Carrying with the theme of using reactive gases in a microwave reactor will quickly lead to hydrogenation and hydrogenolysis techniques. There has been much written on the subject – too much to account for, but I will mention some of the key features and improvements over the last several years. As far back as 1999, Professor Bose at the Stevens Institute of Technology published a paper on transfer hydrogenations for synthetic reactions. In the paper, several considerations to using hydrogen as well as reaction set-ups are discussed: the ability to use an open-system from the in situ generation of hydrogen from a hydrogen donor (ammonium formate, cyclohexadiene, formic acid), specific hydrogenation reactions with the need for higher pressure and elaborate equipment. This was an excellent paper showing CTH applications — ammonium formate with RaNi in ethylene glycol at atmospheric pressure producing high yields in the following azetidinones below. To set the stage correctly however, it should be noted that reactor, closed-vessel technology and the addition of H2 had not yet developed.

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Moving forward — Kappe’s recent books and reviews will provide the most up to date examples of reactions under H2 pressure and CTH methodologies. I have also included an example from his work as well (free access from Angewandte Chemie 2004).

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MW CTH NO2 hydrogenation

OK — we have the starting point and the present, but several things went in between. As I mentioned, several events had to take place. For one, there was a strong belief in the organic community that H2 in a closed microwave reaction was not all that safe. One thing was clear, if the vessel can not handle the pressure or temperature, this was not a good starting point. This was more of a “gas and pressure thing” than the type of reaction itself. A reasonable recent review by Elena Perticci and Maurizio Taddei goes into some detail of some of the developments pre-2007. To set the record straight, all of the commercial vendors have developed safe set-ups to use H2 gas and it comes down to scale, pressure requirements and and the additional chemistry research needs. Heck, even I have fun using the tank and filling the reaction chamber.

Presently there is a need for both type of reaction techniques. Microwave transfer hydrogenations are constantly used — especially with the development of new catalysts. A recent example of 1,4-cyclohexadience with Pd/C used for hydrogen transfer for double-bonds along with N-Cbz  and OBn deprotections (TL 2008). If you feel like reading some more — there is a nice publication on microwave transfer hydrogenations of ketones with Ru(xantphos) complexes to provide the alcohol in near quantitative yield (ChemCatChem 2012). Tying back to earlier thoughts on ionic liquids (IL), CTH under microwave irradiation takes place in an IL medium as well (Synthesis 2002).

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The use of H2 gas under higher pressure also has its’ place on the bookshelf, and there are still many examples where the pressure needs to help the reaction along, even when accelerated by microwave irradiation. Some recent work reflects several examples where much higher pressure is required, even a dearomatization (not such a simple transformation) reaction with 60 bar H2.

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MW CBZ removal H2

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Dearomatization MW H2

Give these techniques some consideration while digging in the organic toolbox, both microwave and reactive gases can be combined as an innovative technique.