Enhancing Reactivity and Site-Selectivity in Hydrogen Atom Transfer from Amino Acid C-H Bonds via Deprotonation

A kinetic study on the reactions of the cumyloxyl radical (CumO(center dot)) with N-Boc-protected amino acids in the presence of the strong organic base DBU has been carried out. CO2H deprotonation increases the electron density at the alpha-C-H bonds activating these bonds toward HAT to the electrophilic CumO(center dot) strongly influencing the intramolecular selectivity. The implications of these results are discussed in the framework of HAT-based aliphatic C-H bond functionalization of amino acids and peptides.