Barrett, Larrosa, Silva, GÃ³mez, Hannen, Ko, Lenger, Linke, White and Wilton. JACS, 2006, ASAP. DOI: 10.1021/ja0662671.
A nice, and short synthesis of this antibiotic/antifungal agent, using an interesting three-component-coupling strategy. First, the retro:
The larger substrate for this tranformation was assembled quickly, and the coupling completed by addition of methyl allyl grignard to the benzyne. The grignard generated in situ was then reacted with the aldehyde partner, completing the coupling.
The required diastereoisomer was recieved along with 21% of the undesired, but this was recycled using the aluminium species shown below. I’ve no idea how this reaction works (does the Al species simply act as a lewis acid, breaking the C-O bond, and then allowing to reform as the thermodynamically more stable product?), but one of the synthesis team now works at Cambridge, so I’ll ask .
Nice work, and completed in ten steps.