B.R.S.M. All this happened, more or less.


Selenium: Include Me Out

No, thanks.

This week I noticed that J. Derek Woollins, head of Chemistry at the University of Saint Andrews and legendary selenium chemist, recently published a review of the research leading to the discovery of his eponymous reagent in Synlett. Although, for reasons of self preservation, I tend to lose interest in the chalcogens after the first row or two, I quite like personal accounts of research so I thought I’d give it a try. Unfortunately, being an organic chemist, I couldn't follow a lot of the inorganic chemistry but I did enjoy some of the stories of things going wrong:

“Paul Kelly also later extended this work by making M–Se–N complexes using tetraselenium tetranitride (Se4N4) as the starting material. This is a very sensitive material. Indeed the first time we prepared it (from a reaction in liquid ammonia), whilst washing the red solid with a solution of potassium cyanide, nitrogen was let into the flask fairly briskly. The resulting turbulence caused an explosion, which destroyed the flask embedding pieces of red selenium into the white shirt Paul was wearing; from a distance this looked like major bleeding. Bravery was not lacking in the group during that era, and Paul Kelly also carried out what remains as the only published reaction of (extraordinarily explosive) pentasulfur hexanitride (S5N6) to give a complex containing the [S2N3]– ligand.”

Ah, wacky fun! I’m quite sure that S5N6 falls into the category of things that shouldn’t really exist, and trying to force them to do so isn’t good for anyone’s nerves.[1] Actually, the group engaged in quite a lot of this kind of lunatic chemistry. Another great example:

“Leaning on our previous work on reactions in liquid ammonia, we prepared sodium selenide (Na2Se) by the simple reduction of selenium with sodium in liquid ammonia. The resulting material is much more soluble than that prepared by the solid state route, though it is worth noting that this wonderfully finely divided solid is also very pyrophoric – on one occasion, around 75 grams caught fire in the port of our glove box with rather unpleasant consequences.

I imagine that ‘rather unpleasant’ probably doesn’t cover it. I can think of few things that would evacuate a building faster than screaming the words ‘selenium fire!’.[2] Fortunately, my own experience of selenium is a lot less exciting - I used phenylselenyl bromide a bit during my Masters to make enones, and aside from a marked decrease in affection from my girlfriend at the time, I suffered few ill effects. In fact, I suspect that beyond the old trick for forming enones (and the related Grieco olefination), many organic chemists would struggle to even think of uses for selenium in the lab. I am aware of one more reaction you can do with it, though, and I'll quickly explain why you shouldn't bother.

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Taxol Time Again: What now, Phil?

Update 20-11-2011: Reference added and a couple of mistakes removed. Why can I never see those the first time?

Scalable Enantioselective Total Synthesis of Taxanes

Baran et al., Nature Chemistry, 2011, [PDF][SI][GROUP]


The taxanes are a large family of 350 or so natural products, of which the best known is taxol itself, a multibillion dollar anticancer drug with a rich and storied history, whose name and distinctive tetracyclic system are instantly recognisable to most organic chemists. Taxol itself has already been the subject of 7 epic total syntheses (see BRSM Reviews: Taxol In 10 Minutes if you need a quick reminder), all using conventional functional group lead approaches to bond formation. Nature's (and Phil's) approach is a bit different, though, as we'll see.

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BRSM Reviews: Taxol In 10 Minutes


If you're reading this then I reckon you've probably heard of taxol, as it's one of the most talked about synthetic targets of all time. It's a molecule with a fascinating history, from its isolation and structural assignment in 1971, to discovery of its potent activity and interesting mode of action, and the ensuing scrabble to solve the supply problems plaguing its development as a drug.[1] Its rise to success as a billion dollar pharmaceutical was stellar, and is one of my favourite examples of how useful and important synthetic organic chemistry is. Although it's been 5 years since the most recently reported synthesis of taxol, last week's Baran synthesis of taxadiene (following his cyclase-oxidase mimic plan for elaboration of this hydrocarbon into taxol) seems to have again gotten chemists talking excitedly about this target. After overhearing things like 'didn't Nicolaou make it first?', 'there've only been x syntheses so far' (where x is 0-6) and other such misinformation in our office I've decided to take action. Yes, there are already numerous reviews, book chapters and even entire books on this subject, but it seems that a lot of people don't have the time or inclination to read them. So, here's a brief summary of the 7 syntheses published so far, in the order they were completed. Hopefully this'll help put recent developments in perspective.

Filed under: BRSM Reviews, Literature, Total Synthesis | 23,606 views | 9 comments Continue reading