Construction of Axially Chiral Dialdehydes via Rhodium-Catalyzed Enantioselective C−H Amidation

Abstract

Achieving axially chiral biaryl dialdehydes through asymmetric catalysis remains significantly challenging due to the lack of efficient strategies. In this report, we developed a rhodium-catalyzed enantioselective C−H amidation through chiral transient directing group strategy. With this new approach, a series of axially chiral amido dialdehydes were achieved in up to 86% yields with 99.5:0.5 er. Furthermore, detailed mechanistic studies indicated that both the imine formation and C−H bond cleavage steps were reversible. More interestingly, the X-ray crystallographic analysis of Int-2 showed probable C−H/π interaction between biaryl group and chiral amine moiety. This process offered a convenient route to access axially chiral dialdehyde derivatives. More broadly, it demonstrated a new tool through transient and C−H/π synergistic interactions, which would stimulate further development of asymmetric catalytic system in enantioselective C−H functionalization.