Beyond the Numbers: Charting Chemical Reaction Space

We present here an informed estimate of the millions of parameter settings that might be required to optimise one typical transition-metal-catalysed reaction. We describe briefly how both Design of Experiments (DoE) and Principal Component Analysis (PCA) techniques may be combined to reduce the number of potential reaction settings to a practical number of experiments without losing critical information. A key feature of this approach is the ability to relate discrete or discontinuous parameters to one another. The methodology is presented so that any reaction may be assessed in a similar way. We believe this represents for the first time an informed estimate of the number of potential permutations that are possible for these types of reactions in particular, and therefore the enormity of the task in optimising them. The powerful combination of DoE and PCA applied systematically and in an experimentally directed approach is beneficial for optimising reactions, particularly challenging transition-metal-catalysed reactions. However, this approach is beneficial to all reactions, especially when dealing with discrete parameters, such as solvents for example.