In my last blog post I talked about solid reagents used for CO generation in situ. Although that is a nice workaround and very creative for doing a number of transformations, there is still nothing like being able to use reactive gas to carry out the chemistry. If you took a look at the post — I still would like to be able to a number of modifications in the microwave at the same time, switching Pd sources, solvents and even reactions — wouldn’t it be cool to run heteroaryl triflates with Hermann’s palladacycle in one vessel and Pd(OAc)2 with halides in the next vessel — with different solvents and different amines and alcohols so that at the end you came out with a slide with arrows to fifteen different products in one microwave method…..ok before I get off the point.

Recent work from Leadbeater and Kromos indicate that hydroxycarboxylations and alkoxycarboxylations can be performed under microwave conditions under a pre-loaded atmosphere of CO in a multimode microwave. It is worth noting that solvent, CO loading and aryl iodides had the most striking results. Since CO is more soluble in alcohol over H2O, these reactions tended to need less temperature. The systems were loaded with 10 bar (for esters)and 14 bar CO (for acids).

Screen Shot 2013-10-25 at 9.49.31 PM

Microwave CO insertion with reactive gas addition (acids and esters)

Leadbeater was also able to show how this process could be scaled up to the 1 mol scale using single reaction chamber (SRC) technology microwave design (shown below). Several things of note: 1) they flushed the system with N2 followed by CO then reloaded with N2 and added on top of that the amount of CO needed for several reactions (6 reactions on the 50 mmol scale) run simultaneously, then the same process was used for the larger scale reactions (scheme 2).

Screen Shot 2013-10-25 at 9.18.41 PM

UltraClave microwave SRC CO insertions

Screen Shot 2013-10-25 at 10.03.44 PM

Evolution of gaseous CO microwave approaches

Newer SRC designs (see SynthWAVE in previous posts) enable multiple gas inlets that can expand the work done here to include flushing and loading with ease as well as mechanical stirring. As the technology changes so should the possibilities — in the article, they are able to perform several reactions simultaneously so it gives me pause for thought that we should be able to do several independent unique reactions under microwave conditions. For SRC, there is a pool of liquid absorbing the microwave energy and controlling the temperature and conditions — with the right solvent in the pool and pre-pressurization, the boiling point of each solvent and the liquid pool is raised, giving the possibility to run different reactions that are otherwise not a good idea in multimode reactors. Although I have started to see this mainly from the inorganic chemists, there is certainly room to play for everyone. We should start to see higher pressure hydrogenations and carbonylations. A recent publication out of Cravotto’s lab indicates that this thinking is ongoing (a nice picture of multiple reactions in the SynthWAVE).

Screen Shot 2013-10-25 at 10.34.04 PM

Multiple microwave Heck reactions with cross-linked cyclodextrin catalysts

Advertisements