So that everyone understands that I feel that microwave approaches are simply a tool at our disposal, I don’t want anyone to think I have a giant sign up in the air saying that microwave should be used every time we have a dry flask ready to go, far from it in fact. In general, however, direct microwave heating can reduce chemical reaction times from days or hours to minutes or even seconds, and therefore suppress undesired side reactions, increase chemical yields, and improve reproducibility. That said, most of the time this applies to reactions that have a thermal component to the process….or one where a catalyst or solvent can be heated and the reaction flows along as a happy participant. There are actually a tremendous number of reactions where this can be used to the advantage, but it requires some thought and willingness to give it a try—-and the last time I checked the cool thing about organic synthesis is that it is an experimental science with a fair amount of art form. SO let’s get the bad out of the way first then go to some positive….high reaction temperatures have been shown to lead to a loss of selectivity, and therefore the percentage of reports with high enantioselective in a microwave is low. That said, I think it also is incumbent on us to look deeper into said processed for areas to tweak and look for new opportunities. Most microwave reviews and books focus on the utility of microwave irradiation for methods, reducing times in complex reactions and generation of advanced products, etc, but have left little time spent for asymmetric processes. We should understand this isn’t to slight the technique or understanding (especially by these chemists) because if the microwave could help with every reaction, we probably wouldn’t be doing anything else, right? Take a look through some of the recent microwave books (Loupy and Kappe) to see what I mean. Below I have listed a few recent chapters in books where microwave approaches have been described in more detail. Also probably one of the more interesting articles talked about involves a careful study on microwave vs. conventional heating, temperature measurement (by it really illustrates how important that FO probe is in doing true temp measurements using a microwave) in an asymmetric approach.

Catalytic Methods in Asymmetric Synthesis 2011 (Ch. 10 Microwave-assisted Transition Metal-Catalysed Asymmetric Synthesis

Catalytic Asymmetric Synthesis 2010

Optimized Methodologies in Asymmetric Organic Synthesis Applying Microwaves (J Mex. Chem. Soc. 2009)

Finally, let’s look at enough examples to show that there is a place for a microwave approach to chiral compounds.

Here is a recent example of an intramolcular aldol condensation to a morphan scaffold under microwave conditions.

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mw: Intramolecular aldol condensation organocatalytic

Well known allylic substitutions:

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Some typical transformations moving from conventional to microwave (J Mex. Chem. Soc. above)

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Moving from Conventional to mw, then standard transformations esterification, saponification and formation of the amides

Total Synthesis of Strychnos Alkaloid (+)-Minfiensine 2008

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MW Intramolecular asymmetric Heck reaction/iminium cyclization followed by microwave promoted hydroboration

There are certainly some opportunities out there. Having re-read many of these examples it is interesting to note where there are examples of low catalyst turnover and therefore a need to drive the reaction might be a good place for some thought here. Also, it does seem that if there is some stereo-direction in the reaction itself, a microwave approach can be a good one. Let’s not write it off just yet. I bet I could come up with a course of examples where this approach would be suited and often better than what was originally done. Take a look through some of your old work in those 30 step natural product routes and see where you might be doing something a little bit different now. I know there are plenty of hydrogenation and gas addition reactions that should be re-examined under microwave irradiation — definitely some opportunity.

Happy Reading!

 

 

 

 

 

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