β-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 β-lactam synthesis. Herein, we report a streamlined method for asymmetric synthesis of β-aryl β-lactams from propanoic acid and aryl iodides via Pd-catalyzed sequential C­(sp3)–H functionalization. The lactam-forming reaction provides an example of PdII-catalyzed enantioselective intramolecular C­(sp3)–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 PdIV 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 PdIV intermediate.

A new protocol for amide-directed Cu-catalyzed aminoalkylation of unactivated alkenes using cyclobutanone oxime esters as alkyl radical donors is developed. Both primary and secondary alkyl groups can be selectively installed at the C4 position of terminal or cis-internal 3-alkenamides in moderate to good yield. This reaction offers a useful method for the diastereoselective synthesis of β-lactams bearing 4-cyanoalkyl β-substituents. The use of a weakly coordinating counteranion as the Cu catalyst is critical for the formation of β-lactam products.