Asymmetric Synthesis of β-Lactam via Palladium-Catalyzed Enantioselective Intramolecular C(sp3)-H Amidation

beta-Lactams are important scaffolds in drug design and frequently used as reactive intermediates in organic synthesis. Catalytic reactions featuring intramolecular C-H amidation of alkyl carboxamide substrates could provide a straightforward disconnection strategy for beta-lactam synthesis. Herein, we report a streamlined method for asymmetric synthesis of beta-aryl beta-lactams from propanoic acid and aryl iodides via Pd-catalyzed sequential C(sp(3))-H functionalization. The lactam-forming reaction provides an example of Pd-II-catalyzed enantioselective intramolecular C(sp(3))-H amidation reaction and proceeds up to 94% ee. The use of a 2-methoxy-5-chlorophenyl iodide oxidant is critical to control the competing reductive elimination pathways of the Pd-IV intermediate to achieve the desired chemoselectivity. Mechanistic studies suggest that both steric and electronic effects of the unconventional aryl iodide oxidant are responsible for controlling the competing C-N versus C-C reductive elimination pathways of the Pd-IV intermediate.