A new acronym has appeared in a recent Organic Letters publication, RCDEYM, standing for ene-yne-ene ring closing metathesis! Perhaps it should be EYERCM: Anyway it was used by the group of Prunet at the university of Glasgow. They used it to construct the tricyclic core of taxol, in an enantiopure state! The reaction sequence is
So you obtain all the bits in the red box, combine them in 13 steps to the cyclohexene, thrown in a catalyst and out pops the tricyclic core of taxol. The trick is to fiddle about with the dienyne metathesis precursor and the catalyst and the reaction conditions. The catalyst used was a variation of the Hoveyda-Grubbs catalyst complex shown below:
This produced the tricyclic ring system in 70% yield along with 20 % of a bicyclic product:
when carried out in toluene reflux with the catalyst concentration at 10 mol%. It is noted by the authors that “The key step of this synthesis is an RCDEYM that leads in one operation to the required tricycle, and we have shown that we can direct the course of this metathesis reaction by adding an extra methyl substituent to the olefin at C13, which does not appear in the structure of the metathesis products. Both the nature of the protecting group and the stereochemistry of the diol at C1−C2 have a profound influence on the outcome of the metathesis reaction, and only the diastereomer with the required stereochemistry for Taxol for the C1−C2 diol protected as a cyclic carbonate, undergoes the desired RCDEYM.”
So this reaction is very finicky and any deviation form these conditions will not provide the desired product in any useful quantities. Examination of the supplementary material makes one wonder how they obtained any useful quantities at all. Carrying out μmol reactions producing around 20mg of the desired product. Nice chemistry but spoilt by the scale and the tight structure requirements for success. It should have been done on at least gram scale to obtain any meaningful information about the reaction. Perhaps on a larger scale things might be very different. If you are going to take the time and trouble to investigate this system, and the authors have done just that, then please scale it up just a little bit. The work invested might just become useful.
