Click, Click Zoom……new Cu catalyst developments, Click Huisgen cycloadditions

Rather than spend a chunk of time outlining developments of monoliths or scavengers, I decided that it would be better to push out some of the new ideas and exploration. We are aware that a number of groups are using Cu catalysts beds and cartridges, but a new publication uses a microchannel itself as the Cu source — followed closely behind the mixing of an azide and alkyne for the requisite step……love it. This process gives way to trying several types of catalysts to look at turnover numbers (TONs) and mechanisms themselves. For me, I would take the best and make a larger catalyst bed out of it so that scaling can be an option as well. Enough of that — collaborative groups out of Japan (Chemistry 2015) show us the way with their investigation of a Huisgen cycloaddition from the generation of 4 microchannel polymeric Cu membranes (will make you read into the formation — it looks elegant and formally pretty easy)– once formed azides and terminal acetylenes are flowed through the microchannels in a 3:1 mixture of Acetone:H2O at 50C in a residence time of 8 sec (some a few seconds longer, hahaha!– there is a difference in the the catalytic activity of each of the microchannel membranes but the reactivity is a significant enhancement over traditional catalysts and worth a note that flow can be a real progress to not only this chemistry but the concept in general.

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Microchannel A or catalyst A if you prefer shows the best results from their study and also helps us recognize the differences in the Cu source and a preferred mechanism. Read further into what they propose as to why the process is so efficient — I have included a snapshot of their photos of the channel following the formation and post 24 hrs. Several options are available in the selection of solvent for the reaction as well. Further reading indicates that the reaction is available for more complexity and added functional groups adding to its’ utility.

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I have included a table for their screening of the membrane A to show that this process is amenable to screening and library development – a criteria now maintained in the flow community for medicinal chemistry traction — hopefully there will be a number of people who take up the role of improving these possibilities rather than rely on commercial availability as a precursor. I see this as a natural trend to the development of these catalysts into a bed or bound so that it is amenable to standard medicinal chemistry processes (they did show some more advanced application to the development)……one can hope, right?

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Enjoy the read!