Applications of mechanochemistry in AgChem Research

Mechanochemistry is emerging as a versatile technology to conduct reactions without bulk solvents and is becoming more widespread as a technique for molecular synthesis with new mechanochemical reactions being discovered at increasing frequency. Previous work has demonstrated the facile generation of organozinc reagents (and subsequent Pd-catalysed Negishi coupling) under mechanochemical conditions which remains a challenge under standard bench conditions, particularly when considering applications in automation/library synthesis. The proposal aims to extend this work to other Zn- or Mn-metal mediated cross-coupling reactions, particularly with a focus on sp2-sp3 or sp3-sp3 couplings which are difficult to achieve using Suzuki-coupling methods. We will target the establishment of an ability to process small focussed libraries of this type of chemistry. Moreover, several emerging methods in the literature; such as radical couplings and nickel catalysed transformations, require the use of these base metals to terminate redox cycles. Thus developing mechanochemical capabilities in house for processing Zn and Mn mediated reactions may allow ready adoption of these new methods whilst reducing our dependence on solvent. Part of this project will involve a 3 month visit to Syngenta for two-way knowledge transfer activities. This project is directly relevant to Physical Sciences, Manufacturing the Future & Living with Environmental Change Themes, both in terms of delivering sustainable alternatives to current methods and directly aligns with Synthetic Organic Chemistry. This project, and resulting publications could have a direct impact on the adoption and investigation of this technique by other chemical manufacturers.