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

Abstract

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.

Enantioselective Reaction of Diynes and Multiynes for the Synthesis of Axially Chiral Compounds

“…Very recently, Li and co-workers described a novel rhodiumcatalyzed asymmetric hydroarylative cyclization of 1,6-diynes with diverse types of arenes via CÀ H bond activation, affording a variety of axially chiral 1,3-dienes in high enantioselectivities. [29] Scheme 12. Synthesis of axially chiral heterobiaryls via organocatalytic asymmetric diyne cycloaddition.…”

Synthesis of axially chiral diaryl ethers via NHC-catalyzed atroposelective esterification

“…Atropisomerically enriched chiral frameworks find widespread applications in materials science, 1 bioactive molecules, 2 and asymmetric catalysis. 3 Accordingly, significant progress has been achieved in the catalytic construction of axially chiral scaffolds, including biaryl atropisomers, 4 axially chiral styrenes, 5 amines, 6 amides, 7 boranes, 8 etc. As distinctive atropisomers, axially chiral diaryl ethers bearing two potential axes find unique applications in bioactive molecules.…”