Cr carbenes at work, plus some old-school hydrolyses

Rodney Fernandes and coworkers have recently put together a chromium carbene-mediated synthesis of a variety of pyranonaphthoquinones, to be published in J. Org. Chem. (DOI: 10.1021/jo3019939).  I’ve been a fan of this kind of chemistry since my grad school days back in the 80’s when William Wulff was publishing a new example of carbene-induced transformations left and right.  I had, of course, forgotten anything I ever knew about the mechanism of the reported benzannulation and so had to dig around a bit to find Minatti and Dötz’s work on the subject (Topics Organometal Chem 2004 13, 123-156).  Here is the benzannulation:

 

This gets us to the required ring system and appendage.  Since my main duties these days are teaching undergraduates, I really like old school stuff, so the continuation of this really caught my eye.  Hydrolysis of the ketal and ester, followed by a few bond rotations, sets everything up for a beautifully simple lactonization as shown below.  From there to one of the target compounds, (-)-juglomycin A, is just a hop, skip, and a jump.

 

All in all, pretty cool.