Rhodium(I)-Catalyzed Asymmetric Hydroarylative Cyclization of 1,6-Diynes to Access Atropisomerically Labile Chiral Dienes

Axially chiral open-chained olefins are an underexplored class of atropisomers, whose enantioselective synthesis represents a daunting challenge due to their relatively low racemization barrier. We herein report rhodium(I)-catalyzed hydroarylative cyclization of 1,6-diynes with three distinct classes of arenes, enabling highly enantioselective synthesis of a broad range of axially chiral 1,3-dienes that are conformationally labile (delta G activation (rac) = 26.6-28.0 kcal/mol). The coupling reactions in each category proceeded with excellent enantioselectivity, regioselectivity, and Z/E selectivity under mild reaction conditions. Computational studies of the coupling of quinoline N-oxide system indicate that the reaction proceeds via initial oxidative cyclization of the 1,6-diyne to give a rhodacyclic intermediate, followed by sigma-bond metathesis between the arene C-H bond and the Rh-C(vinyl) bond, with subsequent C-C reductive elimination being enantio-determining and turnover-limiting. The DFT-established mechanism is consistent with the experimental studies. Significantly, the coupled products of quinoline N-oxides undergo facile visible light-induced intramolecular oxygen-atom transfer, affording chiral epoxides with complete axial-to-central chirality transfer.

(Angew. Chem. Int. Ed. 2023, e202312923)

Congratulations to Panjie Hu. Special thanks also go to our collaborators.