Year: 2026
Type: preprint
Abstract: Self-driving laboratories (SDLs) can accelerate chemical optimisation, yet their application has largely focused on established reaction classes rather than the uncertain and iterative process of developing new reactivity. Here we introduce human-robot collaborative reaction development, in which researchers drive ideation, interpretation and scientific decisionmaking, while an SDL performs the systematic experimentation required to rapidly evaluate emerging reaction concepts. We demonstrate this approach through the development of a photochemical α-(fluoro)alkylation of cyclic secondary amines via in situ imine formation. Starting from an initial human-discovered reactivity hit, RoboChem-Flex was repeatedly deployed as new questions emerged: to establish whether the reaction warranted further development, adapt conditions to di erent substrate classes, rapidly assess coupling partners, and optimise promising but underperforming reactivity. Transfer of knowledge between campaigns further enabled an initially low-yielding α-methylation to be developed in only 11 additional experiments. The resulting methodology accommodates diverse cyclic amines and alkyl iodides and enables downstream derivatisation. More broadly, this work demonstrates how autonomous experimentation can augment human scientific reasoning, accelerating the transition from initial reactivity to synthetic methodology while keeping scientific judgement at the centre of the discovery process.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G1813177081, G2252040367, PhotoScale: Scaling photochemical transformations in a Rotor-Stator Spinning Disk Reactor, G4752879978, G4764974982, C-H Activation for Industrial Renewal, G7443551839, G7454019104, Photocatalysis as a tool for synthetic organic chemistry, G7805334640, Fibre-based plasmonic micro reactor for flow chemistry, INCEPTION: INdustrial roboChEmic PlaTform ImplementatiON, G8205278178, MERGING SUSTAINABLE AND DIGITAL CHEMICAL TECHNOLOGIES FOR THE DEVELOPMENT OF GREENER-BY-DESIGN PHARMACEUTICALS
OpenAlex ID: W7204863257