Thursday, March 01, 2007

RACIOC 22 Highlights Part III

Okay one final post on the conference before I move on to other stuff. Chris Braddock from Imperial College, UK gave an interesting talk entitled: "Towards a Biosynthetically-Inspired Chemical Synthesis of the Obtusallenes". Obtusallenes are halogenated marine natural products and there's at least ten structurally similar compounds within this family (two example are shown to the left). It was nice to see how much thinking had gone into Chris' research. A lot of speculation on a possible biosynthetic pathway and even a publication in Organic Letters on these reflections (DOI: 10.1021/ol062520q) which you don't see that often. I wasn't familiar with the NMR method for determining the location of bromine- and chlorine-substituents that he employed. It looked very useful so if you can't get those crystals for your X-ray you may consider giving that a go (Raynes et al., Mag.Res.Chem., 1997, 35(2), pp. 141-143).
I have spent a significant part of my life attempting to make cyclopropanes and fancy myself rather knowledgeable in this particular area so you can imagine my surprise when Professor Andy Phillips from University of Colorado mentioned the Kulinkovich cyclopropanation out of the blue (talk entitled: "New Reactions and Strategies for the Synthesis of Complex Natural Products"). I have to admit that I was a full-on Kulinkovich virgin. It's a pretty funky reaction producing 1,1,2-trisubstituted hydroxy-cyclopropanes. These are generally not easy to make so I'm surprised I hadn't seen this stuff before. I'm not sure if anyone has attempted to make an asymmetric version of the reaction but in any event using optically active starting materials Professor Phillips Group managed to make optically active stuff (see below).

I didn't get the yield or dr and I don't know if the stuff has been published yet. However, there's a nice entry in Organic Syntheses (OS) on the Kulinkovich cyclopropanation giving two examples (71 and 80% yield to give one diastereoisomer) as well as some background and the mechanism (see mechanistic explanation from OS below).

Anyway, a very good talk by Andy Phillips (and many others that I haven't mentioned). I think I've been beating this conference to death by now so let me finish off with three quotes from oral presentations that made me laugh: (1) ...thio-ether mutant..., (2) ...encourage to die..., (3) ...good quality frog... D!


milkshake said...

Yeah, these Ti+Grignard-promoted cyclopropanations are pretty funky. They work with formamides, too - to produce cyclopropyl amines. Cyclopropyl amines is what we need in our project right now but I have not braved myself up to trying this cyclopropanation reaction yet.

Anonymous said...

100% agree with milkshake, I'm surprised you didn't hear about the Kulinkovitch reaction before as it is a classic in cyclopropanation chemistry. Works intramolecularly too and has been extended to cyclic amides and particularly imides. Titanocene chemistry is pretty funky - but it doesn't work for every substrate so watch out.