Boronic Acids and Their Derivatives as Continuous-Flow-Friendly Alkyl Radical Precursors

Abstract

AbstractSince its recognition as an enabling tool to form challenging C–C and C–heteroatom bonds under mild and sustainable conditions, photoredox catalysis has been in the spotlight within the synthetic community. As a consequence, the interest in developing novel synthetic strategies has spiked together with the need to define suitable technologies to overcome scale-up issues dictated by the Bouguer–Beer–Lambert law. In this context, continuous-flow reactors play a major role in increasing the efficiency of a given photocatalyzed reaction, thus rendering scale-up processes more accessible. In the alkyl radical precursor landscape, boron-based species have begun to play a predominant role. Though the reactivity of trifluoroborates has been deeply investigated, the interest in using other boron species as radical precursors in photocatalyzed reactions has recently arisen. This late exploration lies in the fact that the high oxidation potential of boronic acids (BAs) hinders their possible applications. Nevertheless, to circumvent this issue, a diverse array of activation modes has been developed, exploiting in most cases the inherent Lewis acidity of the boronic acid. The aim of this Account is to highlight our recent contribution to this vibrant field with a focus on broad applicability, selectivity, and scalability via continuous-flow methodology. For the sake of clarity, the Account is discussed under the following sections.1 Introduction2 Why Photochemistry in Flow?2.1 Preliminary Considerations2.2 Batch vs. Flow Photochemical Reactions2.3 Commercially Available Lab-Scale Solutions for Photoflow Chemistry3 Organoboron Compounds3.1 The Evolution of Organoboron Compounds as Radical Precursors in Photoredox Catalysis3.2 Organoboron Compounds in Flow4 Activation of Boronic Acids towards Radical Formation4.1 Giese-Type Addition4.2 Petasis Reaction4.3 Light-Driven Four-Component Reaction4.4 Minisci Reaction5 Conclusion and Future Perspective