Iridium-Catalyzed Borylation of Strong Alkyl C(sp3)–H Bonds of Sulfonamides Enabled by Triflyl Activation

Abstract

The development of new catalytic methods for the functionalization of strong and inert sp3 C–H bonds remains a major area of interest in synthetic chemistry, as it holds the potential to revolutionize strategies for constructing organic molecules. Despite the high demand, difficulties associated with the designing of reactive ligand and catalyst frameworks capable of offering a general platform have restricted its exploration in the field of C–H borylation. Herein, we report a strategy for sp3 C–H borylation of a wide range of acyclic and cyclic amines by incorporating trifluoromethanesulfonyl (triflyl) as an activating group and by employing a commercially available ligand under iridium catalysis. This method demonstrates highly selective borylation of primary C–H bonds at various positions (α-, β-, γ-, and δ-) with good to excellent isolated yield of the desired products. A series of control experiments, along with extensive DFT calculations, demonstrated that both electrostatic interactions and the formation of a strong Ir–C bond are essential for stabilizing the key Ir(V) hydride intermediate. Moreover, the utility of our developed method was established through the application in the regiospecific N-centric alkyl chain modification of important amino acid derivatives, affording structurally diverse and high-valued scaffolds.