Preparative Synthesis of Highly Substituted Tetrahydropyridines via a Rh(I)-Catalyzed C–H Functionalization Sequence

Abstract

We report a Rh­(I)-catalyzed C–H activation/alkenylation/electrocyclization cascade and subsequent reduction for the synthesis of highly substituted tetrahydropyridines. These products can be accessed on a gram scale with low catalyst loadings and at high reaction concentrations. Additionally, a modified Rh-catalyst, prepared from [RhCl­(cod)]₂ as a robust bench-stable precatalyst was developed to enable straightforward reaction set up without the use of a glovebox. To demonstrate the practicality of this reaction, a >100 mmol scale Rh-catalyzed cascade reaction sequence utilizing the air-stable precatalyst [RhCl­(cod)]₂ was performed on the bench to furnish the pure tetrahydropyridine product in 93% yield