Functionalization of anilines through C–H and C–N bonds activation using rhodium and photoredox catalysis

Organic synthesis is undeniably a fundamental science with deep implications in everyday life as part of numerous scientific domains including medicine, agrochemistry, fragrances, energy, or material science. As a result, and considering the extent of organic molecules’ input into everyday life, there is an ever-growing need for straightforward and efficient processes enabling their synthesis starting from widely available, robust and simple building blocks. Among those stand anilines, which are ubiquitous scaffolds found at the core structure of a plethora of natural products as well as biologically active substances both in the pharmaceutical and agrochemical industries. They also constitute one of the most important building blocks in chemistry used in many fields including the dye industry and material science as important isocyanate precursors. Their synthetic access however exclusively originates from the oil industry and the need for alternative sources of chemical feedstocks led to the development of impressively efficient processes valorizing abundant lignin, one of the two main components of wood. Different bio-sourced building blocks that are easily converted to anilines in few chemical steps are therefore now originated from it. Various methods must thereby be developed to further functionalize those lignin-derived building blocks into high value-added chemicals to demonstrate the full potency of the lignin biorefinery. Yet, the selective and direct functionalization of anilines, although being of prime importance, remains fairly challenging depending on the substituent to introduce. Indeed, although many processes relying on pre-functionalized substrates have been reported, these suffer from obvious limitations in terms of time, cost and atom economy. As a consequence, the focus has recently shifted towards the direct and selective functionalization of C–H and C–N bonds which allows for the introduction of various substituents in a more cost-effective manner. Both types of transformations, which are at the core of this work, are still far from being trivial nowadays. In this context, we studied both the C–H bond activation of anilines using organometallic catalysis and a traceless directing group strategy, as well as their C–N bond activation using photoredox catalysis via the formation of ammonium salts, thus offering efficient perspectives for their straightforward functionalization. A comprehensive study of the state of the art regarding the use of transient directing groups in the field of C–H bond functionalization, that enables to overcome the limitations inherent to the use of uncleavable directing groups usually required to achieve selective and efficient processes, will therefore first be presented. Our strategy based on the use of a related traceless directing group to efficiently promote the direct arylation of anilines through the activation of their ortho-C–H bond will next be discussed. Lastly, we will focus on the iridium-catalyzed photoredox approach we envisioned to further functionalize aniline derivatives through C–N bond activation in ammonium salts.

Jaar van publicatie:2022

Trefwoorden:Doctoral thesis

Toegankelijkheid:Closed