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ERC

MAKEITSIMPLE Report Summary

Project ID: 279622
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Final Report Summary - MAKEITSIMPLE (Make it simple: towards a new era for organic synthesis)

Organic synthesis has undeniably made tremendous progress over the past two centuries. Nevertheless, our ability to efficiently synthesise molecules is mostly limited to targets of low structural complexity. Preparing more sophisticated compounds is currently possible; however, their syntheses are highly inefficient: they usually involve a high number of reaction and purification steps, with a consequent increase in waste generation, and a dramatic reduction in overall yields. Consequently, these syntheses are generally not applicable to the sustained production of complex molecules of interest. This observation has led to a general consensus in the scientific community as to the urgent need for new chemical processes supporting the development of a “greener” and more sustainable chemical industry.

Traditional synthetic strategies require the presence of reactive functional groups that are used as handles for further functionalisation. This requirement is one of the factors dramatically enhancing the difficulty of syntheses. The last two decades have seen the emergence of a more straightforward alternative: the direct functionalisation of C-H bonds. Through this strategy the typically inert C-H bonds, ubiquitous in organic molecules, can be activated by transition metal catalysts and subsequently functionalised. This approach has allowed us to dream of a future where any organic molecule could be synthesised in a direct manner by simply replacing the C-H bonds of a substrate with the required functionalities, as if building a ball-and-stick molecular model with our hands. The development of a full set of C-H functionalisation methodologies will impact on all applied areas, such as the synthesis of pharmaceuticals, agrochemicals, and new materials. Furthermore, their atom efficiency and low waste generation ensures a privileged position among the green chemistry methods.

In this project we have investigated several avenues towards the C-H functionalisation of aromatic compounds. In order to tackle this challenge we have adopted a three pronged strategy: 1) the development of catalytic systems able to carry out these reactions under mild conditions (energy efficiency) and with broad functional group tolerance. In this area, we have developed novel methods that are able to proceed at room temperature (instead of the normally required 100-200 °C) thus allowing significant energy savings and minimising possible side reactions. Furthermore, we have been able to develop methods that avoid the use of the common (sometimes toxic) organic solvents, using water instead as a readily available, easily recoverable, green solvent. 2) A second approach has been devoted at developing completely new tools for C-H functionalization in order to access types of functionalization that were not available. In particular, we have been exploring the use of gold as a catalyst, which has shown a completely unprecedented level of precision in performing reactions between two aromatic molecules. Our work in this area has demonstrated that gold can be used as a key catalyst that allows taking two different aromatic compounds, carry out selectively a C-H activation in each of them, and finally join them together with complete selectivity. 3) Finally, we have developed a conceptually new approach for designing new tools for catalytic C-H functionalization that is inspired on the way enzymes catalyse reactions in biological systems. In this work, a transition metal (chromium) is used to enhance the reactivity of the substrate (an aromatic compound) via non-covalent interactions. In the future, we aim at further improving these methods so that they can become one of the tools of choice for the synthesis of pharmaceuticals, polymers, coatings for electronic components and organic light emitting diodes, to cite a few among many other applications.

Reported by

THE UNIVERSITY OF MANCHESTER
United Kingdom
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