B.R.S.M. To strive, to seek, to find and not to give a yield


A Funny Thing Happened On The Way To Hirsutene

Or: Why My Group Hate Me #13572

Apologies for the recent silence - I have just started a new (temporary) postdoc, and I have been busy with the reading for that. I am now an alkaloid chemist! The next few updates will be brief while I settle in.

Many research groups seem to have a weekly problem session, or something similar. In my experience, this usually means a rota (or something less formal) where people take it in turns to set a few chemical problems for everyone to have a go at. Often a sheet is produced, and handed out a few days before so people can have a chance to think/put the structures into Scifinder.

The problems themselves can vary a great deal, and are nowhere near as predictable as, say, undergraduate exams. A common layout is the 'synthesis blankout', where a synthesis from the literature is redrawn but some key reagents and intermediates are missing, to be filled in by the attendees. Alternatively, sometimes a bunch of short reaction sequences are taken from several papers, because they're interesting, or illustrate a particular theme. I've also seen a few more original approaches, such as this one, which I think I downloaded from the Ley group website a few years ago:

In the group where I did my PhD, the sessions were always run by students and postdocs, attendance was optional and the boss never came. Although you might expect that without a scary professor most of the group would go, as we all have to viva at some point, this turned out not to be case, and there was probably never more than a third of us present at any one time. I was a regular, and used to enjoy problem sessions - much like I enjoy crosswords, pub quizzes and, well, being an organic chemist - for the challenge. They're also a great chance to focus on chemistry outside of what your own group does. My PhD was on the synthesis of largely flat - and if not, racemic - heterocyclic natural products, so I tended to set questions about selective transformations in large, stereochemically dense molecules, in order to vicariously experience the thrills and tribulations of modern organic chemistry. Unusual or baffling transformations on seemingly simple systems were another favourite of mine, and I really enjoyed these recent offerings from DrFreddy over at Synthetic Remarks. In that vein, I offer you this question, which I recently set for my group:

Answers in the comments, or via Twitter!

Comments (9) Trackbacks (0)
  1. 1) Thermal 4+2
    2) photochemical 2+2
    3) ?

  2. Diels-Alder followed by intramolecular 2+2 and I think 4pi electrocyclic opening.

    It took me 40 minutes to get the drawings right but I think this is it.

  3. Diels-Alder [4+2], photochemical [2+2], as Anon. O. Mous said, and then a retro [2+2]

    • Yeah, spot on! Also, well done Starvinmarvin – the caged intermediates are a little tricky to draw. It’s taken from Mehta’s synthesis; I might put an answer up today or tomorrow, or you can see the synarchive page: http://www.synarchive.com/syn/195. He also had an approach to dodechedrane via some similar chemistry (he calls it sigma bond metathesis, I believe). Funny to see where the quinone carbonyls end up!

  4. wait a minute, isn’t light for the photchemical [2+2] a reagent?

  5. Well, we could argue the same for heat, now couldn’t we? I think we all can agree that ‘no reagents’ basically boils down to ‘nothing was physically added to the flask’.

  6. The LSD-based problem set reminds me of Marker’s sequence (or degradation) for converting diosgenin into 16-dehydropregnenolone. Legend has it that he never actually recorded how he managed this economically interesting process, and that it was retraced by others, taking into account the chemicals that were found on the shelf of his lab bench: acetic anhydride, potassium hydroxide, chromium(VI)oxide, methanol and acetic acid.

    • That sounds like an interesting tale indeed! Was that when he left Syntex? The wikipage for George Rosenkranz (http://en.wikipedia.org/wiki/George_Rosenkranz) seems to allude to it. If I can find out a bit more of the story I might write something about it.

      • I actually heard the story from my supervisor’s old supervisor (now retired), who did a postdoc with Carl Djerassi in the 1960’s. Apparently Marker left Syntex in a dispute, and had always been very protective of his procedures. All Rozenkranz had to go on were the reagents on Marker’s bench and a few degraded samples of intermediates left here and there.

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