Trip the light fantastic.

Alert! Alert! Shameless plug for my own chemistry contained within!

I would be totally missing an opportunity if I didn’t blog about some chemistry that is very close to my heart, so here’s a little ode to my PhD work. My thesis a.k.a the bane of my life for three whole months that consumed every single waking hour, until my brain felt like it had been pulverised into the ground…*ahem*  …what was I saying?

Oh yes, my thesis was entitled “The Double [3+2] Photocycloaddition reaction“.

I’m sure some of you will have quickly beaten a retreat when you noticed the prefix “photo-” in that there sentence. Photo-chemistry is an oft maligned area of research because it can be quite a fickle mistress, that behaves in unusual ways compared to your standard thermal chemistry (those high energy states just love to do crazy shit!). There are also the many practical considerations you have to account for: purity of reagents, solvent selection, direct or sensitized irradiation (do you need a sensitizer?), the specialist equipment, quantum yield measurements (which are a pain in the behind I can tell you) and the hazards of high energy UV radiation.

Of course, none of this should put you off, because what you can do with photo-chemistry is pretty darn marvelous. You see, one of synthetic organic chemistry’s greatest challenges is to create step-efficient routes toward compounds with high molecular complexity (i.e. to make something complex as possible in as few a steps possible). Therefore, reactions which provide more than one bond in a single step are of significant importance (see the Diels-Alder reaction).

In my own work we reported an intriguing case of a double [3+2] photocycloaddition reaction that resulted in the formation of a complex cis, cis, cis, trans-[5, 5, 5, 5] fenestrane derivative  from a simple aromatic acetal as shown in scheme 1.

Scheme 1 An example depicting the photochemical  reactions of arenyl-diene photosubstrate, including the double [3+2] photocycloaddition reaction.

During this transformation, four carbon-carbon bonds, five new rings and seven potentially new stereocenters are created in an essentially one-pot process using only UV light (at 254 nm). Here’s an X-ray crystall structure of it, because X-ray crystal structures always make your chemistry 100% more legit:

You can’t dispute this little beauty.

The reaction actually occurs in a sequential manner from the linear meta photocycloadduct (for a detailed review of the meta photocycloaddition reaction click here or here), via a secondary [3+2] addition of the alkene across the cyclopropane of the adduct. In addition, an angular meta photocycloadduct also produced in the initial addition step, undergoes an alternative fragmentation-translocation photoreaction to afford an angular triquinane compound. Scheme 2 gives a little idea of mechanistic stuff.

Scheme 2: A mechanistic summary of the reactions involved in the irradiation of the linear meta photocycloadduct.

We also produced a series of other fenestranes (including my favourite nitrogen containing variant) through the same method which can be found in our follow-up paper in JOC. I think we really only scratched the surface of this chemistry, but due to a set of unfortunate circumstances which I’d rather not recollect, the work has had to cease for the time being. I’d like to go back to it some day because it’s quite a unique area.

Fenestranes are quite rare in nature and their synthetic utility is pretty much untapped, but they’ve got bags of potential as possible agrochemicals, chiral auxiliaries, scaffolds, pharmaceuticals and materials. They compare favorably to the steroid class of compound in that they are both conformationally rigid and chemically robust. The real problem with them is the are hard to make (although not using our method)

A selection of naturally occurring fenestranes. Pretty aren’t they?

Penifulvin A shown above actually has notable insecticidal properties, whereas asperaculin was only recently isolated, but being a fungal metabolite it may also prove useful. Laurenene unfortunately is totally useless, but it certainly looks the part!

If you really wanted to see all the nonsense I got up to in my PhD, I have just discovered that you can buy my thesis on Amazon…which feels a bit weird. It’s still pretty cool that you can even buy a kindle version!

The Lab Coat Cowboy


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