An "Ironic" Pauson-Khand

How would you go about making this compound?

(+)-ileabethoxazole

Taking a casual glance, I'd offer up at least a few disconnections. An epoxide-opening cascade, starting from that alcohol in the lower left hand corner. Maybe make the oxazole last, after some funky bismuth rearrangement chemistry. Perhaps you think you could stitch together the middle with some new-wave aryne technology?

Well, the Williams group (Indiana) took a completely different tack: a 9-iron. 

Not the reagent in question.

No, not the golf club, but di-iron nonacarbonyl. This dimeric "precatalyst" is thought to dissociate under the reaction conditions to Fe(CO)4, an unsaturated iron species that can complex to a variety of pi groups. It's been used for the Pauson-Khand for about 20 years, but the Williams group uncovered a new wrinkle last year: according to calculations, the iron might be initiating at the allene using a 3-membered metallacyclic ring! 

Very cool.  

Using these results, the Williams group mentally unzips the cyclopentane to this retrosynthetic intermediate (right). This wasn't the first thing they tried - that MOM ether on the oxazole came only after brominated versions of the heterocycle kept falling apart. Amazingly, the diiron complex ignores the alkyne, oxazole, and the MOM, choosing instead to complex to the end of the allene. Alkyne complexation, CO insertion, et voila! Cyclopentanone, coming right up (61% yield). Three more steps (deprotection, Swern, and base-promoted cyclization) produce the desired four-ring core.

The paper possesses blind alleys, full-stop restarts, theoretical underpinnings, and a good mission - anti-tuberculosis activity. Well worth reading the whole thing.

In Praise of Portmanteaux

Listening to the news on the drive home, some interesting words crossed my ears: Fracking. Locavore. Flexitarian. 


It's clear that we generate neologisms nowadays simply by stitching old words together.

I'm tired of writing this sinfo on microsyn...time for skitter?

The trend has a name: portmanteau words. Attributed to wordsmith Lewis Carroll in the late 19^th Century, the practice has evolved with the internet age to describe complex ideas in tiny verbal bundles. For instance, a locavore is a "local omnivore," or someone who eats foods located sourced from within a certain radius of his home. 


Not that we chemists should be surprised. After all, we're responsible for many of these words, and we use them every day. The aldol reaction takes an aldehyde and an enol to forge new carbon-carbon bonds. Using small organic molecules for catalysis? Organocatalysis. Why talk about reduction and oxidation cycles, when you could just say redox?


So, in an effort to increase synthetic chemists' efficiency, I'd like to propose several new portmanteau words:


sinfo: Supplementary Information
chactalysis: C-H Activation Catalysis
fuells: Fuel cells
meconomy: The "Methanol Economy"
Wots: Western blots
flolumn: Flash-column chromatography
microsyn: Microwave-assisted synthesis
skitter: Scientific Twitter  (Does that make Just Like Cooking a 'sklog?')


We could take this trend to a logical extreme, and repurpose words we already have. For instance, what do you call going back through your lab notebooks for an old prep?      
Retro-synthesis!


Commenters - Feel free to chime in....what have I missed?