Catalytic Asymmetric Synthesis of Tröger’s Base Analogues with Nitrogen Stereocenter

Nitrogen stereocenters are common chiral units in natural
products,
pharmaceuticals, and chiral catalysts. However, their research has
lagged largely behind, compared with carbon stereocenters and other
heteroatom stereocenters. Herein, we report an efficient method for
the catalytic asymmetric synthesis of Tröger’s base
analogues with nitrogen stereocenters via palladium catalysis and
home-developed GF-Phos. It allows rapid construction
of a new rigid cleft-like structure with both a C- and a N-stereogenic
center in high efficiency and selectivity. A variety of applications
as a chiral organocatalyst and metallic catalyst precursors were demonstrated.
Furthermore, DFT calculations suggest that the NH···O
hydrogen bonding and weak interaction between the substrate and ligand
are crucial for the excellent enantioselectivity control.