Spicing things up with Cyanogen Bromide…

Li, Zhou; Gevorgyan, Vladimir Double Duty for Cyanogen Bromide in a Cascade Synthesis of Cyanoepoxides Angew. Chem. Int. Edn. Early View Feb 21 2011

So I’m back (again). Sorry this one took me a while (way to long in my opinion). With all the excitement I’ve been having over the past couple of weeks, I barely even have time to sleep, let alone review. My paper to Organic Letters should be out by early next week in the ASAPs. We had a bit of an issue with the proofing but other than that things went swimmingly. My project with Dr. Leadbeater has already been submitted to Catalyst Communications so I’ll keep you updated on the progress of that. Our OPRD has made it past the attrition stage and is currently being reviewed. I really hope that works out too so that by the end of the month I will have gone from 1 to 4 publications :D. I have already started the collaborative project with Professor Tilley and Dr. Leadbeater in addition to picking up two more project Dr. Leadbeater is interested in. However, we’ve been having some…technical difficulties with our machines lately which has really slowed down the chemistry and forcing us to play mechanic. In the meantime, I have been keeping up with the lit and this one really caught my eye mostly cause its, as usual, very weird, slightly deadly, involves a strained moiety and just plain cool!
So the article starts out with a review of cyanogen bromide (BrCN) and its use in as a synthetic tool. Surprisingly, it hasn’t been used all that much. That may be due, in part, to the fact that it’s a somewhat dangerous reagent to use. Its moisture sensitive, highly volatile and can be absorbed cutaneously or via inhalation. Worse, it is an acute toxin that can lead to death even at an exposure of 25 mg per kg of body weight. But wait, there’s more! Trying to dispose of the stuff requires NaOH and forms cyanide in the process. Moreover, it has a tendency to explode when being disposed of as the reaction is exothermic. So, if I found one major problem with this article is its impracticality. That being said the chemistry is very well done…so let’s get on to it!

Gevorgyan’s group was doing some amazing work in 2008 regarding a somewhat similar reaction to this work. He took haloalkynes and reacted them with enolates. What he got out was quite surprising. He obtained not the expected a-bromoketone, but instead an alkynyl epoxide. What he deemed a dual cascade reaction is simple a one-pot synthesis going through the mechanism seen below

Using this work as a springboard, they believed that cyanogen bromide should do essentially the same thing. They used isobutyrophenone as a screening reagent and NaHMDS as a base to get the whole thing started. They found that they got pretty much what they expected the first run through. Not surprising considering their results from the alkyne project. It was quite fast as the whole reaction was over in only 20 minutes (as compared to the 1 hour for the alkyne reaction)! They really didn’t do much in the way of optimizing other than playing with the solvent and the base. They found the optimal solvent to be DMF and LiHMDS to be a slightly more ideal base (TEA and Cs2CO3 gave no reaction). They quickly switched over to substrate testing and they certainly did a thorough job there. They seemed to have a general trend, they needed to be disubstituted (at the alpha position) aryl ketones.

I think that’s more for simplicity sake than anything (only one acidic proton and no chance for some sort of isomerization). They tried all sorts of aryl moieties (including pyridine and various substituents on benzene). And here is the kicker. That’s it. No application, no nothing. Just pure chemistry. And it was well written and straight to the point! Well, I hope you enjoyed this one as much as I did. I plan on getting another review up soon, since things (hopefully) should get less crazy in the coming days. Ckellz…Signing off…

1 Comment

  1. […] Vladimir Gevorgyan at the University of Illinois at Chicago, whose work I have been following for some time (this being the second article of his I will be featuring). Gevorgyan does chemistry that is near […]

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