Anti-chaos

We fight entropy every day but it costs us in enthalpic terms… Whenever I notice papers where order emerges from chaos, I pay attention. Here is a really fabulous example from the lab of Michael Rubin (Kansas University). This is coming from another one of the talks I heard while attending the Heterocycles conference in the south of Russia last week. Take a look at what’s happening – it is a neat trick: you start with a racemate, you don’t make your life any easier at the next step when you create an awful mixture of diastereomers while installing the amide bond. However, the subsequent step clears it all up as the base does two things: it eliminates HBr and creates the ring system. The coolest thing is that all the unwanted diastereomers converge onto a simple symmetrical sub-structure that is ready to undergo addition. The addition step is not as trivial as one might think because you do not have a typical conjugated olefin. Strain drives it, though (all 52 kcal/mol of it). Michael presented some compelling evidence showing favourable orbital overlap during the addition step (what is it, by the way, endo addition? exo? trig? dig? what? not so straightforward…). Diastereoselectivity is high and is governed by the conformational preferences dictated by the chiral amide. I think all students will appreciate examples of this sort: you have an awful-looking TLC that goes clean towards the end!

Image

http://pubs.acs.org/doi/abs/10.1021/ja900634m

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