Continuous collective analysis of chemical reactions

Modularized synthesis of small organic molecules is transforming our capacity to create medicines and materials. Disruptive acceleration of this molecule building strategy will broadly unlock its functional potential and requires integration of many new assembly chemistries. Recent advances in high-throughput chemistry stand to enable selection of appropriate chemical reaction conditions from the vast range of potential options. However, a disconnect between the rates of exploration and evaluation has limited progress. Here we report how intrinsic fragmentation features of chemical building blocks generalizes their analysis to yield sub-second readouts of reaction outcomes. Central to this advance was identifying that groups typically attached to boron, nitrogen, and oxygen atoms fragment in a specific and selective manner by mass spectrometry, enabling target agnostic analysis. Combining these features with acoustic droplet ejection mass spectrometry we could eliminate slow chromatographic steps and continuously evaluate chemical reaction outcomes in multiplexed formats. This allowed rapid assignment of reaction conditions to molecules derived from ultra-high throughput chemical synthesis experiments.