Ligand-Switchable Lactamization

Regiodivergent

By switching between 1,6- and 1,5-hydrogen atom transfer, this system selectively lactamizes δ- and γ-methylene C–H bonds within the same molecular skeleton.

Au, Chiming · Wong, Allen Ka Wa · Zhang, Ting · Chan, Ka Lok · Lin, Zhenyang · Yu, Michael Wing Yiu

Angewandte Chemie - International Edition 2025

Advantages

Selects stronger C–H

Lactamization of the γ-methylene C-H bond, which is stronger than the δ-benzylic C-H, occurs preferentially, overriding conventional thermodynamic selectivity.

Mechanism verified

Experimental and computational studies confirm the involvement of open-shell Cu(II)-iminyl diradical intermediates.

Applications

• C–H functionalization：Enables site-selective functionalization of methylene C–H bonds within a single skeleton.
• lactam synthesis：Direct access to δ- or γ-lactams without prefunctionalization.
• copper catalysis：Copper/phenanthroline system offers tunable regioselectivity with abundant metal.