Unlocking the Accessibility of Alkyl Radicals from Boronic Acids through Solvent-Assisted Organophotoredox Activation

Despite their prevalence in organic synthesis, the application of boronic acids (BAs) as alkyl radical precursors in visible-light-assisted photocatalyzed reactions has been limited by their high oxidation potential. This study demonstrates the prominent ability of amide solvents, namely, N,N-dimethylacetamide, to participate in hydrogen-bonding interactions with BAs, thus enabling the modulation of their oxidation potential toward the generation of alkyl radicals. The developed protocol is simple and robust and demonstrates broad applicability for alkylation, allylation, and elimination reactions in batch and continuous flow. The application toward dehydroalanine allows the synthesis of unnatural amino acids. Furthermore, the chemoselective generation of radical species from BAs in the presence of boronic ester-containing molecules is now feasible, endorsing plausible boron-selective (bio-) orthogonal modifications.

Automated summary

This study demonstrates the use of amide solvents to modulate the oxidation potential of boronic acids for alkyl radical generation in visible-light-assisted photocatalyzed reactions. The developed protocol is simple and applicable for various reactions, including the synthesis of unnatural amino acids. Furthermore, selective generation of radical species from boronic acids in the presence of boronic ester-containing molecules is now feasible, allowing for potential boron-selective modifications.