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DOI: 10.1055/s-2007-968198
Synthesis of (±)-Chartelline C
Contributor(s):Philip Kocienski, Thomas SnaddonThe Scripps Research Institute, La Jolla, USA
Total Synthesis of (±)-Chartelline C
J. Am. Chem. Soc. 2006, 128: 14028-14029
Publication History
Publication Date:
20 February 2007 (online)
Key words
Heck-Sonogashira reaction - bromination - ring contraction - [1,5]-sigmatropic shift - decarboxylation
Significance
Baran and co-workers previously postulated the biosynthetic origins of the chartellines (P. S. Baran et al. Angew. Chem. Int. Ed. 2005, 44, 3714-3717), and have now disclosed a bio-inspired approach to (±)-chartelline C, the scarcest member of the group. Noteworthy in this synthesis is a remarkable four-step, one-pot cascade sequence that affords the spiro-β-lactam system characteristic of the chartellines.
Comment
A Heck-Sonogashira reaction between indolyl iodide A and terminal alkyne B gave C, which was converted into macrocycle E, comprising the entire carbon scaffold of (±)-chartelline C. Thermolysis of E liberated the free indole that was treated sequentially with NBS and K2CO3/18-C-6 giving G. A [1,5]-sigmatropic N-shift ensued giving the ring-contracted spiro-β-lactam H, that, upon treatment with brine, underwent halogen exchange affording I. Silyl cleavage followed by thermal decarboxylation gave the target molecule.