Palladium-Catalyzed Enantioselective Hydroamination of Alkoxyallenes with 2-Pyridones

A palladium-catalyzed reaction for the hydroamination of alkoxyallenes with 2-pyridones has been developed. This method is highly chemo-, regio-, and enantioselective, providing efficient access to pyridone-containing <i>N</i>,<i>O</i>-acetals in excellent yields (up to 98%) and enantioselectivity (up to 99% ee). DFT mechanistic studies reveal that enantiocontrol originates in the rate-determining proton transfer step, where dual hydrogen-bonding interactions between the diphosphine ligand's amide group, the alkoxyallene, and the 2-pyridone substrate favor the formation of the (<i>S</i>)-configured <i>N</i>,<i>O</i>-acetal product.