An autonomous organic reaction search engine for chemical reactivity

• Published in: Nature communications Vol. 8; no. 1; p. 15733
• Main Authors: Dragone, Vincenza, Sans, Victor, Henson, Alon B., Granda, Jaroslaw M., Cronin, Leroy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/549/973; 639/705/1042; 639/705/1046; Algorithms; Automation; Chemistry; Humanities and Social Sciences; multidisciplinary; Optimization; Reagents; Real time; Science; Science (multidisciplinary); Search engines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15733

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.
While automated reaction systems typically work for the synthesis of pre-defined molecules, automated systems to discover reactivity are more challenging. Here the authors report an autonomous organic reaction search engine that allows discovery of the most reactive pathways in a multi-reagent, multistep reaction system.