The below resources provide a great starting place for how to optimize your reactions and separations. Whether you want to learn more about column selection, substrate selection, designing screens, Design of Experiments (DoE), or why you might want to run reaction screens in the first place, these resources are a good starting point. Check back, as I will try to keep this page updated as I find more resources.
The CSC has a (growing) variety of columns available for LC, SFC, and GC separations and purifications. Each has strengths and weaknesses. You can find a dedicated page with details on the current columns available and a brief description of uses here.
Not sure where to start your substrate scope? Tired of doing a substrate scope on methyl, ethyl, isopropyl, tert-butyl substituted molecules? Or maybe you just want to be efficient in your substrate scope? The Glorius lab has released a new software tool (10.1021/acscentsci.3c01638) to map the Druge Databank and help in substrate selection. The tool is a bit difficult to use, as it requires running python scripts, but I am more than happy to assist if you need it. Just reach out!
Merck KGa scientists recently released a tool called “Screen It!” for generating reaction screen designs (10.1021/acs.oprd.3c00506). While it does not use DoE principles, it can automatically select different reaction parameters (concentration, ligand, metal precursor, solvent, etc.) and pair them in a combinatorial fashion. The software is fairly easy to use with it’s simple GUI, but has a few bugs present and may need a brief tutorial to find output files. One major benefit: the software was designed to output dispensing instructions specifically for the Chemspeed Crystal Powderdose, a solid dispensing robot soon to arrive in the CSC.
This Nature Protocols article (10.1038/s41596-020-00452-7) walks through an example protocol of how to set up a reaction optimization for a Pd-catalyzed cross-coupling reaction. Another similar example is this guide from Shevlin (10.1021/acsmedchemlett.7b00165). If you’re new to screening, or want to learn a bit about how it can be done manually, this is a great starting point.
If you’re looking to learn a lot about HTE, consider this ebook from the American Chemical Society: The Power of High-Throughput Experimentation: General Topics and Enabling Technologies for Synthesis and Catalysis (10.1021/bk-2022-1419). It covers everything from an introduction to HTE, how to set up labs, data visualization, and case studies.
If you are looking for an explainer about what the different methods of reaction optimization are (DoE, OFAT, kinetic modeling, statistical modeling), there is a very good Chem. Rev. article about it (10.1021/acs.chemrev.2c00798).
Need to dispense a solid that’s too powdery, too clumpy, or just need to dispense a very small amount quickly and efficiently? Try using Chembeads. By coating small glass beads with a finely-powdered solid, a researcher can create a material that is approximately uniform in density and easy for robotic platforms to handle. Uniform density also allows for rapid, low precision “dispensing” of Chembeads using pre-calibrated plastic scoops. Find more about how to make your own Chembeads (10.1021/acsmedchemlett.2c00491).