Rhodium-catalyzed pyridine-assisted C–H arylation for the synthesis of planar chiral ferrocenes

Abstract

Planar chiral ferrocenes are widely applied in organic synthesis, materials science, and medicinal chemistry, but their synthesis is not trivial. Herein, a highly efficient synthesis of planar chiral ferrocene-based pyridine derivatives via Rh(I)-catalyzed direct coupling of pyridylferrocenes with aryl halides was developed. Good yields and excellent enantioselectivity (95–>99% ee) are obtained for a wide range of substrates. The compatibility of gram-scale synthesis and relatively low catalyst loading (down to 1 mol% based on [Rh]) enhance the practicality of the current method. The generated coupling products can be readily transformed into chiral ligands. Mechanistic studies suggest that the C–H bond cleavage of pyridylferrocene may be a reversible step and not the rate-determining step. Significant nonlinear effects indicate the existence of multiple metals or ligands in the active.