Want something even cooler, here’s a dyotropic reaction! Characterizing the side-products must have been a lot of fun. As well as monitoring the progress (the major undesired product had the same Rf as the starting material, and good luck with crude NMR). Heads up from amphoteros.
OK, enough electrocyclic reactions. Here’s some C-H activation work from Jin-Quan Yu lab. From [phthalimide-protected] alanine to [phthalimide-protected] substituted phenylalanines in one step! The conditions are somewhat peculiar though. A lot of silver (and quite a lot of palladium) was consumed for this to happen.
Tellurium is not very popular among chemists (and even less among anybody else for that matter), so each successful use of it is worth attention. The authors of this paper managed to find an application for sodium hydrotelluride. As an excuse they wrote this last sentence of discussion: ‘Reduction of the α-azido ketone 31 with PPh3, as in the Staudinger reduction, followed by stirring in air could not deliver 34 in our hands.’
Another unusual thing in the paper is the open call for collaborations: ‘For now, gram scale of 30 and more than 100 mg of 34 [12,12′-azo-13,13′-diepi-Ritterazine N] are available for any interested collaborators.’ I felt obliged to spread the word.
Nicolaou et al. does some medicinal chemistry on prostaglandins. Take a look at this Bobbit‘s salt protocol for deprotection/oxidation combo. It seems like they overload the reaction, compared to the original paper, which used 3 equivalents of the oxidant, but who cares if it works?
I’m not sure I would buy the proposed mechanism for the conversion below. The authors skip ‘−H2‘ step and get away with it by simply writing “the imine intermediate 44 […] underwent tautomerization and a key decarboxylation to generate 45 with higher oxidation state.” Something else is clearly happening under that −CO2 arrow and it’s not mere tautomerization.
A paper with a very straightforward title, “Nineteen-step total synthesis of (+)-phorbol” (neither “concise”, nor “efficient”, “elegant” nor any other vague adjective) was published by Baran lab.
The step that impressed me the most was oxidation of compound 7. Chemo-, regio-, and stereoselectivity of this reaction was “easily predictable based on 100 years of C–H oxidation literature”, according to follow-up blog post, but I wonder how many chemists in the world would bet for this reaction to work so cleanly. Before reading the publication, of course.
Remember Morken reaction? I was daydreaming about streamlining it into bond-by-bond stitching of complex compounds. Turns out that Steven Ley was looking in the same direction, although through slightly different chemistry.
…but hurry up with your diazotransfer, otherwise machines will soon do it for you! A fridge-sized synthesizer of known pharmaceuticals was constructed by chemists and engineers in MIT. Check out more detailed (and realistic) coverage by Derek Lowe.
A collection of OC tidbits selected by Hanessian and Overman groups. Featuring a dozen of natural products, each full of densely-packed stereocenters; 29 oldschoolishly lengthy synthetic schemes including three hundred intermediates that undergo all sorts of electrocyclic reactions and crazy cascades. Read in limited quantities to prevent overexcitement.
And, of course, I liked this guy (or girl?) at the frontispiece (the only thing one can get for free from Angewandte preview without subscription) in high-energy conformation overcoming some activation barrier.
As the legend goes, people from Pfizer approached Phil Baran and told him “You know, we figured out what our problem is. We need more propellers on our molecules.” Phil said “OK, sounds like a good project” and put two grad students on it. Results: the 3-in-1 Science paper, with propellers spinning on every amine, SI, which is longer than my PhD thesis, and happy Pfizer counting cash.
By the way, Baran lab has a cold room for synthesis.
Another great reaction that I was thinking to dedicate a separate post for but will never manage. Just check out this teaser scheme: two steps, two distant stereocenters, great chemoselectivity, and so drug-like!
Brilliant batch-washing of NMR tubes in a vacuum dessicator that has already got some good publicity in the blogosphere but probably won’t get too many citations. In theory, nothing can stop you from applying the same technique to any other glassware that has a solid bottom (flasks, beakers, etc.).
Despite deromantizing total synthesis I do like organic chemistry and do feel aesthetic pleasure from synthetic schemes and mechanisms [note for my future employer, I do enjoy the bench work, too!]. Also, since high school and undergrad years I still have weak spot for org-chem puzzles. So Below are some little nuggets (subjective, of course) from the recent OC papers that I found interesting.
All multi-ton processes start from the small scale, check this cute Kugelrohr apparatus setup by Thiyagarajan et al. for processing of biomass-derived furans (The white stuff in the middle is a zeolite catalyst; ACIE)