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Totally Synthetic by Paul H. Docherty, 12 October 2006

Total Synthesis of Chartelline C


P. S. Baran, R. A. Shenvi, J. Am. Chem. Soc. 2006, 128, 14028-14029.

DOI: 10.1021/ja0659673

As a comment on the previous synthesis pointed out, it’s interesting to see this paper in the same week as Corey’s total synthesis of antheliolide, as both structures show interestingly complex fused ring structures. I’ve simplified the structure somewhat by flattening the ten-member ring, but with three cis-alkenes, the structure drawn in the paper is more realistic (and based on X-ray data). Baran’s approach to this complex system betrays some of his earlier studies with Corey, using a rearrangement on a 5,5 fused system to provide the lactam. But first they need the cyclisation substrate:

I’m not going to discuss the synthesis of the above precursor, as the main elements are shown in the retrosynthesis, but he does it quickly and efficiently, using a nice chemoselective Sonagashira coupling in the first step. Also of note was the ambitious bromination of the alkene, which unfortunately only achieved 36% monobromination. Those bromines are hard work! With the cyclisation substrate in hand, a bit of potassium carbonate does the trick, with a full mechanistic explanation in the paper. Interestingly, the bromide was exchanged for a chloride simply by using brine - nice work!

Only a few more steps were required to complete the synthesis, including a rather tricky decarboxylation. Cu catalysis failed, so they used prolonged heating. A top total synthesis!