Synthesis of Chiral Aldehyde Catalysts by Pd-Catalyzed Atroposelective C-H Naphthylation.

ABSTRACT

Chiral aldehyde catalysis opens new avenues for the activation of simple amines. However, the lack of easy access to structurally diverse chiral aldehyde catalysts has hampered the development of this cutting-edge field. Herein, we report a Pd-catalyzed atroposelective C-H naphthylation with 7-oxabenzonorbornadienes for the preparation of axially chiral biaryls with excellent enantioselectivities (up to >99 % ee). This reaction is scalable and robust, which serves as a key step to provide a rapid access to axially chiral aldehyde catalysts through a three-step C-H functionalization sequence. These chiral aldehydes exhibit better activities and enantioselectivities than the previously reported organocatalysts in the asymmetric activation of glycine derived amides and dipeptides. Moreover, preliminary investigation also discloses that the aldehyde catalyst can effectively override the intrinsic facial selectivity of chiral dipeptide substrates, showcasing the strong chiral induction ability of this type of novel aldehyde catalysts.