Seems that photocatalysis has become front and center in 2015 with no signs of slowing down — much of this has been due to improved methodology and catalyst development – and finding profound chemistries to apply. For me, it has added new and exciting space to flow chemistry, basic research and drug discovery (well specialty chemicals as well). having said that, I still notice a hesitation in application simply because a large percentage of chemists haven’t spent a lot of time around these transformations — couple that with slow traction of chemists digging into flow methods. It is however, something the newer batch (haha!) of chemists are gravitating to and we will start to see a large number of dedicated publications in photo and improvements on flow metalations.
An interesting but not as recent as you would think comes out of the MIT flow group in 2012-2013 utilizing visible light photoredox catalysis in flow. As is with the case of general flow synthesis (over a catalyst bed or at high temp and pressure) the larger surface to volume ratio allows for more control of temp and reaction times — and in this case more efficient irradiation. Within the paper, both oxidative and reductive provide some extremely powerful synthetic manipulations under these conditions and provide a nice framework to advance some of the initial ideas. Overcoming traditional batch light penetration with simple PFA tubing suggests that scale-up of once difficult batch processes will be easily overcome.
Take a look through some schemes that we would normally think of in medicinal chemistry efforts — Easy to perform and powerful — too bad I missed the boat on this one. Enjoy the read — it is thought provoking.
The second area I have been keeping an ear to the ground comes in the newer development in metalation — usually in regard to arenes or heteroarenes and the requisite quench. Expansion out of nBuLi to other Lithiates or Mg, Zn and other possibilities certainly seems to pave a way for new reactions with commercial reactors or at least some ideas on how to apply to your own reactor. Having discussions with fellow chemists on their approach to activate arenes with subsequent quenches remains high on the list of powerful methodologies so improvements that traditional batch chemists can sink their teeth in flow will go a long way in pushing people over to new ways to do their work. A recent publication (Chemical Science, 2015) out of Knochel’s lab provides some insight into a modified flow/batch scheme with Cy2NLi activation in flow followed by a variety of quenches — great to see a commercially available reagent applied with success so that we understand what we can and can’t do….really valuable stuff. Looks to me that we can start to design all sorts of reactions — both high temp/high pressure or simplified kinetic processes over cooling liter reactions to -78C.