An axial-to-axial chirality transfer strategy for atroposelective construction of C–N axial chirality

Abstract

<h2>Summary</h2> C–N axially chiral skeletons are ubiquitous in bioactive natural products, pharmaceuticals, and chiral ligands. However, their atroposelective synthesis remains a formidable challenge because of their innate low configurational stability compared with that of well-developed C–C atropisomers. Herein, we report a general and efficient method for accessing C–N atropisomers through an axial-to-axial chirality transfer strategy based on palladium/chiral norbornene cooperative catalysis. The obtained C–N axial chirality originates 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.