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.

Highly Active, Barely Seen

Bench chemists know it's tough enough to control the multiple variables that go into any one reaction. But what about the ones you never saw coming?

The literature abounds with cautionary tales: Trace nickel (II) in the NHK reaction. Trace phosphate in the GFAJ "arsenic life" saga. "Metal-free" couplings found to rely upon parts-per-billion levels of Pd or Fe contaminants in "pure" sodium carbonate.

In yesterday's post, a volcanic mudpot-dwelling bacterium flourished in lab culture, but only when its growth media was doped with a rare earth element (REE). The authors had quite a bit of trouble eliminating residual metals from the growth media:

"When testing REE dependency (salts > 99% pure), it was observed that standard serum bottles resulted in a highly variable growth. . . Sand is one of the major raw materials of glass and may contain considerable amounts of REE, and Ce may be used as an additive during glass manufacturing. It was concluded that REEs in glass are extractable, at least partly, by the acidic media used."

Whoa! I confess, I've stirred hundreds of acidic solutions in glassware of all shapes and sizes, and never once have I assayed the rare earth content! And the glass wasn't the only cause for concern:

"Contact of the acidic medium with needles used for sampling was minimized as the metal seems to release REE as well. For these experiments, concentrations of trace elements were (in μM): NiCl2, 1; CoCl2, 1; Na2MoO4, 1; ZnSO4, 1; FeSO4, 5; and CuSO4, 10."

For those playing at home, some of these trace metals guest star at the ppm level in this media. Due to the materials used in glass and disposable needle manufacture, I guess there will always be a baseline of (potentially active) metal contaminants in acidic solution.

Want to take bets that one or more play roles in our favorite cross-coupling reactions?

Say it With Me - Fluorophlogopite!

 

Source: Nails, Inc.

The other night, my special someone and I were sitting on the couch, and I was introduced to the "new hot thing" in fashion: magnetic nail polish. 


Apparently, as several DIY blogs explain, the "secret magnetic particles" contained in the polish "activate" in a magnetic field. Of course, a quick glance at the ingredients shows just plain iron powder, which, when dolled up with several layers of lacquer and clays, creates ripple patterns on the nail surface. 


But hey, with companies like LCN and Sephora charging to the tune of $16 USD (for a 10 mL bottle!) the price is comparable to standard lab reagents.

Sodium Zeolite A
Source: British Zeolite Association

But I digress. Looking through the ingredient list of the Trafalgar Square color, I felt totally out of my depth. Luckily, C&EN's "What's That Stuff?" feature came to my rescue, at least for a few of the common components (thanks, Carmen!). 


Of course, there's nitrocellulose, the shiny, potentially explosive major player, found for a time in movie film, gun cotton, and auto paint. Clays familiar to the bench chemist (bentonites, hectorites) make their way in as thickeners, including the fantastically-named bulking agent fluorophlogopite. This synthetic aluminosilicate calls to mind zeolites, inorganic structures used in fuel upgrading, gas storage, and catalysis.

One of the great features of chemical research: Even though you think you've seen it all, there's a surprise around the corner. After nitrocellulose, this particular brand uses an interesting copolymer of adipic acid, neopentyl glycol, and...trimellitic anhydride? I'd seen the first two, but never this, an interesting "triple-reactive" crosslinker (looks like maleic anhydride went for a crazy aromatic spin) which was first isolated in 1830 by Liebig and Wöhler, two heavyweights of 19th Century German chemistry. 


This tetracyclic curing agent, an all-star of the coal tar chemistry in the early 1900s, found use as a curing agent in polymers as early as the '30s. New uses in the last 15 years include protein charge ladders and luminescent materials research.


Update (1/21/2012): Over at Chemical Novelty, Travis has dug deep in the patent literature to really see what this product is all about. Go have a peek!