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DOI: 10.1055/a-2467-5264
Total Synthesis of (+)-Cylindricine C
Dyotropic Rearrangement of β-Lactams: Reaction Development, Mechanistic Study, and Application to the Total Syntheses of Tricyclic Marine Alkaloids.
Angew. Chem. Int. Ed. 2024;
DOI: 10.1002/anie.202414985
Significance
Tang and co-workers report a novel Lewis acid promoted dyotropic rearrangement of β-lactams to afford γ-butyrolactams. The methodology was successfully applied to more than fifty substrates, and it was then showcased in the synthesis of three tricyclic marine alkaloids. At the end of the studies, the authors proposed a mechanism for the rearrangement based on computational and experimental work.
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Comment
Aldehyde A was condensed with p-toluenesulfonamide yielding N-tosyl aldimine B. Addition of ethyl acetate to B followed by condensation delivered β-lactam C. The key dyotropic rearrangement was triggered by EtAlCl2, which furnished γ-butyrolactam D. Reductive homologation of D, and subsequent reduction and protection successfully installed the hydroxymethylene in F. Oxidative cleavage and 1,2-addition delivered allylic alcohol G, which, after oxidation, was engaged in a conjugate addition to access the tricyclic core of the natural product. Desaturation of I, followed by installation of the side chain and silyl deprotection completed the synthesis of ( + )-cylindricine C.
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Publication History
Article published online:
20 December 2024
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