Synthesis of Siphonazole B Through Domino Cycloisomerization-Oxazolonium Ion Rearrangements
Filip Paulsen1,2, Sebastian Clementson1, Henrik von Wachenfeldt1,2
1Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, Lund, SE-221 00, Sweden.
None:
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.
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