Abstract

C–N axially chiral skeletons are ubiquitous in bioactive natural products, pharmaceuticals and chiral ligands. However, their atroposelective synthesis remains a formidable challenge due to the innate low configurational stability as compared to the well-developed C–C atropisomers. Herein, we report a general and efficient method to access C–N atropisomers through an axial-to-axial chirality transfer strategy based on palladium/chiral norbornene cooperative catalysis. The obtained C–N axial chirality is originated from the preformed transient C–C axial chirality with high fidelity. A variety of C–N axially chiral phenanthridinones are obtained in excellent enantioselectivities (44 examples, up to >99% ee). This method can be applied for the construction of two stereogenic axes via double atroposelective C−H arylation or further transformation of the products via axial-to-axial diastereoinduction. Additionally, the reaction mechanism and the chirality transfer process are elucidated by density functional theory calculations.

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