New routes to the activation of organic molecules

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Phosphorus compounds are widely used in Chemistry. They are often used in agriculture, materials, medicines and for the activation of organic molecules (such as carboxylic acids). Often the synthesis of these useful compounds uses, toxic, hazardous and/or energy intensive processes and reagents, examples include: PCl5, PCl3, POCl3, phosgene, Cl2 etc. In order to move to a more sustainable future, chemists must develop alternative reagents and methods that are, safer, more stable and therefore easier to use.The most common transformation used by the pharmaceutical industry is amide bond synthesis, representing 1 in 7 reactions performed. As a result, a wide range of coupling (activating) reagents have been developed to couple carboxylic acids with amine nucleophiles. Phosphorus (V) activating reagents are popular (e.g. T3P, DPPA, BOP etc.) as these reagents produce water soluble by-products that can easily be removed by aqueous washing. However, the synthesis of these compounds requires the use of PCl5. Other issues are also presented with the use of phosphorous activating reagents, such as toxicity, water sensitivity and the production of high molecular weight by-products (this applies to BOP), which leads to poor atom economy. This project aims to address these problems by using other non-toxic, low molecular weight phosphorus reagents as coupling partners, which can be sourced without the need to use chlorine gas and/or other toxic and moisture sensitive reagents. Proposed solution and methodologyWithheld due to confidentiality reasons.