyl chlorides. The synthetic utility of the method is highlighted by its application to both oxazole units of siphonazole B, leading to a concise convergent total synthesis of this natural product.
4-烯基和4-酰氧基恶唑是多种生物活性分子中的重要子结构。因此，合成这些结构单元的实用方法备受关注。在此，我们开发了一种新型多米诺反应，其中环异构化之后通过恶唑鎓离子进行1,2-重排，以由丰富的β-氯-N-苄基炔丙胺和酰氯生成4-烯基恶唑。该方法的合成实用性通过其应用于西波唑B的两个恶唑单元得以凸显，从而实现了该天然产物的简洁汇聚式全合成。
