Dirhodium–Palladium Dual-Catalyzed [1 + 1 + 3] Annulation to Heterocycles Using Primary Amines or H2O as the Heteroatom Sources

Abstract

The ever-increasing demand in chemical biology and medicinal research requires the development of new synthetic methods for the rapid construction of libraries of heterocycles from simple raw materials. In this context, the utilization of primary amines or H₂O as the simple N- or O-sources in the assembly of a heterocyclic ring skeleton is highly desirable from the viewpoint of atom- and step-economy. Herein, we describe a highly efficient three-component reaction of diazo, allylic diacetates, and commercially available anilines (or H₂O) to access structurally diverse pyrrolidine and tetrahydrofuran derivatives. This formal [1 + 1 + 3] annulation reaction features high efficiency, good yields, and broad functional group compatibility, making it a versatile and robust platform for the (formal) synthesis of several important bioactive molecules. Mechanistic studies suggested that the dirhodium–palladium bimetallic relay catalysis should play a key role in the successive steps of the current reaction, including sequential carbene insertion into the X–H bond and double allylic substitutions, thus allowing for building up molecular complexity from these simple raw materials.