Colourful Columns

Like a horse out of the gate that’s been pent up for far too long I have stormed into the lab and made a start on some lovely reactions.
The DIBAL reduction went off with no fires, no tears and no fuss so very happy about that. I have not lost my skill to work with air sensitive materials it seems. This reaction requires you to remove air from flasks and syringes by using nitrogen or argon gas flowing through the apparatus. The best part was simply walking to a tap and pouring in dry solvent. No setting up stills or messing around with sodium metal to dry solvents. I consider myself a fairly competent practical organic chemist but solvent drying still terrifies me. Here there are taps available with various types of dry solvent available so no messing about required.
Crystals pretty much guaranteed pure product but a 128 scan proton and standard carbon NMR confirmed it for sure.
In addition to this I also played around with the synthesis of two different Michael acceptors for some umpolung chemistry. Essentially focusing on N-heterocycle carbene (NHC) catalysis.
This area of chemistry relies on reversing the polarity of molecules. In essense, creating a nucleophilic carbon of a carbonyl group that is naturally electrophilic in character. These Lewis bases generate acyl anions, enolates, and homoenolates in catalytic fashion. The first notable example is probably the benzoin condensation however this used cyanide to generate the acyl anion. In modern approaches we sack off the cyanide and use NHCs as the organocatalyst. Breslow was able to demonstrate the mechanism and intermediates formed (that I have drawn poorly below) which opened the doors for synthetic chemists. D. Macmillan is the main man in this area (and a future Nobel prize winner for sure) as well as Japanese chemist Yurijiro Hayashi. I was fortunate enough to hear him speak in Manchester in 2014 and wow… far too clever for me unfortunately. These guys have used the chemistry building off proline, imidazoles, thiazoles and triazole based organo cats to develop the asymmetric synthesis of a shit tonne of molecules. Aldols, Friedel-Crafts, vinylations, allylations, enolations and diels alders are just an example of some of the transformations possible with this approach.
I am sceptical as to whether I will be able to pull out some interesting results with them or not but for now I’m happy just getting some synthesis in and stretching my legs a little.
Even doing a column didn’t upset my mood… Well maybe just a little but such is the nature of column chromatography. I also successfully blew the fuses in fume hood? Fixed now and hopefully something I can avoid in the future.
It was nice working with something colourful for once n’ all!

Crap yield and still some impurities present though. Most of the red seen here at the top is starting material, benzoylacetonitrile. Thankfully I was able to dig up an alternative yet slightly more archaic approach which should allow for a higher conversion. It involves roasting the nads off it with a heat gun then rapidly cooling it down with piperidine added as a catalyst. Watch this space.
And finally massive shout out to Phil Baran and his group on the latest paper in JACS, found here. In this work they report the total synthesis of araiosamines. This group of alkaloids possess antibacterial properties and with the current lack of antibiotics we are desperate for some new molecules. Interestingly the first Mannich reaction they tried just gave two diastereomers but the reaction preferred the wrong face and was inseparable. A few other approaches seemed to be trialled but the winner came in the form of the Schwartz reagent. This reaction then had to be quenched by loading onto a TLC plate? Wtf? Now I don’t want to go over every step they did as it would make for an entirely separate article alone so I’ll just go over the highlights and quenching on a TLC plate for me is definitely one. Another highlight has to be the final hydrolysis reaction which they bashed out at 90 oC. During a conversation with a colleague on this, he assured me that this step was apparently a mistake that just happened to smash out the final compound. Talk about ridiculous luck!
A postdoc seminar for the JEOL award winners was attended by myself this week. Some good stuff done and certainly the MVP had to be Dr. John Liddon and his wild spirocyclisations and cascade sequences.
Next week I’ll update you all on my medieval approach to the synthesis of these Michael acceptors and see how it goes. I’ve also been asked about putting in practical chemistry hacks and tips in the lab so I will look into getting into a lab hack of the week or something and impart some helpful tips that you only get after experience and not the usual notes you would expect to find in a lab script.
That’s all for now folks so I’ll hit you up next week. As always drop me a line on twitter @LewisMGooch


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