Efficient Construction of Nitrogen-Stereogenic Azepines via Pd(II)-Catalyzed Enantioselective C–H Olefination

The asymmetric construction of N-stereogenic
compounds
is a fundamental challenge in synthetic chemistry, primarily due to
the low energy barrier for pyramidal inversion, leading to rapid racemization.
While established strategies stabilize such centers through structural
rigidification, efficient approaches to flexible N-chiral scaffolds remain scare. Herein, we report the highly enantioselective
synthesis of a broad range of configurationally stable but flexible N-stereogenic tribenzo[b,d,f]azepines via palladium-catalyzed enantioselective C–H olefination
(41 examples, up to >99% ee). The configurational
stability originates from a distinctive saddle-shaped molecular conformationa
strategy different from conventional structural rigidification strategies
that rely on covalently tethering all three N-substituents.
The practicality of this protocol is demonstrated through gram-scale
synthesis and downstream transformations to N-chiral
carboxylic acid ligands. Moreover, these compounds exhibit good circularly
polarized luminescence (CPL) with high dissymmetry factors (glum values up to 0.011), positioning them as
promising candidates for advanced chiroptical materials.