Copper-Catalyzed Petasis-Type Reaction Enables Efficient Synthesis of C1-Substituted Tetrahydro-β-carbolines

High Resolution Image Download MS PowerPoint Slide Petasis and Petasis-type reactions represent a powerful transformation for constructing a wide array of functionalized amines from simple amines, aldehydes, and organoborons. An α-oxygen or α-nitrogen directing group on the aldehyde component is typically required to facilitate carbon transfer from organoboron to the iminium ion. Herein, we report the first Petasis-type reaction of previously unexplored N -alkyl dihydro-β-carbolinium (DHβC) ions with aryl/alkenyl boronates through novel copper catalysis. The efficiency and utility of this protocol were demonstrated by a broad substrate scope (51 examples, up to 99% yield), excellent scalability (gram scale), and versatile transformations of products. Mechanistic studies suggest that this process proceeds via a novel mechanism involving a copper-mediated intramolecular single-electron transfer (SET). This novel Petasis-type reaction not only significantly broadens the scope of Petasis reactions but also reveals new mechanistic pathways.