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


Unnatural Products 2: Dodecahedrane

Second in my somewhat badly thought out Unnatural Products series is dodecahedrane. To be honest, this compound is actually pretty much the main reason for this series. I only found out it had been made at the start of the year (even though Paquette did it way back in 1983),[1] and it blew my mind. I mean look at it – where do you even start? It took me a full hour to draw the damn thing in Chemdraw, and I still can't get it to look right on paper. As Paquette himself said in an abstract ‘the aesthetically pleasing symmetry of the dodecahedral framework was clearly apparent’. In common with the syntheses of the other two compounds above the route involved both Diels-Alder reactions and lots of photochemistry. Let’s take a look.

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Black dot… I mean Linstead notation.

Anyone who's read some of the older chemical literature (or even recent papers by old school chemists) has probably noticed the 'black dot' notation used to depict stereochemistry at ring junctions, particularly by chemists in the US and Canada. Here's a recent example, so you'll know what I'm on about if you don't already.


From Angew. Chem. Int. Ed., 2010, 49, 4864 – 487.[1]

I don't know how things are in the US, but at no point during my chemical education do I ever remember having this notation explained to me. I recall encountering it for the first time at the start of my PhD, asking around a bit, and then just working it out for myself. Turns out it's actually really simple - a black dot at a ring junction just means that the hydrogen there is on the β-face, i.e. above the plane of the paper. To this day I've never seen this explained in a textbook, and have wondered from time to time where the heck it came from. As named reactions become canonised, the references the seminal papers slowly disappear, and clearly the same thing has happened here, as with many other conventions and nomenclatures. However, not having a name for this notation I'd never been able to trace where it started. Until now.

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Woodward Wednesdays 2: Erythromycin A

Update 01/10/11 - It seems that I never actually gave the references for the original papers. The synthesis was actually published in three back-to-back JACS papers - the first is J. Am. Chem. Soc., 1981, 103, 3210, and you can read on from there. I also found the relevant synarchive page to be helpful when writing this.

I hadn't planned to cover this synthesis, Woodward's last, so early in this series, but as a review on the use of thiopyrans as templates in polypropionate syntheses was recently published in Chem. Commun. it seems timely to mention it now.[1] Woodward once said in a talk at CIBA in India that

"Much of the art of directed synthesis involves the design of ways to place constraints on molecular motion, with the aim of bringing about desired changes and suppressing others"

A popular way of doing this, as has been said before, is through the use of cyclic templates, a tactic used extensively by chemists of the Woodward and Corey eras. The ease with which desulfurisation can be accomplished using Raney Nickel makes thianes and thiopyans uniquely suitable as temporary rings which can be cleaved mildly and selectively later on.[2] This property made them the cornerstone of Woodward's approach to erythromycin A where they were used to set 8 of the 10 stereocentres found on the macrocyclic ring.[3]

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Announcing: Woodward Wednesdays

It's been suggested that I need a few more (semi-) regular features, and a number of people seem to have enjoyed some of the work from the older literature I've highlighted (my posts on Eaton's synthesis of cubane and Hoffmann's use of TNT are among the most popular I've written). I considered a few possible ways of combining these two and, after chatting to a wise coworker, I have decided to launch Woodward Wednesdays. Basically, I'll post something about work done by R. B. Woodward on roughly one Wednesday a month until you or I get bored. I'm not going to write a long justification of this - the man was a genius and hopefully we can learn something from him.

The inspiration for this series was probably the recent appearance of Woodward's notes on organic superconductors being published in the current issue of tetrahedron (Tet., 2011, 67, 6771-6797) with a wonderful accompanying article in C&En, which just reminded me what a remarkable individual he was, with an enviable breadth of research interests far beyond organic synthesis. Bits of the tetrahedron article are way over my head, but the C&En article is a very enjoyable read. The latter contains a number of recollections from Woodward's son, including this one from his teenage years:

“My father arrived punctually at home at 6:25 every night for dinner. One night we sat down and he said, ‘I’ve had an inspiration. I think I can make a room-temperature superconductor.’ He described how that would be a material that loses no energy as it conducts electricity over large distances and how that would change the world,” Eric remembers. “He rarely would say anything about chemistry, but this day he was particularly inspired.”

Wow, nothing like setting your sights high! From talking to a few physicists I know, I get the impression we're still nowhere near this goal 40 years later. But Woodward gave it serious thought, producing 699 pages (or around 8") of notes on everything from scraps of paper to hotel stationary and napkins, all bearing his characteristic beautiful hand drawn structures.

Another piece on Woodward's involvement with the Woodward Research Institute in Basel, Switzerland and the work done there appeared in Helvetica Chemica Acta back in June, further illustrating the continued interest in the life and work of this amazing chemist (HCA, 2011, 94, 923-946). So, I'm getting on the Woodward bandwagon. First post next Wednesday. Look forward to it!


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