Metal-Free meta-Selective Alkyne Oxyarylation with Pyridine N-Oxides: Rapid Assembly of Metyrapone Analogues

An efficient metal-free oxyarylation of electron-poor alkynes with pyridine N-oxides has been developed. This transformation affords meta-substituted pyridines analogous to the drug metyrapone in high regioselectivities. Density functional theory (DFT) calculations provided important insight into the mechanism. Evaluation of the inhibitory properties revealed the most active CYP11B1 inhibitor of these derivatives, with two-digit nanomolar inhibitory activity akin to that of metyrapone.