Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PHOTO-BORAD (Boron chemistry in a new light: exploring the radical reactivity of boronate complexes through photochemical strategies)

Teaser

Sunlight driven organic reactions are important processes in Nature, sustaining essential biochemical processes such as photosynthesis, crucial for our biosphere. During the last few decades, researchers have tried to emulate these processes and visible light photochemistry...

Summary

Sunlight driven organic reactions are important processes in Nature, sustaining essential biochemical processes such as photosynthesis, crucial for our biosphere. During the last few decades, researchers have tried to emulate these processes and visible light photochemistry has been recognised as a tremendously versatile tool for organic synthesis, allowing the discovery of a number of powerful methodologies.
In this research we have successfully merged two major pillars of synthetic methodology which were previously unconnected: visible light photochemistry and polar 1,2-metallate rearrangements. The chemistry has opened novel unprecedented strategies for the efficient and selective synthesis of densely functionalised boronic esters and enantioenriched chiral aromatic molecules, which are valuable and versatile building blocks for the synthesis of drugs candidates and medicines.

Work performed

We have demonstrated that merging photoredox chemistry with metallate rearrangements is a successful strategy for building up molecular complexity.
After a brief optimization we found that vinyl boronate complexes could be reacted with radicals under visible light irradiation to access a number of densely functionalised boronic esters, introducing valuable functional groups such as nitriles, sulfones, esters and amides. These structures are particularly interesting for medicinal chemistry and could be easily handled for the synthesis of more complex molecules.
After this achievement, we have extended the process to aromatic systems for the stereoselective synthesis of chiral molecules. Heteroaromatics are usually key motifs in medicinal chemistry and crop science and it is expected that this methodology will pave the way for the invention of new valuable structures.
Finally, our photochemical methodology has been successfully applied to a third project involving strained boronate complex to achieve the stereoselective synthesis of cyclobutanes, challenging synthetic targets with wide application in medicinal chemistry.
The expertise of the fellow in photochemistry and radical chemistry, together with the knowledge of the PI in boron chemistry, have driven a thorough mechanistic understanding of the process with many details being unveiled.
The work has been published in internationally recognised peer-reviewed journals and has been presented in renown international conferences with poster and oral presentation, ensuring prompt dissemination of the results.
In addition, the Fellow has been invited to deliver several seminars in international Universities (in Italy, UK and Switzerland) where he showcased his results to students (undegraduates/post-graduates) and academics. The general public has also been exposed to the results of this research through outreach activities. The Fellow has been presented the results of this research to the lay audience in the Marie-Skłodowska Curie Open Day 2017 in Bristol, published an outreach article: “Shine light on your flask! New opportunities for organic chemistry” available in open source in the University of Bristol website (outreach section) and created a Facebook webpage to promote the outreach activities of Marie-Skłodowska Fellows in Bristol (https://www.facebook.com/groups/1897184747165033/), where pictures of the events are available for free.

Final results

During the last decade, photoredox catalysis has emerged as a tremendously versatile tool for organic synthesis, while metallate rearrangements have been utilised for the stereoselective synthesis of complex molecules. The research funded by this Marie-Skłodowska Curie Fellowship has merged these two powerful fields, significantly enlarging the scope and the potential of both visible light photochemistry and boron chemistry. The new methodology discovered tremendously impacted the field of organic synthesis, and there is no doubt that the new reactions discovered will find broader application, impacting the way valuable molecules and drug candidates are produced in the pharmaceutical industry.
In addition, harnessing chemical technologies effectively and sustainably is a key element for achieving a EU sustainable development. The chemistry discovered significantly impacted society, showing how the use of inexhaustible and green solar light could be harnessed as an alternative energy source for the development of new powerful methodologies for organic chemistry.
Finally, the methodology reported has impacted academia, with other groups developing new chemical methodologies inspired by our results. It is predictable that other groups will further expand the scope of this methodology in the future, contributing to improve the synthetic value of this exciting methodology.

Website & more info

More info: http://www.chm.bris.ac.uk/org/aggarwal/research.php.