That turkey is still keeping me a bit droopy-eyed. Time to shake it off and see what looks interesting. Since some of the theme last week involved asymmetry or chiral processes under thermal control (well ok, under thermal conditions), I thought I would go in a different direction and have a little fun this morning with metathesis processes. Just read the current state of affairs in the catalyst showdown to see what is grabbing the highlights. One of the recent interests involves a ring-opening metathesis followed by a ring-closing metathesis (ROM-RCM). Pretty cool process and one that will continue to get play.

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I think at this point we have seen some elegant examples of the relief of strain in 3/4-membered rings as a thermodynamically favorable process — a bit surprised that more methods haven’t shown up using a microwave ( and even more surprised that more reactions haven’t shown some stability of the chirality in these processes, perfect opportunity — and ethylene gas can be used in the microwave as well with some positive effects). Nevertheless, what if we are looking to form a 4-membered ring? Not so much, huh. Well at least one report (Debleds, 2008) not only illustrates that it is possible in a 1,5-enyne RCM, but with much better yields under microwave radiation and the right catalyst (in fact, this doesn’t show up on our literature radar without it). This is a good read!

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1,5-enyne RCM under mw conditions

To further illustrate the possibilities, Mori’s review (Materials 2010) provides examples of how the reaction has been applied in natural product synthesis. What caught my eye in the general reading (JOC 2010) however was a report on the process in the total synthesis of (±)-grandisol with a 1,5-enyne metathesis as the key transformation (83% yield) in the sequence. Not only did this group utilize the microwave to figure out the transformation, they also were able to screen catalyst and parlay the results into going back to a purely thermal sealed tube once the chemistry was a bit better understood. It was interesting to note that the yields in the thermal process were not as good as performing the transformation in the microwave….seems reasonable to assume there is some superheating in the catalyst. The other thing that sticks out is in their description of the catalysts has to do with thermal stability and it seems the most stable was also the best catalyst (for me this would lead me to conduct additional research on the process).

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Total Synthesis

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mw 1,5-enyne RCM 70C, 30 min

Enjoy the 4-membered ring formations!